Clinical trial NCT01976364
Conditions: Arthritis, Psoriatic
Keywords: Tofacitinib Psoriatic Arthritis Xeljanz CP-690550 Jak-inhibitor oral treatment psoriasis OPAL BALANCE methotrexate pruritus itch DLQI
Sponsor: Pfizer
Start date: 2014-02-17; Completion date: 2019-05-20
Enrollment: 686 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This is a Phase 3, long-term open-label extension study to evaluate the safety, tolerability and efficacy of tofacitinib in subjects with active PsA who have previously participated in randomized studies of tofacitinib for this indication.

This study will include a sub-study to evaluate the efficacy, safety and tolerability of tofacitinib 5 mg BID administered as monotherapy after methotrexate withdrawal compared to tofacitinib 5 mg BID continued in combination with methotrexate. The sub-study will be available to subjects who have completed at least 24 months of participation in the open-label extension study and meet eligibility criteria for the sub-study.

Detailed description:

Arms: arm 1: None
Interventions: intervention 1: Tofacitinib intervention 2: Tofacitinib intervention 3: Methotrexate intervention 4: Placebo Methotrexate
Intervention descriptions: intervention 1: Tofacitinib 5 mg tablet twice daily intervention 2: Tofactinib 10 mg tablet twice daily intervention 3: Methotrexate 7.5-20 mg weekly intervention 4: Placebo to match active methotrexate orally once a week

Protocol documents:
Prot_000.pdf: 
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A LONG-TERM, OPEN-LABEL EXTENSION STUDY OF TOFACITINIB 
(CP-690,550) FOR THE TREATMENT OF PSORIATIC ARTHRITIS
Investigational Product Number:
CP-690,550
Investigational Product Name:
Tofacitinib
United States (US) Investigational New 
Drug (IND) Number:
European Clinical Trial Database 
(EudraCT) Number:
2011-002169-39
Protocol Number:
A3921092
Phase:
3
CCI


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Document History
Document
Version Date
Summary of Changes and Rationale
Amendment 4
12 April 2017

Updated template changes in appropriate sections
and corrected typographical errors.

Protocol Summary updated to reflect new sub-study.

Sections 1.2.2., 1.2.3 and 1.2.4. Updated with 
information from Tofacitinib December 2016 
Investigator’s Brochure.

Incorporated administrative letters in Sections 5.6.1 
and 7.6.9.1.

Section 9. Updated to reflect changes for the 
sub-study.

Section 16. Updated reference style, per template.

Updated abbreviations list, due to missing and with 
addition of sub-study.

Appendix 10-Methotrexate Withdrawal Sub-Study 
added and updated main protocol in appropriate 
sections in reference to the sub-study.
Amendment 3
01 February 2015

Sections 4.2.1, 4.4.6.1, Appendix 9. Additional 
contraceptive requirement for women of childbearing 
potential in Canada based upon Health Canada 
Guidance document: Consideration for Inclusion of 
Women in Clinical Trials and Analysis of Sex 
Differences

Sections 4.2.1, 4.4, 5.6.2, Appendix 3.  Clarification 
of prohibited medications, per regulatory request.

Sections 5.7, Appendix 6. Clarification of rescue 
medication use, per regulatory request.

Section 7.6.8, 9.6. Clarification of requirements for 
events for review/adjudication. Update of 
adjudicated safety review committees to include 
Gastrointestinal Perforation Review Committee.
Amendment 2
13 August 2014

Section 4.1.2. Added “by the central laboratory” to 
inclusion #5.

Section 4.4.6. Inclusion of requirement for 2 highly 
effective contraceptive methods for women of 
child-bearing potential (United Kingdom only).

Section 9.6. Updated adjudication/review committee 
language.

Pfizer protocol template updates including Section 
5.4 (Drug Storage), 5.5 (Drug Accountability), 8
(Adverse Event Reporting) and 15 (Publication of 
Study Results).
Amendment 1
07 February 2014

Updated Introduction to reflect November 2013 
tofacitinib Investigator’s Brochure.

Included certoluzimab minimum treatment duration 
and washout information (Appendix 3) since recent 
marketing approval for PsA.

Section 4.2.1.  Addition of infection exclusion 
criteria #11 and exclusion criteria (#15) for subjects 


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at risk of GI perforation per regulatory request.

Section4.4.6. Clarification of use of sexual 
abstinence as contraceptive method only when 
consistent with preferred and usual subject lifestyle, 
per regulatory request.

Section 4.6.  Modification of rater qualifications for 
Physician’s Global Assessments to include 
healthcare professionals competent to perform the 
assessments.

Section 7.6.3.  Inclusion of requirements for reviewer 
of TB tests per local standard of care per regulatory 
request.
Original protocol
14 May 2013
N/A
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities, institutional review boards/ethics committees 
(IRBs/ECs), etc.


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PROTOCOL SUMMARY
Background and Rationale:
Psoriatic arthritis (PsA) is a chronic inflammatory autoimmune disease characterized by joint 
inflammation and destruction, psoriatic skin lesions, enthesitis, dactylitis, spondylitis, 
progressive disability and adverse effects on quality of life.  Tofacitinib (CP-690,550) is a 
potent and selective inhibitor of the Janus Kinase (JAK) family of kinases.  While tofacitinib 
shows nanomolar inhibitory potency against all JAK family kinases in enzymatic assays, it 
shows functional specificity for JAK1 and JAK1/3 over JAK2 in cell-based assays.  The 
broad effects of JAK1/3 inhibition on multiple cytokine pathways provide rationale for 
developing tofacitinib as treatment for PsA.
Efficacy and safety of oral dosing with tofacitinib in Rheumatoid Arthritis (RA) subjects has 
been demonstrated in Phase 2 and 3 studies and tofacitinib 5 mg twice a day (BID) received 
Food and Drug Administration (FDA) approval 6 November 2012 for this indication.  
Efficacy and safety of oral dosing with tofacitinib in subjects with plaque psoriasis has 
previously been demonstrated in a Phase 2 dose ranging study and is currently being 
investigated in Phase 3 registration studies.
This Phase 3 study is a long-term extension (LTE) study designed to evaluate the safety and 
tolerability of tofacitinib as a treatment for PsA.
An optional sub-study is included to assess the efficacy, safety and tolerability of tofacitinib 
5 mg BID administered as monotherapy after methotrexate (MTX) withdrawal compared to 
tofacitinib 5 mg BID in combination with MTX. Subjects who have completed at least 
24 months of participation in the long term extension study and are currently receiving 
tofacitinib 5 mg BID in combination with oral methotrexate are eligible to participate.  Details 
are included in Appendix 10.
Objectives:

To evaluate the long term safety and tolerability of treatment with 
tofacitinib (5 mg twice daily [BID] and 10 mg BID) in adult subjects with active PsA.

To evaluate the long term efficacy of tofacitinib (5 mg BID and 10 mg BID) in adult 
subjects with active PsA.
Study Design:
This is a Phase 3, long-term, open-label extension study designed to evaluate the safety, 
tolerability and efficacy of tofacitinib in subjects with active PsA.  Subjects with active PsA 
will have previously participated in randomized studies of tofacitinib.  For subjects who are 
completing participation in a randomized study of tofacitinib, the final visit of the qualifying 
study can be combined with screening and baseline visit for this study.  Additional 
assessments and inclusion/exclusion criteria are required for subjects who enroll >14 days


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after completing treatment in their qualifying study.  In this case, a separate screening visit to 
determine subject eligibility is required followed by a baseline visit.
All eligible subjects from qualifying studies A3921091 and A3921125 will receive 
open-label tofacitinib 5 mg BID upon entry into A3921092.  Subjects from A3921091 will 
receive first dose of study medication 1 week after last injection of study medication in that 
qualifying study.  Tofacitinib dose may be increased to 10 mg BID at study visits if, based 
upon investigator’s discretion, subjects receiving tofacitinib 5 mg BID would benefit from a 
higher dose and are not experiencing any tofacitinib-related adverse events, including 
abnormalities in laboratory test results that are judged to be related to tofacitinib.  Tofacitinib 
dose may be decreased (ie, 10 mg BID to 5 mg BID) for safety reasons at any time.  
Treatment duration for subjects participating in the main LTE study is approximately 3 years
(36 standardized 4-week months).  Subjects participating in the sub-study may have up to an 
additional 1 year (12 standardized 4-week months) of treatment for a maximum potential 
total of approximately 4 years (48 standardized 4-week months).
At various time points in this trial, safety measurements, including physical examination, 
clinical laboratory tests, adverse event monitoring, electrocardiograms (ECGs) and vital signs 
will be performed.  All subjects will be monitored for clinical evidence of PsA response to
treatment.  Health Outcomes Measures (ie, Patient Reported Outcomes assessments for pain, 
quality of life, physical function, fatigue, work limitations, health care resource utilization 
and health status) will also be performed at various time points in this trial.  In addition, 
subjects will be monitored for serious infections, lymphadenopathy and lymphoproliferative 
disorder (LPD).
Study design of the sub-study is found in Appendix 10.
Statistical Methods:
There will be 2 sets of analyses: one for the A3921092 long-term extension (LTE) and the 
other for the sub-study. For the A3921092 LTE, the safety analysis will include cumulative 
data from all the subjects and all the data (including the data collected in the sub-study). The 
efficacy analysis will include only the data collected in the A3921092 LTE (the efficacy data 
collected in the sub-study will be evaluated separately for the sub-study).
Statistical methods for the sub-study are found in Appendix 10.
The analyses for the primary endpoints will be descriptive in nature.  Adverse events (AEs), 
Serious Adverse Events (SAEs), laboratory tests and vital signs will be summarized in 
accordance with Pfizer Data Standards.  Secondary endpoints (including additional safety, 
efficacy and Health Outcome Measure endpoints) will be summarized by descriptive 
statistics at each visit at which they are collected.


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Table 1.
Schedule of Activities
SCHEDULE OF ACTIVITIES
The Schedule of Activities table provides an overview of the protocol visits and procedures.  Refer to Study Procedures (Section 6) 
and Assessments (Section 7) for detailed information on each procedure and assessment required for compliance with the protocol.  
Subjects participating in the sub-study should refer to the Schedule of Activities in Appendix 10.
The investigator may schedule visits (unplanned visits) in addition to those listed on the schedule of activities, in order to conduct 
evaluations or assessments required to protect the wellbeing of the subject.
Protocol
Activity
Subjects 
>14 days after 
EOS Visit1
Combined 
with EOS 
Visit2
Separate 
Visit within 
14 days 
after EOS 
Visit3
Month 1
(±7 days)
Month 3
(±7 days)
then
Q6 mos*
(±10 days)
Month 6
then
Q12 mos**
(±10 days)
Month 12 then 
Q12 mos***
Or Early 
Termination
(±10 days)
Follow-Up 
Phone
Call4
Follow-up
Visit5
A
B
C
D
Screen Baseline Screening
/Baseline
Screening
/Baseline
Informed Consent
X
X
X
Medical History, Disease Activity Assessment6
X
CV Risk Assessment7
X
X
X
Register for subject identification number
X
X
X
Complete Physical Exam8
X
X
Targeted Physical Exam8
X
X
X
X
X
Vital signs, temperature
X
X
X
X
X
X
X
Waist and hips circumference
X
X
X
X
12-Lead ECG9
X
X
QuantiFERON or Mantoux PPD /Chest 
Radiograph, if Necessary10
X
X10
LABORATORY TESTING
Hematology, Chemistry Panel11
X
X
X
X
X
X
X
X
CRP11
X
X
X
X
X
X
X
Hemoglobin A1c (HbA1c)11
X
X
X


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Protocol
Activity
Subjects 
>14 days after 
EOS Visit1
Combined 
with EOS 
Visit2
Separate 
Visit within 
14 days 
after EOS 
Visit3
Month 1
(±7 days)
Month 3
(±7 days)
then
Q6 mos*
(±10 days)
Month 6
then
Q12 mos**
(±10 days)
Month 12 then 
Q12 mos***
Or Early 
Termination
(±10 days)
Follow-Up 
Phone
Call4
Follow-up
Visit5
A
B
C
D
Screen Baseline Screening
/Baseline
Screening
/Baseline
Lipid panel (fasting)12
X
X12
X
X
X
CBC with Differential and Chemistry Labs13
As required for Standard Of Care
Lymphocyte subset analysis (FACS)
X
X
X
X
Urinalysis14
X
X
X
X
X
X
X
Urine pregnancy test (hCG)15
X
X
X
X
X
X
X
X
HIV Serology, HBsAg, HBcAb, HCV Ab
X
Stool Examination (Brazilian Sites Only)
X
CLINICAL EVALUATION OF 
RHEUMATOLOGY ENDPOINTS
Tender/Painful Joint Count, Swollen Joint 
Count
X
X
X
X
X
X
X
Physician’s Global Assessment of Arthritis 
(VAS)
X
X
X
X
X
X
Dactylitis Assessment
X
X
X
X
X
Enthesitis Assessment (SPARCC and Leeds 
Index)16
X
X
X
X
X
CLINICAL EVALUATION OF 
RHEUMATOLOGY/DERMATOLOGY 
ENDPOINTS
Physician’s Global Assessment of Psoriatic 
Arthritis (VAS)
X
X
X
X
X
CLINICAL EVALUATION OF 
DERMATOLOGY ENDPOINTS
Physician’s Global Assessment of Psoriasis 
(PGA-PsO)17
X
X
X
X
X
Psoriasis Area and Severity Index (PASI); Body 
X
X
X
X
X


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Protocol
Activity
Subjects 
>14 days after 
EOS Visit1
Combined 
with EOS 
Visit2
Separate 
Visit within 
14 days 
after EOS 
Visit3
Month 1
(±7 days)
Month 3
(±7 days)
then
Q6 mos*
(±10 days)
Month 6
then
Q12 mos**
(±10 days)
Month 12 then 
Q12 mos***
Or Early 
Termination
(±10 days)
Follow-Up 
Phone
Call4
Follow-up
Visit5
A
B
C
D
Screen Baseline Screening
/Baseline
Screening
/Baseline
Surface Area (BSA)17
Nail Psoriasis Severity Index (NAPSI) 18
X
X
X
X
PATIENT REPORTED OUTCOMES19
Patient’s Assessment of Arthritis Pain (VAS); 
Patient’s Global Assessment of Arthritis (VAS); 
HAQ-DI20
X
X
X
X
X
X
Itch Severity Index (ISI)
X
X
X
X
Patient’s Global Joint and Skin Assessment 
(PGJS-VAS)
X
X
X
X
X
Bath Ankylosing Spondylitis Disease Activity 
Index (BASDAI); Ankylosing Spondylitis 
Quality of Life (ASQOL)
X
X
X
X
X
SF-36, FACIT-F, EuroQol EQ-5D, PsA-HCRU, 
WLQ, DLQI20
X
X
X
X
OTHER ACTIVITIES
Adverse Event Assessment
X
X
X
X
X
X
X
X
Prior/Concomitant Treatment
X
X
X
X
X
X
X
X
Dispense study medication/Accountability21
X
X
X
X21
X
X
X21
* Study visit Type B will occur every 6 months after Month 3 (eg, Month 9, 15, 21, 27,22 3322).  See Figure 1.
**Study visit Type C will occur every 12 months after Month 6 (eg, Month 18, 3022).  See Figure 1.
***Study visit Type D will occur every 12 Months after Month 12 (eg, Month 24,22 3622).  See Figure 1.
1.
Subjects who are qualified to enter A3921092 extension study and do so >14 days (but 3 months) after early termination or end of study (EOS) visit in 
qualifying study must undergo re-screening procedures and have separate visit for baseline activities.  Baseline visit must occur 2-28 days after Screening 
visit.
2.
Subjects who are qualified to enter A3921092 extension study and do at the end of study (EOS) visit in qualifying study do not need to be rescreened or have 
an additional baseline visit.


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3.
Subjects who are qualified to enter A3921092 extension study and do not do so at the end of study (EOS) visit but <14 days after early termination or EOS 
in parent study do not need to be re-screened but require procedures performed for baseline.
4.
For those subjects that complete the study, follow-up phone call will be made to subjects within 7 days after the 28 days following EOS visit and adverse 
events noted.
5.
If a subject discontinues from the study due to abnormal hematology or clinical chemistry results which meet criteria as described in Appendix 4, or 
discontinues due to an adverse event, a follow-up visit must be performed after the Early Termination visit within 28 days (7 days) of last dose of study 
treatment.
6.
Disease Activity Assessment must be performed on subjects who enroll >14 days after end of study visit in qualifying study to determine if subject has 
sufficient evidence of PsA disease activity to warrant use of tofacitinib as a DMARD (Section 7.1.1).
7.
Cardiovascular (CV) Risk Factor Assessment includes multiple assessments such as smoking status, average weekly alcohol consumption, and family 
history of premature coronary heart disease (CHD) (See Section 7.4 for complete list).
8.
Complete physical exam should be performed annually (Month 12, 24 and 36) and includes: height, weight, general appearance, skin, HEENT (head, eyes, 
ears, nose and throat), heart, lungs, abdomen, lower extremities, neurologic and lymph nodes.  Targeted physical exam should be performed at other 
scheduled visits and includes: weight, examination of heart, lungs, abdomen, lower extremities (for peripheral edema) and lymph nodes.
9.
12-lead ECG will be taken at annual visits (Month 12, 24 and 36) and Early Termination (ET) visit only.  ECG will be evaluated by a central reader.
10. Tuberculosis screening procedures must be performed if not completed in the last 3 months.  Subjects who have PPD must return within 48-72 hours for 
evaluation.  Annual TB screening will be conducted using Quantiferon-TB® Gold In-Tube test (QFT) for subjects in those countries in which TB incidence 
has been reported at a rate of >50 cases per 100,000 persons (see Section 7.6.3).  All subjects with positive results (and who tested negative at their last QFT) 
must have chest radiograph performed and reviewed by a radiologist or pulmonologist as per local standard of care.
11. Hematology includes: white blood cell (WBC) count/differential, hemoglobin, hematocrit, red blood cell (RBC) count and morphology, reticulocyte and 
platelet counts.  Serum chemistry includes: urea nitrogen, creatinine, glucose, calcium, sodium, potassium, bicarbonate, chloride, total protein, total bilirubin, 
direct bilirubin, indirect bilirubin, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase, gamma-glutamyl transferase (GGT), 
albumin and creatine kinase (CK).  All hematology, clinical chemistry tests and HbA1C will be performed by the central laboratory; C-reactive Protein 
(CRP) will also be measured by central laboratory. 
12. A fasting lipid panel (total cholesterol, LDL, HDL, triglycerides, apolipoprotein A-1 and B) and other lipoprotein tests potentially including particle size 
measurements Table 8 will be collected at the baseline visit for subjects who enroll more than 14 days after their EOS visit from their qualifying study; for 
all subjects at Month 3, Month 6 (Study Visit Type C) and every 6 months thereafter (Study Visits Type C and D).
13. Clinical chemistry as appropriate for standard of care in subjects receiving background non-biologic DMARDs may include creatinine, albumin and liver 
function tests.
14. Urinalysis includes specific gravity, pH, protein, glucose, ketones, blood and leukocyte esterase.  Microscopy and/or culture to be performed if clinically 
indicated or if urinalysis results are positive (blood, protein or leukocyte esterase/WBC).
15. Urine pregnancy testing (human chorionic gonadotropin; -hCG) is required only for women of childbearing potential.
16. Enthesitis will be assessed using the Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index and Leeds Enthesitis Index.
17. Physician Global Assessment of Psoriasis (PGA-PsO), Psoriasis Area and Severity Index (PASI) and Body Surface Area (BSA).  PASI performed only if 
3% of BSA affected at baseline of qualifying study. 
18. Nail Psoriasis Severity Index (NAPSI) will be performed on target nail identified at baseline/Visit 1 of qualifying study.


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19. All Patient Reported Outcomes should be completed prior to any other assessments made at each visit.
20. Subject completed questionnaires include: Health Assessment Questionnaire-Disability Index (HAQ-DI), Short-Form-36 Health Survey (Version 2, Acute) 
(SF-36), EuroQol 5 Dimensions (EQ5D), Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-F), Dermatology Quality of Life Index 
(DLQI), Work Limitation Questionnaire (WLQ).
21. Study medication will not be dispensed at Month 1 or End of Treatment or Early Termination visit; however, drug accountability will be performed.  If the 
subject participates in the sub-study, the investigational product for the main LTE will be collected at the time of entry into the sub-study and accountability 
completed.
22. At Month 24, 27, 30, 33, or 36 of the LTE, subjects may enter the sub-study.  Please refer to Appendix 10 for the sub-study requirements and procedures.
These subjects will complete the study procedures scheduled at the chosen visit (Month 24, 27, 30, 33, or 36) of the LTE and the additional requirements and 
procedures of the sub-study (Appendix 10).
Figure 1.
Assessments at Each Visit Grouped by Letter in Schedule of Activities
Month
    1
     3
      6
       9       12         15         18         21        24         27         30         33      36    
|
    A
     B          C          B          D          B           C         B         D          B          C         B        D    
Letter indicates activities to be performed at that month (See Table 1.
Schedule of Activities).


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TABLE OF CONTENTS
LIST OF TABLES...................................................................................................................17
LIST OF FIGURES .................................................................................................................17
APPENDICES .........................................................................................................................17
1. INTRODUCTION ...............................................................................................................19
1.1. Indication.................................................................................................................19
1.2. Background and Rationale ......................................................................................19
1.2.1. Mechanism of Action .................................................................................19
1.2.2. Summary of Efficacy..................................................................................20
1.2.2.1. Rheumatoid Arthritis.................................................................20
1.2.2.2. Plaque Psoriasis.........................................................................20
1.2.2.3. Phase 3 PsA Studies ..................................................................21
1.2.3. Summary of Safety .....................................................................................22
1.2.4. Overall Risk-Benefit...................................................................................23
1.2.4.1. Potential Benefits ......................................................................23
1.2.4.2. Potential Risks...........................................................................23
1.2.5. Clinical Pharmacokinetics ..........................................................................24
1.2.6. Drug Development and Study Rationale ....................................................25
1.2.7. Dose Selection Rationale............................................................................26
2. STUDY OBJECTIVES AND ENDPOINTS.......................................................................29
2.1. Objectives................................................................................................................29
2.1.1. Primary Objective.......................................................................................29
2.1.2. Secondary Objective...................................................................................29
2.2. Endpoints.................................................................................................................29
2.2.1. Primary Endpoints ......................................................................................29
2.2.2. Secondary Endpoints ..................................................................................30
2.2.3. Other Endpoints..........................................................................................30
3. STUDY DESIGN.................................................................................................................31
4. SUBJECT SELECTION......................................................................................................32
4.1. Inclusion Criteria.....................................................................................................32
4.1.1. Inclusion Criteria That Apply to All Subjects............................................32


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4.1.2. Inclusion Criteria That Apply to Subjects Who Enroll Into This 
Study After the 14 Day Window From the End of Study Visit of the 
Qualifying Study..............................................................................................33
4.2. Exclusion Criteria....................................................................................................34
4.2.1. Exclusion Criteria that Apply to All Subjects ............................................34
4.2.2. Exclusion Criteria That Apply to Subjects Who Enroll Into This 
Study After the 14 Day Window From the End of Study Visit of the 
Qualifying Study..............................................................................................37
4.3. Enrollment Criteria..................................................................................................37
4.4. Life Style Guidelines...............................................................................................37
4.4.1. Non-Pharmacologic Interventions..............................................................38
4.4.2. Vaccine Guidelines.....................................................................................38
4.4.2.1. Subject Vaccination...................................................................38
4.4.2.2. Household Contact with Others Vaccinated .............................38
4.4.3. Dietary Supplements...................................................................................39
4.4.4. Fasting Visit Requirements.........................................................................39
4.4.5. Elective Surgery..........................................................................................39
4.4.6. Contraception..............................................................................................39
4.4.6.1. Contraceptive Methods in Women of Childbearing 
Potential.............................................................................................39
4.4.6.2. Women of Non-Childbearing Potential.....................................41
4.4.7. Contraceptive Methods in Male Subjects...................................................41
4.5. Sponsor Qualified Medical Personnel.....................................................................41
5. STUDY TREATMENTS.....................................................................................................42
5.1. Allocation to Treatment ..........................................................................................42
5.2. Breaking the Blind ..................................................................................................42
5.3. Drug Supplies..........................................................................................................42
5.3.1. Preparation and Dispensing........................................................................43
5.3.2. Administration............................................................................................43
5.3.3. Compliance.................................................................................................43
5.4. Drug Storage ...........................................................................................................43
5.5. Drug Accountability................................................................................................44
5.5.1. Destruction of Investigational Product Supplies ........................................44


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5.6. Concomitant Treatment(s).......................................................................................45
5.6.1. Stable Background Pain or Other Arthritis Therapy ..................................45
5.6.2. Other Medications ......................................................................................46
5.7. Rescue Therapy.......................................................................................................46
5.8. Dosage Reduction and Withholding .......................................................................47
6. STUDY PROCEDURES .....................................................................................................47
6.1. Screening and Baseline ...........................................................................................48
6.1.1. Subjects Requiring Separate Screening and Baseline Visits......................48
6.1.1.1. Screening Visit ..........................................................................48
6.1.1.2. Baseline Visit ............................................................................49
6.1.2. Subjects with Combined End of Study Visit/Baseline Visit ......................50
6.1.3. Subjects with End of Study Visit Separate From Combined 
Screening/Baseline Visit..................................................................................51
6.2. Study Period ............................................................................................................52
6.2.1. Type A Visit: Month 1................................................................................52
6.2.2. Type B Visit: Months 3, 9, 15, 21, 27* and 33*.........................................54
6.2.3. Type C Visit: Months 6, 18 and 30*...........................................................55
6.2.4. Type D Visit: Month 12, 24* and 36*........................................................58
6.2.5. End of Study Follow-up Phone Call...........................................................60
6.2.6. Early Termination Visit..............................................................................60
6.3. Follow-up Visit .......................................................................................................62
6.4. Subject Withdrawal.................................................................................................62
7. ASSESSMENTS..................................................................................................................63
7.1. Efficacy Endpoints ..................................................................................................64
7.1.1. Disease Activity Assessment......................................................................64
7.1.2. ACR Assessments.......................................................................................64
7.1.3. Disease Activity Score Assessment............................................................64
7.1.4. PsA Response Criteria (PsARC) ................................................................65
7.1.5. PsA Joint Activity Index (PsAJAI).............................................................65
7.1.6. Disease Activity Index for Reactive Arthritis/Psoriatic Arthritis 
(DAREA/DAPSA)...........................................................................................65
7.1.7. Composite Psoriatic Disease Activity Index in Psoriatic Arthritis 
(CPDAI)...........................................................................................................65


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7.1.8. Minimal Disease Activity Score.................................................................66
7.1.9. Psoriatic Arthritis Disease Activity Score (PASDAS)...............................66
7.2. Clinical Evaluation of Rheumatology Endpoints....................................................66
7.2.1. Tender/Painful Joint Count (68).................................................................66
7.2.2. Tender/Painful Joint Count (28).................................................................67
7.2.3. Swollen Joint Count (66)............................................................................67
7.2.4. Swollen Joint Count (28)............................................................................67
7.2.5. Physician’s Global Assessment of Arthritis ...............................................67
7.2.6. Physician’s Global Assessment of Psoriatic Arthritis ................................67
7.2.7. Assessment of Dactylitis.............................................................................68
7.2.8. Assessment of Enthesitis ............................................................................68
7.2.9. C-Reactive Protein (CRP)...........................................................................68
7.3. Clinical Evaluation of Dermatologic Endpoints .....................................................68
7.3.1. Physician’s Global Assessment of Psoriasis (PGA-PsO)...........................68
7.3.2. Psoriasis Area and Severity Index (PASI)..................................................70
7.3.3. Body Surface Area (BSA) ..........................................................................71
7.3.4. Nail Psoriasis Severity Index (NAPSI) Score ............................................72
7.4. Cardiovascular (CV) Risk Factor Assessment........................................................72
7.5. Health Outcome Measures ......................................................................................72
7.5.1. Patient’s Assessment of Arthritis Pain .......................................................73
7.5.2. Patient’s Global Assessment of Arthritis....................................................73
7.5.3. Health Assessment Questionnaire-Disability Index (HAQ-DI) .................73
7.5.4. Patient’s Global Joint and Skin Assessment (PGJS-VAS).........................73
7.5.5. Assessment of Spondylitis..........................................................................74
7.5.6. Dermatology of Life Quality Index (DLQI)...............................................74
7.5.7. Itch Severity Item (ISI)...............................................................................74
7.5.8. Functional Assessment of Chronic Illness Therapy (FACIT-Fatigue 
Scale)................................................................................................................74
7.5.9. SF-36 Health Survey (Version 2, Acute)....................................................75
7.5.10. EuroQol EQ-5D Health State Profile .......................................................75
7.5.11. PsA Healthcare Resource Utilization Questionnaire................................75
7.5.12. Work Limitations Questionnaire ..............................................................75


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7.6. Safety.......................................................................................................................75
7.6.1. Vital Signs and Temperature ......................................................................75
7.6.2. Electrocardiogram.......................................................................................76
7.6.3. Tuberculosis Screening...............................................................................76
7.6.3.1. Quantiferon- TB Gold In-Tube Test .......................................77
7.6.3.2. Purified Protein Derivative (PPD) Tuberculin Test ..................77
7.6.3.3. Chest Radiograph (CXR) ..........................................................78
7.6.4. Complete Physical Examination.................................................................78
7.6.5. Targeted Examination.................................................................................78
7.6.6. Weight, Waist and Hips Circumference and Height ..................................78
7.6.7. Clinical Safety Laboratory Tests ................................................................79
7.6.7.1. Pregnancy Testing.....................................................................80
7.6.8. Events for Adjudication/Review Committee Submission..........................81
7.6.9. Triggered Requirements .............................................................................81
7.6.9.1. Monitoring Criteria ...................................................................81
7.6.9.2. Discontinuation Criteria ............................................................82
7.6.10. Country Specific Laboratory Testing Requirements ................................83
7.7. Exploratory Biomarkers ..........................................................................................83
7.7.1. Lymphocyte Subset Analysis .....................................................................83
7.8. Rater Qualifications.................................................................................................83
8. ADVERSE EVENT REPORTING......................................................................................84
8.1. Adverse Events........................................................................................................84
8.2. Reporting Period .....................................................................................................84
8.3. Definition of an Adverse Event...............................................................................84
8.4. Medication Errors....................................................................................................85
8.5. Abnormal Test Findings..........................................................................................86
8.6. Infections.................................................................................................................86
8.6.1. Serious Infections .......................................................................................86
8.6.2. Treated Infections.......................................................................................86
8.7. Serious Adverse Events...........................................................................................87
8.7.1. Protocol-Specified Serious Adverse Events...............................................87
8.7.2. Potential Cases of Drug-Induced Liver Injury............................................87


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8.8. Hospitalization ........................................................................................................88
8.9. Severity Assessment................................................................................................89
8.10. Causality Assessment............................................................................................90
8.11. Exposure During Pregnancy..................................................................................90
8.12. Occupational Exposure .........................................................................................91
8.13. Withdrawal Due to Adverse Events (See Also the Section 6.4 Subject 
Withdrawal)...............................................................................................................91
8.14. Eliciting Adverse Event Information ....................................................................92
8.15. Reporting Requirements........................................................................................92
8.15.1. Serious Adverse Event Reporting Requirements .....................................92
8.15.2. Non-Serious Adverse Event Reporting Requirements .............................92
8.15.3. Sponsor’s Reporting Requirements to Regulatory Authorities ................93
9. DATA ANALYSIS/STATISTICAL METHODS...............................................................93
9.1. Sample Size Determination.....................................................................................93
9.2. Safety Analysis........................................................................................................93
9.2.1. Analysis of Safety Endpoints......................................................................93
9.3. Efficacy Analysis ....................................................................................................94
9.4. Interim Analysis ......................................................................................................94
9.5. Data Monitoring Committee ...................................................................................94
9.6. Safety Event Adjudication/Review Committees.....................................................94
10. QUALITY CONTROL AND QUALITY ASSURANCE.................................................95
11. DATA HANDLING AND RECORD KEEPING .............................................................96
11.1. Case Report Forms/Electronic Data Record .........................................................96
11.2. Record Retention...................................................................................................96
12. ETHICS..............................................................................................................................97
12.1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) ............97
12.2. Ethical Conduct of the Study ................................................................................97
12.3. Subject Information and Consent..........................................................................97
12.4. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH 
GCP ...........................................................................................................................98
13. DEFINITION OF END OF TRIAL...................................................................................99
13.1. End of Trial in a Member State.............................................................................99
13.2. End of Trial in all Other Participating Countries ..................................................99


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14. SPONSOR DISCONTINUATION CRITERIA ................................................................99
15. PUBLICATION OF STUDY RESULTS..........................................................................99
15.1. Communication of Results by Pfizer ....................................................................99
15.2. Publications by Investigators ..............................................................................100
16. REFERENCES ................................................................................................................102
LIST OF TABLES
Table 1.
Schedule of Activities.............................................................................................6
Table 2.
Component Scoring Criteria for the Physician's Global Assessment 
(PGA-PsO)............................................................................................................69
Table 3.
Physician's Global Assessment (PGA-PsO) Score...............................................69
Table 4.
Component Scoring Criteria for the Psoriasis Area and Severity Index 
(PASI)...................................................................................................................70
Table 5.
Psoriasis Area and Severity Index (PASI) Area Score Criteria............................71
Table 6.
Psoriasis Area and Severity Index (PASI) Lesions Body Region Weighting ......71
Table 7.
Handprint Determination of Body Region Surface Area .....................................72
Table 8.
Clinical Laboratory Testing..................................................................................80
LIST OF FIGURES
Figure 1.
Assessments at Each Visit Grouped by Letter in Schedule of Activities.............10
Figure 2.
Probability of Achieving Target Effect for Efficacy (ACR20, ACR50 and 
ACR70) and Safety (Incidence of Anemia) Endpoints Based on Modeling 
of Study A3921025 Data in RA Patients..............................................................27
Figure 3.
Probability of Achieving Target Effect for Efficacy (PASI75 and PGA 
Responses) and Safety (Incidence of Hemoglobin Change) Endpoints 
Based on Dose/Exposure Response Modeling of Study A3921047 Data in 
Psoriatic Patients...................................................................................................28
APPENDICES
Appendix 1. Abbreviations....................................................................................................106
Appendix 2. Cockcroft-Gault Calculation.............................................................................110
Appendix 3. Prohibited Concomitant Medications................................................................111
Appendix 4. Guidelines for Safety Monitoring, Dose Adjustments and Discontinuation ....114


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Appendix 4.1. Safety Monitoring ..........................................................................................114
Appendix 4.2. Guidelines for Dose Adjustments of Tofacitinib ...........................................115
Appendix 4.3. Discontinuation Criteria.................................................................................116
Appendix 4.4. Discontinuation/End of Treatment Follow-up Safety Monitoring.................117
Appendix 5. Approximate Equivalent Morphine Doses of Opioid Analgesics.....................118
Appendix 6. Rescue Therapy.................................................................................................119
Appendix 7. Composite Psoriatic Disease Activity Index (CPDAI)22 score 0-15.................121
Appendix 8. Evaluation of Potentially Malignant Tumors, Suspicious 
Lymphadenopathy, Possible Extranodal Lymphoproliferative Disorder 
(LPD)..................................................................................................................122
Appendix 9. Contraceptive Methods (for Canada)................................................................123
Appendix 10. Methotrexate Withdrawal Sub-Study..............................................................124


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1. INTRODUCTION
1.1. Indication
Tofacitinib is being developed for the treatment of adult subjects with active Psoriatic 
Arthritis (PsA).
1.2. Background and Rationale
PsA is a chronic inflammatory autoimmune disease characterized by joint inflammation and 
destruction, psoriatic skin lesions, enthesitis, dactylitis, spondylitis, progressive disability and 
adverse effects on quality of life.1,2  PsA presents significant health and socioeconomic 
burdens for the individual and society.  There is currently no cure for PsA.  The purpose of 
treatment is to control disease activity, alleviate signs and symptoms, maintain physical 
function, optimize quality of life, and, if possible, induce complete remission.
There is very little clinical study data to support the efficacy of traditional disease-modifying 
anti-rheumatic drugs (DMARDs) in PsA (eg, methotrexate, sulfasalazine).2  Traditional 
DMARDs may not always slow or prevent progressive joint damage and may be associated 
with clinical tolerability and/or safety issues.  Tumor Necrosis Factor inhibitors (TNFi) have 
demonstrated in published clinical studies evidence of both efficacy (signs, symptoms and 
retardation of joint damage) and safety and are the only biologic agents indicated for the 
treatment for PsA.3  Use of TNF inhibitors remains limited with inconvenience of the 
required parenteral routes of administration and apparent loss of initial efficacy with 
continued use in a significant proportion of patients.  There is therefore potential unmet 
medical need for new DMARDs in the PsA patient population.
This open-label study will evaluate the long-term safety and tolerability of tofacitinib for 
treatment of PsA.
An optional sub-study is included to assess the efficacy, safety and tolerability of tofacitinib 
5 mg BID administered as monotherapy after methotrexate (MTX) withdrawal compared to 
tofacitinib 5 mg BID in combination with MTX. Subjects who have completed at least 
24 months of participation in the long term extension study and are currently receiving 
tofacitinib 5 mg BID in combination with oral methotrexate are eligible to participate. 
Details are included in Appendix 10.
1.2.1. Mechanism of Action
Tofacitinib is a potent, selective inhibitor of the JAK family of kinases with a high degree of 
selectivity against other kinases in the human genome.  In kinase assays, tofacitinib inhibits 
JAK1, JAK2, JAK3, and to a lesser extent TyK2.  In cellular settings where JAK kinases 
signal in pairs, tofacitinib preferentially inhibits signaling by heterodimeric receptors 
associated with JAK3 and/or JAK1 with functional selectivity over receptors that signal via 
pairs of JAK2.  Inhibition of JAK1 and JAK3 by tofacitinib blocks signaling through the 
common gamma chain-containing receptors for several cytokines, including IL-2, 4, 7, 9, 15 
and 21.4,5,6  These cytokines are integral to lymphocyte activation, proliferation, and function 
and inhibition of their signaling may thus result in suppression of multiple aspects of the 


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immune response.  In addition, inhibition of JAK1 will result in attenuation of signaling by 
additional pro-inflammatory cytokines, such as IL-6 and type I interferons.  At higher 
exposures, inhibition of erythropoietin signaling could occur via inhibition of JAK2 
signaling.  In addition to interfering with Th1 and Th2 cell differentiation, tofacitinib has 
been shown to interfere with the production of inflammatory Th17 cells.7  These effects 
provide the basis for use in diseases in which the immune response plays a pathogenic role 
such as PsA.8,9
1.2.2. Summary of Efficacy
1.2.2.1. Rheumatoid Arthritis
Efficacy and safety of oral dosing with tofacitinib in Rheumatoid Arthritis (RA) subjects has 
been demonstrated in Phase 2 and 3 studies and tofacitinib 5 mg BID received FDA approval 
for this indication. 
In the tofacitinib twice daily RA program, there were 6300 adult patients exposed to 
tofacitinib BID as of May 2016 in the Phase 2 and Phase 3 studies and an ongoing Phase 3b/4 
post authorization safety study. These studies, which are summarized in the tofacitinib 
Investigator’s Brochure, ranged from 6 to 24 weeks in duration.  Subjects enrolled in these 
qualifying studies had the opportunity to roll-over into either one of two long-term, 
open-label extension studies to continue with tofacitinib active treatment (A3921024 or 
A3921041, also summarized in the tofacitinib Investigator’s Brochure).
The tofacitinib RA clinical development program has conclusively demonstrated the efficacy 
of tofacitinib 5 mg BID and 10 mg BID in treating moderate to severe RA in patients who 
had experienced an inadequate response or intolerance to DMARDs, most commonly MTX.  
Consistent and sustained improvements were observed in efficacy measures that are 
clinically relevant to patients and practitioners and across a variety of clinical scenarios 
within populations that would be eligible for treatment within the RA indication.  A 
comparison of various measures of efficacy, including improvements in signs and symptoms, 
physical function and radiographic data indicated that the efficacy of tofacitinib is generally 
comparable between 5 mg BID and 10 mg BID, with potential for greater probability of 
response with the 10 mg BID dose in the more stringent outcomes such as remission and 
Low Disease Activity (LDA).  Onset of benefit with tofacitinib use was rapid and response 
was durable.  Improvement in signs and symptoms was demonstrated after as little as 
2 weeks of treatment with tofacitinib, and maintained after more than 7 years of continued 
treatment in the uncontrolled LTE studies.  More detailed information can be found in 
Section 6.2 of the Investigator’s Brochure.
1.2.2.2. Plaque Psoriasis
The tofacitinib development program in patients with moderate to severe chronic plaque 
psoriasis was comprised of 2 Phase 3 randomized, placebo-controlled studies (A3921078 and 
A3921079), 1 Phase 3 placebo-controlled active comparator study (A3921080), 1 Phase 3 
withdrawal/retreatment study (A3921111) and 1 Phase 3 open-label LTE study (A3921061). 
The primary efficacy outcomes in the program included the proportion of patients with a 
Physician’s Global Assessment (PGA) response of “clear” or “almost clear” and the 


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proportion of patients with at least a 75% reduction in Psoriasis Area and Severity Index 
(PASI) relative to baseline (ie, PASI75) response.
Tofacitinib 5 mg BID or 10 mg BID treatment resulted in consistent and significant 
improvement in multiple variables:

Clinically meaningful improvements in the PGA response of “clear” or “almost clear”
and PASI75 response were demonstrated in the tofacitinib 5 mg BID and 10 mg BID 
dose groups relative to placebo.  In studies A3921078 and A3921079, the PGA and 
PASI75 response rate were statistically superior to placebo at the 16-week primary 
time point.

Tofacitinib 10 mg BID was statistically significantly superior to placebo and 
non-inferior to high-dose etanercept (50 mg twice weekly subcutaneously) at 
12 weeks in the PGA and PASI75 responses in study A3921080.
Additional information on completed and ongoing psoriasis studies can be found in the 
current version of the tofacitinib Investigator’s Brochure.
1.2.2.3. Phase 3 PsA Studies
The tofacitinib Phase 3 program was designed to evaluate the efficacy of tofacitinib 
5 mg BID and 10 mg BID in patients with active PsA.  The 2 tofacitinib Phase 3 pivotal 
studies (A3921091 and A3921125) compared the efficacy of both tofacitinib doses to that of 
placebo over 3 months for improvements in multiple PsA domains, examined the onset of 
efficacy, and assessed the persistence of efficacy of both tofacitinib doses in conventional 
synthetic disease-modifying anti-rheumatic drug-inadequate responder (csDMARD-IR)
TNFi-naïve and TNFi-IR populations. All study participants randomized to placebo were 
advanced in a blinded fashion at Month 3 to either tofacitinib 5 mg BID or 10 mg BID and 
treatment duration was a total of 12 months in A3921091 and 6 months in A3921125.
The first Phase 3 PsA study, A3921091 has completed and the primary endpoints were met.  
The American College of Rheumatology 20% response rate (ACR20) was statistically
significantly greater for both tofacitinib 5 mg BID and 10 mg BID dose treatment groups 
than the placebo treatment group at Month 3.  The mean change from baseline (decrease) in 
the Health Assessment Questionnaire-Disability Index (HAQ-DI) was statistically 
significantly greater than placebo for both tofacitinib 5 mg BID and 10 mg BID dose 
treatment groups at Month 3.  Evidence of efficacy was also observed across other PsA 
domains (secondary endpoints) and was maintained to Month 12.10
Results from the second Phase 3 PsA study, A3921125 demonstrated that there were 
significantly greater improvements in ACR20 response rate and HAQ-DI for both doses 
versus placebo; improvement persisted to Month 6.11


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1.2.3. Summary of Safety
The clinical development program for oral tofacitinib includes healthy volunteers and 
subjects with RA, plaque psoriasis, inflammatory bowel disease (Crohn’s disease and
ulcerative colitis), ankylosing spondylitis, psoriatic arthritis and renal transplants enrolled in 
Phase 1, 2 and 3 studies.
Over 22,000 subjects have received at least one oral dose of tofacitinib in a clinical trial as of 
January 2016.  Of these, approximately 8700 subjects have continued clinical trial 
participation by enrolling in long-term extension studies or other types of continuation 
studies.
Potential safety risks for subjects treated with tofacitinib are based on the totality of the data 
including nonclinical and clinical data across the entire tofacitinib development program with 
the majority of clinical data coming from studies in RA and PsO patient populations, 
including open-label extension studies.  These risks include serious and other important 
infections such as tuberculosis, opportunistic infections and herpes zoster (HZ) infections, 
potential for malignancies including lymphoma, and the potential for gastrointestinal (GI)
perforations.  Subjects receiving tofacitinib may be at increased risk for non-melanoma skin 
cancer (NMSC).  Based on nonclinical data, there is potential for tofacitinib to have effects 
on pregnancy and the fetus. 
It has long been recognized that RA is associated with accelerated atherosclerosis and 
increased cardiovascular (CV) mortality and morbidity. The incidence of CV events during 
treatment with tofacitinib in RA patients was evaluated by an independent, external CV 
adjudication committee.  No evidence of heightened CV risk was found.  Tofacitinib was not 
associated with an increase in adjudicated CV events within the PsO development program.
Interstitial lung disease (ILD) is a serious comorbidity in RA patients.  Risk factors for the 
development of ILD in RA include Asian race, older age, male gender, higher RA disease 
activity and treatment with corticosteroids or MTX.  The incidence rate of ILD and 
geographic variation seen in patients treated with tofacitinib are consistent with what has 
been reported in literature. For additional information, please refer to Section 6.2.3.1.5 of 
the IB.
Laboratory changes associated with the oral use of tofacitinib treatment in humans include 
decreases in hemoglobin levels, absolute neutrophil counts (ANC), and absolute lymphocyte 
count, increases in total cholesterol, HDL cholesterol, LDL cholesterol, transaminases, serum 
creatinine, and creatine kinase (CK).  Recovery of laboratory changes upon discontinuation 
of tofacitinib treatment is characteristically observed.  The safety profile of tofacitinib in both 
rheumatoid arthritis and psoriasis subject populations is qualitatively similar. The current 
safety profile for the treatment of PsA across both studies, A3921091 and A3921125 is 
similar to that reported for RA and no new risks have been identified.10,11
Interpretation of these results and the possible risks associated with the administration of 
tofacitinib are summarized in Section 6.2.3 (Special Safety) and Section 7 (Summary of Data 
and Guidance for the Investigator) of the Investigator's Brochure.


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1.2.4. Overall Risk-Benefit
1.2.4.1. Potential Benefits
Given the chronic nature of this disorder and the limited available therapies, there remains an 
unmet medical need for an effective oral treatment for PsA.
The benefits to individual subjects participating in this study will be the potential continued 
control of their PsA disease activity including rheumatological signs and symptoms (eg, joint 
swelling/tenderness, enthesitis, dactylitis and spondylitis), dermatological manifestations
(eg, skin plaques), physical function and fatigue.  All subjects may also benefit from gaining 
knowledge about their health status through study tests and physician assessments, as well as 
having close monitoring of their disease. 
1.2.4.2. Potential Risks
The risks associated with tofacitinib are similar to the risks associated with the use of other 
immunosuppressive agents, including a potential increased risk for serious and other 
important infections, eg, tuberculosis and viral reactivation such as herpes zoster.  In the RA 
program, the serious infection rate in tofacitinib-treated subjects was consistent with the rates 
of serious infections in patients treated with other therapeutic interventions including 
biologic DMARDs.  In the PsO program the serious infections overall rate was lower than 
was observed for the RA program.  Serious infections were more frequent among the elderly 
(>65 years), subjects with diabetes mellitus and subjects treated previously with biological 
agents. Caution is also recommended in subject with a history of chronic lung disease as 
these patients may be more prone to infections. Rates of herpes zoster infections in 
tofacitinib-treated subjects with RA were increased compared with placebo-treated RA 
subjects and historical controls; this included an increased risk of herpes zoster infections in 
Asian RA patients compared with non-Asian RA patients. In the tofacitinib RA clinical 
development program, the rate of HZ varied significantly across countries and regions.  The 
incidence rates of HZ in Japan and Korea were notably higher than the rates observed in 
other regions/countries.  The reason for the increased risk of HZ in Japan and Korea is 
unclear.
Decreases in white blood cell counts, particularly neutrophils and lymphocytes, and 
decreases in hemoglobin have been observed.  These effects were usually mild to moderate 
and returned to normal after discontinuation of therapy.  Anemia is a possible consequence of 
JAK2 inhibition.  Experience to date indicates that anemia is easily monitored, usually 
manageable without discontinuation of drug, and reversible upon discontinuation of 
tofacitinib. Neutropenia is of primary concern by virtue of its relationship to an increased 
risk of infection.  Thus far, no association between the occurrence of neutropenia and 
infection has been observed in the tofacitinib program. 
Treatment with tofacitinib was associated with increases in levels of LDL and HDL 
cholesterol, with the ratios of mean LDL/HDL cholesterol unchanged.  In the previous 
controlled trials, elevation of LDL cholesterol generally returned to pre-treatment levels after 
discontinuation of tofacitinib. In light of the association of RA and accelerated 
atherosclerosis, CV mortality and morbidity CV events were evaluated by an independent 
CV adjudication committee. Review of cardiovascular events by the committee reported in 


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the RA and PsO studies suggests that tofacitinib was not associated with an increase in major 
adverse cardiovascular events.
Also seen in previous studies were slight increases in measured serum creatinine and serum 
transaminases.  This effect generally returned to normal after discontinuation of therapy.  A 
single RA subject experienced possible drug-induced liver injury (DILI) while being treated 
with tofacitinib and methotrexate.  Tofacitinib was discontinued and she recovered following 
treatment with prednisone and azathioprine.  The time course of her biochemical 
abnormalities were atypical for DILI, however investigations did not reveal an alternative 
etiology. No additional possible DILI cases and no confirmed Hy’s Law cases have been 
identified during adjudication by the Hepatic Event Review Committee (HERC).
NMSC has been acknowledged as an adverse drug reaction for tofacitinib based on review of 
data in the RA subjects.  There has been no identified increased risk of other types of 
malignancy for tofacitinib, although an increased incidence of post-transplant
lymphoproliferative disorders (PTLD) was observed in tofacitinib-treated subjects in a renal 
transplant study where combination of multiple potent immunosuppressants was used in 
conjunction with tofacitinib. Other malignancies observed (at varying frequencies depending 
upon the population under study) include lung and breast cancer, lymphoma, melanoma, 
colon and prostate cancer.  Pancreatic and other cancers have also been reported less 
frequently.
Cases of GI perforation were observed in RA subjects taking tofacitinib, often in the setting 
of diverticulitis.  All affected subjects had underlying risk factors, including a history of
concomitant drug treatment with non-steroidal anti-inflammatory drugs (NSAIDs) and/or 
corticosteroids that have been associated with an increased risk of GI tract injury.12,13  
Isolated events of gastrointestinal perforation have also been reported in clinical trials in 
other tofacitinib indications including one (preferred term: appendicitis) in the A3921091 
study.
ILD, a complex co-morbidity in RA patients, has also been reported in RA patients receiving 
tofacitinib.  While data from the RA development program do not identify a pulmonary 
toxicity for tofacitinib, an increased risk of ILD was observed in Asian RA patients as 
compared to non-Asian RA patients but there was no consistent dose relationship.
Based on nonclinical data, there is a potential risk for teratogenicity with tofacitinib. 
A more detailed discussion of tofacitinib safety can be found in the Investigator’s Brochure
in Section 6.2.3.
1.2.5. Clinical Pharmacokinetics
The pharmacokinetic (PK) profile of tofacitinib is characterized by rapid absorption, rapid 
elimination (terminal half-life of ~3 hours) and dose proportional PK.  Co-administration 
with a high fat meal increased the tofacitinib AUC by 14% and decreased Cmax by 26%; no 
dosage adjustments or meal restrictions during chronic dosing are warranted.  The clearance 
mechanisms for tofacitinib in humans appear to be both non-renal and renal excretion of the 
parent drug, the former accounting for approximately 2/3 of the total clearance.  The 


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metabolism of tofacitinib appears to be primarily mediated by CYP3A4 with minor 
contribution from CYP2C19 as suggested by data from poor metabolizers of CYP2C19.  
The PK of tofacitinib is similar between Caucasians and Japanese healthy volunteers.
In vitro studies have shown that tofacitinib does not significantly inhibit the major drug 
metabolizing CYPs, indicating a low potential for tofacitinib to increase the exposure of 
other drugs.  This was demonstrated in a clinical study where tofacitinib did not have an 
effect on the pharmacokinetics of an oral dose of midazolam (a highly sensitive 
CYP3A substrate) in healthy volunteers.  On the other hand, inhibitors and inducers of 
CYP3A4/5 are likely to alter the disposition of tofacitinib.  Co-administration of tofacitinib 
with fluconazole, a moderately potent inhibitor of CYP3A4 and a potent inhibitor of 
CYP2C19, resulted in 79% and 27% increases in the AUC and Cmax of tofacitinib, 
respectively.  Co-administration of tofacitinib with methotrexate had no effect on the PK of 
tofacitinib and resulted in an approximate 10% decrease in the AUC of methotrexate.  The 
extent of decrease in methotrexate exposure does not warrant modifications to the 
individualized dosing of methotrexate.  Co-administration of tofacitinib with cyclosporine 
and oral tacrolimus, moderate and weak CYP3A4 inhibitors, respectively, resulted in 
increases of 73% and 21% in AUCinf of tofacitinib.  In both cases, tofacitinib Cmax was 
decreased slightly; ratio 91%, for tacrolimus and 83%, for cyclosporine.
Consistent with the ~30% contribution of renal clearance to the total clearance of tofacitinib, 
mean exposure in end stage renal disease (ESRD) subjects (on a non-dialysis day) was 
approximately 40% higher compared with historical healthy subject data.  In contrast, in a 
separate study, mean exposure was approximately 125% higher in subjects with severe renal 
impairment compared with healthy subjects.  Mild and moderate renally impaired subjects 
had 37% and 43% higher exposure, respectively, compared with healthy subjects.
Based on these data, subjects with estimated creatinine clearance <40 mL/min will be 
excluded from this study as will concomitant use of moderate to potent inhibitors of 
CYP3A4/5.
Further clinical pharmacology background information on tofacitinib can be found in the 
current version of the tofacitinib Investigator’s Brochure.
1.2.6. Drug Development and Study Rationale
Tofacitinib has demonstrated efficacy in RA as both monotherapy (Phase 2 dose ranging 
Studies A3921019, A3921035, A3921040 and Phase 3 Study A3921045) and in combination 
with methotrexate (Phase 2 dose ranging studies A3921025, A3921039 and Phase 3 studies 
A3921032, A3921044, A3921046 [methotrexate, sulfasalazine and other traditional 
DMARDs] and A3921064).  Efficacy in relieving signs and symptoms and in restoring 
physical function was demonstrated at the ACR20 primary endpoint, and secondary efficacy 
endpoints including ACR50, ACR70, Disease Activity Score 28 (DAS 28) and the HAQ-DI.  
The safety of tofacitinib in RA patients at doses lower than 15 mg was also demonstrated.  
After review of the Phase 2 dose ranging studies, tofacitinib doses of 5 mg and 10 mg BID 
were selected to be used in the Phase 3 registration program for RA.


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Tofacitinib has demonstrated efficacy and safety in plaque psoriasis in the PsO program and 
more recently in the 2 Phase 3 PsA studies that have just completed.
This Phase 3 study is intended to provide long-term safety and tolerability data for tofacitinib 
when dosed at 5 mg BID or 10 mg BID in adult patients with PsA.
1.2.7. Dose Selection Rationale
Doses of tofacitinib (5 mg BID and 10 mg BID) that were previously demonstrated to be 
efficacious in the RA and psoriasis Phase 2 development programs are currently being, or 
have been, studied in their respective Phase 3 programs.  These tofacitinib doses of 5 mg BID 
and 10 mg BID will also be evaluated in this long-term extension study in PsA subjects.
Tofacitinib doses of 5 and 10 mg BID were selected for the Phase 3 programs for each of 
these indications based on modeling of extensive Phase 2 dose-response data.  The Phase 2 
programs include 5 studies in RA patients (A3921019, A3921025, A3921035, A3921039 and 
A3921040) and 1 study in psoriatic patients (A3921047).  The dose selection for RA was 
based primarily on study A3921025, which evaluated 5 doses (1, 3, 5, 10 and 15 mg BID 
tofacitinib and placebo for up to 24 weeks).  The dose selection for psoriasis was based 
primarily on study A3921047 in which 3 doses of tofacitinib were studied (2, 5 and 15 mg 
BID) for up to 12 weeks.
For each program, a review of several efficacy and safety outcomes was performed to 
identify key drivers for dose selection.  The selection of doses for RA was based on 
longitudinal dose-response modeling of the ACR20, ACR50 and ACR70 responses for 
efficacy and changes in hemoglobin (and associated anemia incidence) for safety.  Similarly, 
the selection of doses for psoriasis was based on modeling of PASI75 and PGA endpoints for 
efficacy and changes in hemoglobin for safety.  Dose selection was principally based on the 
probability of achieving a clinically meaningful target effect (PTE), where the target effect 
was defined in terms of a placebo-adjusted difference at a specific time point that is 
considered to be clinically meaningful.  Doses that were considered for Phase 3 were those 
that achieved a PTE of approximately 50% or higher on each endpoint.  The relationships
between tofacitinib dose and PTE are displayed in Figure 2 and Figure 3 for RA and 
psoriasis, respectively.  As shown in the figures, the 5 and 10 mg BID doses met the criteria 
(PTE of approximately 50% or higher on nearly all endpoints) for progression into 
Phase 3 for both indications.


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Figure 2.
Probability of Achieving Target Effect for Efficacy (ACR20, ACR50 and 
ACR70) and Safety (Incidence of Anemia) Endpoints Based on Modeling of 
Study A3921025 Data in RA Patients


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Figure 3.
Probability of Achieving Target Effect for Efficacy (PASI75 and PGA 
Responses) and Safety (Incidence of Hemoglobin Change) Endpoints Based 
on Dose/Exposure Response Modeling of Study A3921047 Data in Psoriatic 
Patients
In RA patients, the inclusion of tofacitinib 5 mg BID as the lowest dose for Phase 3 reflects 
the predicted increased PTE over, for example, the 3 mg BID dose on ACR50 (77% for 
5 mg BID vs 49% for 3 mg BID) and ACR70 (50% for 5 mg BID vs. 14% for 3 mg BID), 
without any loss in the PTE for anemia.  The inclusion of tofacitinib 10 mg BID in the 
Phase 3 program reflects the possibility of increased benefit over the 5 mg BID dose on 
ACR70 (80% PTE for 10 mg BID vs 50% for 5 mg BID), and/or for structure preservation 
while maintaining a sufficiently conservative safety profile.  ACR20/50/70 results observed 
in the RA Phase 3 studies confirmed the selection of tofacitinib 5 mg BID and 10 mg BID 
doses in that population.
In psoriasis patients, the tofacitinib 5 and 10 mg BID doses provided acceptable PTE for 
PASI75 (49% and 99%, respectively) and a high probability of observing a placebo-adjusted 
incidence rate <5% for a hemoglobin decrease of >2 g/dL from baseline (100% and 87%, 
respectively), although 5 mg BID did not achieve the desired PTE for PGA response 
(23% ie, less than the target of 50%).  However, the model predictions for the 5 mg BID 
suggested an adequate placebo-adjusted response rate for both PASI75 and PGA (50% and 
46%, respectively) at this dose level.  Thus, the inclusion of the 5 mg BID dose as the lowest 
dose for Phase 3 reflects the lowest dose that can achieve efficacy of the desired product 
profile.  The inclusion of 10 mg BID in the Phase 3 studies reflects an increased benefit over 
the 5 mg BID dose on both PASI75 and PGA responses; predicted response rates are over 
10% higher in the 10 mg BID dose group compared to the 5 mg BID group.


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As tofacitinib has demonstrated efficacy and acceptable safety in both RA and plaque 
psoriasis, there is rationale to expect that it will be efficacious and acceptably safe in PsA.
Patients with peripheral joint involvement from PsA typically respond to those drugs that are 
indicated for the treatment of rheumatoid arthritis.  The psoriatic skin involvement in PsA 
patients responds to those drugs that are indicated for the treatment for psoriasis.  Thus drugs 
that are efficacious for both rheumatoid arthritis and psoriasis may therefore be expected to 
work in patients that have PsA.  The doses of four TNFi currently approved for use in PsA 
are either the same or are very similar to the doses approved for their respective treatment of 
RA or psoriasis and all may be used with or without methotrexate.  Although TNF inhibitors 
have a different mechanism of action than tofacitinib, there is rationale to expect that 
tofacitinib will demonstrate efficacy and safety in PsA comparable to that of tofacitinib 
treatment of RA.
Patients with PsA may be expected to respond to the same doses of tofacitinib that are safe 
and efficacious in rheumatoid arthritis and psoriasis.  Tofacitinib 5 mg BID has been 
determined to be the minimum clinically important dose for both RA and plaque psoriasis, 
and this dose is selected as the lower dose to be studied in Phase 3 PsA parent studies 
(A3921091, A3921125).  Additionally since tofacitinib 10 mg BID may offer benefit for 
patients with PsA, tofacitinib 10 mg BID was selected as the higher dose to be studied in the 
PsA Phase 3 studies.  Therefore, both 5 mg BID and 10 mg BID tofacitinib doses will be 
included in this open label extension study.
Complete information for tofacitinib can be obtained from the current version of the 
tofacitinib Investigator’s Brochure, which is the single reference safety document (SRSD) for 
this study. A summary of selected, relevant information is presented in this Introduction.
2. STUDY OBJECTIVES AND ENDPOINTS
2.1. Objectives
2.1.1. Primary Objective

To evaluate the long term safety and tolerability of treatment with 
tofacitinib (5 mg twice daily [BID] and 10 mg BID) in adult subjects with active 
Psoriatic Arthritis (PsA).
2.1.2. Secondary Objective

To evaluate the long term efficacy of treatment with tofacitinib (5 mg BID and
10 mg BID) in adult subjects with active Psoriatic Arthritis (PsA).
2.2. Endpoints
2.2.1. Primary Endpoints

Incidence and severity of adverse events.

Incidence of clinical abnormalities and change from baseline (in this and/or prior 
study) in clinical laboratory values during treatment.


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2.2.2. Secondary Endpoints

ACR20, ACR50 and ACR70 response rate at all time points.

HAQ-DI score at all time points.

Psoriatic Arthritis Response Criteria (PsARC) response at all time points. 

Physician’s Global Assessment of Psoriasis (PGA-PsO) response at all time points.

Psoriasis Area and Severity Index 75 (PASI75) response ie, the proportion of subjects 
achieving at least a 75% reduction in PASI relative to baseline (in this and/or prior 
study) and PASI/PASI component scores at all time points.

Dactylitis severity score at all time points.

Enthesitis score (using Spondyloarthritis Research Consortium of Canada (SPARCC) 
Enthesitis Index and Leeds Index) at all time points.

Bath Ankylosing Spondylitis Disease Assessment Index (BASDAI) at all time points.

Physical function/other patient reported outcomes to be assessed at 
Month 1, Month 6 (and every 6 months thereafter): Short-Form 36 (version 2, Acute); 
EQ5D; Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F).
2.2.3. Other Endpoints

DAS28-3 C-reactive protein (CRP) at all time points.

Psoriatic Arthritis Joint Activity Index (PsAJAI), Disease Activity Index for Reactive 
Arthritis/PsA (DAREA/DAPSA), Composite Psoriasis Disease Activity Index 
(CPDAI), Psoriatic Arthritis Disease Activity Score (PASDAS), Minimal Disease 
Activity (MDA) score and their components at all time points.

Presence of dactylitis at all time points.

Nail Psoriasis Severity Index (NAPSI) Score at Month 1, Month 6 (and every 
6 months thereafter).

Itch Severity Index (ISI) at Month 1, Month 6 (and every 6 months thereafter).

Patient’s Global Joint and Skin Assessment (PGJS-VAS) at all time points.

Ankylosing Spondylitis Quality of Life questionnaire (ASQOL) at all time points.

Physical function/other patient reported outcomes to be assessed at 
Month 1, Month 6 (and every 6 months thereafter): Dermatology Life Quality Index 
(DLQI); PsA Healthcare Resource Utilization Questionnaire (PsA HCRU); Work 
Limitations Questionnaire (WLQ).


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
Incidence of investigator-reported clinically significant changes in physical 
examination from baseline (in this and/or prior study) during treatment.

Incidence of electrocardiogram (ECG) abnormalities and change from baseline (in 
this and/or prior study) in ECG measurements during treatment.

Incidence of vital sign (blood pressure and pulse rate) abnormalities and changes 
from baseline (in this and/or prior study) in vital sign measurements during treatment.
3. STUDY DESIGN
This is a Phase 3, long-term, open-label extension study designed to evaluate the safety, 
tolerability and efficacy of tofacitinib in subjects with active PsA who have previously 
participated in randomized PsA clinical studies with tofacitinib.  For subjects who complete 
participation in such a randomized clinical study with tofacitinib, the final visit of the 
qualifying study can be combined with the screening and baseline visit for this study.  
Additional assessments and inclusion/exclusion criteria are required for subjects who enroll 
>14 days after completing treatment in their qualifying study.  In this case, a separate 
screening visit to determine subject eligibility is required followed by a baseline visit.
All eligible subjects from qualifying studies A3921091 and A3921125 will receive 
open-label tofacitinib 5 mg BID upon entry into A3921092.  Subjects from A3921091 will 
receive first dose of study medication 1 week after last injection of study medication in that 
qualifying study.  Tofacitinib dose may be increased to 10 mg BID at study visits if, based 
upon investigator’s discretion, subjects receiving tofacitinib 5 mg BID would benefit from a 
higher dose and are not experiencing any tofacitinib-related adverse events, including 
abnormalities in laboratory parameters that are judged to be related to tofacitinib.  Tofacitinib 
dose may be decreased (ie, 10 mg BID to 5 mg BID) for safety reasons at any time during the 
study.  Treatment duration for subjects participating in the LTE study is approximately 
3 years (36 standardized 4-week months).  Subjects participating in the sub-study may have 
up to an additional 1 year (12 standardized 4-week months) of treatment for a maximum 
potential total of approximately 4 years (48 standardized 4-week months).
At various time points in this trial, safety measurements, including physical examination, 
clinical laboratory tests, adverse event monitoring, electrocardiograms (ECGs) and vital signs 
will be performed.  All subjects will be monitored for clinical evidence of response of PsA to 
treatment.  Health Outcome Measures (ie, Patient Reported Outcomes assessment 
questionnaires for pain, quality of life, physical function, fatigue, work limitations, health 
care resource utilization and health status) will also be performed at various time points in 
this trial.  In addition, subjects will be monitored for serious infections, lymphadenopathy 
and lymphoproliferative disorder (LPD).
Study design of the sub-study is found in Appendix 10.


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4. SUBJECT SELECTION
This study can fulfill its objectives only if appropriate subjects are enrolled.  The following 
eligibility criteria are designed to select subjects for whom protocol treatment is considered 
appropriate.  All relevant medical and non-medical conditions should be taken into 
consideration when deciding whether this protocol is suitable for a particular subject.
4.1. Inclusion Criteria
Subject eligibility will be reviewed and documented by an appropriately qualified member of 
the investigator’s study team before subjects are included in the study.
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the 
study.
4.1.1. Inclusion Criteria That Apply to All Subjects
1. Evidence of a personally signed and dated informed consent document indicating that 
the subject (or a legal representative) has been informed of all pertinent aspects of the 
study.
2. Subjects who are willing and able to comply with scheduled visits, treatment plan, 
laboratory tests, and other study procedures.
3. Subjects must have a diagnosis of PsA and previously completed participation in a 
qualifying study of tofacitinib for the treatment of PsA or have required earlier 
discontinuation of treatment in a qualifying study for reasons other than 
treatment-related adverse events (exception being injection-related AEs) with the 
written approval of the Pfizer Clinician.
4. Subject must be at least 18 years of age (20 years old for subjects in Taiwan) or older
at the Screening visit.
5. Subjects receiving permitted traditional non-biologic background DMARDs, eg, 
methotrexate, sulfasalazine or leflunomide, must be dosed in accordance with the 
local regulatory label. 
All local standard of care practices for administration of non-biologic background 
DMARD therapy, including laboratory testing, contraceptive requirements, follow-up 
care and contraindications, should be performed according to the local standards of 
care throughout the study.

Methotrexate: Maximum dose of 20 mg/week.  Minimum duration of therapy 
4 months and dose stable for 4 weeks prior to first dose of study drug.  
Subjects on methotrexate should be on an adequate and stable dose of folate 
supplementation (not less than 5 mg weekly based on folic acid, unless such 
doses would violate the local label guidelines or standard of care) for at least 
4 weeks prior to the first dose of study drug (see Section 5.6).  Subjects must 


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not have had previous serious toxicity while on methotrexate and not be 
expected to require evaluation for possible methotrexate toxicity (eg, require a 
liver biopsy for methotrexate toxicity) during the study.

Sulfasalazine: Maximum dose of 3 gm/day.  Minimum duration of therapy 
2 months and dose stable for 4 weeks prior to first dose of study drug.

Leflunomide: Maximum dose of 20 mg/day.  Minimum duration of therapy 
4 months and dose stable for 4 weeks prior to first dose of study drug.

Other traditional non-biologic DMARDs not listed as a prohibited 
concomitant medication (see Appendix 3) may be considered after discussion 
with the Sponsor.
6. Subjects who are already taking oral corticosteroids (but not injectable) may 
participate in the study:

Oral corticosteroids: Subjects who are already receiving oral corticosteroids 
must be on a stable dose of 10 mg/day of prednisone or equivalent for 
4 weeks prior to first dose of study drug.

Injected (eg, intraarticular, intramuscular or intravenous) corticosteroids: 
Discontinued 4 weeks prior to the first dose of study drug.
7. Subjects who are already taking NSAIDs/Cyclooxygenase-2 (COX-2) inhibitors may 
participate in the study provided that that the dose is stable for one week prior to first 
dose of study drug.
4.1.2. Inclusion Criteria That Apply to Subjects Who Enroll Into This Study After the 
14 Day Window From the End of Study Visit of the Qualifying Study
1. Time from End of Study visit of qualifying study must be 3 months.
2. In the opinion of the investigator, the subject must have sufficient evidence of PsA 
disease activity to warrant use of tofacitinib as a DMARD.
3. Subject has discontinued all disallowed concomitant medications for the required 
time prior to the first dose of study medication and is taking only those concomitant 
medications in doses and frequency allowed by the protocol (see Appendix 3).  
Subjects who are receiving any investigational or marketed treatment for PsA or 
psoriasis not mentioned elsewhere must have that treatment discontinued for 4 weeks 
or 5 half-lives, whichever is longer.  Discontinuation criteria for biologics not 
otherwise mentioned must be discussed with the Pfizer Study Clinician.
4. Screening 12-lead electrocardiogram (ECG) that does not demonstrate clinically 
relevant abnormalities (as determined by central reader) which may affect subject 
safety (eg, pattern of acute myocardial infarction, acute ischemia or serious 


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arrhythmia) or interpretation of study results (eg, continuously paced ventricular 
rhythm or complete left bundle branch block).
5. No evidence of active or latent or inadequately treated infection with Mycobacterium 
tuberculosis (TB) as defined by all of the following:

A negative QuantiFERON-GoldIn-Tube test performed by the central 
laboratory within the 3 months prior to screening.  A negative Purified Protein 
Derivative (PPD) test can be substituted for the QuantiFERON Gold (QFT-G) 
In-Tube test only if the central laboratory is unable to perform the test or cannot 
determine the results to be positive or negative and the Pfizer Study Clinician 
approves it, on a case by case basis.  Subjects with a history of Bacille Calmette 
Guérin (BCG) vaccination will be tested with the QFT-G test.

No local QFT-G testing will be accepted for meeting the inclusion criterion.

A chest radiograph taken within the 3 months prior to screening and reviewed by 
a radiologist or pulmonologist as per local standard of care and documented to be 
without changes suggestive of active TB infection.

No history of either untreated or inadequately treated latent or active TB 
infection.

If a subject has previously received an adequate course of therapy for either latent 
(9 months of isoniazid in a locale where rates of primary multi-drug resistant TB 
infection are <5% or an acceptable alternative regimen) or active (acceptable 
multi-drug regimen) TB infection, neither a PPD test nor a QuantiFERON-Gold
In-Tube test need be obtained but a chest radiograph must still be obtained if not 
done so within the prior 3 months.  A subject who is currently being treated for 
either latent or active TB infection can only be enrolled with confirmation of 
current incidence rates of multi-drug resistant TB infection, documentation of an 
adequate treatment regimen, and prior approval of the Sponsor.
4.2. Exclusion Criteria
Subjects presenting with any of the following characteristics/conditions will not be included 
in the study:
4.2.1. Exclusion Criteria that Apply to All Subjects
1. Currently have non-plaque forms of psoriasis, eg erythrodermic, guttate or pustular, 
with the exception of nail psoriasis, which is allowed.
2. Subjects who are investigational site staff members directly involved in the conduct 
of the trial and their family members, site staff members otherwise supervised by the 
investigator, or subjects who are Pfizer employees, including their family members,
directly involved in the conduct of the trial.


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3. Pregnant females, breastfeeding females and females of child-bearing potential who 
are unwilling or unable to use a highly effective method(s) of contraception as 
outlined in this protocol for the duration of the study and for at least one ovulatory 
cycle after last dose of investigational product or females planning pregnancy.  
Women of childbearing potential must test negative for pregnancy prior to enrollment 
in this study.  Subjects in Canada who are women of child-bearing potential, and 
sexually active, are required to use one highly effective method and one additional 
effective method of contraception (see Appendix 9). (Further description of the 
requirements and a list of contraceptives considered highly effective and acceptable 
for use in this study will be found in Section 4.4.6).
4. Current or recent history of uncontrolled renal, hepatic, hematological, 
gastrointestinal, metabolic (including hypercholesterolemia), endocrine, pulmonary, 
cardiovascular, or neurologic disease.
5. History of any autoimmune rheumatic disease other than PsA (including systemic 
lupus erythematosis, mixed connective tissue disease, scleroderma, polymyositis) or 
known diagnosis of fibromyalgia, without approval by Sponsor.  Also excluded are 
subjects with prior history of, or current, rheumatic inflammatory disease other than 
PsA (eg, gout, reactive arthritis, chronic Lyme disease) without approval by Sponsor.
6. A subject with known immunodeficiency disorder or a first degree relative with a 
hereditary immunodeficiency.
7. Functional Class IV status as defined by the American College of Rheumatology 
classification of functional status for RA, ie, limited in ability to perform usual 
self-care, vocational and avocational activities.15
8. History of an infected joint prosthesis at any time, with the prosthesis still in situ.
9. History of any lymphoproliferative disorder, such as Epstein Barr Virus (EBV) 
related lymphoproliferative disorder, history of lymphoma, leukemia, or signs and 
symptoms suggestive of current lymphatic disease.
10. History of recurrent (more than one episode) herpes zoster or disseminated (a single 
episode) herpes zoster or disseminated (a single episode) herpes simplex.
11. History of active infection (including localized infection):

Requiring hospitalization, parenteral antimicrobial therapy, or as otherwise judged 
clinically significant by the investigator, within the 3 months prior to the first dose
of study medication;

Requiring oral antimicrobial therapy within 2 weeks prior to the first dose of 
study medication.


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12. Any prior treatment with non-B cell-specific lymphocyte depleting agents/therapies 
[eg, alemtuzumab (Campath), efalizumab (Raptiva)], alkylating agents 
(eg, cyclophosphamide or chlorambucil), or total lymphoid irradiation.
13. Any subject who has been vaccinated with live or attenuated vaccines within the 
6 weeks prior to the first dose of study medication or is to be vaccinated with these 
vaccines at any time during treatment or within 6 weeks following discontinuation of 
study medication.  (See Section 4.4.2 Vaccine Guidelines for further information 
regarding avoidance of household contacts who may be vaccinated).
14. A subject with any condition possibly affecting oral drug absorption, eg, gastrectomy, 
clinically significant diabetic gastroenteropathy, or certain types of bariatric surgery 
such as gastric bypass.  Procedures such as gastric banding, that simply divide the 
stomach into separate chambers, are NOT exclusionary.
15. A subject that is considered at increased risk for GI perforation (eg, patients with 
diverticulitis) by the Investigator or Sponsor.
16. A subject with a malignancy or with a history of malignancy, with the exception of 
adequately treated or excised non-metastatic basal cell or squamous cell cancer of the 
skin or cervical carcinoma in situ.
17. A subject requiring prohibited concomitant medications (See Appendix 3).  For a 
medical condition in which it is important for the subject’s safety to continue a 
prohibited drug described in Appendix 3, and there is no study-permitted alternative, 
the subject must not participate in this study. Subjects receiving non-prohibited 
concomitant medications must be on a stable regimen which is defined as not starting 
a new drug or changing dosage within seven days or 5 half-lives (whichever is 
longer) prior to the baseline visit.
18. A subject known to be infected with human immunodeficiency virus (HIV), 
hepatitis B virus or hepatitis C virus or any chronic infection.

HBsAg+ is exclusionary; subjects who are HBsAg- but HBcAb+ must undergo 
further testing and be HBsAb+ to be considered for enrollment.

Subjects who are HCV Ab+ must undergo further testing for HCV RNA and are 
allowed to enroll if negative.
19. A subject with evidence of skin conditions (eg, eczema) at the time of the screening 
or baseline visit that would interfere with evaluation of psoriasis.
20. Other severe acute or chronic medical or psychiatric condition or laboratory 
abnormality that may increase the risk associated with study participation or 
investigational product administration or may interfere with the interpretation of 
study results and, in judgement of investigator, would make subject inappropriate for 
entry into this study.


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21. A subject who, in the opinion of the investigator or Pfizer (or designee), will be 
uncooperative or unable to comply with study procedures.
22. Participation in other studies involving investigational drug(s) (Phases 1-4) during 
study participation.
4.2.2. Exclusion Criteria That Apply to Subjects Who Enroll Into This Study After the 
14 Day Window From the End of Study Visit of the Qualifying Study
Laboratory assessments at the Screening Visit or within 3 months prior to the baseline visit 
include:

Evidence of hematopoietic disorders or evidence of hemoglobin levels <10 g/dL;

An absolute white blood cell (WBC) count of <3.0 x 109/L (<3000/mm3);

Absolute neutrophil count of 1.5 x 109/L (1500/mm3); 

Absolute lymphocyte count <1.0 x109/L (<1000/mm3);

Platelet count <100 x 109/L (<100,000/mm3).
Laboratory assessments at the Screening Visit only:

Estimated creatinine clearance <40 mL/min by Cockroft Gault equation 
(Appendix 2);

Total bilirubin, Aspartate Aminotransferase (AST) or Alanine Aminotransferase 
(ALT) >1.5x the upper limit of normal at screening visit.
4.3. Enrollment Criteria
Subjects will be enrolled into the study provided they have signed an informed consent 
document to participate in the study, have undergone all screening procedures as required, 
and have met all inclusion and exclusion criteria for participation in the study at 
Baseline/Day 1.  Subjects will be assigned a subject identification number that will be 
retained throughout the study.
4.4. Life Style Guidelines
In order to participate in the study, subjects must be made aware of the following life style 
guidelines and restrictions that apply during and after the study period.  Details of these life 
style guidelines are provided in the sections as noted.

On designated study visit days, comply with fasting requirements for at least 9 hours 
prior to visit (See Section 6).


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
On study visit days, do not smoke or ingest caffeine (eg, tea, coffee, some soft 
drinks/colas/energy drinks and power bars) during the 30 minutes prior to blood 
pressure and pulse (heart) rate measurements.

On study visit days, showering or bathing is permitted prior to attending the study 
visit, but do not moisturize.

Avoid vaccinations with live or attenuated live vaccines and contact with individuals 
who have recently received live or attenuated live vaccines (See Section 4.4.2).

Discontinue and avoid using certain medications and treatments used to treat PsA or 
psoriasis (see Inclusion Criteria and list of prohibited medications Appendix 3).  
Discontinue and avoid using certain other prohibited medications and treatment (see 
Appendix 3) not used to treat PsA or psoriasis.  For a medical condition in which it is 
important for the subject’s safety to continue using the prohibited drug, and there is 
no study-permitted alternative, the subject must not participate in this study.

Contact the study site investigator if there are any changes or additions to 
concomitant medications.

Avoid having elective surgery (See Section 4.4.5).

Agree to use highly effective contraceptive methods per Section 4.4.6.
4.4.1. Non-Pharmacologic Interventions
The subject should continue all non-pharmacological therapies, such as physical therapy, as 
indicated.
4.4.2. Vaccine Guidelines
4.4.2.1. Subject Vaccination
Vaccination with any live vaccine (whether attenuated or not) is prohibited during the study 
and for 6 weeks after last dose of study drug. Vaccines that are allowed would include: 
inactivated, subunit, toxoid and DNA.  It is recommended that subjects be up to date on 
vaccinations prior to enrollment in this study.
4.4.2.2. Household Contact with Others Vaccinated
During the study and for 6 weeks following the last dose of study drug, subjects should avoid 
routine household contact with children or adults who have been vaccinated with live or 
attenuated live vaccines.  Some of these vaccines include varicella (“chickenpox”) vaccine, 
oral polio vaccine, and the inhaled flu vaccine.  Following vaccination with live component 
vaccines, the virus may be shed in bodily fluids, including stool, and there is potential risk 
that the virus may be transmitted.  General guidelines suggest that exposure should be 
avoided following vaccination with these vaccines for the stated period:
a.
Varicella or attenuated typhoid fever vaccination for 4 weeks following vaccination;


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b. Oral polio vaccination for 6 weeks following vaccination;
c.
Attenuated rotavirus vaccine for 10 days following vaccination;
d. FluMist® (inhaled flu vaccine) for 1 week following vaccination.
4.4.3. Dietary Supplements
For the purposes of this protocol, dietary supplements are defined as vitamins, minerals, 
purified food substances, and herbals with pharmaceutical properties.
Vitamins, minerals and purified food substances are allowed in amounts not known to be 
associated with adverse effects (such as hypervitaminosis).  Herbals with pharmaceutical 
properties are allowed only if there is acceptable evidence of no CYP3A inhibition or 
induction.  Otherwise, herbals with pharmaceutical properties must be discontinued for at 
least 4 weeks prior to first dose of study drug, unless there is sufficient data available 
regarding the duration of an herbal medication’s pharmacokinetic and pharmacodynamic 
effects to allow a shorter washout to be specified (eg, 5 half-lives).  Please direct any 
questions to the Sponsor.
Glucosamine sulfate and chondroitin sulfate are allowed in the study but should be stably 
dosed beginning at least 1 week prior to first dose of study medicine.
4.4.4. Fasting Visit Requirements
On visit days when fasting lipid panels are scheduled to be collected, all subjects should 
refrain from all food and liquids (water and medications permitted, if appropriate) for at least 
9 hours prior to scheduled safety laboratory tests.  Visits that require fasting are Baseline (if 
subject enrolls in A3921092 >14 days after end of qualifying study visit), Month 3, Month 6
and every 6 months thereafter, End of Treatment/Early Termination Visit and Follow-Up 
Visit (if required).
4.4.5. Elective Surgery
During the course of this trial, no elective surgery should be scheduled without first 
consulting the Pfizer Clinician.
Subjects who do require surgery should temporarily discontinue study drug for one week 
prior to the surgical procedure and remain off study drug after the surgical procedure until 
sutures/staples are removed.  If absorbing sutures or chemical closure methods are utilized, 
study drug can be resumed when the operative site is sufficiently healed and risk of infection 
is minimal.
4.4.6. Contraception
4.4.6.1. Contraceptive Methods in Women of Childbearing Potential
Administration of tofacitinib in preclinical studies was shown to have teratogenic effects on 
the offspring of treated rats and viability of their fetuses.  Due to this hypothetical risk, 
women of childbearing potential will not be administered tofacitinib until pregnancy is 
excluded and should use a highly effective method(s) of contraception during therapy with 


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tofacitinib and for at least one ovulatory cycle after study treatment is discontinued.  They must 
have a negative urine pregnancy test at the baseline visit prior to the first dose of study drug 
and at every visit during the study (or more frequently if required by local practices), if a 
menstrual cycle is missed, or if potential pregnancy is otherwise suspected or if the subject 
has become sexually active.
For the purposes of this protocol, female subjects must either use adequate contraception or 
be of non-childbearing potential.  The investigator, in consultation with the subject, will 
select an appropriate method(s) of contraception for women of child-bearing potential who 
are sexually active from the permitted list of contraception methods, and instruct the subject 
in their consistent and correct use.  The investigator, at each study visit, will confirm and 
document consistent and correct use.  In addition, the investigator will instruct the subject to 
call immediately if a selected birth control method(s) is discontinued or if pregnancy is 
known or suspected. Subjects in the United Kingdom that are women of childbearing 
potential are required to use two highly effective methods of birth control. Subjects in 
Canada who are women of childbearing potential, and sexually active, are required to use one 
highly effective method and one additional effective method of contraception (see 
Appendix 9).
Highly effective methods of contraception are those that, alone or in combination, result in a 
failure rate of less than 1% per year when used consistently and correctly (ie, perfect use) and 
include:
1. Established use of oral, injected, injected or implanted hormonal methods of 
contraception are allowed provided the subject remains on the same treatment 
throughout the entire study and has been using that hormonal contraceptive for an 
adequate period of time to ensure effectiveness.
2. Correctly placed copper containing intrauterine device (IUD) or intrauterine system 
(IUS).
3. Male condom or female condom used WITH a spermicide (ie, foam, gel, film, cream, 
suppository). For countries where spermicide is not available or condom plus 
spermicide is not accepted as highly effective contraception, this option is not 
appropriate.
4. Sterilization of male partner with appropriately confirmed absence of sperm in the 
post-vasectomy ejaculate.
5. Bilateral tubal ligation or bilateral salpingectomy or bilateral tubal occlusive 
procedure (provided that occlusion has been confirmed in accordance with the 
device’s label).
NOTE: Sexual abstinence, defined as completely and persistently refraining from all 
heterosexual intercourse (including during the entire period of risk associated with the study 
treatments) may obviate the need for contraception ONLY if this is the preferred and usual 
lifestyle of the subject.


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4.4.6.2. Women of Non-Childbearing Potential
Female subjects of non-childbearing potential must meet at least one of the following 
criteria:

Have undergone documented hysterectomy and/or bilateral oophorectomy;

Have medically confirmed ovarian failure; or 

Achieved post-menopausal status defined as: cessation of regular menses for at least 
12 consecutive months with no alternative pathological or physiological cause; status 
may be confirmed by having serum follicle stimulating hormone (FSH) level within 
the laboratory’s reference range for post-menopausal females. 
All other female subjects (including females with tubal ligations) will be considered to be of 
childbearing potential.
4.4.7. Contraceptive Methods in Male Subjects
Administration of tofacitinib in preclinical trials demonstrated no effects on male sperm or 
offspring in any studies conducted to date.  No effect on human male fertility is expected and 
male subjects need not take contraceptive precautions unless required by other concomitant 
medications (eg, methotrexate).
4.5. Sponsor Qualified Medical Personnel
The contact information for the sponsor’s appropriately qualified medical personnel for the 
trial is documented in the study contact list that is located in the study portal.
To facilitate access to appropriately qualified medical personnel on study related medical 
questions or problems, subjects are provided with a contact card.  The contact card contains, 
at a minimum, protocol and investigational compound identifiers, subject study number, 
contact information for the investigational site and contact details for a contact center in the 
event that the investigational site staff cannot be reached to provide advice on a medical 
question or problem originating from another healthcare professional not involved in the 
subject’s participation in the study.  The contact number can also be used by investigational 
staff if they are seeking advice on medical questions or problems, however it should only be 
used in the event that the established communication pathways between the investigational 
site and the study teams are not available.  It is therefore intended to augment, but not 
replace, the established communication pathways between the investigational site and study 
team for advice on medical questions or problems that may arise during the study.  The 
contact number is not intended for use by the subject directly and if a subject calls that 
number, they will be directed back to the investigational site.


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5. STUDY TREATMENTS
For the purposes of this study, and per International Conference on Harmonisation (ICH) 
guidelines, investigational product is defined as a pharmaceutical form of an active 
ingredient or placebo being tested or used as a reference/comparator in a clinical trial, 
including a product with a marketing authorization when used or assembled (formulated or 
packaged) in a way different from the approved form, or when used for an unapproved 
indication, or when used to gain further information about an approved use (ICH E6 1.33).
Study drug will be dispensed to subjects to self-administer after appropriate training and 
specific written instructions are provided.  Tofacitinib will be taken orally 5 mg BID 
(approximately every 12 hours). The investigator has the option to increase the dose to 
10 mg BID in those subjects who are receiving 5 mg BID and, in the investigator’s opinion, 
has PsA symptoms that are not adequately controlled.  Changes in the dose are only 
permitted at scheduled study visits, unless a reduction to 5 mg BID is required due to safety 
abnormalities as outlined in Appendix 4.  Study treatment will continue in the LTE portion of 
the study until the subject discontinues from the study or has received approximately 3 years
(36 standardized 4-week months) of treatment.
5.1. Allocation to Treatment
Subjects who enroll in this study from qualifying studies will first receive tofacitinib 5 mg 
BID, administered orally, in open-label dosing.  Allocation of subjects to treatment will 
proceed through the use of an interactive response technology (IRT) system (interactive 
Web-based response (IWR).  The site personnel (study coordinator or specified designee) 
will be required to enter or select information including but not limited to the user’s 
identification (ID) and password, the protocol number, and the subject’s number. The site 
personnel will then be provided with a randomization number and container number(s) when 
investigational product is being supplied via the IRT system.  The IRT system will provide a 
confirmation report containing the subject number, randomization number and container 
number(s) assigned.  The confirmation report must be stored in the site’s files.
5.2. Breaking the Blind
This is an open-label study.  Assignment to tofacitinib will be open to the Investigator, 
subjects and Pfizer study team.
5.3. Drug Supplies
Each tofacitinib bottle will be labeled as appropriate for this open-label study.  Study 
medication will be taken according to the instructions provided to the subject.  The specific 
subject instructions will also direct the subject to bring the study medication bottle(s) to the 
clinic on study visit days.  Any permitted dose adjustments that may occur between 
scheduled study visits (ie, dose reduction for safety reasons) must be clearly documented on 
the subject’s chart and verified for start date and dose when the subject returns for their next 
scheduled visit.


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5.3.1. Preparation and Dispensing
Tofacitinib medication will be dispensed in bulk bottles.  At each dispensing visit, subjects 
will receive a sufficient quantity of study drug to last until their next scheduled dispensing 
visit.  For subjects who are taking 5 mg BID, one bottle of study drug will be dispensed at 
each dispensing visit.  If a subject is receiving 10 mg BID, 2 bottles will be dispensed.  At all 
study visits, subjects must return all containers and unused study medications for 
accountability and the amount of study drug returned will be recorded.
5.3.2. Administration
Tofacitinib should be administered orally, twice daily, approximately 12 hours apart, once in 
the morning and once in the evening.  Subjects receiving 5 mg BID will receive 1 tablet in 
the morning and 1 tablet in the evening. Subjects receiving 10 mg BID will receive 2 tablets 
in the morning and 2 tablets in the evening.  Tofacitinib may be administered with or without 
food.  If a tofacitinib dose is missed and the interval to the next scheduled dose is less than 
6 hours, the missed dose of tofacitinib should not be administered.  Subjects should be 
instructed to document any missed doses.
5.3.3. Compliance
Subject compliance with dosing administration will be verified by accounting of returned 
containers and trial medication at each visit. 
Compliance for the tablets will be monitored by the accounting of unused medication and 
will be documented.  Subjects who demonstrate <80% compliance should be counseled by 
the investigator or designee and ensure steps are taken to improve compliance.  Subjects who 
are <80% compliant with dosage regimen for any two consecutive visit periods should be 
withdrawn from the study.
If the subject is over-compliant with study drug (intentional or accidental) the investigator or 
designee is to counsel the subject and ensure correct understanding of the study drug dosing 
regimen.  The investigator should contact the Pfizer Study Clinician promptly with any 
over-compliance (>120% in a visit period) that may potentially impact the safe use of study 
drug or that may result in a serious adverse event.
5.4. Drug Storage 
The investigator, or an approved representative (eg, pharmacist), will ensure that all 
investigational product, including any comparative agents and/or marketed products are
stored in a secured area with controlled access under recommended storage conditions and in 
accordance with applicable regulatory requirements.
Investigational product should be stored in its original container and in accordance with the 
drug label.  See the drug label for storage conditions of the product.
Storage conditions stated in the single reference safety document (SRSD), ie Investigator’s 
Brochure (IB) will be superseded by the storage conditions stated in the labeling.


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Site systems must be capable of measuring and documenting (for example, via a log), at a 
minimum, daily minimum and maximum temperatures for all site storage locations (as 
applicable, including frozen, refrigerated and/or room temperature products).  This should be 
captured from the time of investigational product receipt throughout the study.  Even for 
continuous monitoring systems, a log or site procedure which ensures active daily evaluation 
for excursions should be available.  The operation of the temperature monitoring device and 
storage unit (for example, refrigerator), as applicable, should be regularly inspected to ensure 
it is maintained in working order.
Any excursions from the product label storage conditions should be reported to Pfizer upon 
discovery.  The site should actively pursue options for returning the product to labeled 
storage conditions, as soon as possible.  Deviations from the storage requirements, including 
any actions taken, must be documented and reported to the sponsor.
Once an excursion is identified, the investigational product must be quarantined and not used 
until the sponsor provides documentation of permission to use the investigational product.  It 
will not be considered a protocol deviation if Pfizer approves the use of the investigational 
product after the temperature excursion.  Use of the investigational product prior to Pfizer 
approval will be considered a protocol deviation.  Specific details regarding information the 
site should report for each excursion will be provided to the site.
Site staff will instruct subjects on the storage requirements for take home investigational 
products.
5.5. Drug Accountability
The investigator’s site must maintain adequate records documenting the receipt, use, loss or 
other disposition of the investigational product supplies. To ensure adequate records, all 
investigational product supplies will be accounted for in the drug accountability inventory 
forms as instructed by Pfizer and will be monitored by the accounting of unused 
investigational product returned by the subjects.  All study drug bottles must be returned to 
the investigator by the subject and the investigator will return the bottles to Pfizer.  At the 
end of the clinical study, all drug supplies unallocated or unused by the subjects must be 
returned to Pfizer or its appointed agent, or destroyed in an approved manner unless 
otherwise authorized by Pfizer.  In either case, the forms must identify the study drug, 
including batch or code numbers, and account for its disposition on a subject-by-subject 
basis, including specific dates and quantities.  The forms must be signed by the individual 
who dispensed the drug.
5.5.1. Destruction of Investigational Product Supplies
The sponsor or designee will provide guidance on the destruction of unused investigational 
product (eg, at the site).  If destruction is authorized to take place at the investigator site, the 
investigator must ensure that the materials are destroyed in compliance with applicable 
environmental regulations, institutional policy, and any special instructions provided by 
Pfizer, and all destruction must be adequately documented.


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For all containers returned to the investigator by the subject, the investigator will maintain 
the returned supply until destruction is authorized or release to a third party for destruction is 
granted.
5.6. Concomitant Treatment(s)
It is important to be aware of, and document, all concomitant treatments including: 
prescription, non-prescription (ie, over-the-counter) and herbal medications.
A subject who is receiving an allowed concomitant medication for any reason must be on a 
locally-approved medication and dose that is considered standard-of-care for the treated 
indication, and this must be documented in the case report form.  Subjects are not allowed to 
receive any other investigational drug during the study.
It is recommended that subjects avoid changing non-prohibited prescription or 
non-prescription drugs, vitamins, and dietary supplements within 7 days or 5 half-lives 
(whichever is longer) prior to the first dose of study medication and prior to study visits 
unless otherwise noted below, throughout the study.
Treatments that are taken in the Screening period (after informed consent is obtained and 
before the first dose of study drug) will be documented as prior treatments.  Treatments taken 
after the first dose of study drug has been administered will be documented as concomitant 
treatments.  All concomitant treatments taken during the study must be recorded in the study 
records with indication (as appropriate), daily dose and start and stop dates of administration.  
Subjects will be queried about concomitant treatments at each study visit.
Minimum guidelines for folate supplementation during study: Subjects on methotrexate must 
receive folate supplementation according to local methotrexate label guidelines and standard 
of care.  A minimum of 5 mg weekly based on folic acid should be given unless local 
guidelines or standard of care state otherwise.
5.6.1. Stable Background Pain or Other Arthritis Therapy
Use of background medication (eg, methotrexate, leflunomide or sulfasalazine) by a subject 
is not a requirement.  However, if used, the concomitant DMARD should be the same 
medication as the subject was receiving in the qualifying study. Adjustment of background 
medications are allowed for reasons of inadequate efficacy of current treatment, or may be 
tapered or discontinued due to disease improvement.  Adjustments for safety reasons may be 
done at any time, but if this leads to changes in excess of those allowed, the investigator must 
receive approval from the Pfizer Clinician to allow the subject to continue in the trial.  Dose 
adjustments of the permitted concomitant DMARDs should not occur any more frequently 
than every 3 months.  If adjustment of the concomitant DMARD is required for safety, it can 
occur at any time.  If the concomitant DMARD requires adjustment for efficacy, it should be 
completed at the visit or within 14 days.
If a concomitant DMARD is discontinued during the course of the study, it should not be 
re-initiated.  Addition of any new concomitant DMARD is not allowed; subjects are only 
permitted to receive one concomitant DMARD in the study.


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Dose adjustments may be made, or background NSAID/COX-2 inhibitors may be switched, 
but should be no more frequently than every 3 months, and should be more than 14 days 
prior to a study visit.  Oral corticosteroid dose should not exceed 10 mg prednisone or its 
equivalent daily.  Daily dosage of NSAIDs/COX-2 inhibitors and corticosteroids must not be 
modified within the 24 hours prior to any study visit, except if adjustment is needed to 
protect a subject’s safety.
Methotrexate doses may be adjusted no more frequently than every 3 months (and remaining 
20 mg/week).  Adjustments should not be made more than 4 weeks prior to a study visit.  
Intra-articular steroids should be administered in a total dosage of no more than 80 mg of 
methylprednisolone or equivalent every 6 months.  Intra-articular hyaluronate sodium 
injections may be administered for indications in accordance with the local label.  Injected 
joints will be considered to have their pre-injection status for efficacy assessments during the 
remainder of the study.  Intra-articular injections should be administered more than 6 weeks 
prior to a study visit (See Appendix 6).
The total daily dose of acetaminophen may not exceed 2.6 grams per day, and the total daily 
dose of opioid may not exceed the potency equivalent of 30 mg of orally-administered 
morphine (See Appendix 5, Appendix 6).
Daily dosage of opioids and acetaminophen/paracetamol must not be modified within 
the 24 hours prior to any study visit, except if adjustment is needed to protect a subject’s 
safety.
5.6.2. Other Medications
Prohibited drugs and dietary supplements must be discontinued according to protocol 
guidelines: a list of prohibited drugs with specific discontinuation recommendations is listed 
in Appendix 3.  Herbals with pharmaceutical properties are allowed only if there is 
acceptable evidence of no CYP3A inhibition or induction.  Otherwise, herbals with 
pharmaceutical properties must be discontinued for at least 4 weeks prior to first dose of 
study drug, unless there is sufficient data available regarding the duration of an herbal 
medication’s pharmacokinetic and pharmacodynamic effects to allow a shorter washout to be 
specified (eg, 5 half-lives).  All concomitant treatment taken during the study must be 
recorded with indication (as required), daily dose, and start and stop dates of administration.
5.7. Rescue Therapy
The only medications that are allowed for rescue are listed in Appendix 6. Subjects who 
require rescue medication for more than 10 consecutive days should be discontinued from the 
study.  There is no limit to the duration of nonconsecutive use of rescue medications.  In 
addition, subjects must not be dosed with rescue medication during the 24 hours prior to a 
study visit except if adjustment is needed because subject is experiencing intolerable pain.  
Baseline stable use of acetaminophen/paracetamol or opioids should NOT be discontinued in 
advance of study visits.


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5.8. Dosage Reduction and Withholding
All subjects will receive tofacitinib 5 mg BID upon entry into A3921092.  Dosage of 
tofacitinib may be increased to 10 mg BID only at scheduled study visits to provide greater 
control of the subject’s PsA, if the investigator feels the subject would benefit and the subject 
is not experiencing any tofacitinib-related adverse events, including abnormalities in 
laboratory parameters that are judged to be related to tofacitinib.
For those subjects whose tofacitinib dose has been increased to 10 mg:

Dosage of tofacitinib may be reduced back to 5 mg BID for mild to moderate 
cytopenias, other mild to moderate AEs, or any other safety-related issues, either 
temporarily or for the duration of the study.

Definitions of mild to moderate cytopenias are as follows:

Mild to moderate neutropenia: 1000-1500 neutrophils/mm3, confirmed;

Mild to moderate anemia: a decrease of hemoglobin from 1.0-2.0 g/dL from 
baseline, inclusive, provided the hemoglobin remains >8.0 g/dL;

Mild to moderate thrombocytopenia: 75,000-100,000 platelets/mm3.
For all subjects:

Dosage of tofacitinib may be temporarily discontinued for up to 28 consecutive days, 
for more severe cytopenias, for infections which do not meet criteria for serious 
infections (ie, those requiring parenteral antimicrobial therapy or hospitalization), for 
surgical procedures or other moderately severe AEs.

Treatment with tofacitinib will be discontinued and the subject withdrawn from this 
study for toxicities as defined in Appendix 4.
6. STUDY PROCEDURES
Subjects from any qualifying tofacitinib PsA study who elect to participate should complete a 
combined screening/baseline visit on the same day they end participation in the previous 
randomized tofacitinib study or within 14 days to be eligible for rollover into A3921092.  
Eligible subjects enrolling outside of the 14 day window (but 3 months) will be required to 
participate in the full Screening visit and Baseline visit.
The study investigator or a sub-investigator will discuss with each subject the nature of the 
study, its requirements, and its restrictions.  Written informed consent must be obtained prior 
to performance of any protocol-specific procedures.
Subjects who are on prohibited medications, and are deriving a beneficial response from 
them, should not be entered into this study.


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6.1. Screening and Baseline
6.1.1. Subjects Requiring Separate Screening and Baseline Visits
Subjects who enter this study from their qualifying study outside of the 14 day window after 
their last study visit in the prior study must participate in a Screening Visit to determine 
eligibility and a Baseline Visit for enrollment in this study.  To be eligible, enrollment into 
A3921092 must occur 3 months after last visit in the qualifying study.
6.1.1.1. Screening Visit

Informed consent obtained.

Register for subject identification number.

Medical history: Include history of previous vaccinations, specifically influenza, 
pneumococcal and zoster.  The medical history should also include Cardiovascular 
(CV) Risk Factor Assessment (Section 7.4) which includes smoking status, average 
weekly alcohol consumption and family history of premature coronary heart disease 
(CHD).  Premature coronary heart disease is defined as CHD in a male first-degree 
relative first observed at <55 years or CHD in female first-degree relative first 
observed at <65 years.

Disease Activity Assessment (Section 7.1.1).

Prior/concomitant treatments ongoing or started since last visit in the qualifying study 
not exceeding the last 12 months.

Temperature (oral, tympanic or temporal preferred), blood pressure and pulse rate 
(vital signs).

12-lead ECG.

Complete Physical Examination: Height, weight, general appearance, skin (presence 
of rash), HEENT (head, eyes, ears, nose and throat), lungs (auscultation), heart 
(auscultation for presence of murmurs, gallops, rubs), lower extremities (presence of 
peripheral edema), abdomen (palpation and auscultation), neurologic (mental status, 
station, gait, reflexes, motor and sensory function, coordination) and lymph nodes.

QuantiFERON Goldtest or Mantoux Purified Protein Derivative (PPD) skin test 
where applicable and/or chest radiograph where applicable (unless done in the prior 
3 months).  Subjects who have PPD must return within 48-72 hours for evaluation.

Blood and urine specimen testing: Central laboratory tests including: Hematology, 
Chemistry Panel, Urinalysis, CRP, HIV serology, HBsAg, HBcAb, HCV Ab, Stool 
examination for parasites (Brazil only).  Screening lab tests may be repeated a single 
time if the initial result is inconsistent with previous documented subject laboratory 
history.


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
Urine pregnancy test for women of child-bearing potential only.

Tender/Painful Joint Count (68), Swollen Joint Count (66).
6.1.1.2. Baseline Visit
This visit must occur 2-28 days after screening visit.
Subjects are required to fast for at least 9 hours prior to the visit, however, blood 
collection for laboratory testing may be taken up to 48 hour prior to the Baseline/Day 0 visit 
as necessary to ensure the samples are collected in a fasting state.
All Patient Reported Outcomes should be performed before any other study procedures.  
These include the following:

Patient’s Assessment of Arthritis Pain (VAS).

Patient’s Global Assessment of Arthritis (VAS).

Health Assessment Questionnaire – Disability Index (HAQ-DI).

BASDAI.

ASQOL.

Patient’s Global Joint and Skin Assessment (PGJS-VAS). 

SF-36 Version 2 (Acute).

DLQI.

FACIT Fatigue Scale.

EuroQol 5 Dimensions (EQ-5D).

ISI.

WLQ.

PsA-HCRU.
Procedures that will be performed prior to enrollment and the first dose of study drug on 
Visit 1, Day 1 for baseline include:

Targeted Physical Examination: (weight, examination of hearts, lungs, abdomen, 
lower extremities and lymph nodes). 

Vital signs: blood pressure, pulse rate and temperature (tympanic, oral or temporal 
preferred).


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
Waist and hips circumference.

Blood and urine specimen testing: Central laboratory tests include: Hematology, 
Chemistry Panel, Lymphocyte subset analysis (FACS), Hemoglobin A1c (HbA1c),
C-Reactive Protein (CRP), Lipid Profile (fasting), Urinalysis. 

Urine Pregnancy Test (for women of childbearing potential only).

Clinical Evaluation of Rheumatology Endpoints:

Tender/painful joint counts (68);

Swollen joint counts (66);

Physician’s Global Assessment of Arthritis (VAS);

Assessment of presence and severity of dactylitis;

Assessment of enthesitis using the Spondyloarthritis Research Consortium of 
Canada (SPARCC) Enthesitis Index and Leeds Enthesitis Index.

Clinical Evaluation of Dermatology Endpoints:

Physician’s Global Assessment of Psoriasis (PGA-PsO);

Psoriasis Area and Severity Index (PASI);

Body Surface Area (BSA);

Nail Psoriasis Severity Index (NAPSI).

Clinical Evaluation of Rheumatology and Dermatology Endpoint: Physician’s Global 
Assessment of Psoriatic Arthritis (VAS).

Drug dispensing.

Monitoring of adverse events and concomitant treatment.
6.1.2. Subjects with Combined End of Study Visit/Baseline Visit
For subjects combining the End of Study (EOS) Visit from qualifying study with 
Screening/Baseline visit for A3921092, subjects must complete activities as indicated from 
EOS visit and the following procedures:

Informed consent obtained.

Register for subject identification number.

Dispense study medication/schedule next visit.


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6.1.3. Subjects with End of Study Visit Separate From Combined Screening/Baseline 
Visit
Subjects who complete their combined screening/baseline visit within 14 days of the last visit 
of the qualifying study but not on the same day must complete the following procedures at 
the combined screening/baseline visit.

Informed consent obtained.

Register for subject identification number.
All Patient Reported Outcomes should be performed before any other study procedures.  
These include the following: 

Patient’s Assessment of Arthritis Pain (VAS). 

Patient’s Global Assessment of Arthritis (VAS).

Health Assessment Questionnaire – Disability Index (HAQ-DI).
Procedures that will be performed prior to enrollment and the first dose of study drug on 
Visit 1, Day 1 for baseline include:

Targeted Physical Examination: (weight, examination of hearts, lungs, abdomen, 
lower extremities and lymph nodes). 

Vital signs: blood pressure, pulse rate and temperature (tympanic, oral or temporal 
preferred).

Blood and urine specimen testing: Central laboratory tests include: Hematology, 
Chemistry Panel, C-Reactive Protein (CRP), Urinalysis. 

Urine Pregnancy Test (for women of childbearing potential only).

Clinical Evaluation of Rheumatology Endpoints:

Tender/painful joint counts (68);

Swollen joint counts (66);

Physician’s Global Assessment of Arthritis (VAS).

Drug dispensing.

Monitoring of adverse events and concomitant treatments.


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6.2. Study Period
Subjects who have met all inclusion criteria and have no exclusion criteria present may 
participate in the study.
Standard of Care Testing.  Safety laboratory tests should be repeated as appropriate for 
subjects receiving permitted concomitant non-biologic DMARD therapy, eg, subjects on 
background methotrexate should have complete blood count (CBC) and differential count 
with safety chemistries as appropriate for the local standard of care.
The blood collection for laboratory testing at specified visits [eg, Month 3, Month 6 (and 
every 6 months thereafter), Month 12 (and every 12 months thereafter)] requiring a fasting 
state (at least 9 hours) may be taken up to 48 hours prior to or after the visit to ensure 
samples are collected in a fasting state.  If the subject has not fasted for at least 9 hours, the 
visit should be rescheduled to occur within 48 hours in the fasting state. 
Prior to attending the study visits, subjects are allowed to shower or bathe that morning but 
should not moisturize with topical emollient.
Subjects should complete the Patient Reported Outcome questionnaires at the clinic prior to 
any other study procedures.  This sequence of study procedures will reduce the risk of 
inadvertently introducing bias in a subject’s responses through study staff interactions.  In the 
unlikely event that a Patient Reported Outcome (PRO) questionnaire(s) is not able to be 
administered by the study site staff and completed by the subject at the clinic visit, the PRO 
questionnaire(s) should not be administered.
All rheumatological and dermatological assessments will be performed by qualified, trained 
assessors.  To ensure consistency and reduce intra-individual variability, the same qualified 
assessor should score all evaluations for a particular assessment for a given subject 
throughout the study.  The visit window for this study as well as the qualifying study utilizes
28 days for a month.
6.2.1. Type A Visit: Month 1 
The window for this visit is 7 days.
All Patient Reported Outcomes should be completed prior to any other study procedures.  
These include the following: 

Patient’s Assessment of Arthritis Pain (VAS).

Patient’s Global Assessment of Arthritis (VAS).

Health Assessment Questionnaire – Disability Index (HAQ-DI).

Patient’s Global Joint and Skin Assessment (PGJS-VAS).

BASDAI.


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
ASQOL.

SF-36 Version 2 (Acute).

DLQI.

FACIT Fatigue Scale.

EuroQol 5 Dimensions (EQ-5D).

WLQ.

PsA-HCRU.

ISI. 
Procedures that will be performed include:

Targeted physical examination (weight, examination of heart, lungs, abdomen, lower 
extremities, and lymph nodes).

Vital signs: blood pressure, pulse rate and temperature (tympanic, oral or temporal 
preferred).

Waist and hips circumference.

Blood and urine specimen testing: Central laboratory tests including: Hematology, 
Chemistry Panel, CRP, Urinalysis.

Urine Pregnancy Test (for women of women of childbearing potential only).

Clinical Evaluation of Rheumatology Endpoints: 

Tender/Painful Joint Counts (68);

Swollen Joint Count (66);

Physician’s Global Assessment of Arthritis (VAS);

Assessment of presence and severity of dactylitis;

Assessment of enthesitis using the Spondyloarthritis Research Consortium of 
Canada [SPARCC] Enthesitis Index and Leeds Index.

Clinical Evaluation of Dermatology Endpoints:

Physician’s Global Assessment of Psoriasis (PGA-PsO);


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
Psoriasis Area and Severity Index (PASI);

Body Surface Area (BSA);

Nail Psoriasis Severity Index (NAPSI).

Clinical Evaluation of Rheumatology and Dermatology Endpoint: Physician’s Global 
Assessment of Psoriatic Arthritis (VAS).

Monitoring of adverse events and concomitant treatments.  Record any modifications, 
deletions or additions.

Drug accountability.
6.2.2. Type B Visit: Months 3, 9, 15, 21, 27* and 33*
The window for the Month 3 visit is 7 days and 10 days for visits thereafter. 
At the Month 3 visit only, subjects are required to fast for at least 9 hours prior to the 
visit.  Blood collection may be taken up to 48 hours prior to or following this visit as 
necessary to ensure samples are collected in a fasted state.
All Patient Reported Outcomes should be completed prior to any other study procedures.  
These include the following: 

Patient’s Assessment of Arthritis Pain (VAS).

Patient’s Global Assessment of Arthritis (VAS).

BASDAI.

ASQOL.

Patient’s Global Joint and Skin Assessment (PGJS-VAS).

Health Assessment Questionnaire – Disability Index (HAQ-DI). 
Procedures that will be performed include:

Targeted physical examination (weight, examination of heart, lungs, abdomen, lower 
extremities, and lymph nodes).

Vital signs: blood pressure, pulse rate and temperature (tympanic, oral or temporal 
preferred).


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
Blood and urine specimen testing: Central laboratory tests including: Hematology, 
Chemistry Panel, Lymphocyte subset analysis (FACS), CRP, Urinalysis, Lipid panel 
(fasting) at Month 3 only.

Urine Pregnancy Test (for women of women of childbearing potential only).

Clinical Evaluation of Rheumatology Endpoints: 

Tender/Painful Joint Counts (68);

Swollen Joint Count (66);

Physician’s Global Assessment of Arthritis (VAS);

Assessment of presence and severity of dactylitis;

Assessment of enthesitis using the Spondyloarthritis Research Consortium of 
Canada [SPARCC] Enthesitis Index and Leeds Index.

Clinical Evaluation of Dermatology Endpoints:

Physician’s Global Assessment of Psoriasis (PGA-PsO);

Psoriasis Area and Severity Index (PASI);

Body Surface Area (BSA).

Clinical Evaluation of Rheumatology and Dermatology Endpoint: Physician’s Global 
Assessment of Psoriatic Arthritis (VAS).

Monitoring of adverse events and concomitant treatments.  Record any modifications, 
deletions or additions.

Drug accountability.

Drug dispensing.
*At Month 27 or Month 33, subjects who meet entry criteria of the sub-study can be enrolled 
in the sub-study.  These subjects will complete the study procedures at this visit and will end 
study participation in the LTE.  At the Switch/Baseline visit of the sub-study, all 
investigational product from the main A3921092 LTE study will be collected for 
accountability under the main protocol.  New tofacitinib supplies will be dispensed under the 
sub-study.  Please refer to Appendix 10 for additional requirements and procedures.
6.2.3. Type C Visit: Months 6, 18 and 30*
The window for these visits is 10 days. 


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Subjects are required to fast for at least 9 hours prior to the visit.  Blood collection may 
be taken up to 48 hours prior to or following this visit as necessary to ensure samples are 
collected in a fasted state.
All Patient Reported Outcomes should be completed prior to any other study procedures.  
These include the following: 

Patient’s Assessment of Arthritis Pain (VAS).

Patient’s Global Assessment of Arthritis (VAS).

BASDAI.

ASQOL.

Patient’s Global Joint and Skin Assessment (PGJS-VAS). 

Health Assessment Questionnaire – Disability Index (HAQ-DI).

SF-36 Version 2 (Acute).

DLQI.

FACIT Fatigue Scale.

EuroQol EQ-5D.

ISI.

WLQ.

PsA-HCRU.
Procedures that will be performed include:

Cardiovascular Risk Assessment: smoking status, average weekly alcohol 
consumption and family history of premature coronary heart disease (see
Section 7.4).

Physical Examination: Targeted physical examination (weight, examination of heart, 
lungs, abdomen, lower extremities and lymph nodes).

Vital signs: blood pressure, pulse rate and temperature (tympanic, oral or temporal 
preferred).


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
Blood and urine specimen testing: Central laboratory tests including: Hematology, 
Chemistry Panel, CRP, HbA1c, Lipid Panel (fasting), Urinalysis, Lymphocyte subset 
analysis (FACS). 

Urine Pregnancy Test (for women of childbearing potential only).

Waist and hips circumference.

Clinical Evaluation of Rheumatology Endpoints:

Tender/Painful Joint Counts (68);

Swollen Joint Count (66);

Physician’s Global Assessment of Arthritis (VAS);

Assessment of presence and severity of dactylitis;

Assessment of enthesitis using the Spondyloarthritis Research Consortium of 
Canada [SPARCC] Enthesitis Index and Leeds Index.

Clinical Evaluation of Dermatology Endpoints:

Physician’s Global Assessment of Psoriasis (PGA-PsO);

Psoriasis Area and Severity Index (PASI);

Body Surface Area (BSA);

Nail Psoriasis Severity Index (NAPSI).

Clinical Evaluation of Rheumatology and Dermatology Endpoint: Physician’s Global 
Assessment of Psoriatic Arthritis (VAS).

Monitoring of adverse events and concomitant treatments.  Record any modifications, 
deletions or additions.

Drug accountability.

Drug dispensing.
*At Month 30, subjects who meet entry criteria of the sub-study can be enrolled in the 
sub-study.  These subjects will complete the study procedures at this visit and will end study 
participation in the LTE.  At the Switch/Baseline visit of the sub-study, all investigational 
product from the main A3921092 LTE study will be collected for accountability under the 
main protocol.  New tofacitinib supplies will be dispensed under the sub-study.  Please refer 
to Appendix 10 for additional requirements and procedures.


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6.2.4. Type D Visit: Month 12, 24* and 36*
The window for these visits is 10 days. 
Subjects are required to fast for at least 9 hours prior to the visit.  Blood collection may 
be taken up to 48 hours prior to or following this visit as necessary to ensure samples are 
collected in a fasted state.
All Patient Reported Outcomes should be completed prior to any other study procedures.  
These include the following: 

Patient’s Assessment of Arthritis Pain (VAS).

Patient’s Global Assessment of Arthritis (VAS).

BASDAI.

ASQOL.

Patient’s Global Joint and Skin Assessment (PGJS-VAS).

Health Assessment Questionnaire – Disability Index (HAQ-DI).

SF-36 Version 2 (Acute).

DLQI.

FACIT Fatigue Scale.

EuroQol EQ-5D.

ISI.

WLQ.

PsA-HCRU.
Procedures that will be performed include:

Cardiovascular Risk Assessment: smoking status, average weekly alcohol 
consumption and family history of premature coronary heart disease (see
Section 7.4).

Physical Examination: Complete physical examination (height, weight, general 
appearance, skin (presence of rash), HEENT (head, eyes, ears, nose and throat), lungs 
(auscultation), heart (auscultation for presence of murmurs, gallops, rubs), extremity 
exam (presence of peripheral edema), abdomen (palpation and auscultation), 
neurologic (mental status, station, gait, reflexes, motor and sensory function, 
coordination) and lymph nodes.


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
Vital signs: blood pressure, pulse rate and temperature (tympanic, oral or temporal 
preferred).

Blood and urine specimen testing: Central laboratory tests including: Hematology, 
Chemistry Panel, CRP, HbA1c, Lipid Profile (fasting), Urinalysis, Lymphocyte 
subset analysis (FACS). 

QuantiFERON Gold® In-Tube Test (QFT) only for subjects: 1) in countries for which 
TB incidence has been reported >50 cases per 100,000 persons (see Section 7.6.3) 
and 2) who tested negative at their last QFT. Subjects newly testing positive must 
have chest radiograph performed and reviewed by a radiologist or pulmonologist as 
per local standard of care.  Please note: subjects with a new positive QFT and a chest 
x-ray that does not show active disease (and no other evidence of active disease) are 
required to be treated for latent tuberculosis infection.

Urine Pregnancy Test (for women of childbearing potential only).

Waist and hips circumference.

12-lead electrocardiogram.

Clinical Evaluation of Rheumatology Endpoints:

Tender/Painful Joint Counts (68);

Swollen Joint Count (66);

Physician’s Global Assessment of Arthritis (VAS);

Assessment of presence and severity of dactylitis;

Assessment of enthesitis using the Spondyloarthritis Research Consortium of 
Canada [SPARCC] Enthesitis Index and Leeds Index.

Clinical Evaluation of Dermatology Endpoints:

Physician’s Global Assessment of Psoriasis (PGA-PsO);

Psoriasis Area and Severity Index (PASI);

Body Surface Area (BSA);

Nail Psoriasis Severity Index (NAPSI).

Clinical Evaluation of Rheumatology and Dermatology Endpoint: Physician’s Global 
Assessment of Psoriatic Arthritis (VAS).


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
Monitoring of adverse events and concomitant treatments.  Record any modifications, 
deletions or additions.

Drug accountability.

Drug dispensing (except at Month 36 visit).
*At Month 24 or Month 36, subjects who meet entry criteria of the sub-study can be enrolled 
in the sub-study.  These subjects will complete the study procedures at this visit and will end 
study participation in the LTE. At the Switch/Baseline visit of the sub-study, all 
investigational product from the main A3921092 LTE study will be collected for 
accountability under the main protocol.  New tofacitinib supplies will be dispensed under the 
sub-study.  Please refer to Appendix 10 for additional requirements and procedures.
6.2.5. End of Study Follow-up Phone Call
Subjects will be contacted within 7 days after the 28 days following End of Study visit and 
any adverse events will be documented. 
6.2.6. Early Termination Visit
Subjects are required to fast for at least 9 hours prior to the visit.  Blood collection may 
be taken up to 48 hours prior to or following this visit as necessary to ensure samples are 
collected in a fasted state.
All Patient Reported Outcomes should be completed prior to any other study procedures. 
These include the following: 

Patient’s Assessment of Arthritis Pain (VAS).

Patient’s Global Assessment of Arthritis (VAS).

Health Assessment Questionnaire – Disability Index (HAQ-DI).

Patient’s Global Joint and Skin Assessment (PGJS-VAS).

BASDAI.

ASQOL.

SF-36 Version 2 (Acute).

DLQI.

FACIT Fatigue Scale.

EuroQol EQ-5D.


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
ISI.

WLQ.

PsA-HCRU
Procedures that will be performed include:

Cardiovascular Risk Assessment: smoking status, average weekly alcohol 
consumption and family history of premature coronary heart disease (see
Section 7.4).

Complete Physical Examination: weight, general appearance, skin (presence of rash), 
HEENT (head, eyes, ears, nose and throat), lungs (auscultation), heart (auscultation 
for presence of murmurs, gallops, rubs), extremity exam (presence of peripheral 
edema), abdomen (palpation and auscultation), neurologic (mental status, station, 
gait, reflexes, motor and sensory function, coordination) and lymph nodes.

Vital signs: blood pressure, pulse rate and temperature (tympanic, oral or temporal 
preferred).

Blood and urine specimen testing: Central laboratory tests including: Hematology, 
Chemistry Panel, Lymphocyte subset analysis (FACS), CRP, HbA1c, Lipid Profile 
(fasting), Urinalysis. 

Urine Pregnancy Test (for women of childbearing potential only).

Waist and hips circumference.

12-lead electrocardiogram.

Clinical Evaluation of Rheumatology Endpoints:

Tender/Painful Joint Counts (68);

Swollen Joint Count (66);

Physician’s Global Assessment of Arthritis (VAS);

Assessment of presence and severity of dactylitis;

Assessment of enthesitis using the Spondyloarthritis Research Consortium of 
Canada [SPARCC] Enthesitis Index and Leeds Index.

Clinical Evaluation of Dermatology Endpoints:

Physician’s Global Assessment of Psoriasis (PGA-PsO);


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
Psoriasis Area and Severity Index (PASI);

Body Surface Area (BSA);

Nail Psoriasis Severity Index (NAPSI).

Clinical Evaluation of Rheumatology and Dermatology Endpoint: Physician’s Global 
Assessment of Psoriatic Arthritis (VAS).

Monitoring of adverse events and concomitant treatments.  Record any modifications, 
deletions or additions.

Drug accountability.
6.3. Follow-up Visit
If a subject discontinues from the study with abnormalities in hematology or clinical 
chemistry results which meet criteria as defined in Appendix 4, or a subject discontinues 
from the study due to an adverse event, a follow-up visit must be performed after the Early 
Termination study visit within 28 days (7 days) of last dose of study treatment.
Subjects are required to fast for at least 9 hours prior to the visit.  Blood collection may 
be taken up to 48 hours prior to or following this visit as necessary to ensure samples are 
collected in a fasted state.
The following procedures will be performed:

Blood testing: Central laboratory tests may include: Hematology, Chemistry Panel; 
Lipid Panel (fasting). 

Urine Pregnancy Test (for women of childbearing potential only).

Adverse event reporting and concomitant treatment use.
If abnormalities in hematology or clinical chemistry results are still observed at the follow-up 
visit, the subject must continue to be followed until the laboratory abnormality stabilizes or 
returns to baseline levels as approved by the Sponsor.
6.4. Subject Withdrawal
Subjects may withdraw from the study at any time at their own request, or they may be 
withdrawn at any time at the discretion of the investigator or sponsor for safety or behavioral 
reasons, or the inability of the subject to comply with the protocol required schedule of study 
visits or procedures at a given study site. 
If a subject does not return for a scheduled visit, every effort should be made to contact the 
subject.  In any circumstance, every effort should be made to document subject outcome, if 
possible.  The investigator should inquire about the reason for withdrawal, request the subject 


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return all unused investigational product(s), request the subject return for a final visit, and 
follow-up with the subject regarding any unresolved adverse events (AEs).
If the subject withdraws from the study, and also withdraws consent for disclosure of future 
information, no further evaluations should be performed, and no additional data should be 
collected.  The Sponsor may retain and continue to use any data collected before such 
withdrawal of consent.  Withdrawal due to adverse event should be distinguished from 
withdrawal due to insufficient response according to the definition of adverse event noted in
Section 8.3.  Withdrawal due to a subject being no longer willing to participate in the study 
should be distinguished from withdrawal due to “lost to follow-up” (LTFU).  Every effort 
should be made to identify and contact subjects who are potentially LTFU.  A subject should 
not be considered a withdrawal due to LTFU until at least 3 attempts to contact the subject by 
multiple methods have been unsuccessful.  All methods of attempted contact with the subject 
must be clearly documented (dated and initialed) in the subject’s source documents and 
recorded on appropriate case report form (CRF) page.  All potential LTFU subjects must be 
discussed with the Pfizer study team or designee prior to assigning LTFU status.
If a subject discontinues from the study due to any abnormality in hematology or clinical 
chemistry results which meet the criteria as defined in Appendix 4, a follow-up visit must be 
performed within 28 days (7 days) of last dose of study treatment.
If a subject has any clinically significant, treatment-emergent, abnormalities at the conclusion 
of the study, the Sponsor (or designated representative) should be notified and every effort 
should be made to arrange follow-up evaluations at appropriate intervals to document the 
course of the abnormality.  All abnormal laboratory events of clinical significance should be 
followed until the laboratory values have returned to normal or baseline levels.
Subjects who require rescue doses of acetaminophen/paracetamol or opioid for more than 
10 consecutive days, subjects interrupting study drug for more than 28 consecutive days (see 
Appendix 4), or subjects who are <80% compliant with the dosage regimen for any two 
consecutive visit periods should be withdrawn from the study.
7. ASSESSMENTS
Every effort should be made to ensure that the protocol required tests and procedures are 
completed as described.  However it is anticipated that from time to time there may be 
circumstances, outside of the control of the investigator that may make it unfeasible to 
perform the test.  In these cases the investigator will take all steps necessary to ensure the 
safety and wellbeing of the subject.  When a protocol required test cannot be performed the 
investigator will document the reason for this and any corrective and preventive actions 
which he/she has taken to ensure that normal processes are adhered to as soon as possible.  
Single missed assessments, if justified, would not be considered as non-adherence to 
protocol; reason for missed evaluation must be documented.  Two or more consecutively 
missed assessments for any endpoint would be considered non-adherence and be reported.  
The study team should be informed of these incidents in a timely fashion.


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7.1. Efficacy Endpoints
7.1.1. Disease Activity Assessment
Subjects who enroll >14 days after their End of Study Visit in their qualifying study must, in 
the opinion of the investigator, have sufficient evidence of PsA disease activity to warrant 
use of tofacitinib as a DMARD (Inclusion criteria #2, Section 4.1.2).
7.1.2. ACR Assessments
The American College of Rheumatology’s definition for calculating improvement in 
RA (ACR20) is calculated as a 20% improvement in tender and swollen joint counts and 
20% improvement in 3 of the 5 remaining ACR-core set measures: patient and physician 
global assessments, pain, disability, and an acute-phase reactant.16  Similarly, ACR50, 70 and 
90 are calculated with the respective percent improvement.  This efficacy measurement will 
be made at every study visit.  The specific components of the ACR Assessments that will be 
used in this study are:
1. Tender/Painful Joint count (68).
2. Swollen Joint Count (66).
3. Patient’s Assessment of Arthritis Pain (VAS).
4. Patient’s Global Assessment of Arthritis (VAS).
5. Physician’s Global Assessment of Arthritis (VAS).
6. C-Reactive Protein (CRP).
7. Health Assessment Questionnaire – Disability Index (HAQ-DI).
7.1.3. Disease Activity Score Assessment
The Disease Activity Score (DAS)17 is a derived measurement with differential weighting 
given to each component.  DAS 28-3 (CRP) will be calculated from measurements made at 
all study visits.
The components of the DAS 28-3 arthritis assessment are:
1. Tender/Painful Joint Count (28);
2. Swollen Joint Count (28);
3. C-Reactive Protein (CRP).
4. Tender/painful and swollen joint counts used are as described in Sections 7.2.2
and 7.2.4.


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7.1.4. PsA Response Criteria (PsARC)
The PsARC18,19 will be collected at all study visits in addition to the ACR response criteria.  
The PsARC consists of 4 measurements:
1. Tender joint count (68). 
2. Swollen joint count (66). 
3. Physician’s Global Assessment of Arthritis (VAS). 
4. Patient’s Global Assessment of Arthritis (VAS). 
The same tender/painful joint count and swollen joint count used for ACR response criteria 
will be applied to the PsA Response Criteria.  In order to be a ‘PsARC responder’, subjects 
must achieve improvement in 2 of 4 measures, one of which must be joint pain or swelling, 
without worsening in any measure.
7.1.5. PsA Joint Activity Index (PsAJAI)
The PsA Joint Activity Index (PsAJAI)20 is a weighted sum of 30% improvement in the 
7 core measures of the ACR with weights of 2 given to the joint count measures (JNT), CRP 
and the Physician’s Global Assessment of Arthritis (MDGDA).  Weights of 1 are given to the 
remaining 30% improvement measures including Patient’s Assessment of Arthritis Pain 
(PAIN), Patient’s Global Assessment of Arthritis (PtGDA) and HAQ.  The values are 
summed to get a score out of 9.  The score is calculated as follows:
PsAJAI= 2 x 30%JNT + 2 x 30%CRP + 2 x 30%MDGDA + 30%PtGDA + 30%
PAIN + 30%HAQ. 
7.1.6. Disease Activity Index for Reactive Arthritis/Psoriatic Arthritis 
(DAREA/DAPSA)
DAREA/DAPSA21 is a composite instrument to assess peripheral joint involvement that is 
based upon numerical summation of 5 variables of disease activity: tender/painful joint count 
+ swollen joint count (using SJC66/ TJC68 assessments), Patient’s Global Assessment of 
Arthritis (PtGA), Patient’s Assessment of Arthritis Pain (PAIN) and CRP (in mg/dL).  Since 
DAREA/DAPSA reflects domains found important in PsA, it has been proposed to serve as a 
Disease Activity Index for Psoriatic Arthritis (DAPSA).  DAREA/DAPSA is calculated as 
follows:
DAREA/DAPSA = SJC66 + TJC68 + PtGA + PAIN + CRP.
7.1.7. Composite Psoriatic Disease Activity Index in Psoriatic Arthritis (CPDAI)
CPDAI22 is a composite psoriatic disease activity index incorporating 5 domains including 
joint disease, skin involvement, enthesitis, dactylitis and spinal disease.  For dactylitis, a 
simple dactylitic digit count is applied.  For enthesitis, the Leeds Enthesitis Index (LEI) is 
used.  For spinal involvement, the Bath Ankylosing Disease Activity Index (BASDAI) and 


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the Ankylosing Spondylitis Quality of Life questionnaire (ASQOL) are used. In addition, the 
dermatology quality of life index (DLQI) is used as a measure of the impact of skin disease.  
Using these instruments, and ranges of values based upon literature review, disease activity 
under each domain will be graded as not involved, mild, moderate and severe giving a range 
of attainable CPDAI scores of between 0 and 15 [See Appendix 7].
7.1.8. Minimal Disease Activity Score
A psoriatic arthritis patient is defined as having Minimal Disease Activity (MDA)23 when the 
subject meets 5 of the 7 following criteria: 1) tender/painful joint count 1; 2) swollen joint 
count 1; 3) PASI score 1 or BSA 3%; 4) Patient Assessment of Arthritis Pain (VAS) 
15 mm; 5) Patient’s Global Assessment of Arthritis (VAS) 20 mm; 6) HAQ-DI score 
0.5; 7) tender entheseal points (using Leeds Enthesitis Index) 1.
7.1.9. Psoriatic Arthritis Disease Activity Score (PASDAS)
PASDAS24 is a composite PsA disease activity score that includes the following components: 
Patient’s Global Skin and Joint Assessment (VAS), Physician’s Global Assessment of 
Psoriatic Arthritis (VAS), swollen and tender/painful joint counts (66/68), Leeds Enthesitis 
Index score, tender dactylitic digit score, physical component summary score (PCS) of SF-36 
and CRP.
7.2. Clinical Evaluation of Rheumatology Endpoints
All rheumatological evaluations will be performed by qualified, trained assessors.  To ensure 
consistency and reduce intra-individual variability, the same qualified assessor should score 
all evaluations for a given assessment for a given subject throughout the study.
7.2.1. Tender/Painful Joint Count (68)
Sixty-eight (68) joints will be assessed by a joint assessor to determine the number of joints 
that are considered tender or painful.  The response to pressure/motion on each joint will be 
assessed using the following scale: Present/Absent/Not Done/Not Applicable (to be used for 
artificial or missing joints).  Artificial joints will not be assessed.  Injected joints will be 
counted according to their pre-injection status for the remainder of the study.
The 68 joints to be assessed are:

Upper Body: temporomandibular, sternoclavicular, acromioclavicular.

Upper Extremity: shoulder, elbow, wrist (includes radiocarpal, carpal and 
carpometacarpal considered as one unit), metacarpophalangeals (MCP I, II, III, IV, 
V), thumb interphalangeal (IP), proximal interphalangeals (PIP II, III, IV, V), distal 
interphalangeals (DIP II, III, IV, V).

Lower Extremity: hip, knee, ankle, tarsus (includes subtalar, transverse tarsal and 
tarsometatarsal considered as one unit), metatarsophalangeals (MTP I, II, III, IV, V), 


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great toe interphalangeal (IP), proximal and distal interphalangeals combined (PIP II, 
III, IV, V).
7.2.2. Tender/Painful Joint Count (28)
Twenty-eight tender/painful joint counts include the following joints: shoulders, elbows, 
wrists, metacarpophalangeal joints (MCP), proximal interphalangeal joints (PIP), and knees.  
This count will be calculated by Sponsor from the 68 tender/painful joint count assessed by 
the joint assessor as described in Section 7.2.1.
7.2.3. Swollen Joint Count (66)
The joint assessor will also assess joints for swelling using the following scale: 
Present/Absent/Not Done/Not Applicable (to be used for artificial or missing joints).
Sixty-six (66) joints will be assessed for swelling, the same as those listed above for 
tenderness/pain, except that the right and left hip joints are not included in the swollen joint 
count.  Artificial joints will not be assessed.  Injected joints will be counted according to their 
pre-injection status for the remainder of the study.
7.2.4. Swollen Joint Count (28)
This measurement will include the same joints as described in Section 7.2.3 and will be 
calculated by Sponsor from the 66 swollen joint count assessed by the joint assessor.
7.2.5. Physician’s Global Assessment of Arthritis
The investigator or qualified assessor will assess how the subject’s overall arthritis appears at 
the time of the visit.  This is an evaluation based on the subject’s disease signs, functional 
capacity and physical examination, and should be independent of the Patient’s Global 
Assessment of Arthritis.  The investigator’s response will be recorded using a 100 mm visual 
analog scale (VAS).
THE PATIENT’S ARTHRITIS AT THIS TIME IS:
(PLEASE MAKE AN X MARK ON THE LINE BELOW).
Very Good ______________________________________________________ Very Poor
[Note: Scale will be 100 mm in length]
7.2.6. Physician’s Global Assessment of Psoriatic Arthritis
The investigator or qualified assessor will assess how the subject’s overall PsA appears at the 
time of the visit.  This may include any element of the disease that is related to their PsA and 
may include arthritis, psoriasis, enthesitis, dactylitis or spondylitis.  The investigator’s 
response will be recorded using a 100 mm visual analog scale (VAS).


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THE PATIENT’S OVERALL PSORIATIC ARTHRITIS AT THIS TIME IS:
(PLEASE MAKE AN X MARK ON THE LINE BELOW).
Not active at all ___________________________________________Extremely active
[Note: Scale will be 100 mm in length]
7.2.7. Assessment of Dactylitis
The number of digits in hands and feet with dactylitis will be evaluated by a qualified 
assessor.  In addition, dactylitis severity will be scored based upon digit tenderness using a 
scale of 0–3, where 0 = no tenderness and 3 = extreme dactylitis, in each digit of the hands 
and feet.  The range of total dactylitis scores for a subject would be 0-60.
7.2.8. Assessment of Enthesitis
Number of sites with enthesitis will be evaluated by a qualified assessor using the 
Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index25 and Leeds 
Enthesitis Index.26  The 16 sites assessed using SPARCC Index include (right and left): 
medial epicondyle humerus, lateral epicondyle humerus, supraspinatus insertion into greater 
tuberosity of humerus, greater trochanter, quadriceps insertion into superior border of patella, 
patellar ligament insertion into inferior pole of patella or tibial tubercle, Achilles tendon 
insertion into calcaneum and plantar fascia insertion into calcaneum.  The 6 sites assessed 
using the Leeds Enthesitis Index include (right and left): lateral epicondyle humerus, medial 
femoral condyle and Achilles tendon insertion.
7.2.9. C-Reactive Protein (CRP)
Blood samples will be collected at each visit for analysis of CRP using an assay analyzed by 
the central laboratory. 
7.3. Clinical Evaluation of Dermatologic Endpoints
All dermatological evaluations will be performed by qualified, trained assessors.  To ensure 
consistency and reduce intra-individual variability, the same qualified assessor should score 
all evaluations for a given assessment for a given subject throughout the study.
7.3.1. Physician’s Global Assessment of Psoriasis (PGA-PsO)
The Physician’s Global Assessment of Psoriasis is scored on a 5-point scale, reflecting a 
global consideration of the erythema, induration and scaling across all psoriatic lesions.  
Average erythema, induration and scaling are scored separately over the whole body 
according to a 5-point severity scale (0 to 4) as defined by morphologic descriptors (Table 2).  
The severity scores are summed and averaged after which the total average is rounded to the 
nearest whole number score to determine the PGA-PsO score and category presenting greater 
severity of psoriasis (Table 3).


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Table 2.
Component Scoring Criteria for the Physician's Global Assessment 
(PGA-PsO)
Component Score
Description
Erythema (E)
0
No evidence of erythema (post-inflammatory hyperpigmentation and/or 
hypopigmentation may be present)
1
Light pink
2
Light red
3
Red
4
Dark, deep red
Induration (I)
0
No evidence of plaque elevation
1
Barely palpable
2
Slight, but definite elevation, indistinct edges
3
Elevated with distinct edges
4
Marked plaque elevation, hard/sharp borders
Scaling (S)
0
No evidence of scaling
1
Occasional fine scale
2
Fine scale predominates
3
Coarse scale predominates
4
Thick, coarse scale predominates
Table 3.
Physician's Global Assessment (PGA-PsO) Score
Physician’s Global Assessment
Description
0
Clear
Cleared, except for any residual discoloration
1
Almost Clear
Majority of lesions have individual scores for (E + I + S)/3 that 
rounds to 1
2
Mild
Majority of lesions have individual scores for (E + I + S)/3 that 
rounds to 2
3
Moderate
Majority of lesions have individual scores for (E + I + S)/3 that 
rounds to 3
4
Severe
Majority of lesions have individual scores for (E + I + S)/3 that 
rounds to 4
Note: Calculated arithmetic average of individual signs severity scores [(E + I + S)/3] is rounded to the nearest 
whole number score (eg, if total 2.49, score = 2; if total 2.50, score = 3).


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7.3.2. Psoriasis Area and Severity Index (PASI)
The Psoriasis Area and Severity Index (PASI)27 quantifies the severity of a subject’s 
psoriasis based on both lesion severity and the percent of body surface area (BSA) affected.  
PASI is a composite scoring by the investigator of degree of erythema, induration, and 
scaling (each scored separately) for each of four body regions, with adjustment for the 
percent of BSA involved for each body region and for the proportion of the body region to 
the whole body.  The calculation of BSA is described in Section 7.3.3.  Note: PASI should 
only be performed if 3% of subject’s BSA was affected at baseline.
Lesion Severity: the basic characteristics of psoriatic lesions – erythema, induration and 
scaling – provide a means for assessing the severity of lesions.  Assessment of these three 
main signs is performed separately for four body regions: head and neck, upper limbs, trunk, 
(including axillae and groin) and lower limbs (including buttocks).  Average erythema, 
induration and scaling are scored for each body region according to a 5-point scale: 0, no 
involvement; 1, slight; 2, moderate; 3, marked; 4, very marked.  Appropriate morphologic 
descriptors for each severity score are shown below (Table 4).
Table 4.
Component Scoring Criteria for the Psoriasis Area and Severity 
Index (PASI)
Component Score
Description
Erythema (E)
0
No involvement
None; may have residual hyperpigmentation
1
Slight
Pink or light red
2
Moderate
Darker pink-red
3
Marked
Red
4
Very Marked
Extremely red, “beefy” red
Induration (I)
0
No involvement
None
1
Slight
Minimal elevation relative to normal surrounding skin
2
Moderate
Easily palpable with rounded edges
3
Marked
Elevated with hard, sharp borders
4
Very Marked
Very elevated with very hard, sharp borders
Scaling (S)
0
No involvement
None
1
Slight
Mainly fine scale, some lesion partially covered
2
Moderate
Coarser thin scale, most lesions partially covered
3
Marked
Coarser thick scale, nearly all lesions covered, rough
4
Very Marked
Very thick scale, all lesions covered, very rough
Percent BSA with Psoriasis: the extent (%) to which each of the four body regions is 
involved with psoriasis is categorized using a non-linear scaling method to a numerical area 
score according to the following BSA scoring criteria (Table 5). 


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Table 5.
Psoriasis Area and Severity Index 
(PASI) Area Score Criteria
Percent Body Surface Area (BSA) 
with Psoriasis
Area Score
0%
0
>0-9%
1
10-29%
2
30-49%
3
50-69%
4
70-89%
5
90-100%
6
Body Region Weighting: each body region is weighted according to its approximate 
percentage of the whole body (Table 6).
Table 6.
Psoriasis Area and Severity Index (PASI) Lesions 
Body Region Weighting
Body Region
Body Region Weighting
Head and Neck
0.1
Upper Limbs
0.2
Trunk (including axillae and groin)
0.3
Lower Limbs (including buttocks)
0.4
In each body region, the sum of the Severity Scores for erythema, induration and scaling is 
multiplied by the Area Score and by the Body Region Weighting to provide a body region 
value, which is then summed across all four body regions resulting in a PASI score as 
described in the following equation:
PASI =
0.1Ah(Eh+Ih+Sh) + 0.2Au(Eu+Iu+Su) + 0.3At(Et+It+St) + 0.4Al(El+Il+Sl)
where A = Area Score; E = erythema; I =induration; S = scaling; h = head and neck; u = upper 
limbs; t = trunk; l = lower limbs.
The PASI score can vary in increments of 0.1 and range from 0.0 to 72.0, with higher scores 
representing greater severity of psoriasis.
7.3.3. Body Surface Area (BSA)
Assessment of BSA with psoriasis will be performed separately for four body regions: head
and neck, upper limbs, trunk (including axillae and groin), and lower limbs (including
buttocks).28  The percent surface area with psoriasis is estimated by means of the handprint 
method, where the full palmar hand of the patient (ie, the subject’s fully extended palm,
fingers and thumb together) represents approximately 1% of the total BSA. The total BSA 
with psoriasis is the sum of the numbers of handprints over the 4 body regions, which ranges 
from 0 to 100% (Table 7).


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Table 7.
Handprint Determination of Body Region Surface Area
Body Region
Total Number of Handprints 
in Body Region
Surface Area of Body Region 
Equivalent of One Handprint
Head and Neck
10
10%
Upper Limbs
20
5%
Trunk (including axillae 
and groin)
30
3.33%
Lower Limbs (including 
buttocks)
40
2.5%
7.3.4. Nail Psoriasis Severity Index (NAPSI) Score
A target nail that was selected at the Baseline/Visit 1 in the qualifying study will continue to 
be assessed using the NAPSI scale.29  Each quadrant of the target nail is graded for nail 
matrix psoriasis (including any of the following parameters: pitting, leukonychia, red spots in 
lunula, nail plate crumbling) and nail bed psoriasis (including any of the following 
parameters: onycholysis, splinter hemorrhages, oil drop (salmon patch) discoloration, nail 
bed hyperkeratosis), giving that 1 target nail a score of 0-8.
7.4. Cardiovascular (CV) Risk Factor Assessment
The CV Risk Factor Assessment should be addressed at the time of medical history review at 
Screening for subjects who enroll >14 days after their end of study visit in the qualifying 
study.  This will be updated every 6 months through Month 36.

Smoking status.

Average weekly alcohol consumption: units/week, where a unit contains 12 g of pure 
alcohol, an amount equivalent to that contained in 5 oz (a glass) of wine, 12 oz of 
beer, or 1.5 oz of 90 proof spirits.

Atrial fibrillation, diabetes mellitus, hypertension.

Coronary heart disease (CHD).

Carotid artery disease.

Family history of premature CHD: CHD in a male first degree relative <55 years of 
age, CHD in a female first degree relative <65 years of age.
7.5. Health Outcome Measures
All questionnaires should be completed by subjects prior to any procedures being performed 
at the study visit.  Forms should be checked by site staff for completeness.
In the unlikely event that a PRO questionnaire(s) is not able to be administered by study site 
staff and completed by the subject as directed at the clinic visit, the PRO questionnaire(s) 


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should not be administered.  PRO questionnaires should also be reviewed for potential 
adverse events.
7.5.1. Patient’s Assessment of Arthritis Pain
Subjects will assess the severity of their arthritis pain using a 100 mm visual analog scale 
(VAS) by placing a mark on the scale between 0 (no pain) and 100 (most severe pain), which 
corresponds to the magnitude of their pain.
MY PAIN AT THIS TIME IS:
(PLEASE MAKE AN X MARK ON THE LINE BELOW).
No Pain ________________________________________________________
Most Severe Pain
[Note: Scale will be 100 mm in length]
7.5.2. Patient’s Global Assessment of Arthritis
Subjects will answer the following question, “Considering all the ways your arthritis affects 
you, how are you feeling today?”  The subject’s response will be recorded using a 100 mm 
visual analog scale (VAS).
CONSIDERING ALL THE WAYS YOUR ARTHRITIS AFFECTS YOU, HOW ARE YOU FEELING 
TODAY?
(PLEASE MAKE AN X MARK ON THE LINE BELOW).
Very Well ______________________________________________________
Very Poorly
[Note: Scale will be 100 mm in length]
7.5.3. Health Assessment Questionnaire-Disability Index (HAQ-DI)
The HAQ-DI30 assesses the degree of difficulty a subject has experienced during the past 
week in 8 domains of daily living activities: dressing and grooming, arising, eating, walking, 
hygiene, reach, grip, and other activities.  Each activity category consists of 2-3 items.  For 
each question in the questionnaire, the level of difficulty is scored from 0 to 3 with 
0 representing “no difficulty,” 1 as “some difficulty,” 2 as “much difficulty,” and 3 as 
“unable to do.”  Any activity that requires assistance from another individual or requires the 
use of an assistive device adjusts to a minimum score of 2 to represent a more limited 
functional status. 
7.5.4. Patient’s Global Joint and Skin Assessment (PGJS-VAS)
Subject’s perception of disease will be assessed using a 100 mm visual analog scale (VAS) 
by placing a mark on the scale between 0 (excellent) and 100 (poor).31  The rating 
corresponds to the way in which the subject felt over the past week in terms of how they 
were affected by their: 1) psoriasis and arthritis (global, PGA); 2) arthritis only (PJA) and 
3) psoriasis only (PSA). 


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
Global (PGA)
In all the ways in which your PSORIASIS and ARTHRITIS, as a whole, affects you, how would you rate the 
way you felt over the past week?
Excellent ________________________________________________ Poor

Joints (PJA)
In all the ways your ARTHRITIS affects you, how would you rate the way in which you felt over the past 
week?
Excellent ________________________________________________ Poor

Skin (PSA)
In all the ways your PSORIASIS affects you, how would you rate the way in which you felt over the past week?
Excellent _________________________________________________ Poor
[Note: Scale will be 100 mm in length]
7.5.5. Assessment of Spondylitis
Subject spondylitis symptoms will be evaluated using the Bath Ankylosing Spondylitis 
Disease Activity Index (BASDAI) and Ankylosing Spondylitis Quality of Life (ASQOL) 
questionnaire.32,33  BASDAI consists of VAS scales that will be used by subjects to answer 
six questions pertaining to 5 symptoms including: fatigue, spinal pain, joint pain/swelling, 
areas of localized tenderness and morning stiffness.  ASQOL questionnaire consists of 
18 questions for assessing quality of life in subjects with spondylitis.
7.5.6. Dermatology of Life Quality Index (DLQI)
The DLQI34 is a general dermatology questionnaire that consists of 10 items that assess 
subject health-related quality of life (daily activities, personal relationships, symptoms and 
feelings, leisure, work and school, and treatment).  It has been extensively used in clinical 
trials for psoriasis.  The DLQI is a psychometrically valid and reliable instrument that has 
been translated into several languages, and the DLQI total scores have been shown to be 
responsive to change.  The minimally important difference for the DLQI has been estimated 
as a 2 to 5 point change from baseline.
7.5.7. Itch Severity Item (ISI)
The severity of itch (pruritus) due to psoriasis will be assessed using the ISI, a single-item,
horizontal numeric rating scale.  Subjects will be asked to rate “your worst itching due to 
psoriasis over the past 24 hours” on a numeric rating scale anchored by the terms “No 
itching” (0) and “Worst possible itching” (10) at the ends.
7.5.8. Functional Assessment of Chronic Illness Therapy (FACIT-Fatigue Scale)
The FACIT – Fatigue Scale35 is a patient completed questionnaire consisting of 13 items that 
assess fatigue.  Instrument scoring yields a range from 0 to 52, with higher scores 
representing better subject status (less fatigue).


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7.5.9. SF-36 Health Survey (Version 2, Acute)
The SF-36 v.2 (Acute) is a 36-item generic health status measure.36  It measures 8 general 
health domains: physical functioning, role limitations due to physical health, bodily pain, 
general health perceptions, vitality, social functioning, role limitations due to emotional 
problems, and mental health.  These domains can also be summarized as physical and mental 
component scores.
7.5.10. EuroQol EQ-5D Health State Profile
The EuroQol EQ-5D Health State Profile37 is a copyrighted, patient completed instrument 
designed to assess impact on health-related quality of life in five domains: mobility, 
self-care, usual activities, pain/discomfort, and anxiety/depression.  Additionally, scores from 
the five domains may be used to calculate a single index value, also known as a utility score.  
The validity and reliability of the EuroQol EQ-5D has been established in a number of 
disease states, including rheumatoid arthritis. 
7.5.11. PsA Healthcare Resource Utilization Questionnaire
The PsA Healthcare Resource Utilization Questionnaire (PsA-HCRU) is a seventeen-item 
questionnaire that is designed to assess healthcare usage during the previous three months 
across a wide number of direct medical cost domains.  The scale also assesses indirect costs 
associated with functional disability and impaired productivity at home and at work.
7.5.12. Work Limitations Questionnaire
The Work Limitations Questionnaire (WLQ)38 is a twenty five-item scale that evaluates the 
degree to which health problems interfere with an ability to perform job roles along four 
dimensions.  The Time Management scale (Question 1) contains five items addressing 
difficulty performing a job’s time and scheduling demands.  The Physical Demands scale 
(Question 2) covers a person’s ability to perform job tasks that involve bodily strength, 
movement, endurance, coordination and flexibility.  The Mental/Interpersonal Demands 
Scale (Questions 3 and 4) has nine items.  Six items pertain to difficulty performing cognitive 
job tasks and/or tasks involving the processing of sensory information.  Three items address a 
person’s problems interacting with people on-the-job.  The Output Demands scale 
(Question 5) contains five items concerning decrements in a person’s ability to meet 
demands for quantity, quality, and timeliness of completed work.
7.6. Safety
Safety will be assessed by the spontaneous reporting of adverse events (AEs), physical 
examinations and clinical laboratory results in all subjects who receive at least one dose of 
study drug.  Investigators and Pfizer clinicians will review individual subject data throughout 
the conduct of the study to ensure the subjects’ well-being.
7.6.1. Vital Signs and Temperature
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It is preferred that body temperature be collected using the tympanic, oral or temporal 
methods.  The method chosen should be used consistently by the investigational site 
throughout the study.
Blood pressure (BP) will be measured using a standard calibrated blood pressure measuring 
device.  The following method should be used to record the blood pressure:

Subjects should be seated in a chair with feet flat on the floor, back supported and 
their arms bared (free of restrictions, such as rolled up sleeves, etc) and supported at 
heart level.

Measurements should be taken on the same arm at each visit (preferably nondominant 
arm).

Subjects should refrain from smoking or ingesting caffeine during the 30 minutes 
preceding the measurements.

Measurements should begin after at least 5 minutes of rest.

BP should be recorded to the nearest mmHg value.

When the timing of BP and pulse (pulse rate) measurements coincides with a blood 
collection or other study procedures, BP and pulse (heart) rate should be obtained 
first.
7.6.2. Electrocardiogram
Twelve-lead electrocardiograms (ECGs) will be obtained on subjects who enroll into this 
study >14 days after end of study visit in qualifying study, at annual (Month 12, 24 and 36) 
and Early Termination visits.  All ECGs should be performed after the subject has rested 
quietly for at least 10 minutes. ECG data will be submitted to a central laboratory for 
measurement.  Any clinically significant changes from the baseline ECG (from qualifying 
study for those subjects who enroll <14 days after end of study visit or from Screening visit 
in A3921092 for those subjects who enroll into this study >14 days after end of study visit in 
qualifying study), will be recorded as adverse events and evaluated further, as clinically 
warranted.
7.6.3. Tuberculosis Screening
For those subjects who enroll into this study >14 days after end of study visit in qualifying 
study, it must be determined and documented that a subject does not have evidence of active 
or latent or inadequately treated infection with Mycobacterium tuberculosis (TB) per the 
Inclusion Criteria.  The results of TB screening conducted in the 3 months prior to Screening 
visit or during the screening period must be documented in study records prior to Baseline/ 
visit.  The reviewer or reviewers, as per local standard of care, of the results of the 
Quantiferon-TB Gold In-Tube Test (QFT) and/or Mantoux Purified Protein Derivative (PPD) 
test and the x-ray and must provide his/her opinion about the eligibility of each patient for the 
study; this opinion must be documented in the subject’s study records.


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Annual TB testing will be performed using the QFT for subjects in those countries for which 
TB incidence has been reported at a rate of >50 cases per 100,000 persons, eg, Russian 
Federation and Taiwan [using China incidence rate] (World Health Organization, 2016).39  
All subjects with positive results must have a chest radiograph performed and reviewed by a 
radiologist or pulmonologist as per local standard of care and the radiograph must be 
negative for active TB infection for the subject to continue study participation.  Subjects 
identified as having latent TB should be treated appropriately; for subjects remaining on 
study during their treatment, the only acceptable regimen is 9 months of isoniazid.  Note: 
QFT should not be performed in subjects who had positive result during prior testing 
(screening visit or prior annual visits) and/or previously received adequate treatment for TB.
7.6.3.1. Quantiferon- TB Gold In-Tube Test
QuantiFERON-TB Gold In-Tube is an in vitro diagnostic test using a peptide cocktail 
simulating ESAT-6, CFP-10 and TB 7.7 proteins to stimulate cells in heparinized whole 
blood.  Detection of interferon-by Enzyme-Linked Immunosorbent Assay is used to 
identify in vitro responses to these peptide antigens that are associated with Mycobacterium 
tuberculosis infection.  QuantiFERON-TB Gold In-Tube is an indirect test for 
M. tuberculosis infection (including disease) and is intended for use in conjunction with risk 
assessment, radiography and other medical and diagnostic evaluations.40
Test results will be reported as positive, negative or indeterminate.  In the case of an 
indeterminate result, repeat tests may be permitted for the purpose of determining eligibility 
of subjects to enroll in this study.  PPD testing will be allowed if there are two repeated 
indeterminate results at the discretion of the Sponsor.  The procedure for using this test and 
interpreting the results is described fully in the laboratory manual, which will be provided to 
investigators.
7.6.3.2. Purified Protein Derivative (PPD) Tuberculin Test
If the QuantiFERON-TB Gold In-Tube test is indeterminate, a second sample may be tested 
and, if still indeterminate, subjects can be screened or evaluated at the annual visit using a 
Mantoux Purified Protein Derivative (PPD) test using 5 tuberculin units per 0.1 mL within 
the 3 months prior to a given screening visit at the discretion of the Sponsor.  Subjects must 
have a PPD tuberculin test administered and then evaluated by a health care professional in 
order to be eligible for the study, unless this test has been performed and documented within 
the last 3 months.
If 5 Tuberculin Units (TU) is not available, then the PPD may be performed according to 
local standards in 0.1 mL of solution on the volar aspect of the forearm, using a short beveled 
26-or 27-gauge needle (Mantoux test).  The test is read 48-72 hours later.  A negative 
Mantoux/PPD tuberculin skin test result (5 TU PPD result of <5 mm of induration) is 
required to meet inclusion criteria.


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7.6.3.3. Chest Radiograph (CXR)
A chest radiograph will be obtained at the Screening Visit in all subjects unless it has been 
taken and documented within the 3 months prior.  To be considered eligible for the study, the 
radiograph must be reviewed by a radiologist or pulmonologist as per local standard of care 
and documented as negative for active tuberculosis infection.
In addition, annual screening for latent and/or active TB will be conducted using QFT for 
subjects in those countries for which TB incidence has been reported at a rate of >50 cases 
per 100,000 persons.  All subjects with a new positive QFT must have a chest radiograph 
performed and reviewed by a radiologist or pulmonologist as per local standard of care and 
the radiograph must be negative for active TB infection for the subject to remain in the study.
7.6.4. Complete Physical Examination
A standard complete physical examination will be performed at Screening (for those subjects 
who enroll in A3921092 >14 days after end of study visit in qualifying study), annual study 
visits (Month 12, 24 and 36) and Early Termination visit.  The following parameters and 
body systems will be examined and any abnormalities described: height, weight, general 
appearance, skin (presence of rash), HEENT (head, ears, eyes, nose, throat), lungs 
(auscultation), heart (auscultation for presence of murmurs, gallops, rubs), lower extremity 
exam (for peripheral edema), abdomen (palpation and auscultation), neurologic (mental 
status, station, gait, reflexes, motor and sensory function, coordination) and lymph nodes.  
Any clinically significant changes from Baseline should be recorded as adverse events (AEs).  
Baseline is defined according to the time subject entered A3921092 from qualifying study 
(see Appendix 8).
Recommendations for evaluation of emergent lymphadenopathy or other findings suggestive 
of lymphoproliferative disorder are provided in Appendix 8.
7.6.5. Targeted Examination
At all other visits, an abbreviated physical examination will be performed assessing the 
following: weight, lungs, heart, abdomen, lower extremities (for peripheral edema) and 
lymph nodes.  Any clinically significant changes from baseline should be recorded as adverse 
events (AEs).  Baseline is defined according to the time subject entered A3921092 from 
qualifying study (see Appendix 4).
7.6.6. Weight, Waist and Hips Circumference and Height
It is recommended that weight be measured in kilograms (kg) with shoes removed.  Waist 
and hip measurements should be taken directly on the skin without clothing, in the standing 
position, and at the end of normal expiration.  Waist circumference should be measured 
immediately above the iliac crest.  Hip circumference should be measured by positioning the 
measure tape around the maximum circumference of the buttocks; for women typically at the 
groin level and for men, typically 2-4 inches (5.1-10.2 cm) below the navel.  Additional 
guidelines for weight and for waist and hip circumference measurement will be provided to 
study sites.


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Weight should be measured to the nearest 0.1 kg.  Waist and hip measurements should be 
measured to the nearest 0.1 cm.
It is recommended that height be measured in centimeters (cm) with shoes removed.
7.6.7. Clinical Safety Laboratory Tests
Blood and urine samples will be collected at the time points identified in the protocol.  
Unscheduled clinical laboratory tests may be performed at any time during the study to 
assess any perceived safety concerns.  Any laboratory test that is not analyzable should be 
repeated as soon as possible, but no later than the next visit.
Subjects will be excluded for hepatitis B infection.  Subjects enrolling >14 days after end of 
qualifying study visit will be tested for HBsAg and HBcAb at Screening.  Any subject who is 
HBsAg+ must be excluded from study participation.  Subjects who are HBsAg- but HBcAb+
must undergo further testing for HBsAb by the central laboratory to be considered for 
enrollment.  Subjects who are HBsAg-/HBcAb+/HBsAb+ may be eligible for enrollment.  
Subjects who are HBsAg-/HBcAb+/HBsAb- are excluded from study participation.
Subjects will also be excluded for hepatitis C infection.  Subjects enrolling >14 days after 
end of qualifying study visit will be tested for HCV Ab and, if positive, must undergo further 
testing for HCV RNA and may be allowed to enroll if negative.


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Table 8.
Clinical Laboratory Testing
Laboratory Testing Profile
Tests Included
Laboratory Tests Required at Screening 
Only
Hepatitis C virus antibody (HCV Ab), hepatitis C virus RNA 
(HCV RNA)a.  hepatitis B surface antigen (HBsAg),  hepatitis B 
core antibody (HBcAb), hepatitis B surface antibody (HBsAb)b, 
HIV-1/HIV-2 antibody screen, stool examination for parasites 
(Brazil only). 
FSH (optional for post-menopausal women only)
Hematology
Hemoglobin, hematocrit, RBC, RBC morphology, reticulocyte 
(abs); White blood cell (WBC) count and differential, 
[neutrophils (%, abs), lymphocytes (%, abs), monocytes (%, abs), 
eosinophils (%, abs), basophils (%, abs)], platelets 
Hemoglobin A1c (HbA1c)
Chemistry Panel
Urea nitrogen, creatinine, glucose, calcium, sodium, potassium, 
bicarbonate, chloride, total protein, total bilirubin, direct bilirubin, 
indirect bilirubin, alanine transaminase (ALT), aspartate 
transaminase (AST), alkaline phosphatase, gamma-glutamyl 
transferase (GGT), albumin, creatine kinase (CK)
Lipid Panel
Fasting total cholesterol, HDL, LDL, triglyceride; apolipoprotein 
A-1, B and other lipoprotein tests potentially including particle 
size measurements
Tuberculosis Screening
QuantiFERON-TB Gold In-Tubec
Urinalysis
Specific gravity, pH, protein, glucose, ketones, blood, leukocyte 
esterase.  Urine hCG pregnancy testing for women of 
childbearing potential.
Microscopy and/or culture to be performed if clinically indicated 
or if urinalysis results positive (blood, protein or leukocyte 
esterase/WBC).
Acute Phase Reactants
C-reactive protein (CRP, tested centrally)
FACS Analysis of Lymphocyte Subsets
CD3(%, abs), CD3+CD4+ (%, abs), CD3+CD8+ (%, abs), 
CD19+ (%, abs), CD56+CD16+ (%, abs)
a Only subjects who are HCV Ab positive should be reflex tested for HCV RNA.
b Only subjects who are HBsAg- and HBcAb+ should be reflex tested for HBsAb.
c.Performed at Screening Visit and annually for those subjects in countries which have high endemic TB rates and who 
tested negative at their last QFT.
Abnormal test results determined to be caused from laboratory error should not be reported 
as AEs.  Patients who present with clinically significant laboratory findings at the final 
assessment must have a follow-up visit within 28 days 7 days after last dose of study 
treatment.  Clinically significant laboratory findings should be followed to resolution or 
until determined by the Investigator to be stabilized.  Repeat tests may be needed to establish 
this.
7.6.7.1. Pregnancy Testing
For female subjects of childbearing potential, a urine pregnancy test, with sensitivity of at 
least 25 mIU/mL, will be performed at screening, before investigational product 
administration at the baseline visit and at each visit.  A negative pregnancy result is required 
before the subject may receive the investigational product.  Pregnancy tests will also be done 
whenever one menstrual cycle is missed during the active treatment period (or when potential 
pregnancy is otherwise suspected) and at the end of the study to confirm the subject has not 


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become pregnant during the study.  Pregnancy tests may also be repeated as per request of 
Institutional Review Board/Independent Ethics Committees (IRB/IECs) or if required by 
local regulations.
If at any point during the study there is a case of a positive urine human Chorionic
Gonadotropin (hCG) test, the subject will have the study drug stopped and the subject will be 
withdrawn from the study and all necessary follow-up be conducted.
7.6.8. Events for Adjudication/Review Committee Submission
The Sponsor or designee will provide a listing of specific documents needed to support event 
adjudication by Adjudication/Review Committees (see Section 9.6 Safety Event 
Adjudication/Review Committees).  Obtaining and submitting the documentation will be the 
responsibility of the study site.  Event documentation will vary with the event requiring 
adjudication and may include (but not be limited to): hospital discharge summaries, operative 
report, clinic notes, ECGs, diagnostic tests, pathology reports, autopsy reports and death 
certificate information, as applicable. 
7.6.9. Triggered Requirements
7.6.9.1. Monitoring Criteria
The following laboratory abnormalities require prompt retesting, ideally within one week:

Any single hemoglobin value that drops >2 g/dL (or 20 g/L) below baseline, if 
indicated after review by the Pfizer Study Clinician or Investigator.  Factors that will 
be considered include stability of hemoglobin values, and their relationship to the 
standard reference range.

Absolute neutrophil count <1.2 x 109/L (<1200/mm3).

Absolute lymphocyte counts <0.5 x 109/L (<500/mm3).

Platelet count <100 x 109/L (<100,000/mm3).

Serum creatinine increase >50% OR an absolute increase in serum creatinine 
>0.5 mg/dL (or 44 mol/l) over the average of screening and baseline values, if 
indicated after review by the Pfizer Study Clinician or Investigator.  Factors that will 
be considered include stability of the serum creatinine values, and their relationship to 
the standard reference range.

Any creatine kinase (CK) >5x upper limit of normal (ULN) (repeat laboratory testing 
should also include cardiac troponin).
If the abnormality is confirmed after re-test, follow-up should be discussed with the Sponsor 
and frequency of monitoring increased.  Confirmation should be done based upon central 
laboratory results, but local laboratory results will be acceptable, particularly if these may be 
done more promptly. 


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For additional laboratory abnormalities that require prompt retesting, preferably within 
48 hours from awareness of the abnormal results, see Section 8.7.2 Potential Cases of 
Drug-Induced Liver Injury.
7.6.9.2. Discontinuation Criteria
Study drug will be discontinued and the subject withdrawn from the study in the event of any 
of the following:

Requirement of rescue medications for more than 10 consecutive days.

Serious infections, defined as any infection (viral, bacterial, or fungal) requiring 
parenteral antimicrobial therapy or hospitalization for treatment, or meeting other 
criteria that require the infection to be classified as a serious adverse event (see
Section 8.7).

Two sequential absolute neutrophil counts <1.0 x 109/L (<1000/mm3).

Two sequential absolute lymphocyte counts <0.5x109/L (<500/mm3).

Two sequential hemoglobin values <8.0 g/dL (80 g/L) or decreases of >30% from 
baseline value.

Two sequential platelet counts <75 x 109/L (<75,000/mm3).

Two sequential AST or ALT elevations 3 times the upper limit of normal with at 
least one total bilirubin value 2 times the upper limit of normal.a

Two sequential AST or ALT elevations 3 times the upper limit of normal 
accompanied by signs or symptoms consistent with hepatic injury (eg, new onset 
elevated Prothrombin Time/International Normalized Ratio [PT/INR]).a

Two sequential AST or ALT elevations >5 times the upper limit of normal, regardless 
of total bilirubin or accompanying signs or symptoms.a

Two sequential increases in serum creatinine >50% AND an absolute increase in 
serum creatinine >0.5 mg/dL (44 mol/l) over the average of screening and baseline 
values.

Two sequential creatine kinase (CK) elevations >10 times the upper limit of normal, 
unless the causality is known not to be medically serious (eg, exercise or trauma 
induced).

A confirmed positive urine pregnancy test in a woman of childbearing potential.

Any opportunistic infection considered significant by investigator or Sponsor.


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
Other serious or severe adverse events, in the opinion of the investigator or Sponsor.  
Whenever possible, the investigator should consult with a member of the Pfizer study 
team before discontinuation of the subject.
If a subject discontinues from the study due to abnormalities in hematology or clinical 
chemistry parameters which meet criteria as defined in Appendix 4, a follow-up visit must be 
performed within 28 days (7 days) of last dose of study treatment.  For a confirmed increase 
in serum creatinine of >50% and >0.5 mg/dL above the average of screening and baseline, 
laboratory values will be followed with retesting until the creatinine elevation has stabilized 
(ie, stopped increasing) over at least 3 consecutive tests obtained monthly.
a 
In each case, there is a need for additional investigations, such as review of ethanol, recreational drug and 
dietary supplement consumption; testing for acute hepatitis A, B or C infection and biliary tract imaging should 
be promptly discussed with the Sponsor or designee.
7.6.10. Country Specific Laboratory Testing Requirements
Brazil: Parasitological testing of the stool should be performed in accordance with Brazilian 
regulatory guidelines at the Screening Visit for those subjects who enroll in this study 
>14 days after end of study visit in their qualifying study.
7.7. Exploratory Biomarkers
7.7.1. Lymphocyte Subset Analysis
Fluorescence-activated Cell Sorting (FACS) analysis for lymphocyte subset markers will be 
performed to assess the effects of repeat doses of tofacitinib on T cell (CD4+CD3+, CD8+), 
B cell (CD19+) and NK cell (CD16+CD56+ cell) numbers. Whole blood samples will be 
collected at Baseline (for subjects who enter study >14 days after end of study visit or early 
termination in qualifying study), Month 3 and every 3 months thereafter. 
7.8. Rater Qualifications
Individuals who perform the Physician’s Global Assessment of Arthritis and Physician’s 
Global Assessment of PsA must be a physician or other healthcare professional who is 
competent to perform the assessments.  Individuals who perform Physician’s Global 
Assessment of Psoriasis will be similarly qualified, however, with previous psoriasis clinical 
experience.  The following procedures require a health care professional who is competent to 
perform the assessments:  Tender/painful joint count; swollen joint count; assessment of 
dactylitis; assessment of enthesitis; PASI, Body Surface Area (BSA); NAPSI.
Completion of the study “Delegation Log” (including date of training completion) for the 
assessors will constitute verification that the individual is competent to conduct these 
assessments.


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8. ADVERSE EVENT REPORTING
8.1. Adverse Events
All observed or volunteered AEs regardless of treatment group or suspected causal 
relationship to the investigational product(s) will be reported as described in the following 
sections. 
For all AEs, the investigator must pursue and obtain information adequate both to determine 
the outcome of the AE and to assess whether it meets the criteria for classification as a
Serious Adverse Event (SAE) requiring immediate notification to Pfizer or its designated 
representative.  For all AEs, sufficient information should be obtained by the investigator to 
determine the causality of the AE.  The investigator is required to assess causality.  
Follow-up by the investigator may be required until the event or its sequelae resolve or 
stabilize at a level acceptable to the investigator, and Pfizer concurs with that assessment.
8.2. Reporting Period
For SAEs, the active reporting period to Pfizer or its designated representative begins from 
the time that the subject provides informed consent, which is obtained prior to the subject’s 
participation in the study, ie, prior to undergoing any study-related procedure and/or 
receiving investigational product, through and including 28 calendar days after the last 
administration of the investigational product.  Serious adverse events occurring to a subject 
after the last active reporting period has ended should be reported to the Sponsor if the 
investigator becomes aware of them; at a minimum, all SAEs that the investigator believes 
have at least a reasonable possibility of being related to investigational product are to be 
reported to the Sponsor. 
AEs (serious and non-serious) should be recorded on the case report form (CRF) from the 
time the subject has taken at least one dose of investigational product through the subject’s 
last visit.
8.3. Definition of an Adverse Event
An AE is any untoward medical occurrence in a clinical investigation subject administered a 
product or medical device; the event need not necessarily have a causal relationship with the 
treatment or usage.  Examples of AEs include but are not limited to:

Abnormal test findings;

Clinically significant symptoms and signs;

Changes in physical examination findings;

Hypersensitivity;

Progression/worsening of underlying disease; 

Drug abuse;


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
Drug dependency.
Additionally, they may include the signs or symptoms resulting from:

Drug overdose;

Drug withdrawal;

Drug misuse; 

Drug interactions;

Extravasation;

Exposure during pregnancy (EDP);

Exposure via breastfeeding;

Medication error;

Occupational exposure.
8.4. Medication Errors
Serious Adverse Event Reporting Requirements Medication errors may result, in this study, 
from the administration or consumption of the wrong product, by the wrong subject, at the 
wrong time, or at the wrong dosage strength.  Such medication errors occurring to a study 
participant are to be captured on the medication error case report form (CRF) which is a 
specific version of the adverse event (AE) page, and on the SAE form when appropriate.  In 
the event of medication dosing error, the sponsor should be notified immediately.
Medication errors are reportable irrespective of the presence of an associated AE/SAE, 
including:

Medication errors involving subject exposure to the investigational product;

Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the participating subject.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is captured on the medication error version of the adverse 
event (AE) page and, if applicable, any associated AE(s) are captured on an AE CRF page.


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8.5. Abnormal Test Findings
The criteria for determining whether an abnormal objective test finding should be reported as 
an AE are as follows: 
Test result is associated with accompanying symptoms, and/or

Test result requires additional diagnostic testing or medical/surgical intervention, 
and/or

Test result leads to a change in study dosing or discontinuation from the study, 
significant additional concomitant drug treatment, or other therapy, and/or

Test result is considered to be an AE by the investigator or sponsor.
Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an AE.  Any abnormal test result that is determined to be an error does not require 
reporting as an AE.
8.6. Infections
All treated infections occurring during the study, including, but not limited to, respiratory 
infections, cutaneous infections, urinary tract infections and episodes of suspicious or febrile 
diarrhea, should be cultured and any identified organisms noted in the Case Report Form.
Infections should be classified as either serious infections or treated infections, as defined 
below.
8.6.1. Serious Infections
A serious infection is any infection that requires hospitalization for treatment or requires 
parenteral antimicrobial therapy or meets other criteria that require it to be classified as a 
serious adverse event.  A subject who experiences a serious infection should be discontinued 
from the study and the serious adverse event should be listed as the reason for 
discontinuation in the Case Report Form.  Appropriate laboratory investigations, including 
but not limited to cultures should be performed to establish the etiology of any serious 
infection.  All adverse events, including serious adverse events, should be reported as 
described in Section 8 on Adverse Event Reporting.
8.6.2. Treated Infections
A treated infection is any infection that requires antimicrobial therapy by any route of 
administration or any surgical intervention (eg, incision and drainage).  Subjects who 
experience infections that require treatment can have their study drug temporarily 
discontinued during antimicrobial therapy in consultation with the Sponsor.  This information 
should be noted in the Case Report Form.


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8.7. Serious Adverse Events
A Serious Adverse Event is any untoward medical occurrence at any dose that:

Results in death;

Is life-threatening (immediate risk of death);

Requires inpatient hospitalization or prolongation of existing hospitalization;

Results in persistent or significant disability/incapacity (substantial disruption of the 
ability to conduct normal life functions);

Results in congenital anomaly/birth defect.
Medical and scientific judgment is exercised in determining whether an event is an important 
medical event.  An important medical event may not be immediately life-threatening and/or 
result in death or hospitalization.  However, if it is determined that the event may jeopardize 
the subject or may require intervention to prevent one of the other AE outcomes, the 
important medical event should be reported as serious.
Examples of such events are intensive treatment in an emergency room or at home for 
allergic bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization; 
or development of drug dependency or drug abuse.
8.7.1. Protocol-Specified Serious Adverse Events
There are no protocol-specified SAEs in this study.  All SAEs will be reported by the 
investigator as described in the previous sections and will be handled as SAEs in the safety 
database (see the Section on Serious Adverse Event Reporting Requirements).
8.7.2. Potential Cases of Drug-Induced Liver Injury 
Abnormal values in aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) 
levels concurrent with abnormal elevations in total bilirubin level that meet the criteria 
outlined below in the absence of other causes of liver injury are considered potential cases of 
drug-induced liver injury (potential Hy’s Law cases) and should always be considered 
important medical events.
The threshold of laboratory abnormalities for a potential case of drug-induced liver injury 
depends on the subject’s individual baseline values and underlying conditions.  Subjects who 
present with the following laboratory abnormalities should be evaluated further to 
definitively determine the etiology of the abnormal laboratory values:

Subjects with AST or ALT and total bilirubin baseline values within the normal range 
who subsequently present with AST or ALT values 3 times the upper limit of 
normal (X ULN) concurrent with a total bilirubin value 2 X ULN with no evidence 
of hemolysis and an alkaline phosphatase value 2 X ULN or not available.


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
For subjects with preexisting ALT OR AST OR total bilirubin values above the upper 
limit of normal, the following threshold values should be used in the definition 
mentioned above:

For subjects with pre-existing AST or ALT baseline values above the normal 
range: AST or ALT values 2 times the baseline values and 3 X ULN, or 
8 X ULN (whichever is smaller).

Concurrent with

For subjects with pre-existing values of total bilirubin above the normal range: 
Total bilirubin increased from baseline by an amount at least 1X ULN or if 
the value reaches 3X ULN (whichever is smaller).
The subject should return to the investigational site and be evaluated as soon as possible, 
preferably within 48 hours from awareness of the abnormal results.  This evaluation should 
include laboratory tests, detailed history and physical assessment.  In addition to repeating 
measurements of AST and ALT, laboratory tests should include albumin, creatine kinase, 
total bilirubin, direct and indirect bilirubin, gamma-glutamyl transferase, prothrombin time 
(PT)/international normalized ratio (INR), and alkaline phosphatase.  A detailed history, 
including relevant information, such as review of ethanol, acetaminophen, recreational drug 
and supplement consumption, family history, occupational exposure, sexual history, travel 
history, history of contact with a jaundiced person, surgery, blood transfusion, history of liver 
or allergic disease, and work exposure, should be collected.  Further testing for acute 
hepatitis A, B, or C infection and liver imaging (eg, biliary tract) may be warranted.  All 
cases confirmed on repeat testing as meeting the laboratory criteria defined above, with no 
other cause for LFT abnormalities identified at the time should be considered potential Hy’s 
Law cases irrespective of availability of all the results of the investigations performed to 
determine etiology of the abnormal LFTs.  Such potential Hy’s Law cases should be reported 
as SAEs.
8.8. Hospitalization
Hospitalization is defined as any initial admission (even less than 24 hours) in a hospital or 
equivalent healthcare facility or any prolongation of an existing admission.  Admission also 
includes transfer within the hospital to an acute/intensive care unit (eg, from the psychiatric 
wing to a medical floor, medical floor to a coronary care unit, or neurological floor to a 
tuberculosis unit).  An emergency room visit does not necessarily constitute a hospitalization; 
however, the event leading to the emergency room visit should be assessed for medical 
importance.
Hospitalization does not include the following:

Rehabilitation facilities;

Hospice facilities;

Respite care (eg, caregiver relief);


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
Skilled nursing facilities;

Nursing homes;

Same day surgeries (as outpatient/same day/ambulatory procedures).
Hospitalization or prolongation of hospitalization in the absence of a precipitating, clinical 
AE is not in itself an SAE.  Examples include: 

Admission for treatment of a preexisting condition not associated with the 
development of a new AE or with a worsening of the preexisting condition (eg, for 
work-up of persistent pre-treatment laboratory abnormality);

Social admission (eg, subject has no place to sleep);

Administrative admission (eg, for yearly physical examination);

Protocol-specified admission during a study (eg, for a procedure required by the study 
protocol);

Optional admission not associated with a precipitating clinical AE (eg, for elective 
cosmetic surgery);

Hospitalization for observation without a medical AE;

Pre-planned treatments or surgical procedures.  These should be noted in the baseline 
documentation for the entire protocol and/or for the individual subject.
Diagnostic and therapeutic non-invasive and invasive procedures, such as surgery, should not 
be reported as AEs.  However, the medical condition for which the procedure was performed 
should be reported if it meets the definition of an AE.  For example, an acute appendicitis 
that begins during the AE reporting period should be reported as the AE, and the resulting 
appendectomy should be recorded as treatment of the AE.
8.9. Severity Assessment
If required on the AE case report forms (CRFs), the investigator will use the adjectives 
MILD, MODERATE, or SEVERE to describe the maximum intensity of the AE.  For 
purposes of consistency, these intensity grades are defined as follows:
MILD
Does not interfere with subject's usual function.
MODERATE
Interferes to some extent with subject's usual function.
SEVERE
Interferes significantly with subject's usual function.
Note the distinction between the severity and the seriousness of an AE.  A severe event is not 
necessarily an SAE.  For example, a headache may be severe (interferes significantly with 
subject's usual function) but would not be classified as serious unless it met one of the 
criteria for SAEs, listed above.


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8.10. Causality Assessment
The investigator’s assessment of causality must be provided for all AEs (serious and 
non-serious); the investigator must record the causal relationship in the CRF, as appropriate, 
and report such an assessment in accordance with the serious adverse reporting requirements 
if applicable.  An investigator’s causality assessment is the determination of whether there 
exists a reasonable possibility that the investigational product caused or contributed to an 
AE; generally the facts (evidence) or arguments to suggest a causal relationship should be 
provided.  If the investigator does not know whether or not the investigational product caused 
the event, then the event will be handled as “related to investigational product” for reporting 
purposes, as defined by the Sponsor (see Section on Reporting Requirements).  If the 
investigator's causality assessment is “unknown but not related to investigational product”, 
this should be clearly documented on study records.
In addition, if the investigator determines an SAE is associated with study procedures, the 
investigator must record this causal relationship in the source documents and CRF, as 
appropriate, and report such an assessment in accordance with the SAE reporting 
requirements, if applicable.
8.11. Exposure During Pregnancy
For investigational products both unapproved/unlicensed products and for marketed products, 
an exposure during pregnancy occurs if:
1. A female becomes, or is found to be, pregnant either while receiving or being 
exposed (eg, because of treatment or environmental exposure) to the investigational 
product; or the female becomes, or is found to be pregnant after discontinuing and/or
being exposed to the investigational product.
An example of environmental exposure would be a case involving direct contact with 
a Pfizer product in a pregnant woman (eg, a nurse reports that she is pregnant and has 
been exposed to chemotherapeutic products).
2. A male has been exposed (eg, because of treatment or environmental exposure) to the 
investigational product prior to or around the time of conception and/or is exposed 
during his partner’s pregnancy.
If a study subject or study subject’s partner becomes or is found to be pregnant during the 
study subject’s treatment with the investigational product, the investigator must submit this 
information to the Pfizer Drug Safety Unit on a SAE Report Form and Exposure During 
Pregnancy (EDP) supplemental form, regardless of whether an SAE has occurred.  In 
addition, the investigator must submit information regarding environmental exposure to a 
Pfizer product in a pregnant woman (eg, a subject reports that she is pregnant and has been 
exposed to a cytotoxic product by inhalation or spillage) using the EDP supplemental form.  
This must be done irrespective of whether an AE has occurred and within 24 hours of 
awareness of the exposure.  The information submitted should include the anticipated date of 
delivery (see below for information related to termination of pregnancy).


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Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with unknown outcome.  The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer of the outcome as a follow-up 
to the initial EDP supplemental form.  In the case of a live birth, the structural integrity of the 
neonate can be assessed at the time of birth.  In the event of a termination, the reason(s) for 
termination should be specified and, if clinically possible, the structural integrity of the 
terminated fetus should be assessed by gross visual inspection (unless pre-procedure test 
findings are conclusive for a congenital anomaly and the findings are reported).
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy, 
spontaneous abortion, intrauterine fetal demise, neonatal death, or congenital anomaly [in a 
live born baby, a terminated fetus, an intrauterine fetal demise, or neonatal death]), the 
investigator should follow the procedures for reporting SAEs.
Additional information about pregnancy outcomes that are reported as SAEs follows: 

Spontaneous abortion includes miscarriage and missed abortion;

Neonatal deaths that occur within 1 month of birth should be reported, without regard 
to causality, as SAEs.  In addition, infant deaths after 1 month should be reported as 
serious adverse events when the investigator assesses the infant death as related or 
possibly related to exposure to the investigational product.
Additional information regarding the exposure during pregnancy may be requested by the 
investigator.  Further follow-up of birth outcomes will be handled on a case-by-case basis 
(eg, follow-up on preterm infants to identify developmental delays).  In the case of paternal 
exposure, the investigator will provide the study subject with the Pregnant Partner Release of 
Information Form to deliver to his partner.  The Investigator must document on in the source 
documents that the subject was given the Pregnant Partner Release of Information Form to 
provide to his partner.
8.12. Occupational Exposure
An occupational exposure occurs when, during the performance of job duties, a person 
(whether a healthcare professional or otherwise) gets unplanned direct contact with the 
product, which may or may not lead to the occurrence of an adverse event.
An occupational exposure is reported to the drug safety unit within 24 hours of the
Investigator’s awareness, using the SAE Report form, regardless of whether there is an 
associated AE/SAE.  Since the information does not pertain to a subject enrolled in the study, 
the information is not reported on a Case Report Form (CRF), however a copy of the 
completed SAE Report form is maintained in the study investigator site file.
8.13. Withdrawal Due to Adverse Events (See Also the Section 6.4 Subject Withdrawal)
Withdrawal due to AEs should be distinguished from withdrawal due to other causes, 
according to the definition of AE noted earlier, and recorded on the appropriate AE CRF 
page.


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When a subject withdraws because of an SAE, the SAE must be reported in accordance with 
the reporting requirements defined below.
8.14. Eliciting Adverse Event Information
The investigator is to report all directly observed AEs and all AEs spontaneously reported by 
the study subject.  In addition, each study subject will be questioned about AEs.
8.15. Reporting Requirements
Each AE is to be assessed to determine if it meets the criteria for SAEs.  If an SAE occurs, 
expedited reporting will follow local and international regulations, as appropriate.
8.15.1. Serious Adverse Event Reporting Requirements
If an SAE occurs, Pfizer is to be notified within 24 hours of investigator awareness of the 
event.
In particular, if the SAE is fatal or life-threatening, notification to Pfizer must be made 
immediately, irrespective of the extent of available AE information.  This timeframe also 
applies to additional new information (follow-up) on previously forwarded SAE reports as 
well as to the initial and follow-up reporting of exposure during pregnancy, exposure via 
breastfeeding and occupational exposure cases. 
In the rare event that the investigator does not become aware of the occurrence of an SAE 
immediately (eg, if an outpatient study subject initially seeks treatment elsewhere), the 
investigator is to report the event within 24 hours after learning of it and document the time 
of his/her first awareness of the AE.
For all SAEs, the investigator is obligated to pursue and provide information to Pfizer in 
accordance with the timeframes for reporting specified above.  In addition, an investigator 
may be requested by Pfizer to obtain specific additional follow-up information in an 
expedited fashion.  This information collected for SAEs is more detailed than that captured 
on the AE CRF.  In general, this will include a description of the AE in sufficient detail to 
allow for a complete medical assessment of the case and independent determination of
possible causality.  Information on other possible causes of the event, such as concomitant 
medications, vaccines and/or illnesses must be provided.  In the case of a subject death, a 
summary of available autopsy findings must be submitted as soon as possible to Pfizer or its 
designated representative. 
8.15.2. Non-Serious Adverse Event Reporting Requirements
All AEs will be reported on the AE page(s) of the CRF.  It should be noted that the form for 
collection of SAE information is not the same as the AE CRF.  Where the same data are 
collected, the forms must be completed in a consistent manner.  For example, the same AE 
term should be used on both forms.  AEs should be reported using concise medical 
terminology on the CRFs as well as on the form for collection of SAE information.


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8.15.3. Sponsor’s Reporting Requirements to Regulatory Authorities
Adverse event reporting, including suspected unexpected serious adverse reactions, will be 
carried out in accordance with applicable local regulations.
9. DATA ANALYSIS/STATISTICAL METHODS
Methodology for summary and statistical analyses of the data collected in this trial are given 
here and further detailed in a statistical analysis plan, which will be dated and maintained by 
Pfizer.  This analysis plan may modify what is outlined in the protocol; however, any major 
modifications of the primary endpoint definitions or their analyses will also be reflected in a 
protocol amendment.
There will be 2 sets of analyses: one for the A3921092 LTE and the other for the sub-study. 
For the A3921092 LTE, the safety analysis will include cumulative data from all the subjects 
and all the data (including the data collected in the sub-study). The efficacy analysis for the 
LTE will only include the data collected in the A3921092 LTE (the efficacy data collected in 
the sub-study will be excluded from the LTE analysis).
Statistical methods for the sub-study are found in Appendix 10.
9.1. Sample Size Determination
The sample size of this study is determined by the number of subjects who enroll from 
qualifying randomized PsA studies with tofacitinib.
9.2. Safety Analysis
The primary focus of this study is the long term safety and tolerability of tofacitinib in adult 
subjects with PsA.
9.2.1. Analysis of Safety Endpoints 
All the safety data will be summarized descriptively through appropriate data tabulations, 
and descriptive statistics.  To help better understand and interpret the observed safety results, 
registry databases will be utilized to construct an appropriate contemporaneous and/or 
historical control group.

Incidence and severity of adverse events during treatment.

Incidence of clinical abnormalities and change from baseline (in this and/or prior 
study) in clinical laboratory values during treatment.  Special attention will be given 
to the following safety criteria: neutrophil counts, lymphocyte counts, serum 
creatinine levels, platelet counts, transaminase levels, bilirubin levels (and other 
measures of liver function), events of anemia.

Incidence of vital sign (blood pressure and pulse rate) abnormalities and changes 
from baseline (in this and/or prior study) in vital sign measurements during treatment.


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
Incidence of adjudicated safety events.
9.3. Efficacy Analysis
The measures of efficacy will be summarized using descriptive statistics, such as number and 
percent, mean, standard deviation and quartiles at each visit where measured.  Displays using 
stratification by participation in qualifying studies will also be included.  Exploratory 
analyses may also be performed.
Complete details will be specified in the statistical analysis plan.
9.4. Interim Analysis 
Interim analyses to review safety data along with some efficacy data may be performed.  As 
this is an open-label study with no formal hypothesis testing, there are no issues of protecting 
the Type I error rate.
Data-cuts will be performed as needed to support tofacitinib registration.  Additional data 
reviews may be performed as needed by the study team for safety evaluations or for 
administrative purposes.
9.5. Data Monitoring Committee
This study will use an External Data Monitoring Committee (E-DMC). 
The E-DMC will be responsible for ongoing monitoring of the efficacy and safety of subjects 
in the study according to the Charter.  The recommendations made by the E-DMC to alter the 
conduct of the study will be forwarded to Pfizer for final decision.  Pfizer will forward such 
decisions, which may include summaries of aggregate analyses of endpoint events and of 
safety data which are not endpoints, to regulatory authorities, as appropriate. 
Information about the E-DMC can be found in the E-DMC Charter, which outlines the 
operating procedures of the committee, including specific description of the scope of their 
responsibilities, including a plan where communication timelines are defined.
9.6. Safety Event Adjudication/Review Committees
To help assess the specific safety events in this and other Phase 3 studies for the oral 
tofacitinib PsA program, adjudication committees have been established to harmonize and 
standardize selected safety event assessment.  Members of these safety event adjudication 
committees will be blinded to treatment assignment in order to allow for unbiased 
assessments.  These committees include a Cardiovascular Endpoint Adjudication Committee 
(CV EAC), Opportunistic Infection Review Committee (OIRC), Malignancy Adjudication 
Committee (MAC), Hepatic Event Review Committee (HERC) and Gastrointestinal 
Perforation Review Committee (GIPRC).  In addition to these external committees, an 
internal committee of medically qualified Pfizer personnel with expertise in the assessment 
and diagnosis of respiratory disease will review and categorize potential events of interstitial 
lung disease (Interstitial Lung Disease Review Committee, ILDRC).  Further information 
about these committees can be found in their respective charters, including specific 


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descriptions of the scope of their responsibilities and the process and definitions to review 
and assess specific safety events. 
Additional safety event adjudication review committees may be established as considered 
appropriate.  As described above, individual committee charters will provide specific 
descriptions of the scope of responsibilities and the processes and definitions used to review 
and assess specific safety events.
In addition to the event adjudication or review committees described above, all biopsies of 
potentially malignant tumors, suspicious lymphadenopathy, or possible extranodal 
lymphoproliferative disorder (LPD), should be submitted to the central laboratory for review 
by central laboratory pathologists.  In some instances, additional expert pathology review of 
submitted samples may be performed.  Description of the scope of review and the processes 
used to obtain and assess biopsies is described in the Histopathology Review for Potential 
Malignancy charters.  Further details on central laboratory review of biopsies of suspected 
malignancies are found in Appendix 8. 
10. QUALITY CONTROL AND QUALITY ASSURANCE
During study conduct, Pfizer or its agent will conduct periodic monitoring visits to ensure 
that the protocol and Good Clinical Practices (GCPs) are being followed.  The monitors may 
review source documents to confirm that the data recorded on CRFs is accurate.  The 
investigator and institution will allow Pfizer monitors/auditors or its agents and appropriate 
regulatory authorities direct access to source documents to perform this verification. This 
verification may also occur after study completion.
During study conduct and/or after study completion, the investigator site may be subject to 
review by the Institutional Review Board/Ethics Committee (IRB/EC), and/or to quality 
assurance audits performed by Pfizer, or companies working with or on behalf of Pfizer, 
and/or to inspection by appropriate regulatory authorities.
The investigator(s) will notify Pfizer or its agents immediately of any regulatory inspection 
notification in relation to the study.  Furthermore, the investigator will cooperate with Pfizer 
or its agents to prepare the investigator site for the inspection and will allow Pfizer or its 
agent, whenever feasible, to be present during the inspection.  The investigator site and 
investigator will promptly resolve any discrepancies that are identified between the study 
data and the subject's medical records.  The investigator will promptly provide copies of the 
inspection findings to Pfizer or its agent.  Before response submission to the regulatory 
authorities, the investigator will provide Pfizer or its agents with an opportunity to review 
and comment on responses to any such findings.
It is important that the investigator(s) and their relevant personnel are available during the 
monitoring visits and possible audits or inspections and that sufficient time is devoted to the 
process.


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11. DATA HANDLING AND RECORD KEEPING
11.1. Case Report Forms/Electronic Data Record
As used in this protocol, the term CRF should be understood to refer to either a paper form or 
an electronic data record or both, depending on the data collection method used in this study.
A CRF is required and should be completed for each included subject.  The completed 
original CRFs are the sole property of Pfizer and should not be made available in any form to 
third parties, except for authorized representatives of Pfizer or appropriate regulatory 
authorities, without written permission from Pfizer.
The investigator has ultimate responsibility for the collection and reporting of all clinical, 
safety and laboratory data entered on the CRFs and any other data collection forms (source 
documents) and ensuring that they are accurate, authentic/original, attributable, complete, 
consistent, legible, timely (contemporaneous), enduring and available when required.  The 
CRFs must be signed by the investigator or by an authorized staff member to attest that the 
data contained on the CRFs is true.  Any corrections to entries made in the CRFs, source 
documents must be dated, initialed and explained (if necessary) and should not obscure the 
original entry.
In most cases, the source documents are the hospital or the physician subject chart.  In these 
cases, data collected on the CRFs must match the data in those charts. 
In some cases, the CRF may also serve as the source document.  In these cases, a document 
should be available at the investigator site as well as at Pfizer that clearly identify those data 
that will be recorded in the CRF, and for which the CRF will stand as the source document.
11.2. Record Retention
To enable evaluations and/or audits from regulatory authorities or Pfizer, the investigator 
agrees to keep records, including the identity of all participating subjects (sufficient 
information to link records, eg, CRFs and hospital records), all original signed informed 
consent documents, copies of all CRFs, safety reporting forms, source documents, and
detailed records of treatment disposition, and adequate documentation of relevant 
correspondence (eg, letters, meeting minutes, telephone calls reports).  The records should be 
retained by the investigator according to International Conference on Harmonisation (ICH), 
according to local regulations, or as specified in the Clinical Study Agreement (CSA), 
whichever is longer.
If the investigator becomes unable for any reason to continue to retain study records for the 
required period (eg, retirement, relocation), Pfizer should be prospectively notified.  The 
study records must be transferred to a designee acceptable to Pfizer, such as another 
investigator, another institution, or to an independent third party arranged by Pfizer.  
Investigator records must be kept for a minimum of 15 years after completion or 
discontinuation of the study or for longer if required by applicable local regulations.


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The investigator must obtain Pfizer's written permission before disposing of any records, 
even if retention requirements have been met.
12. ETHICS
12.1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC)
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, informed consent documents, and other relevant documents, 
eg, recruitment advertisements, if applicable, from the IRB/IEC.  All correspondence with 
the IRB/IEC should be retained in the Investigator File.  Copies of IRB/IEC approvals should 
be forwarded to Pfizer.
The only circumstance in which an amendment may be initiated prior to IRB/IEC approval is 
where the change is necessary to eliminate apparent immediate hazards to the subjects.  In 
that event, the investigator must notify the IRB/IEC and Pfizer in writing immediately after 
the implementation.
12.2. Ethical Conduct of the Study
The study will be conducted in accordance with the protocol, legal and regulatory 
requirements, and the general principles set forth in the International Ethical Guidelines for 
Biomedical Research Involving Human Subjects (Council for International Organizations of 
Medical Sciences 2002), ICH Guideline for Good Clinical Practice, and the Declaration of 
Helsinki.
12.3. Subject Information and Consent
All parties will ensure protection of subject personal data and will not include subject names 
or other identifiable data in any reports, publications, or other disclosures, except where 
required by law. 
When study data are compiled for transfer to Pfizer and other authorized parties, subject 
names, addresses, and other identifiable data will be replaced by numerical codes based on a 
numbering system provided by Pfizer in order to de-identify study subjects.  The investigator 
site will maintain a confidential list of subjects who participated in the study, linking each 
subject’s numerical code to his or her actual identity.  In case of data transfer, Pfizer will 
maintain high standards of confidentiality and protection of subjects’ personal data consistent 
with applicable privacy laws.
When study data are compiled for transfer to Pfizer and other authorized parties, subject 
names, addresses, and other identifiable data will be replaced by numerical codes based on a 
numbering system provided by Pfizer in order to de-identify study subjects.  The investigator 
site will maintain a confidential list of subjects who participated in the study, linking each 
subject’s numerical code to his or her actual identity.  In case of data transfer, Pfizer will 
maintain high standards of confidentiality and protection of subjects’ personal data consistent 
with applicable privacy laws.


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The informed consent documents and any subject recruitment materials must be in 
compliance with ICH GCP, local regulatory requirements, and legal requirements, including 
applicable privacy laws.
The informed consent documents used during the informed consent process and any subject 
recruitment materials must be reviewed and approved by Pfizer, approved by the IRB/EC 
before use, and available for inspection.
The investigator must ensure that each study subject or his or her legally acceptable 
representative is fully informed about the nature and objectives of the study and possible 
risks associated with participation.
Whenever consent is obtained from a subject’s legally acceptable representative, the 
subject’s assent (affirmative agreement) must subsequently be obtained when the subject has 
the capacity to provide assent, as determined by the IRB/EC.  If the investigator determines 
that a subject’s decisional capacity is so limited he/she cannot reasonably be consulted, then, 
as permitted by the IRB/EC and consistent with local regulatory and legal requirements, the 
subject’s assent may be waived with source documentation of the reason assent was not 
obtained.  If the study subject does not provide his or her own consent, the source documents 
must record why the subject did not provide consent (eg, minor, decisionally impaired adult), 
how the investigator determined that the person signing the consent was the subject’s legally 
acceptable representative, the consent signer’s relationship to the study subject (eg, parent, 
spouse), and that the subject’s assent was obtained or waived.  If assent is obtained verbally, 
it must be documented in the source documents.
The investigator or a person designated by the investigator will obtain written informed 
consent from each subject or the subject's legally acceptable representative before any 
study-specific activity is performed.  The investigator will retain the original of each subject's 
signed consent document.
Tofacitinib will be provided to subjects during the study and upon study completion, the 
subject should be assessed for appropriate treatment with approved products for the PsA 
indication.  In limited situations, in accordance with country regulatory requirements, the IP 
may be available for continued treatment.
12.4. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH GCP
In the event of any prohibition or restriction imposed (ie, clinical hold) by an applicable 
regulatory authority in any area of the world, or if the investigator is aware of any new 
information which might influence the evaluation of the benefits and risks of the 
investigational product, Pfizer should be informed immediately. 
In addition, the investigator will inform Pfizer immediately of any urgent safety measures 
taken by the investigator to protect the study subjects against any immediate hazard, and of 
any serious breaches of this protocol or of ICH GCP that the investigator becomes aware of.


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13. DEFINITION OF END OF TRIAL
13.1. End of Trial in a Member State 
End of Trial in a Member State of the European Union is defined as the time at which it is 
deemed that sufficient subjects have been recruited and completed the study as stated in the 
regulatory application (ie, Clinical Trial Application [CTA]) and ethics application in the 
Member State.  Poor recruitment (recruiting less than the anticipated number in the CTA) by 
a Member State is not a reason for premature termination but is considered a normal 
conclusion to the study in that Member State.
13.2. End of Trial in all Other Participating Countries 
End of Trial in all other participating countries is defined as Last Subject Last Visit. 
14. SPONSOR DISCONTINUATION CRITERIA
Premature termination of this study may occur because of a regulatory authority decision, 
change in opinion of the IRB/IEC, investigational product safety problems, or at the 
discretion of Pfizer.  In addition, Pfizer retains the right to discontinue development of 
tofacitinib at any time.
If a study is prematurely terminated or discontinued, Pfizer will promptly notify the 
investigator.  After notification, the investigator must contact all participating subjects and 
the hospital pharmacy (if applicable) within one week.  As directed by Pfizer, all study 
materials must be collected and all CRFs completed to the greatest extent possible.
15. PUBLICATION OF STUDY RESULTS
15.1. Communication of Results by Pfizer
Pfizer fulfills its commitment to publicly disclose clinical trial results through posting the 
results of this study on www.clinicaltrials.gov (ClinicalTrials.gov), the European Clinical 
Trials Database (EudraCT), and www.pfizer.com, and other public registries in accordance 
with local laws/regulations. 
In all cases, study results are reported by Pfizer in an objective, accurate, balanced, and 
complete manner and are reported regardless of the outcome of the study or the country in 
which the study was conducted.
www.clinicaltrials.gov
Pfizer posts clinical trial US Basic Results on www.clinicaltrials.gov for Pfizer-sponsored 
interventional studies (conducted in patients) that evaluate the safety and/or efficacy of a 
Pfizer product, regardless of the geographical location in which the study is conducted.  US 
Basic Results are submitted for posting within 1 year of the primary completion date (PCD) 
for studies in adult populations or within 6 months of the PCD for studies in pediatric 
populations.


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PCD is defined as the date that the final subject was examined or received an intervention for 
the purposes of final collection of data for the primary outcome, whether the clinical study 
concluded according to the prespecified protocol or was terminated.
EudraCT
Pfizer posts European Union (EU) Basic Results on EudraCT for all Pfizer-sponsored 
interventional studies that are in scope of EU requirements.  EU Basic Results are submitted 
for posting within 1 year of the PCD for studies in adult populations or within 6 months of 
the PCD for studies in pediatric populations.
www.pfizer.com
Pfizer posts Public Disclosure Synopses (clinical study report synopses in which any data 
that could be used to identify individual patients has been removed) on www.pfizer.com for 
Pfizer-sponsored interventional studies at the same time the US Basic Results document is 
posted to www.clinicaltrials.gov.
15.2. Publications by Investigators
Pfizer supports the exercise of academic freedom and has no objection to publication by the 
principal investigator (PI) of the results of the study based on information collected or 
generated by the PI, whether or not the results are favorable to the Pfizer product.  However, 
to ensure against inadvertent disclosure of Confidential Information or unprotected 
Inventions, Investigator will provide Pfizer an opportunity to review any proposed 
publication or other type of disclosure of the results of the study (collectively, “publication”)
before it is submitted or otherwise disclosed.
The investigator will provide any publication to Pfizer at least 30 days before it is submitted 
for publication or otherwise disclosed. If any patent action is required to protect intellectual 
property rights, Investigator agrees to delay the disclosure for a period not to exceed an 
additional 60 days.
Investigator will, on request, remove any previously undisclosed confidential information 
before disclosure except for any study- or Pfizer product-related information necessary to the 
appropriate scientific presentation or understanding of the study results.
If the study is part of a multi-center study, the investigator agrees that the first publication is 
to be a joint publication covering all investigator sites and that any subsequent publication by 
the PI will reference the primary publication.  However, if a joint manuscript has not been 
submitted for publication within 12 months of completion or termination of the Study at all 
participating sites, the investigator is free to publish separately, subject to the other 
requirements of this section.
For all publications relating to the study, the institution will comply with recognized ethical 
standards concerning publications and authorship, including Section II - “Ethical 
Considerations in the Conduct and Reporting of Research” of the Uniform Requirements for 


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Manuscripts Submitted to Biomedical Journals, http://www.icmje.org/index.html#authorship, 
established by the International Committee of Medical Journal Editors.
Publication of study results is also provided for in the Clinical Study Agreement (CSA) 
between Pfizer and the institution.  In this section entitled Publications by Investigators, the 
defined terms shall have the meanings given to them in the CSA.
If there is any conflict between the CSA and any attachments to it, the terms of the CSA 
control.  If there is any conflict between this protocol and the CSA, this protocol will control 
as to any issue regarding treatment of study subjects, and the CSA will control as to all other 
issues.


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Janus Kinase Inhibitor, in Patients with Active Psoriatic Arthritis and an Inadequate 
Response to Tumor Necrosis Factor Inhibitors: OPAL Beyond, a Randomized, Double 
Blind, Placebo-Controlled, Phase 3 Trial [abstract]. Arthritis Rheumatol 2016;68 (suppl 
10). http://acrabstracts.org/abstract/efficacy-and-safety-of-tofacitinib-an-oral-janus-
kinase-inhibitor-in-patients-with-active-psoriatic-arthritis-and-an-inadequate-response-
to-tumor-necrosis-factor-inhibitors-opal-beyond-a-randomize/. 


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12.
Van Vollenhoven RF, Keystone EC, Furie R, et al. Gastrointestinal safety in patients 
with rheumatoid arthritis treated with tocilizumab: data from Roche clinical trials 
[abstract]. Arthritis Rheum 2009; 60 Suppl 10: 1613.
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Curtis JR, Xie F, Chen L et al. The incidence of gastrointestinal perforations among 
rheumatoid arthritis patients. Arthritis Rheum 2011; 63(2): 346-351.
14.
Taylor W, Gladman D, et al; CASPAR Study Group. Classification criteria for 
psoriatic arthritis: development of new criteria from a large international study. Arthritis 
Rheum 2006; 54(8):2665-73.
15.
Hochberg MC, Chang RW, Dwosh I et al. The American College of Rheumatology 
1991 revised criteria for the classification of global function status in rheumatoid 
arthritis. Arthritis Rheum 1992 35(5): 498-502.
16.
Felson DT, Anderson JJ, et al. The American College of Rheumatology Preliminary 
Core Set of Disease Activity Measures for Rheumatoid Arthritis Clinical Trials. 
Arthritis Rheum 1993; 36:729-740.
17.
DAS-score.nl: Disease activity score in rheumatoid arthritis.  Available online at: 
http://www.das-score.nl/das28/en/.
18.
Clegg DO, Reda DJ et al. Comparison of sulfasalazine and placebo in the treatment of 
psoriatic arthritis. A Department of Veterans Affairs Cooperative Study. Arthritis 
Rheum 1996; 39(12):2013-20.
19.
Mease PJ, Gladman DD et al. Adalimumab for the treatment of patients with 
moderately to severely active psoriatic arthritis. Arthritis Rheum 2005; 52: 3279-3289.
20.
Gladman DD, Tom B et al. Informing response criteria for psoriatic arthritis (PsA). II: 
Further considerations and a proposal- the PsA joint activity index. J. Rheumatol 2010; 
37:2559-65.
21.
Schoels M, Aletaha D et al.  Application of the DAREA/DAPSA score for the 
assessment of disease activity in psoriatic arthritis. Ann Rheum Dis 2010; 69: 
1441-1447.
22.
Mumatz A, Gallagher P et al. Development of a preliminary composite disease activity 
index in psoriatic arthritis. Ann Rheum Dis 2011; 70:272-277.
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Coates LC, Fransen J and PS Helliwell.  Defining minimal disease activity in psoriatic 
arthritis: a proposed objective target for treatment Ann Rheum Dis 2008; 69: 48-53.
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Helliwell PS, Fitzgerald O et al.  The development of candidate composite disease 
activity and responder indices for psoriatic arthritis (GRACE project). Ann Rheum Dis 
2012; first published as 10.1136/annrheumdis-2012-201341.


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Maksymowych WP, Mallon C et al. Development and validation of the 
Spondyloarthritis Research Consortium of Canada (SPARCC) Enthesitis Index. Ann 
Rheum Dis 2009; 68:948-953.
26.
Healy, P and P Helliwell.  Measuring clinical enthesitis in psoriatic arthritis: assessment 
of existing measures and development of an instrument specific to psoriatic arthritis. 
Arthritis Care and Res 2008; 59: 686-91.
27.
Fredriksson T, Pettersson U. Severe psoriasis – oral therapy with a new retinoid. 
Dermatologica 1978;157(4):238-44.
28.
Finlay, AY. Current Severe Psoriasis and the Rule of Tens. Br J Dermatol 2005;
152:861-7.
29.
Rich P, Scher RK. Nail Psoriasis Severity Index: a useful tool for evaluation of nail 
psoriasis. J Am Acad Dermatol 2003; 49(2):206-12.
30.
Fries JF, Spitz PW, Young DY.  The dimensions of health outcomes: The Health 
Assessment Questionnaire, disability and pain scales. J Rheum 1982; 9(5):789-793.
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Cauli A, Gladman D et al. Patient global assessment (PGA) in psoriatic arthritis (PsA). 
A multicentre GRAPPA and OMERACT study. J. Rheumatol 2011; 38(5): 898-903.
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Garrett S, Jenkinson T, Kennedy LG, et al.  A new approach to defining disease status 
in ankylosing spondylitis: the Bath Ankylosing Spondylitis Disease Activity Index. J 
Rheum 1994; 21: 2286-91.
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Doward LC, Spoorenberg A et al. Development of ASQoL: a quality of life instrument 
specific to ankylosing spondylitis. Ann Rheum Dis 2003; 62:20-26.
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Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI) – a simple practical 
measure for routine clinical use. Clin Exp Dermatol 1994; 19(3):210-6.
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Cella, D, Lai, JS, Chang, CH, et al.  Fatigue in cancer patients compared with fatigue in 
the general population. Cancer 2002; 94(2):528-538.
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Ware JE, Kosinski M., Dewey JE.  How to score version two of the SF 36 Health
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Hurst NP, Kind P, Ruta D, et al.  Measuring health-related quality of life in rheumatoid 
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World Health Organization: Tuberculosis Country Profiles.  Online.  Accessed 09 
December 2016. Available: http://www.who.int/tb/country/data/profiles/en/index.html.
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tuberculosis Infection, United States. Online. Available: 
http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5415a4.htm.


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Appendix 1. Abbreviations
Abbreviation
Term
Ab
Antibody
AE
Adverse Event
ACR
American College of Rheumatology
ALT
Alanine Aminotransferase
ANCOVA
Analysis of Covariance
Anti-CCP
Anti-cyclic citrullinated protein antibody
ASQoL
Ankylosing Spondylitis Quality of Life
AST
Aspartate Aminotransferase
BASDAI
Bath Ankylosing Spondylitis Disease Activity Index
BID
Twice daily
BP
Blood Pressure
BSA
Body surface area
CASPAR
Classification Criteria for Psoriatic Arthritis
CCP
Cyclic Citrullinated Peptide
CHD
Coronary Heart Disease
CI
Confidence Interval
CK
Creatine Kinase
CL/F
Oral Clearance
COX-2
Cyclooxygenase-2
CPDAI
Composite Psoriasis Disease Activity Index 
CRF
Case Report Form
CRP
C-reactive Protein
CSA
Clinical Study Agreement
csDMARD
Conventional synthetic Disease-Modifying Anti-Rheumatic Drugs
CTA
Clinical Trial Application
CV
Cardiovascular
CV-SEAC
Cardiovascular Safety Endpoint Adjudication Committee
CYP
Cytochrome P 
CXR
Chest X-ray
DAPSA
Disease Activity Index for Psoriatic Arthritis
DAREA
Disease Activity Index for Reactive Arthritis
DAS
Disease Activity Score 
DIP
Distal interphalangeal
DLQI
Dermatology Life Quality Index
DMARDs
Disease-Modifying Anti-Rheumatic Drugs
EBV
Epstein-Barr Virus
ECG
Electrocardiogram
eDMC
External Data Monitoring Committee
EDP
Exposure During Pregnancy
EIU
Exposure in Utero


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Abbreviation
Term
EQ-5D
The EuroQol EQ-5D Health State Profile
EU
European Union
FACIT-F
Functional Assessment of Chronic Illness Therapy-Fatigue
FACS
Fluorescence Activated Cell Sorting
FAS
Full Analysis Set
FDA
Food and Drug Administration
FSH
Follicle Stimulating Hormone
GCP
Good Clinical Practice
GGT
Gamma Glutamyl Transferase
GI
Gastrointestinal
gm
gram
HAQ-DI
Health Assessment Questionnaire-Disability Index
HbA1c
Hemoglobin A1c
HBcAb
Hepatitis B core Antibody
HBsAb
Hepatitis B surface Antibody
HBsAg
Hepatitis B surface antigen
HCG
Human Chorionic Gonadotrophin
HCV
Hepatitis C virus
HDL
High Density Lipoprotein
HEENT
Head, eyes, ears, nose, throat
HIV
Human Immunodeficiency Virus
IB
Investigator’s Brochure
ICF
Informed Consent Form
ID
Identification
IEC
Independent Ethics Committee
ILD
Interstitial Lung Disease
ILDRC
Interstitial Lung Disease Review Committee
IP
Interphalangeal
IRB
Institutional Review Board
IRC
Internal Review Committee
IRT
Interactive Response Technology
ISI
Itch Severity Index
IUD
Intrauterine Device
IUS
Intrauterine System
IWR
Interactive Web-based Response
JAK
Janus kinase
LDA
Low Disease Activity
LDL
Low density Lipoprotein
LEI
Leeds Enthesitis Index
LPD
Lymphoproliferative Disease
LSLV
Last Subject Last Visit
LTE
Long-Term Extension


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Abbreviation
Term
LTFU
Long-Term Follow-Up
MCP
Metacarpophalangeals
MCS
Mental Component Summary
MCTD
Mixed Connective Tissue Disease
MDA
Minimal Disease Activity
mg
Milligrams
MMRM
Mixed Model for Repeated Measures
MR=NR
Missing Response=Non Response
MTP
Metatarsophalangeal
MTX
Methotrexate
NAPSI
Nail Psoriasis Severity Score
NRI
Non-responder imputation
NRS
Numerical Rating Scale
NSAIDs
Non-Steroidal Anti-Inflammatory Drugs
PASDAS
Psoriatic Arthritis Disease Activity Score
PASI
Psoriasis Area Severity Index
PASI75
Psoriasis Area and Severity Index 75
PCD
Primary Completion Date
PCS
Physical Component Summary
PGA-PsO
Physician’s Global Assessment of Psoriasis
PGJS-VAS
Patient’s Global Joint and Skin Assessment
PI
Principal Investigator
PIP
Proximal Interphalangeals
PK
Pharmacokinetics
PPD
Purified Protein Derivative
PRO
Patient Reported Outcome
PsA
Psoriatic Arthritis
PsARC
Psoriatic Arthritis Response Criteria
PsA-HCRU
Psoriatic Arthritis Healthcare Resource Utilization Questionnaire
PsAJAI
Psoriatic Arthritis Joint Activity Index
PtGA
Patient’s Global Assessment of Arthritis
PT-INR
Prothrombin Time- International Normalized Rate
QFT-G
Quantiferon Gold
RA
Rheumatoid Arthritis
RBC
Red Blood Cell
RF
Rheumatoid Factor
SAE
Serious Adverse Event
SAP
Statistical Analysis Plan
SD
Standard Deviation
SF-36
36-Item Short-Form Health Survey
SLE
Systemic Lupus Erythematosus
SPARCC
Spondyloarthritis Research Consortium of Canada


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Abbreviation
Term
SPC
Summary of Product Characteristics
SRSD
Single Reference Safety Document
TB
Tuberculosis
TNF
Tumor Necrosis Factor
TNFi
Tumor Necrosis Factor Inhibitor
TU
Tuberculin Units
ULN
Upper Limit of Normal
US
United States
UVB
Ultraviolet B
VAS
Visual Analog Scale
WBC
White Blood Cell
WHO
World Health Organization
WLQ
Work Limitation Questionnaire


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Appendix 2. Cockcroft-Gault Calculation
Creatinine Clearance (estimated) / Conventional mL/min =
((140 - Age (years)) X Weight (kg) X Factora) / (72 X Serum Creatinine (mg/dL))
a Factor is equal to 0.85 in females and 1.00 in males.


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Appendix 3. Prohibited Concomitant Medications
Subjects taking certain medications for PsA, and deriving inadequate benefit from them, may 
enter the study after a sufficient washout period for that medication.  Subjects receiving 
certain medications for psoriasis may enter the study after a sufficient washout period for that 
medication (Section 4.1.2, criterion #3). 
All biologic DMARDs are prohibited and require a specific washout period (as listed in the 
protocol or based upon Sponsor review) prior to first dose of study treatment.  Subjects on 
TNF inhibitors must discontinue according to the following criteria:

Etanercept (Enbrel): Discontinued at least 4 weeks prior to the first dose of study 
drug;

Adalimumab (Humira): Discontinued at least 10 weeks prior to first dose of study 
drug;

Infliximab (Remicade): Discontinued at least 8 weeks prior to the first dose of study 
drug;

Golimumab (Simponi): Discontinued at least 10 weeks prior to the first dose of 
study drug;

Certoluzimab (Cimzia): Discontinued at least 10 weeks prior to the first dose of 
study drug.
Patients entering from studies in which adalimumab (Humira) was administered in a 
double-blind manner must have a minimum of 1 week washout after their last injection 
(placebo or adalimumab) and prior to their first dose of tofacitinib in this study.
Subjects receiving biologic agents for the treatment of psoriasis must discontinue according 
to the following criteria:

Ustekinumab (Stelara) must be discontinued for at least 12 weeks prior to first dose 
of study drug;

Alefacept (Amevive) must be discontinued for at least 8 weeks prior to first dose of 
study drug;

Efalizumab (Raptiva) is prohibited per exclusion criterion #12.
Other biologic agents used as DMARDs or used for the treatment of psoriasis are prohibited 
and require a 6 month washout period unless otherwise specified above. 
The following traditional non-biologic DMARDs are prohibited: azathioprine, cyclosporine, 
mizoribin, tacrolimus and tetracycline (used as a DMARD).  In the sub-study, sulfasalazine 
and leflunomide are considered prohibited medications.


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All of these prohibited non-biologic DMARDs require a 4 week washout period prior to first 
dose of study drug.
Injectable (intravenous, intramuscular) corticosteroids are prohibited during the study
(Section 4.1.1); intra-articular injections of corticosteroids are only permitted as rescue 
medication (Appendix 6).
Medications used to treat psoriasis are prohibited (Section 4.1.2).  This also includes topical 
treatments that could affect psoriasis, eg, corticosteroids, tars, keratolytics, anthralin, vitamin 
D analogs, and retinoids and must be discontinued at least 2 weeks prior to first dose of study 
drug. Also prohibited is ultraviolet B (UVB) (narrowband or broadband) phototherapy that 
must be discontinued at least 2 weeks prior to first dose of study drug.  Psoralens + 
ultraviolet A (UVA) phototherapy (PUVA) must be discontinued at least 4 weeks prior to 
first dose of study drug.

Exceptions- the following topical treatments are allowed: non-medicated emollients 
for use over the whole body; topical steroids including hydrocortisone and 
hydrocortisone acetate 1% for the palms, soles, face and intertriginous areas only; 
tar and salicylic acid preparations for the scalp only and shampoos free of 
corticosteroid for the scalp only.
All non-biologic Investigational Drugs or marketed treatments for PsA or psoriasis not 
otherwise specified are prohibited (unless otherwise approved by the Sponsor) and require a 
4 week (5 half-lives) washout period prior to first dose of study treatment (Section 4.1.2).
All other prohibited drugs (see below) require at least a 7 day or 5 half-life (whichever is 
longer) washout period prior to the first dose of study treatment. In the table version below, 
those drugs requiring washout longer than 7 days are in bold and italicized.  Note: efavirenz, 
nevirapine, barbiturates, carbamezipine, Phenobarbital, St. John’s Wort, rifabutin and 
rifapentene should be discontinued at least 30 days prior to first dose of study drug based on 
half life of these drugs, and that amiodarone should be discontinued at least 290 days prior to 
the first dose of study drug based on a half-life of 58 days. For a medical condition (other 
than PsA) where it is important for the subject’s safety to continue a prohibited drug, 
and where there is no study-permitted alternative, the subject must not participate in 
this study. Note that the list of prohibited medications includes, for example, 
anti-seizure and antiviral drugs for chronic use.

Topical (including skin or mucous membranes) application of antibacterial 
(eg, clarithromycin, erythromycin and norfloxacin) and antifungal (fluconazole, 
ketoconazole, clotrimazole and itraconazole) medications is permitted.

Potent inhibitors and inducers of CYP3A (shown below) are not permitted in the 
study except in emergency situations requiring no more than one day of 
administration or as approved by the Pfizer Study Clinician.


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Potent CYP3A Inhibitors
Potent CYP3A Inducers
HIV antivirals:
-indinavir (Crixivan)
-nelfinavir (Viracept)
-ritonavir (Kaletra, Norvir)
efavirenz (Sustiva)
clarithromycin (Biaxin, Prevpac)
nevirapine (Viramune)
itraconazole (Sporanox)
barbiturates
ketoconazole (Nizoral)
carbamazepine (Carbatrol, Tegretol)
nefazodone (Serzone)
modafinil (Provigil)
phenobarbital
phenytoin (Dilantin, Phenytek)
rifabutin (Mycobutin)
rifampin (Rifadin, Rifamate, Rifater)
rifapentine (Priftin)

Subjects may be initiated on moderate inhibitors (except amiodarone) and inducers 
(shown below), as required, if the total duration of treatment lasts less than or equal to 
7 days.

Consumption of juice from grapefruit, pomelos and Seville oranges is permitted up to 
8 oz or 236 mL (total) in a day.  It is recommended to separate their coadministration 
with study medication by at least 1 hour.
Moderate CYP3A Inhibitors
Moderate CYP3A Inducers
HIV antivirals:
- atazanavir (Reyataz)
- delavirdine (Rescriptor)
- saquinavir (Fortovase)
St. John’s wort
amiodarone (Cordarone, Pacerone)
cimetidine (Tagamet)
clotrimazole
diethyl-dithiocarbamate
diltiazem (Cardizem, Tiazac)
erythromycin
fluconazole (Diflucan)
fluvoxamine (Luvox)
grapefruit or grapefruit-related citrus fruits, juices 
(eg, Seville oranges, pomelos)
mibefradil
mifepristone (Mifeprex, RU486)
norfloxacin (Shibroxin, Noroxin)
verapamil (Calan SR, Covera HS, Isoptin SR, Tarka, 
Verelan)
voriconazole


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Appendix 4. Guidelines for Safety Monitoring, Dose Adjustments and Discontinuation
The following protocol-specified guidelines for safety monitoring and discontinuation are to 
be implemented.
For guidelines that reference changes from baseline, the baseline reference value is the 
baseline value from the qualifying study for all subjects who enter A3921092 within 2 weeks 
of the EOS visit of the qualifying study.  For any subject who has >14 days between the EOS 
visit of the qualifying study and entry into A3921092, the baseline reference value is the 
value from the baseline visit of the A3921092 study.
Appendix 4.1. Safety Monitoring
The following laboratory abnormalities require prompt retesting, ideally within one week:

Any single hemoglobin value that drops >2 g/dL (or 20 g/L) below baseline, if 
indicated after review by the Pfizer Study Clinician or Investigator.  Factors that will 
be considered include stability of hemoglobin values, and their relationship to the 
standard reference range.

Absolute neutrophil count <1.2 x 109/L (<1200/mm3).

Absolute lymphocyte count <0.5 x 109/L (<500/mm3).

Platelet count <100 x 109/L (<100,000/mm3).

Serum creatinine increase >50% OR an absolute increase in serum creatinine 
>0.5 mg/dL (or 44 mol/l) over the average of screening and baseline values, if 
indicated after review by the Pfizer Study Clinician or Investigator.  Factors that will 
be considered include stability of the serum creatinine values, and their relationship to 
the standard reference range.

Any single AST and/or ALT elevation >3 times the upper limit of normal (repeat 
laboratory testing must also include CK, total bilirubin, direct and indirect bilirubin, 
GGT, PT [prothrombin time], and alkaline phosphatase), regardless of the total 
bilirubin.

Any creatine kinase (CK) >5x ULN (repeat laboratory testing should also include 
cardiac troponin).
Additional individual subject safety monitoring in addition to these guidelines is at the 
discretion of the investigator and dependent on any perceived safety concerns.  Unscheduled 
laboratory testing through the central laboratory may be obtained at any time during the study 
to assess such concerns, and a subject may be withdrawn at any time at the discretion of the 
investigator.  Changes in values from the qualifying study should be considered.


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Appendix 4.2. Guidelines for Dose Adjustments of Tofacitinib
The maximum tofacitinib dose allowed is 10 mg BID.  All subjects will receive tofacitinib 
5 mg BID upon entry into study.  Tofacitinib dose may be increased from 5 mg BID to 10 mg 
BID based upon investigator discretion and should be modified during the study in the 
following manner:

Subjects taking tofacitinib 5 mg BID may have their dose increased to 10 mg BID if 
the investigator feels that the subject’s PsA symptoms are not adequately controlled 
and the subject is not experiencing any tofacitinib-related adverse events, including 
abnormalities in laboratory parameters that are judged to be related to tofacitinib.

Dose increases may only occur at scheduled study visits.
Other dosage adjustments that may occur at any time may include:

Subjects receiving tofacitinib 10 mg BID may reduce dose to 5 mg BID in response 
to mild to moderate AEs at the discretion of the investigator, either temporarily or for 
the duration of the study.  If the dose has already been decreased to 5 mg BID, the 
dose may be temporarily discontinued for up to 28 days.

Subjects receiving tofacitinib 10 mg BID may reduce dose to 5 mg BID either 
temporarily or for the duration of the study, after laboratory abnormalities specified in 
Appendix 4.1 are repeated and confirmed.  If the dose has already been decreased to 
5 mg BID, the dose may be temporarily discontinued for up to 28 days.

Dosage of tofacitinib (5 mg or 10 mg BID) may be temporarily discontinued for up to 
28 consecutive days, for laboratory abnormalities, for infections which do not meet 
criteria for serious infections (those requiring parenteral antimicrobial therapy or 
hospitalization), for surgical procedures or other moderately severe AEs.  If treatment 
must be discontinued for more than 28 days, the subject should be withdrawn from 
the study.

If a subject is temporarily discontinued from study drug for up to 28 days due to 
laboratory abnormalities, safety labs need to be repeated prior to resumption of 
treatment.

If a subject taking tofacitinib 10 mg BID is temporarily discontinued from study drug 
for up to 28 days due to laboratory abnormalities, mild to moderate AEs or for 
infections that do not meet criteria for serious infections (those requiring parenteral 
antimicrobial therapy or hospitalization), their study drug should be restarted at 
5 mg BID.


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Appendix 4.3. Discontinuation Criteria
Study drug will be discontinued and the subject withdrawn from the study for:

Requirement of rescue medication for more than 10 consecutive days.

Serious infections, defined as any infection (viral, bacterial, and fungal) requiring 
parenteral antimicrobial therapy or hospitalization for treatment, or meeting other 
criteria that require the infection to be classified as a serious adverse event (see
Section 8.7).

Two sequential absolute neutrophil counts <1.0 x 109/L (<1000/mm3).

Two sequential hemoglobin values <8.0 g/dL (80 g/L) or decreases of >30% from 
baseline value.

Two sequential platelet counts <75 x 109/L (<75,000/mm3).

Two sequential absolute lymphocyte counts <0.5x109/L (<500/mm3).

Two sequential AST or ALT elevations 3 times the upper limit of normal with at 
least one total bilirubin value 2 times the upper limit of normal.a

Two sequential AST or ALT elevations 3 times the upper limit of normal 
accompanied by signs or symptoms consistent with hepatic injury (eg, new onset 
elevated PT/INR).a

Two sequential AST or ALT elevations >5 times the upper limit of normal, regardless 
of total bilirubin or accompanying signs or symptoms.a

Two sequential increases in serum creatinine >50% AND an absolute increase in 
serum creatinine >0.5 mg/dL (44 mol/l) over the average of screening and baseline 
values.

Two sequential creatine kinase (CK) elevations >10 times the upper limit of normal, 
unless the causality is known not to be medically serious (eg, exercise or trauma 
induced).

A confirmed positive urine pregnancy test in a woman of childbearing potential.

Any opportunistic infections considered significant by the investigator or the 
Sponsor.

Other serious or severe adverse events, in the opinion of the investigator or Sponsor.  
Whenever possible, the investigator should consult with a member of the Pfizer study 
team before discontinuation of the subject.
a 
In each case, there is a need for additional investigations, such as review of ethanol, recreational drug and 
dietary supplement consumption; testing for acute hepatitis A, B or C infection and biliary tract imaging should 
be promptly discussed with the Sponsor or designee.


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Appendix 4.4. Discontinuation/End of Treatment Follow-up Safety Monitoring
If a subject discontinues from the study due to abnormalities in hematology or clinical 
chemistry parameters which meet criteria as defined in Appendix 4.3, a follow-up visit must 
be performed within 28 days (7 days) of last dose of study treatment.
All abnormal laboratory events of clinical significance should be followed until the 
laboratory values have returned to normal or baseline levels or are deemed clinically stable.  
For a confirmed increase in serum creatinine of >50% and >0.5 mg/dL above the average of 
screening and baseline, laboratory values will be followed with retesting until the creatinine 
elevation has stabilized (ie, stopped increasing) over at least 3 consecutive tests obtained 
monthly.


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Appendix 5. Approximate Equivalent Morphine Doses of Opioid Analgesics
Common Opioid Analgesics
Drug
Maximum Allowed 
Total Daily Dose
Relative potency to 
oral morphine
Half-Life
Morphine 
30 mg
1
1.5 – 4 hrs
Hydrocodone (Vicodin, 
Lortab)
30 mg
1
3.8 – 4.5 hrs
Hydromorphone (Dilaudid)
7.5 mg
4
2.5 hrs
Meperidine (Demerol, 
Pethidine)
300 mg
0.1
3.2 – 3.7 hrs
Methadone (Dolophine, 
Methadose, Physeptone)
10 mg
3.0
23 hrs
Codeine (Paveral, Tylenol 
#2 and #3)
200 mg
0.15
2.5 – 3.5 hrs
Oxycodone [Roxicodone; 
Percocet, Tylox]
15 mg
~2
3.2 hrs
Tramadol [Ultram, Zydol; 
Zamadol, Ultracet, Tramal]
300 mg
~0.1
4.7 – 5.1 hrs
Sites should contact project team for acceptable alternative preparations and related data.
References:
1.  Twycross R, Wilcock A, Thorp S.  Palliative Care Formulary. Abingdon: Radcliffe Medical Press, 1998.
2.  Twycross R.  Pain relief in advanced cancer. Edinburgh: Churchill Livingstone, 1994.


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Appendix 6. Rescue Therapy
Acetaminophen/ paracetamol is allowable as rescue medication if dosed no more than 
2.6 gm/day for no more than 10 consecutive days. If a subject is already taking stable 
background doses of acetaminophen/ paracetamol, s/he may increase the dose up to 
2.6 gm/day for up to 10 consecutive days for rescue purposes.
The following paradigm should be used to determine appropriate opioid rescue 
therapy:
For subjects who are NOT on stable, background opioid therapy: any of the following 
single opioid agents may be given as rescue medication (with or without acetaminophen/ 
paracetamol) for no more than 10 consecutive days in the following total daily doses:
1. Hydrocodone (with or without acetaminophen/paracetamol), not to exceed 30 mg 
total daily dose.
2. Oxycodone (with or without acetaminophen/paracetamol), not to exceed 15 mg total 
daily dose.
3. Tramadol (with or without acetaminophen/paracetamol), not to exceed 300 mg total 
daily dose.
For subjects who ARE on stable, background opioid therapy:

They may NOT add a second opioid agent for rescue.

If their background medication is 1 of the 3 listed above, they may, within the above 
maximum total dosage limits, increase the dosage for up to 10 consecutive days for 
rescue purposes.

If their background medication is a short-acting (half-life <5 hrs, Appendix 5) opioid 
that is not one of those listed above, they may increase the dosage for up to 
10 consecutive days (up to a total daily dose which must not exceed the potency 
equivalent of 30 mg of orally-administered morphine [Appendix 5]) for rescue 
purposes;

Sustained release opioid formulations (eg, OxyContin, MS Contin) and opioids 
with half-lives greater than 5 hours (eg, methadone) may NOT be USED for rescue 
medication.
Sustained release opioid formulations (eg, OxyContin, MS Contin) and opioids with 
half-lives greater than 5 hours (eg, methadone; see also Appendix 5) may NOT be 
INCREASED for rescue purposes.


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Intravenous or intramuscular corticosteroids, biologic response modifiers and DMARDs, 
other than methotrexate, sulfasalazine and leflunomide, are not allowed during this study.  
Intra-articular corticosteroids may be given in no more than two joints, in a cumulative dose 
of no more than 80 mg methylprednisolone or its equivalent in any 6 month study period.  
Intra-articular hyaluronate sodium injections may be administered for indications in 
accordance with the local label at least 6 months from the last hyaluronate injection in no 
more than two joints in any 6 month study period.  Injections should be avoided for 6 weeks 
before any study visit.  Injected joints will also be considered as having their pre-injection 
status (swollen and/or painful/tender) and should not be counted for the remainder of the 
trial. 
Acetaminophen/paracetamol is not permitted as a part of combination products such as 
over-the-counter “cold remedies” or in combination with opioids if the 
acetaminophen/paracetamol dose will exceed 2.6 gm/day.  Subjects who require rescue for 
more than 10 consecutive days should be discontinued from the trial. There is no limit to the 
duration of nonconsecutive use of rescue medications. In addition, subjects must not be 
dosed with rescue acetaminophen/paracetamol or opioids within 24 hours prior to a study 
visit except if adjustment is needed because subject is experiencing intolerable pain.  
Baseline stable acetaminophen/paracetamol or opioids should NOT be discontinued in 
advance of study visits.
Subjects must not be dosed with any rescue intervention within 24 hours prior to a 
study visit except if adjustment is needed because subject is experiencing intolerable 
pain.


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Appendix 7. Composite Psoriatic Disease Activity Index (CPDAI)22 score 0-15
Not 
involved
(0)
Mild
(1)
Moderate
(2)
Severe
(3)
Peripheral 
arthritis
4 Joints 
(swollen/tender); 
normal function 
(HAQ <0.5)*
4 Joints but function 
impaired; or >4 joints, 
normal function
>4 Joints and 
function impaired
Skin disease
PASI 10 and DLQI 
10
PASI 10 but DLQI 
>10; or PASI >10 but 
DLQI 10
PASI >10 and DLQI 
>10
Enthesitis
3 Sites; normal 
function (HAQ <0.5)*
3 Sites but function 
impaired; or >3 sites 
but normal function
>3 Sites and 
function impaired
Dactylitis
3 Digits; normal 
function (HAQ <0.5)*
3 Digits but function 
impaired; or >3 digits 
but normal function
>3 Digits and has 
function impaired
Spinal disease
BASDAI <4; normal 
function (ASQoL <6)
BASDAI >4 but normal 
function; BASDAI <4 
but function impaired
BASDAI >4 and 
function impaired
*Health assessment questionnaire (HAQ) only counted if clinical involvement of domain 
(joint/enthesitis/dactylitis) present.
ASQoL, ankylosing spondylitis quality of life; BASDAI, Bath ankylosing spondylitis disease 
activity index; DLQI, dermatological life quality index; PASI, psoriasis area severity index.


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Appendix 8. Evaluation of Potentially Malignant Tumors, Suspicious 
Lymphadenopathy, Possible Extranodal Lymphoproliferative Disorder (LPD)
The following steps should be taken in the event of potentially malignant tumors, suspicious 
lymphadenopathy or possible extranodal lymphoproliferative disorder (LPD) which might 
arise in the course of this study.
When there is a decision to biopsy a potentially malignant tumor, lymph node, or other 
tissue, the investigator and/or consultants should contact the Pfizer study team to discuss the 
issue and any decisions as soon as possible.  It is recommended that specialists with 
experience in the evaluation of immunosuppressed patients be consulted.
If a biopsy for lymphadenopathy or lymphoma is to be performed, the investigator or 
consultant should refer to the instructional slide deck in the Lymph Node Biopsy kit and 
review the following points with the surgeon and pathologist:

Fine needle aspiration and core needle biopsy are strongly discouraged; excisional 
biopsy is required for accurate diagnosis.

Tissue must be sent fresh to the pathology laboratory; the pathologist must be 
consulted before the procedure.

Archive multiple frozen tissue samples, if possible.

Include flow cytometry and cytogenetics as part of the pathologic evaluation.

Culture for mycobacterium and fungi, if indicated.

Collect and snap freeze peripheral blood lymphocytes for germ line evaluation 
(DNA).

Archive multiple aliquots of serum samples.
For all biopsies, please request the pathologist to send the original slides used to make the 
definitive diagnosis, ancillary study reports, and the pathologist’s report to the central 
laboratory.


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Appendix 9. Contraceptive Methods (for Canada)
Subjects in Canada who are woman of childbearing potential and sexually active must use 
two contraceptive methods at the same time, one highly effective contraceptive method and 
one additional effective contraceptive method. 
Highly effective contraceptive methods may include hormonal contraceptives (eg, combined 
oral contraceptives, patch, vaginal ring, injectables, and implants), intrauterine device (IUD) 
or intrauterine system (IUS), vasectomy or tubal ligation (see Section 4.4.6).
Effective methods may include barrier methods of contraception (eg, male condom, female 
condom, cervical cap, diaphragm or contraceptive sponge).  The proper use of diaphragm or 
cervical cap includes use of spermicide and is considered one barrier method. The cervical 
cap and contraceptive sponge are less effective in parous women. The use of spermicide 
alone is not considered a suitable barrier method for contraception.


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Appendix 10. Methotrexate Withdrawal Sub-Study
The purpose of this sub-study is to assess the efficacy, safety and tolerability of tofacitinib 
5 mg BID administered as monotherapy after methotrexate (MTX) withdrawal compared to 
tofacitinib 5 mg BID continued in combination with MTX in subjects with active PsA. 
Subjects who have completed at least 24 months of participation in the long term extension 
study A3921092 and are currently receiving methotrexate may be included.  Not all countries 
participating in the LTE will be included in this sub-study. 
Subjects will be randomized to the 2 treatment arms in a 1:1 ratio, one in which they will 
receive open label tofacitinib 5 mg tablets BID and blinded methotrexate capsules (oral dose 
range from 7.5 mg to 20 mg per week) and the second in which they will receive open label 
tofacitinib 5 mg tablets BID and blinded MTX placebo capsules. The sub-study will be 
approximately 12 (standardized 4-week) months in duration and visits will occur at Baseline, 
Months 1, 3, 6, 9 and 12. The sub-study baseline will occur at the same time as a scheduled 
study visit at or after Month 24 of A3921092. This visit will be referred to as Sub-study 
Switch visit or Baseline visit (Sub-study Switch/Baseline visit).
Throughout this Appendix, Sections 4.5, 7, 8, 9.5 to 15.2 will be referenced to the main LTE 
protocol to avoid duplication.


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SUB-STUDY TABLE 1.
SCHEDULE OF ACTIVITIES 
The Schedule of Activities table provides an overview of the sub-study visits and procedures. Refer to Sub-study Procedures
(Section 6) and Assessments (Section 7) for detailed information on each procedure and assessment required for compliance with the 
protocol.
The investigator may schedule visits (unplanned visits) in addition to those listed on the schedule of activities, in order to conduct 
evaluations or assessments required to protect the wellbeing of the subject.
Protocol Activity
Combined 
A3921092 
Sub-study 
Switch/Baseline1
Sub-study 
Month 1
(7 days)
Sub-study 
Month 3
(7 days)
Sub-study 
Month 6
(7 days)
Sub-study 
Month 9
(7 days)
Sub-study Month 12 
Or Early
Termination
(7 days)
Follow-up
Visit
(28 days 7)2
Informed Consent
X
Register for subject identification number and 
Randomization
X
Complete Physical Exam4
X
X
Targeted Physical Exam4
X
X
X
X
Vital signs, temperature
X
X
X
X
X
Waist and hips circumference
X
X
X
X
Cardiovascular Risk Assessment3
X
X
12-Lead ECG5
X
X
QuantiFERON or Mantoux PPD /Chest
Radiograph, if Necessary6
X
X
X
X
X
X
LABORATORY TESTING
Hematology, Chemistry Panel7
X
X
X
X
X
X
CRP7
X
X
X
X
X
Lipid panel (fasting)8
X
8
X
X
X
CBC with Differential and Chemistry Labs7,9
As per standard of Care
Lymphocyte subset analysis (FACS)
X
X
X
X
Urinalysis10
X
X
X
X
X
Urine pregnancy test (hCG)11
X
X
X
X
X
X


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Protocol Activity
Combined 
A3921092 
Sub-study 
Switch/Baseline1
Sub-study 
Month 1
(7 days)
Sub-study 
Month 3
(7 days)
Sub-study 
Month 6
(7 days)
Sub-study 
Month 9
(7 days)
Sub-study Month 12 
Or Early
Termination
(7 days)
Follow-up
Visit
(28 days 7)2
CLINICAL EVALUATION OF
RHEUMATOLOGY ENDPOINTS
Tender/Painful Joint Count (68), Swollen Joint Count 
(66)
X
X
X
X
X
X
Physician’s Global Assessment of Arthritis (VAS)
X
X
X
X
X
Dactylitis Assessment
X
X
X
X
X
Enthesitis Assessment (Leeds Index)12
X
X
X
X
X
CLINICAL EVALUATION OF
RHEUMATOLOGY/DERMATOLOGY
ENDPOINTS
Physician’s Global Assessment of Psoriatic 
Arthritis (VAS)
X
X
X
X
X
CLINICAL EVALUATION OF
DERMATOLOGY ENDPOINTS
Physician’s Global Assessment of Psoriasis 
(PGA-PsO)
X
X
X
X
X
X
Body Surface Area (BSA)
X
X
X
X
X
PATIENT REPORTED OUTCOMES13
Patient’s Assessment of Arthritis Pain (VAS); 
Patient’s Global Assessment of Arthritis (VAS);
HAQ-DI 14
X
X
X
X
X
Patient’s Global Joint and Skin Assessment 
(PGJS-VAS)
X
X
X
X
X
SF-36v2, FACIT-F, EQ-5D14
X
X
X
X
X
OTHER ACTIVITIES
Adverse Event Assessment
X
X
X
X
X
X
Prior/Concomitant Treatment
X
X
X
X
X
X
Dispense study medication/Accountability15
X16
X
15
X
X
X
X
15


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1.
Subjects who are qualified to enter into the MTX withdrawal sub-study, the combined A3921092 Sub-study Switch/Baseline visit will occur at a scheduled 
study visit at Month 24, Month 27, Month 30, Month 33 or Month 36 of the long term extension study A3921092. Any study procedure required for the 
sub-study baseline visit that was not included as part of the A3921092 study must be completed during this visit. There will be no separate Baseline visit for 
the sub-study.
2.
If a subject discontinues from the study due to abnormal hematology or clinical chemistry results which meet criteria as described in Appendix 4, or
discontinues due to an adverse event, a follow-up visit must be performed after the Early Termination visit within 28 days (7 days) of last dose of study
treatment.
3.
Cardiovascular (CV) Risk Factor Assessment includes multiple assessments such as smoking status, average weekly alcohol consumption, and family history of
premature coronary heart disease (CHD) (See Section 7.4 of LTE for complete list). This should be done as part of the Month 24 visit in study A3921092.
4.
Complete physical exam should be performed annually (Baseline and Month 12 or Early Termination) and includes: height, weight, general appearance, skin,
HEENT (head, eyes, ears, nose and throat), heart, lungs, abdomen, lower extremities, neurologic and lymph nodes.  Targeted physical exam should be
performed at other scheduled visits except Follow-Up and includes: weight, examination of heart, lungs, abdomen, lower extremities (for peripheral edema)
and lymph nodes.
5.
12-lead ECG will be taken at sub-study baseline and Month 12 or Early Termination (ET) visit only. ECG will be evaluated by a central reader.
6.
Tuberculosis annual screening procedures must be performed if not completed during the Month 24 LTE study visit in appropriate subjects.  Annual TB
screening will be conducted using Quantiferon-TBGold In-Tube test (QFT) for subjects in those countries in which TB incidence has been reported at a rate 
of >50 cases per 100,000 persons (see Section 7.6.3).
All subjects with positive results (and who tested negative at their last QFT) must have chest
radiograph performed and reviewed by a radiologist or pulmonologist as per local standard of care. Subjects who must have a PPD administered must return
within 48-72 hours for evaluation.
7.
Hematology includes: white blood cell (WBC) count/differential, hemoglobin, hematocrit, red blood cell (RBC) count and morphology, reticulocyte and
platelet counts.
Serum chemistry includes: urea nitrogen, creatinine, glucose, calcium, sodium, potassium, bicarbonate, chloride, total protein, total bilirubin,
direct bilirubin, indirect bilirubin, alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase, gamma-glutamyl transferase (GGT),
albumin and creatine kinase (CK). All hematology, clinical chemistry tests and HbA1C will be performed by the central laboratory; C-reactive Protein (CRP)
will also be measured by central laboratory (results will be blinded).
8.
A fasting lipid panel (total cholesterol, LDL, HDL, triglycerides, apolipoprotein A-1 and B) and other lipoprotein tests potentially including particle size
measurements per Sub-Study Table 7 in Section 7.6.7 will be collected at the sub-study combined/baseline visit; Month 6, and Month 12, Early Termination 
or Follow-up visits.
9.
Clinical chemistry as appropriate for standard of care in subjects receiving background non-biologic DMARDs may include creatinine, albumin and liver
function tests.
10. Urinalysis includes specific gravity, pH, protein, glucose, ketones, blood and leukocyte esterase.
Microscopy and/or culture to be performed if clinically
indicated or if urinalysis results are positive (blood, protein or leukocyte esterase/WBC).
11. Urine pregnancy testing (human chorionic gonadotropin; -hCG) is required only for women of childbearing potential.
12. Enthesitis will be assessed using only the Leeds Enthesitis Index per Section 7.2.8 of the LTE.
13. All Patient Reported Outcomes should be completed prior to any other assessments made at each visit.


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14. Subject completed questionnaires include: Health Assessment Questionnaire-Disability Index (HAQ-DI), Short-Form-36 Health Survey (Version 2, Acute)
(SF-36), Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-F), EQ-5D.
15. Study medication will not be dispensed at Month 1 or End of Treatment or Early Termination visit; however, drug accountability and compliance assessment 
will be performed.
16. At the Switch/Baseline visit, all investigational product from the main A3921092 LTE study will be collected for accountability under the main protocol.  
New tofacitinib supplies will be dispensed under the sub-study.


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1. INTRODUCTION
1.1. Indication
Tofacitinib is being developed for the treatment of adult subjects with active Psoriatic 
Arthritis (PsA).
1.2. Background and Rationale
Psoriatic arthritis (PsA) is a chronic inflammatory autoimmune disease characterized by joint 
inflammation and destruction, psoriatic skin lesions, enthesitis, dactylitis, spondylitis,
progressive disability and adverse effects on quality of life.1,2 Treatment recommendations 
for the cardinal clinical manifestations of the disease have been developed in recent years by 
a consensus of rheumatologists and dermatologists.41 Treatment of subjects with PsA is 
frequently influenced by the severity of each domain and treatment recommendations vary 
depending on what disease domain is more severely affected.43,44 Some of the agents 
recommended for the treatment of PsA include non-steroidal anti-inflammatory drugs 
(NSAIDs), intra-articular glucocorticoid injections, conventional synthetic (cs) DMARDs 
and TNF inhibitors.42,44 The csDMARDs are either prescribed as monotherapy or in 
combination with other agents.43 Methotrexate (MTX) is a widely used csDMARD for the 
treatment PsA and commonly one of the first agents administered to patients.42,43,44 Despite 
its popular use, there are only a few randomized placebo controlled trials comparing MTX to 
placebo in the treatment of PsA and none of them have clearly demonstrated efficacy of this 
therapy.44 One of the few placebo-controlled trials of MTX in psoriatic arthritis failed to find 
evidence for MTX improving synovitis and showed no advantage of MTX over placebo with 
respect to rheumatology related global responses.45 MTX is frequently used in combination 
with other therapies also recommended for the treatment of PsA, such as biologics or other 
csDMARDs.42,43,44  Liver toxicity and other secondary effects related to the long term use of 
MTX continue to be a concern for treating physicians and patients.42 Understanding the
disease activity of subjects that discontinue one of the agents in their combination treatment 
will help the medical community determine the usefulness of a step down process of 
treatment. 
The majority of subjects who participated in the tofacitinib PsA development program 
continue therapy on a stable dose of one background DMARD for the duration of their 
participation in the long term extension study.
This sub-study is designed to assess the efficacy of tofacitinib 5 mg BID as monotherapy after 
MTX withdrawal compared to tofacitinib 5 mg BID in combination with concomitant MTX. 
In addition, the sub-study will assess the safety and tolerability of tofacitinib 5 mg BID as a 
treatment for PsA in a MTX withdrawal population.
1.2.1. Single Reference Safety Document (SRSD)
Complete information for tofacitinib may be found in the single reference safety document 
(SRSD, which for this study is the tofacitinib IB.  The SRSD for methotrexate is the 
Summary of Product Characteristics (SPC).


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2. STUDY OBJECTIVES AND ENDPOINTS
2.1. Objectives
2.1.1. Primary Objective

To assess the efficacy of tofacitinib 5 mg BID monotherapy as compared to 
tofacitinib 5 mg BID with background MTX in subjects who have received prior 
treatment of tofacitinib in combination with MTX. 
2.1.2. Secondary Objective

To assess the safety and tolerability of tofacitinib 5 mg BID monotherapy as 
compared to tofacitinib 5 mg BID with background MTX in subjects who had 
received prior treatment of tofacitinib in combination with MTX. 
2.2. Endpoints
2.2.1. Primary Endpoints

Change from baseline () in HAQ-DI at 6 months.

∆PASDAS at 6 months.
2.2.2. Secondary Endpoints

HAQ-DI score at all time points except Month 6.

PASDAS at all time points except Month 6.

Psoriatic Arthritis Response Criteria (PsARC) response at all time points.

in Physician’s Global Assessment of Psoriasis (PGA-PsO) at all time points.

%in BSA at all time points.

in Dactylitis severity score at all time points.

Dactylitis absence at all time points.

in Enthesitis score (using Leeds Enthesitis Index, [LEI]) at all time points.

Enthesitis absence (using LEI) at all time points. 

MDA response at all time points.


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
in ACR components (tender/painful joint count (68), swollen joint count (66), 
Physician’s Global Assessment of Arthritis, Patient’s Global Assessment of Arthritis, 
Patient’s Assessment of Arthritis Pain, CRP) at all time points.

Physical function/other patient reported outcomes to be assessed at all time points: 

in Short-Form 36 (version 2, Acute) (8 domains and Physical Component 
Summary [PCS] score and Mental Component Summary [MCS] score); 

FACIT-F (Total score, Experience domain and Impact domain scores);

EuroQol-5D Health Questionnaire (EQ-5D) (Scores from the five domains and 
an EQ-Visual Analog Scale (VAS) score on the subject’s health state today 
(EQ-VAS).

Incidence and severity of adverse events.

Incidence of clinical abnormalities and change from baseline in clinical laboratory
values during treatment.
2.2.3. Other Endpoints

DAS28-3 (CRP) at all time points.

MDA component response at all time points.

in Patient’s Global Joint and Skin Assessment (PGJS-VAS) at all time points.

Incidence of investigator-reported clinically significant changes in physical
examination from baseline during treatment.

Incidence of electrocardiogram (ECG) abnormalities and change from baseline in 
ECG measurements during treatment.

Incidence of vital sign (blood pressure and pulse rate) abnormalities and changes
from baseline in vital sign measurements during treatment.
3. SUB-STUDY DESIGN
This sub-study within Study A3921092 is a Phase 3, randomized, double-blind, 
placebo-controlled, parallel group estimation study designed to assess the efficacy, safety and
tolerability of tofacitinib 5 mg BID versus tofacitinib 5 mg BID in combination with 
concomitant MTX in subjects with active PsA.  Subjects with active PsA will have previously 
completed at least 24 months of treatment with tofacitinib in Study A3921092 and will be on a 
stable dose of tofacitinib 5 mg BID for at least 3 months prior to the first dose of sub-study 
drug and be on a stable dose of oral MTX at least 4 weeks prior to the first dose of sub-study 
drug. This sub-study will be referred to as A3921092 Sub-study. For subjects who are


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qualified to enter into the sub-study, the Combined A3921092 Sub-study Switch/Baseline visit 
will occur at a scheduled study visit at or after Month 24 of A3921092. There will be no 
separate Baseline visit for the sub-study. The visit window will remain as in the LTE in 
which a month is considered 28 days.  Once a subject enters the sub-study, they will complete
their participation in the sub-study portion and be unable to re-enter the main study.  Subjects 
may be discontinued from the sub-study at any time during the sub-study in the event of 
deterioration of response as determined by the investigator.
Eligible subjects from study A3921092, will be randomized into A3921092 sub-study in a 
1:1 ratio to tofacitinib 5 mg BID + MTX placebo or tofacitinib 5 mg BID + MTX.  MTX will 
be blinded to the subjects, investigators and the sponsor.  The subjects in the tofacitinib
5 mg BID + MTX group will receive blinded MTX capsules (range dose of 7.5-20 mg a 
week based upon the pre-existing dose) and the subjects in the tofacitinib 5 mg BID group 
will receive the matching MTX placebo capsules. For the duration of the sub-study 
tofacitinib dose must remain stable at 5 mg BID. The MTX dose and oral route of 
administration must remain stable for the 12 month duration of the sub-study. All subjects 
will receive open-label tofacitinib 5 mg BID throughout the sub-study without dose increase. 
The total number of subjects randomized will be approximately 180 (Sub-Study Table 2).
Sub-Study Table 2 
Treatment Group
Double blind placebo controlled period
Number of Subjects
B
Tofacitinib 5 mg BID + Placebo
90
C
Tofacitinib 5 mg BID + Methotrexate
90
Treatment duration for subjects participating in this sub-study is approximately 12 months.
At various time points in this trial, safety measurements, including physical examination, 
clinical laboratory tests, adverse event monitoring, electrocardiograms (ECGs) and vital signs 
will be performed.  All subjects will be monitored for clinical evidence of PsA response to 
treatment.  Health Outcomes Measures (ie, Patient Reported Outcomes assessments for pain, 
quality of life, physical function, fatigue and health status) will also be performed at various 
time points in this trial. In addition, subjects will be monitored for serious infections, 
lymphadenopathy and lymphoproliferative disorder (LPD).
4. SUBJECT SELECTION
This sub-study can fulfill its objectives only if appropriate subjects are enrolled.  The 
following eligibility criteria are designed to select subjects for whom protocol treatment is 
considered appropriate. All relevant medical and non-medical conditions should be taken 
into consideration when deciding whether this protocol is suitable for a particular subject.
4.1. Sub-Study Inclusion Criteria
Subject eligibility will be reviewed and documented by an appropriately qualified member of 
the investigator’s study team before subjects are included in the study.


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Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the 
study.
1. Evidence of a personally signed and dated informed consent document indicating that
the subject (or a legal representative) has been informed of all pertinent aspects of the
study.
2. Subjects who are willing and able to comply with scheduled visits, treatment plan,
laboratory tests, and other study procedures.
3. Subjects must have previously completed at least 24 months of treatment with 
tofacitinib for the treatment of PsA in the long term extension study A3921092. 
4. Subjects must be receiving tofacitinib 5 mg BID and be on a stable dose for a 
minimum of 3 months before the first dose of blinded MTX.  Subject receiving 
tofacitinib 10 mg BID must reduce the tofacitinib dose to 5 mg BID 3 months prior to 
randomization into the sub-study.
5. Subjects must be receiving oral MTX as their permitted traditional non-biologic
background DMARDs, and must be dosed in accordance with the A3921092 
requirements.

All local standard of care practices for administration of non-biologic background
DMARD therapy, including laboratory testing, contraceptive requirements, 
follow-up care and contraindications, should be performed according to the local 
standards of care throughout the sub-study.

MTX administered orally: Subjects receiving non-oral forms of methotrexate 
in study A3921092 should switch to an oral route of administration at least 
12 weeks before the sub-study entry and remain on it for the duration of the 
sub-study. 

Dosing of MTX should be stable (dose range allowed from a minimum dose 
of 7.5 mg/week and maximum dose of 20 mg/week) 4 weeks prior to entry to 
the sub-study and remain stable for the duration of it. 

All subjects should be on an adequate and stable dose of folate 
supplementation (not less than 5 mg weekly based on folic acid, unless such
doses would violate the local label guidelines or standard of care) for at least 
4 weeks prior to the first dose of blinded study drug (see Section 5.6).
6. Subjects who are already taking oral corticosteroids (but not injectable) may
participate in the sub-study:

Oral corticosteroids: Subjects who are already receiving oral corticosteroids in 
study A3921092 must remain on a stable dose of 10 mg/day of prednisone or 


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equivalent.  The dose must be stable for four weeks prior to sub-study entry and 
remain stable for the duration of the sub-study.

Subjects who received injectable (eg, intraarticular, intramuscular or intravenous) 
corticosteroids in study A3921092 should have discontinued their use 12 weeks 
prior to the of sub-study entry.
7. Subjects who are already taking NSAIDs/COX-2 inhibitors may participate in the
sub-study provided that that the dose is stable for one week prior to sub-study entry 
and remain stable for the duration of it. 
4.2. Sub-Study Exclusion Criteria
Subjects presenting with any of the following characteristics/conditions will not be included 
in the study:
1. Subjects who are receiving other concomitant non-biologic csDMARDs, 
eg, leflunomide, sulfasalazine. 
2. Subjects receiving MTX by a route other than oral. 
3. Subjects receiving MTX at a dose lower than 7.5 mg per week or >20 mg per week. 
4. Subjects who are investigational site staff members directly involved in the conduct
of the trial and their family members, site staff members otherwise supervised by the 
investigator, or subjects who are Pfizer employees directly involved in the conduct of
the trial.
5. Subjects that have become pregnant during study A3921092 and breastfeeding 
females and females of child-bearing potential who are unwilling or unable to use a
highly effective method(s) of contraception as outlined in this protocol for the 
duration of the study and for at least one ovulatory cycle after last dose of 
investigational product or females planning pregnancy.
6. Women of childbearing potential must test negative for pregnancy prior to enrollment 
in this study.  (Further description of the requirements and a list of contraceptives 
considered highly effective and acceptable for use in this study will be found in
Section 4.4.6).
7. Current or recent history of uncontrolled renal, hepatic, hematological, 
gastrointestinal, metabolic (including hypercholesterolemia), endocrine, pulmonary,
cardiovascular, or neurologic disease.
8. Subjects who have been diagnosed with any autoimmune rheumatic disease other 
than PsA (including systemic lupus erythematosis, mixed connective tissue disease, 
scleroderma, polymyositis) or diagnosis of fibromyalgia, without approval by
Sponsor.  Also excluded are subjects with prior history of, or current, rheumatic 


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inflammatory disease other than PsA (eg, gout, reactive arthritis, chronic Lyme
disease) without approval by Sponsor.
9. A subject who has been diagnosed with immunodeficiency disorder during study 
A3921092.
10. Functional Class IV status as defined by the American College of Rheumatology
classification of functional status for RA, ie, limited in ability to perform usual 
self-care, vocational and avocational activities.15
11. History of an infected joint prosthesis at any time, with the prosthesis still in situ.
12. History of any lymphoproliferative disorder, such as Epstein Barr Virus (EBV)
related lymphoproliferative disorder, history of lymphoma, leukemia, or signs and
symptoms suggestive of current lymphatic disease.
13. History of recurrent (more than one episode) herpes zoster or disseminated (a single 
episode) herpes zoster or disseminated (a single episode) herpes simplex.
14. History of active infection (including localized infection):

Requiring hospitalization, parenteral antimicrobial therapy, or as otherwise judged
clinically significant by the investigator, within the 3 months prior to sub-study 
entry;

Requiring oral antimicrobial therapy within 2 weeks prior to enrolling in the 
sub-study.
15. Any subject who has been vaccinated with live or attenuated vaccines within the
6 weeks prior to the first dose of sub-study medication or is to be vaccinated with 
these vaccines at any time during treatment or within 6 weeks following 
discontinuation of study medication.  (See Section 4.4.2 Vaccine Guidelines of LTE
study for further information regarding avoidance of household contacts who may be 
vaccinated).
16. A subject with any condition possibly affecting oral drug absorption, eg, gastrectomy,
clinically significant diabetic gastroenteropathy, or certain types of bariatric surgery
such as gastric bypass.  Procedures such as gastric banding, that simply divide the
stomach into separate chambers, are NOT exclusionary.
17. A subject who is considered at increased risk for GI perforation (eg, patients with 
diverticulitis) by the Investigator or Sponsor.
18. A subject with a malignancy or with a history of malignancy, with the exception of
adequately treated or excised non-metastatic basal cell or squamous cell cancer of the
skin or cervical carcinoma in situ.


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19. A subject requiring prohibited concomitant medications (See Appendix 3). For a
medical condition in which it is important for the subject’s safety to continue a
prohibited drug described in Appendix 3, and there is no study-permitted alternative,
the subject must not participate in this study. Subjects receiving non-prohibited
concomitant medications must be on a stable regimen which is defined as not starting 
a new drug or changing dosage within seven days or 5 half-lives (whichever is
longer) prior to the baseline visit.
20. A subject known to be infected with human immunodeficiency virus (HIV),
hepatitis B virus or hepatitis C virus or any chronic infection.
21. A subject with evidence of skin conditions (eg, eczema) at the time of the screening 
or baseline visit that would interfere with evaluation of psoriasis.
22. Other severe acute or chronic medical or psychiatric condition or laboratory
abnormality that may increase the risk associated with study participation or 
investigational product administration or may interfere with the interpretation of 
study results and, in judgement of investigator, would make subject inappropriate for
entry into this study.
23. A subject who, in the opinion of the investigator or Pfizer (or designee), will be 
uncooperative or unable to comply with study procedures.
24. Participation in other studies involving investigational drug(s) (Phases 1-4) during 
sub-study participation.
4.3. Sub-Study Enrollment Criteria
Subjects will be enrolled into the sub-study provided they have signed an informed consent 
document to participate in the sub-study, have undergone all Sub-study Switch /Baseline visit
procedures as required, and have met all inclusion and exclusion criteria for participation in 
the sub-study at the Combined A3921092 Sub-study Switch/Baseline visit.  Subjects will be 
assigned a new subject identification number that will be retained throughout the sub-study. 
4.4. Life Style Guidelines
In order to participate in the study, subjects must be made aware of the following life style 
guidelines and restrictions that apply during and after the study period.  Details of these life 
style guidelines are provided in the sections as noted.

On designated study visit days, comply with fasting requirements for at least 9 hours
prior to visit (See Sub-Study Section 6).

On study visit days, do not smoke or ingest caffeine (eg, tea, coffee, some soft
drinks/colas/energy drinks and power bars) during the 30 minutes prior to blood
pressure and pulse (heart) rate measurements.


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
On study visit days, showering or bathing is permitted prior to attending the study 
visit, but do not moisturize.

Avoid vaccinations with live or attenuated live vaccines and contact with individuals
who have recently received live or attenuated live vaccines (See Section 4.4.2 of main
LTE study).

Discontinue and avoid using certain medications and treatments used to treat PsA or
psoriasis (see Inclusion Criteria and list of prohibited medications Appendix 3).
Discontinue and avoid using certain other prohibited medications and treatment (see
Appendix 3) not used to treat PsA or psoriasis.  For a medical condition in which it 
is important for the subject’s safety to continue using the prohibited drug, and there is
no study-permitted alternative, the subject must not participate in this study.

Contact the study site investigator if there are any changes or additions to 
concomitant medications.

Avoid having elective surgery (See Section 4.4.5).

Agree to use highly effective contraceptive methods per Section 4.4.6.
4.4.1. Non-Pharmacologic Interventions
The subject should continue all non-pharmacological therapies, such as physical therapy, as 
indicated.
4.4.2. Vaccine Guidelines
For guidance on administration of vaccines to a subject and management of household 
contacts with others vaccinated refer to Section 4.4.2 of the main study A3921092. 
4.4.3. Dietary Supplements
For the purposes of this protocol, dietary supplements are defined as vitamins, minerals, 
purified food substances, and herbals with pharmaceutical properties.
Vitamins, minerals and purified food substances are allowed in amounts not known to be 
associated with adverse effects (such as hypervitaminosis). Herbals with pharmaceutical 
properties are allowed only if there is acceptable evidence of no CYP3A inhibition or 
induction.  Otherwise, herbals with pharmaceutical properties must be discontinued for at 
least 4 weeks prior to first dose of study drug, unless there is sufficient data available 
regarding the duration of an herbal medication’s pharmacokinetic and pharmacodynamic 
effects to allow a shorter washout to be specified (eg, 5 half-lives).  Please direct any 
questions to the Sponsor.
Glucosamine sulfate and chondroitin sulfate are allowed in the study but should be stably 
dosed beginning at least 1 week prior to first dose of study medicine.


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4.4.4. Fasting Visit Requirements
On visit days when fasting lipid panels are scheduled to be collected, all subjects should 
refrain from all food and liquids (water and medications permitted, if appropriate) for at least 
9 hours prior to scheduled safety laboratory tests. Visits that require fasting are Baseline, 
Month 6 and Month 12, End of Treatment/Early Termination Visit and Follow-Up Visit (if 
required).
4.4.5. Elective Surgery
During the course of this trial, no elective surgery should be scheduled without first 
consulting the Pfizer Study Clinician.
Subjects who do require surgery should temporarily discontinue study drug for one week 
prior to the surgical procedure and remain off study drug after the surgical procedure until 
sutures/staples are removed.  If absorbing sutures or chemical closure methods are utilized, 
study drug can be resumed when the operative site is sufficiently healed and risk of infection 
is minimal.
4.4.6. Contraception
4.4.6.1. Contraceptive Methods in Women of Childbearing Potential
Administration of tofacitinib in preclinical studies was shown to have teratogenic effects on 
the offspring of treated rats and viability of their fetuses.  Due to this hypothetical risk, 
women of childbearing potential will not be administered tofacitinib until pregnancy is 
excluded and should use a highly effective method(s) of contraception during therapy with 
tofacitinib and for at least one ovulatory cycle after study treatment is discontinued. They 
must have a negative urine pregnancy test at the baseline visit prior to the first dose of study 
drug and at every visit during the study (or more frequently if required by local practices), if 
a menstrual cycle is missed, or if potential pregnancy is otherwise suspected or if the subject 
has become sexually active.
In this study, male subjects who are able to father children and female subjects who are of 
childbearing potential will receive MTX or placebo in a blinded manner. MTX has been 
associated with teratogenic risk. For subjects who are sexually active and at risk for
pregnancy with their partner(s) must agree to use with their partner(s) two (2) methods of 
highly effective contraception throughout the study and continue for at least 3 months after 
the last dose of sub-study drug. 
For the purposes of this protocol, female subjects must either use adequate contraception or 
be of non-childbearing potential.  The investigator, in consultation with the subject, will 
select an appropriate method(s) of contraception for women of child-bearing potential who 
are sexually active from the permitted list of contraception methods, and instruct the subject 
in their consistent and correct use.  The investigator, at each study visit, will confirm and 
document consistent and correct use.  In addition, the investigator will instruct the subject to 
call immediately if a selected birth control method(s) is discontinued or if pregnancy is 


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known or suspected. Subjects in the United Kingdom that are women of childbearing 
potential are required to use two highly effective methods of birth control. 
Highly effective methods of contraception are those that, alone or in combination, result in a 
failure rate of less than 1% per year when used consistently and correctly (ie, perfect use) and 
include:
1. Established use of oral, injected, injected or implanted hormonal methods of
contraception are allowed provided the subject remains on the same treatment 
throughout the entire study and has been using that hormonal contraceptive for an
adequate period of time to ensure effectiveness.
2. Correctly placed copper containing intrauterine device (IUD) or intrauterine system
(IUS).
3. Male condom or female condom used WITH a spermicide (ie, foam, gel, film, cream,
suppository).  For countries where spermicide is not available or condom plus
spermicide is not accepted as highly effective contraception, this option is not 
appropriate.
4. Sterilization of male partner with appropriately confirmed absence of sperm in the
post-vasectomy ejaculate.
5. Bilateral tubal ligation or bilateral salpingectomy or bilateral tubal occlusive
procedure (provided that occlusion has been confirmed in accordance with the 
device’s label).
NOTE: Sexual abstinence, defined as completely and persistently refraining from all 
heterosexual intercourse (including during the entire period of risk associated with the study 
treatments) may obviate the need for contraception ONLY if this is the preferred and usual 
lifestyle of the subject.
4.4.6.2. Women of Non-Childbearing Potential
Female subjects of non-childbearing potential must meet at least one of the following 
criteria:

Have undergone documented hysterectomy or bilateral oophorectomy;

Have medically confirmed ovarian failure; or

Achieved post-menopausal status defined as: cessation of regular menses for at least
12 consecutive months with no alternative pathological or physiological cause; status
may be confirmed by having serum FSH level within the laboratory’s reference range
for post-menopausal females.


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All other female subjects (including females with tubal ligations) will be considered to be of 
childbearing potential.
4.4.6.3. Contraceptive Methods in Male Subjects
Administration of tofacitinib in preclinical trials demonstrated no effects on male sperm or 
offspring in any studies conducted to date. Due to the concomitant administration of MTX in 
this study, male subjects need to take contraceptive precautions as described in the previous 
section.
4.5. Sponsor Qualified Medical Personnel 
Please refer to Section 4.5 of the main Study Protocol A3921092.
5. SUB-STUDY STUDY TREATMENTS
For the purposes of this study, and per International Conference on Harmonisation (ICH) 
guidelines, investigational product is defined as a pharmaceutical form of an active 
ingredient or placebo being tested or used as a reference/comparator in a clinical trial, 
including a product with a marketing authorization when used or assembled (formulated or 
packaged) in a way different from the approved form, or when used for an unapproved 
indication, or when used to gain further information about an approved use (ICH E6 1.33).  
For this sub-study, the investigational products are tofacitinib and methotrexate.
5.1. Sub-Study Allocation to Treatment
The following medication will be supplied by Pfizer Inc:

Tofacitinib 5 mg tablets (open-label).

Methotrexate 2.5 mg capsules.

Placebo capsules that match Methotrexate capsules. 
Both the open-label tofacitinib 5 mg and blinded MTX will be dispensed to subjects to 
self-administer after appropriate training and specific written instructions are provided.
Tofacitinib will be taken orally 5 mg BID (approximately every 12 hours). Methotrexate or 
MTX placebo will be taken orally once a week. The dose of MTX must be the same oral 
dose as taken prior to sub-study entry; allowed doses of MTX entry may range from 7.5 mg 
to a maximum of 20 mg a week but must be stable 4 weeks prior to entering the sub-study, 
and must not be changed with the following exception. Reductions in the dose of MTX are 
permitted if there is evidence of toxicity.  For subjects who are on a MTX dose higher than 
7.5 mg per week, the MTX dose may be reduced to 7.5 mg per week on one occasion and 
with Sponsor’s approval. Dose re-adjustments of MTX will be allowed with Sponsor’s 
approval. Reductions of tofacitinib dose are not permitted. Temporary withdrawals of any 
of the sub-study drugs (tofacitinib and methotrexate/placebo) are only permitted if required 


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due to safety concerns.  Study treatment will continue until the subject discontinues from the 
study or has received approximately 12 months of treatment.
Allocation of subjects to treatment will proceed through the use of an interactive response 
technology (IRT) system (interactive Web-based response (IWR).  During the sub-study 
Baseline visit, the site personnel (study coordinator or specified designee) will be required to 
enter or select information including but not limited to the user’s identification (ID) and 
password, the protocol number, and the subject’s number. The site personnel will then be 
provided with a randomization number and container number(s) when investigational product 
is being supplied via the IRT system.  The confirmation report must be stored in the site’s 
files.
5.2. Sub-Study Breaking the Blind
This sub-study will be subject-, investigator- and Sponsor blinded. 
In regards to each sub-study drug:

Tofacitinib 5 mg BID will be open label;

The assignment of MTX/MTX placebo will be subject-, investigator-, and 
Sponsor-blinded. 
At the initiation of the sub-study the investigator site will be instructed on the method for 
breaking the blind. The method will be an electronic process using the IRT system.  Blinding 
codes should be broken only in exceptional circumstances when knowledge of the actual 
treatment code is absolutely essential for further management of the subject.  Investigators 
are encouraged to discuss with a member of the study team if they believe that unblinding is 
necessary.  When the blinding code is broken, the reason must be fully documented on the 
case report form (CRF).
5.3. Sub-Study Drug Supplies
The Sponsor will provide tofacitinib 5 mg tablets in a bottle that will be labeled as 
appropriately for this sub-study.  MTX 2.5 mg capsules and matching placebo will also be 
provided by the Sponsor. Study medication will be taken according to the instructions 
provided to the subject. The specific subject instructions will also direct the subject to bring 
the study medication bottle(s) to the clinic on study visit days.  Dose increases for both 
tofacitinib and blinded MTX are not permitted during this sub-study. Temporary 
withdrawals of any study drug or MTX dose reductions due to safety concerns may occur 
between scheduled study visits and must be clearly documented on the subject’s chart and 
verified for start date and dose when the subject returns for their next scheduled visit.
5.3.1. Sub-Study Preparation and Dispensing
Tofacitinib, blinded MTX and the corresponding MTX placebo will be dispensed in bottles.  
At each dispensing visit, subjects will receive a sufficient quantity of all study drugs to last 


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until their next scheduled dispensing visit. The subject should be instructed to maintain the 
product in the container provided throughout the course of dosing and return the containers at 
the next study visit.  At all study visits, subjects’ returned containers will be assessed for 
accountability and the amount of study drug returned will be recorded.
5.4. Sub-Study Administration
All investigational products will be self-administered by the subject as specified in the dosing 
card.  Tofacitinib should be administered orally, twice daily, approximately 12 hours apart, 
once in the morning and once in the evening. During the sub-study all subjects will receive a 
dose of 5 mg BID taking 1 tablet in the morning and 1 tablet in the evening. If a tofacitinib 
dose is missed and the interval to the next scheduled dose is less than 6 hours, the missed 
dose of tofacitinib should not be administered. 
At the time of enrollment (eg, the Combined A3921092 Sub-study Switch/Baseline visit), 
subjects must discontinue the use of their personal (commercial) supply of MTX. MTX or its 
matching placebo will be provided by the Sponsor and must be administered orally once a 
week (the same day of the week) in a predetermined dose that may range from 7.5 mg/week 
to 20 mg/week. Subjects will receive the corresponding number of MTX or matching 
placebo 2.5 mg capsules to complete their individual preselected dose of oral MTX 
(Sub-Study Table 3). Subjects should be instructed to document any missed doses.
Sub-Study Table 3
Assigned Dose of MTX
Corresponding number of MTX 2.5 mg 
capsules or matching placebo
7.5 mg/week
3 capsules
10 mg/week
4 capsules
12.5 mg/week
5 capsules
15 mg/week
6 capsules
17.5 mg/week
7 capsules
20 mg/week
8 capsules
Subjects who are randomized to tofacitinib 5 mg BID + MTX placebo will experience a full 
withdrawal of MTX (eg, no tapering) at the time of randomization. 
Study medications may be administered with or without food, with exception of the day of 
the study visits that require fasting. 
Medication errors may result in the sub-study from the administration or consumption of the 
wrong product, by the wrong subject, at the wrong time, or at the wrong dose. Such 
medication errors occurring to a study participant are to be captured on the adverse event 
page of the CRF and on the SAE form when appropriate. In the event of a dosing error, the 
sponsor should be notified immediately. Whether or not the medication error is accompanied 
by an AE, as determined by the investigator, it is captured on an adverse event (AE) CRF 


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page as well as any AEs associated with the medication error (refer to Section 8 of main LTE 
protocol). 
5.5. Sub-Study Compliance
Subject compliance with dosing administration for both tofacitinib and MTX/placebo will be 
verified by accounting of returned containers and trial medication at each visit.
Compliance for the tofacitinib tablets and MTX/placebo capsules will be monitored by the 
accounting of unused medication and will be documented. Subjects who demonstrate 
<80% compliance to either study drug should be counseled by the investigator or designee 
and ensure steps are taken to improve compliance.  Subjects who are <80% compliant with 
dosage regimen for any of the 2 study medications, for two consecutive visit periods should 
be withdrawn from the study.
If the subject is over-compliant with either study drug (intentional or accidental) the 
investigator or designee is to counsel the subject and ensure correct understanding of the 
study drug dosing regimen.  The investigator should contact the Pfizer Study Clinician 
promptly with any over-compliance (>120% in a visit period) that may potentially impact the 
safe use of study drug or that may result in a serious adverse event.
5.6. Sub-Study Drug Storage
The investigator, or an approved representative (eg, pharmacist), will ensure that all 
investigational product, including any comparative agents and/or marketed products are 
stored in a secured area with controlled access under recommended storage conditions and in 
accordance with applicable regulatory requirements.
Both investigational products should be stored in its original container and in accordance 
with the drug label.  See the drug label for storage conditions of the product.
Storage conditions stated in the single reference safety document (SRSD), tofacitinib IB and 
SPC for methotrexate), will be superseded by the storage conditions stated in the labeling.
Site systems must be capable of measuring and documenting (for example, via a log), at a 
minimum, daily minimum and maximum temperatures for all site storage locations (as 
applicable, including frozen, refrigerated and/or room temperature products).  This should be 
captured from the time of investigational product receipt throughout the study.  Even for 
continuous monitoring systems, a log or site procedure which ensures active daily evaluation 
for excursions should be available. The operation of the temperature monitoring device and 
storage unit (for example, refrigerator), as applicable, should be regularly inspected to ensure 
it is maintained in working order.
Any excursions from the product label storage conditions should be reported upon discovery. 
The site should actively pursue options for returning the product to labeled storage 
conditions, as soon as possible. Deviations from the storage requirements, including any 
actions taken, must be documented and reported to the sponsor.


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Once an excursion is identified, the investigational product must be quarantined and not used 
until the sponsor provides documentation of permission to use the investigational product.  It 
will not be considered a protocol deviation if Pfizer approves the use of the investigational 
product after the temperature excursion.  Use of the investigational product prior to Pfizer 
approval will be considered a protocol deviation.
Specific details regarding information the site should report for each excursion will be 
provided to the site.
Site staff will instruct subjects on the storage requirements for take home medications.
5.7. Sub-Study Drug Accountability
The investigator’s site must maintain adequate records documenting the receipt, use, loss or 
other disposition of the investigational product supplies. At the Switch/Baseline visit of the 
sub-study, all investigational product from the main A3921092 LTE study will be collected 
for accountability under the main protocol.  New tofacitinib supplies will be dispensed under 
the sub-study. 
To ensure adequate records, all investigational product supplies will be accounted for in the 
drug accountability inventory forms as instructed by Pfizer and will be monitored by the 
accounting of unused study drug returned by the subjects. All study drug bottles must be 
returned to the investigator by the subject and the investigator will return the bottles to Pfizer. 
At the end of the clinical study, all drug supplies unallocated or unused by the subjects must 
be returned to Pfizer or its appointed agent, or destroyed in an approved manner unless 
otherwise authorized by Pfizer.  In either case, the forms must identify the study drug, 
including batch or code numbers, and account for its disposition on a subject-by-subject 
basis, including specific dates and quantities.  The forms must be signed by the individual 
who dispensed the drug.
5.7.1. Destruction of Investigational Product Supplies
Process for destruction will be as noted in Section 5.5.1 of the LTE protocol.
5.8. Concomitant Treatment(s)
It is important to be aware of, and document, all concomitant treatments including: 
prescription, non-prescription (ie, over-the-counter) and herbal medications.
A subject who is receiving an allowed concomitant medication for any reason must be on a 
locally-approved medication and dose that is considered standard-of-care for the treated 
indication, and this must be documented in the case report form. Subjects are not allowed to 
receive any other investigational drug during the study.
It is recommended that subjects avoid changing non-prohibited prescription or
non-prescription drugs, vitamins, and dietary supplements within 7 days or 5 half-lives 


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(whichever is longer) prior to the first dose of study medication and prior to study visits 
unless otherwise noted below, throughout the study.
Treatments that are taken before the first dose of study drug will be documented as prior 
treatments.  Treatments taken after the first dose of study drug has been administered will be 
documented as concomitant treatments. All concomitant treatments taken during the study 
must be recorded in the study records with indication (as appropriate), daily dose and start 
and stop dates of administration. Subjects will be queried about concomitant treatments at 
each study visit.
Minimum guidelines for folate supplementation during study: All subjects must receive 
folate supplementation according to local methotrexate label guidelines and standard of care. 
A minimum of 5 mg weekly based on folic acid should be given unless local guidelines or 
standard of care state otherwise.
5.8.1. Stable Background Pain or Other Arthritis Therapy
Adjustments for safety reasons may be done at any time, but if this leads to changes in excess 
of those allowed, the investigator must receive approval from the Pfizer Study Clinician to 
allow the subject to continue in the trial.
For subjects receiving background NSAID/COX-2 inhibitors, dose adjustments are not 
permitted in the first 6 months of the sub-study unless there is a safety concern. Switching to 
other NSAIDs/COX-2 inhibitors is not allowed during the sub-study.  Oral corticosteroid 
dose should not exceed 10 mg prednisone or its equivalent daily.  Daily dosage of 
corticosteroids must not be modified during the sub-study, except if adjustment is needed to 
protect a subject’s safety.
The total daily dose of acetaminophen may not exceed 2.6 grams per day, and the total daily 
dose of opioid may not exceed the potency equivalent of 30 mg of orally-administered 
morphine (See Appendix 5, Appendix 6).
Daily dosage of opioids and acetaminophen/paracetamol must not be modified in the first 
6 months of the sub-study, except if adjustment is needed to protect a subject’s safety.
5.8.2. Other Medications
Prohibited drugs and dietary supplements must be discontinued according to protocol 
guidelines: a list of prohibited drugs with specific discontinuation recommendations is listed 
in Appendix 3. Herbals with pharmaceutical properties are allowed only if there is 
acceptable evidence of no CYP3A inhibition or induction.  Otherwise, herbals with 
pharmaceutical properties must be discontinued for at least 4 weeks prior to first dose of 
study drug, unless there is sufficient data available regarding the duration of an herbal 
medication’s pharmacokinetic and pharmacodynamic effects to allow a shorter washout to be
specified (eg, 5 half-lives).  All concomitant treatment taken during the study must be 
recorded with indication (as required), daily dose, and start and stop dates of administration.


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5.9. Rescue Therapy
The only medications that are allowed for rescue are listed in Appendix 6. Subjects who 
require rescue medication for more than 10 consecutive days should be discontinued from the 
study. There is no limit to the total duration of nonconsecutive use of rescue medications. In 
addition, subjects must not be dosed with rescue medication during the 24 hours prior to a 
study visit except if adjustment is needed because subject is experiencing intolerable pain.
Baseline stable use of acetaminophen/paracetamol or opioids should NOT be discontinued in 
advance of study visits.
5.9.1. Dosage Reduction and Withholding
All subjects will receive open-label tofacitinib 5 mg BID and MTX or matching placebo 
upon entry into the sub-study.  Dosage of both tofacitinib and MTX (predetermined dose as 
described in Sub-Study Section 5.1) must remain stable for the duration of the sub-study.
If the investigator deems it necessary to withhold any of the study medications to treat a 
non-serious infection or other medical condition, temporary withholding is permitted for up 
to 5 days of tofacitinib and 1 weekly dose of MTX. If the study drug administration is 
interrupted for more than 5 days or 1 weekly dose of MTX due to a medical reason, the 
investigator must contact the Pfizer study clinician for approval. 
Temporary withholding of study medication, as described above, is permitted once during the 
study without obtaining prior approval from Pfizer Study clinician. Any additional request(s) 
for temporary withholding of study drug require(s) documented approval by the Pfizer Study 
Clinician.
Dosage of tofacitinib and/or MTX may be temporarily discontinued for up to 14 consecutive 
days or 2 weekly doses, for severe cytopenias, for infections which meet criteria for serious 
infections (ie, those requiring parenteral antimicrobial therapy or hospitalization), for surgical 
procedures or other moderately severe AEs.
Treatment with tofacitinib will be discontinued and the subject withdrawn from this study 
due to safety issues as defined in Appendix 4.3.
6. SUB-STUDY PROCEDURES
Subjects from the long term extension study who elect to participate in the sub-study should 
complete a combined A3921092 Sub-study Switch/Baseline visit on the same day of the 
scheduled A3921092 study visit at or after Month 24.
The study investigator or a sub-investigator will discuss with each subject the nature of the 
study, its requirements, and its restrictions.  Written informed consent must be obtained prior 
to performance of any protocol-specific procedures.


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Subjects who are on prohibited medications, and are deriving a beneficial response from 
them, should not be entered into this sub-study.  Subjects may be discontinued from the 
sub-study at any time during the sub-study in the event of deterioration of response as 
determined by the investigator.
6.1. Combined A3921092 & Sub-Study Switch/Baseline Visit
The Combined A3921092 Sub-study Switch/Baseline visit occurs at Month 24, Month 27, 
Month 30, Month 33, or Month 36 of A3921092. Since not all of the study procedures and 
assessments needed for the Baseline of the sub-study are collected at these visits of 
A3921092, any assessment or activity that was not completed as part of the A3921092 visit 
needs to be completed at this combined visit. At the Switch/Baseline visit of the sub-study, 
all investigational product from the main A3921092 LTE study will be collected for 
accountability under the main protocol.  New tofacitinib supplies will be dispensed under the 
sub-study.  Details of the required activities are listed below. 
Subjects are required to fast for at least 9 hours prior to the visit. Blood collection may 
be taken up to 48 hours prior to or following this visit as necessary to ensure samples are 
collected in a fasted state.
All Patient Reported Outcomes should be completed prior to any other study procedures.
6.1.1. Combined A3921092 & Sub-Study Switch/Baseline Visit at Month 24 or 
Month 36
For subjects with the Combined A3921092 Sub-study Switch/Baseline visit conducted at the 
scheduled A3921092 study visit of Month 24 (M24) or Month 36 (M36), subjects must
complete activities as indicated from M24 or M36 visit of A3921092 in addition to the
following procedures:

Informed consent obtained.

Collect tofacitinib LTE investigational product supplies and complete accountability 
for the last visit of the main LTE study.

Register for subject identification number.

Randomization completed.

Dispense study medication/schedule next visit.

Observe subject taking the study drugs (tofacitinib and MTX or placebo) and record 
the dosing in the dosing log CRF.


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6.1.2. Combined A3921092 & Sub-Study Switch/Baseline Visit at Month 27 or 
Month 33 
For subjects with the Combined A3921092 Sub-study Switch/Baseline visit conducted at the 
scheduled A3921092 study visit of Month 27 or Month 33, the subjects must complete 
activities as indicated from M27 or M33 visit of A3921092 in addition to the following 
procedures.

Informed consent obtained.

Collect tofacitinib LTE investigational product supplies and complete accountability 
for the last visit of the main LTE study.

Register for subject identification number.

Randomization completed.

SF-36 Version 2 (Acute).

FACIT-F.

EQ-5D.
The following additional procedures will also be performed:

Cardiovascular Risk Assessment: smoking status, average weekly alcohol
consumption and family history of premature coronary heart disease (see Section 7.4
of LTE study).

Physical Examination: Complete physical examination (height, weight, general
appearance) skin (presence of rash), HEENT (head, eyes, ears, nose and throat), lungs 
(auscultation), heart (auscultation for presence of murmurs, gallops, rubs), extremity 
exam (presence of peripheral edema), abdomen (palpation and auscultation),
neurologic (mental status, station, gait, reflexes, motor and sensory function, 
coordination) and lymph nodes.

Waist and hips circumference.

Blood testing: Central laboratory testing of Lipid Profile (fasting).

Yearly TB testing if applicable.

12-lead electrocardiogram.

Monitoring of adverse events and concomitant treatments. Record any modifications, 
deletions or additions.


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
Drug dispensing.

Observe subject taking the study drugs (tofacitinib and MTX or placebo) and record 
the dosing in the dosing log CRF.
6.1.3. Combined A3921092 & Sub-Study Switch/Baseline Visit at Month 30 
For subjects with the Combined A3921092 Sub-study Switch/Baseline visit conducted at the 
scheduled A3921092 study visit of Month 30, the subjects must complete activities as 
indicated from M30 visit of A3921092 in addition to the following procedures at the 
combined screening/baseline visit.

Informed consent obtained;

Collect tofacitinib LTE investigational product supplies and complete accountability 
for the last visit of the main LTE study.

Register for subject identification number.

Randomization completed.
The following additional procedures will also be performed:

Physical Examination: Complete physical examination (height, weight, general
appearance) skin (presence of rash), HEENT (head, eyes, ears, nose and throat), lungs 
(auscultation), heart (auscultation for presence of murmurs, gallops, rubs), extremity 
exam (presence of peripheral edema), abdomen (palpation and auscultation),
neurologic (mental status, station, gait, reflexes, motor and sensory function, 
coordination) and lymph nodes.

12-lead electrocardiogram.

Yearly TB testing if applicable.

Monitoring of adverse events and concomitant treatments. Record any modifications, 
deletions or additions.

Drug dispensing.

Observe subject taking the study drugs (tofacitinib and MTX or placebo) and record 
the dosing in the dosing log CRF.
6.2. Study Period
The blood collection for laboratory testing at specified visits (ie, Month 1, Month 3, Month 6, 
Month 9 and Month 12) requiring a fasting state (at least 9 hours) may be taken up to 
48 hours prior to or after the visit to ensure samples are collected in a fasting state.  If the 


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subject has not fasted for at least 9 hours, the visit should be rescheduled to occur within 
48 hours in the fasting state. Prior to attending the study visits, subjects are allowed to 
shower or bathe that morning but should not moisturize with topical emollient.
Subjects should complete the Patient Reported Outcome questionnaires at the clinic prior to 
any other study procedures.  This sequence of study procedures will reduce the risk of 
inadvertently introducing bias in a subject’s responses through study staff interactions. In the 
unlikely event that a PRO questionnaire(s) is not able to be administered by the study site 
staff and completed by the subject at the clinic visit, the PRO questionnaire(s) should not be 
administered.
All rheumatological and dermatological assessments will be performed by qualified, trained 
assessors.  To ensure consistency and reduce intra-individual variability, the same qualified 
assessor should score all evaluations for a particular assessment for a given subject 
throughout the study.  The visit window for this sub-study utilizes 28 days for a month.
6.2.1. Sub-Study Month 1
The window for this visit is 7 days.
All Patient Reported Outcomes should be completed prior to any other study procedures. 
These include the following:

Patient’s Assessment of Arthritis Pain (VAS);

Patient’s Global Assessment of Arthritis (VAS);

HAQ-DI;

PGJS-VAS;

SF-36 Version 2 (Acute);

FACIT-F;

EQ-5D.
Procedures that will be performed include:

Targeted physical examination (weight, examination of heart, lungs, abdomen, lower
extremities, and lymph nodes).

Vital signs: blood pressure, pulse rate and temperature (tympanic, oral or temporal
preferred).

Blood and urine specimen testing: Central laboratory tests including: Hematology,
Chemistry Panel, CRP, Urinalysis.


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
Urine Pregnancy Test (for women of women of childbearing potential only).

Yearly TB testing if applicable.

Clinical Evaluation of Rheumatology Endpoints:

Tender/Painful Joint Count (68);

Swollen Joint Count (66);

Physician’s Global Assessment of Arthritis (VAS);

Assessment of presence and severity of dactylitis;

Assessment of enthesitis using LEI.

Clinical Evaluation of Dermatology Endpoints:

PGA-PsO;

BSA.

Clinical Evaluation of Rheumatology and Dermatology Endpoint: PGA-PsA (VAS).

Monitoring of adverse events and concomitant treatments.  Record any
modifications, deletions or additions.

Drug accountability.
6.2.2. Sub-Study Months 3, 6 And 9
The window for the Month 3, 6 and 9 visits is 7 days.
Subjects are required to fast for at least 9 hours prior to the visit. Blood collection may be 
taken up to 48 hours prior to or following this visit as necessary to ensure samples are 
collected in a fasted state.
All Patient Reported Outcomes should be completed prior to any other study procedures.  
These include the following:

Patient’s Assessment of Arthritis Pain (VAS);

Patient’s Global Assessment of Arthritis (VAS);

PGJS-VAS;

HAQ-DI;


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
SF-36 Version 2 (Acute);

FACIT-F;

EQ-5D.
Procedures that will be performed include:

Targeted Physical Examination: Targeted physical examination (weight, examination 
of heart, lungs, abdomen, lower extremities and lymph nodes).

Vital signs: blood pressure, pulse rate and temperature (tympanic, oral or temporal
preferred).

Blood and urine specimen testing: Central laboratory tests including: Hematology,
Chemistry Panel, CRP, Lipid Profile (fasting)-only Month 6, Urinalysis, Lymphocyte
subset analysis (FACS). 

Urine Pregnancy Test (for women of childbearing potential only).

Yearly TB testing if applicable.

Waist and hips circumference.

Clinical Evaluation of Rheumatology Endpoints:

Tender/Painful Joint Count (68);

Swollen Joint Count (66);

Physician’s Global Assessment of Arthritis (VAS);

Assessment of absence/presence and severity of dactylitis;

Assessment of enthesitis using LEI.

Clinical Evaluation of Dermatology Endpoints:

PGA-PsO;

BSA.

Clinical Evaluation of Rheumatology and Dermatology Endpoint: PGA-PsA (VAS).

Monitoring of adverse events and concomitant treatments.  Record any
modifications, deletions or additions.


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
Drug Accountability;

Drug Dispensing. 
6.2.3. Sub-Study Month 12 or Early Termination Visit
The window for these visits is 7 days.
Subjects are required to fast for at least 9 hours prior to the visit. Blood collection may 
be taken up to 48 hours prior to or following this visit as necessary to ensure samples are 
collected in a fasted state.
All Patient Reported Outcomes should be completed prior to any other study procedures. 
These include the following:

Patient’s Assessment of Arthritis Pain (VAS);

Patient’s Global Assessment of Arthritis (VAS);

CV Risk Factor Assessment;

PGJS-VAS;

HAQ-DI;

SF-36 Version 2 (Acute);

FACIT- F;

EQ-5D.
Procedures that will be performed include:

Physical Examination: Complete physical examination (height, weight, general
appearance, skin (presence of rash), HEENT (head, eyes, ears, nose and throat), lungs 
(auscultation), heart (auscultation for presence of murmurs, gallops, rubs), extremity 
exam (presence of peripheral edema), abdomen (palpation and auscultation),
neurologic (mental status, station, gait, reflexes, motor and sensory function, 
coordination) and lymph nodes.

Vital signs: blood pressure, pulse rate and temperature (tympanic, oral or temporal
preferred).

Blood and urine specimen testing: Central laboratory tests including: Hematology,
Chemistry Panel, CRP, Lipid Profile (fasting), Urinalysis, Lymphocyte subset 
analysis (FACS).


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
Urine Pregnancy Test (for women of childbearing potential only).

Yearly TB testing if applicable;

Waist and hips circumference.

12-lead electrocardiogram.

Clinical Evaluation of Rheumatology Endpoints:

Tender/Painful Joint Count (68);

Swollen Joint Count (66);

Physician’s Global Assessment of Arthritis (VAS);

Assessment of absence/presence and severity of dactylitis;

Assessment of enthesitis using LEI.

Clinical Evaluation of Dermatology Endpoints:

PGA-PsO;

BSA.

PGA-PsA (VAS).

Monitoring of adverse events and concomitant treatments. Record any modifications, 
deletions or additions.

Drug accountability.
6.2.4. Sub-Study Follow-Up Visit
If a subject discontinues from the study with abnormalities in hematology or clinical 
chemistry results which meet criteria as defined in Appendix 4, or a subject discontinues 
from the study due to an adverse event, a follow-up visit must be performed after the Early 
Termination study visit within 28 days (7 days) of last dose of study treatment.
Subjects are required to fast for at least 9 hours prior to the visit. Blood collection may 
be taken up to 48 hours prior to or following this visit as necessary to ensure samples are 
collected in a fasted state.


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The following procedures will be performed:

Blood testing: Central laboratory tests may include: Hematology, Chemistry Panel;
Lipid Panel (fasting);

Urine Pregnancy Test (for women of childbearing potential only);

Tender/Painful Joint Count (68);

Swollen Joint Count (66);

PGA-PsO;

Adverse event reporting and concomitant treatment use.
If abnormalities in hematology or clinical chemistry results are still observed at the follow-up
visit, the subject must continue to be followed until the laboratory abnormality stabilizes or 
returns to baseline levels as approved by the Sponsor.
6.3. Subject Withdrawal
Subjects may withdraw from the study at any time at their own request, or they may be 
withdrawn at any time at the discretion of the investigator or sponsor for safety or behavioral 
reasons or the inability of the subject to comply with the protocol required schedule of study 
visits or procedures at a given study site.
If a subject does not return for a scheduled visit, every effort should be made to contact the 
subject. In any circumstance, every effort should be made to document subject outcome, if 
possible. The investigator should inquire about the reason for withdrawal, request the subject 
return all unused investigational product(s), request the subject return for a final visit, and 
follow-up with the subject regarding any unresolved adverse events (AEs).
If the subject withdraws from the study, and also withdraws consent for disclosure of future 
information, no further evaluations should be performed, and no additional data should be 
collected. The Sponsor may retain and continue to use any data collected before such 
withdrawal of consent.  Withdrawal due to adverse event should be distinguished from 
withdrawal due to insufficient response according to the definition of adverse event noted in 
Section 8.3 of the LTE study A3921092. Withdrawal due to a subject being no longer 
willing to participate in the study should be distinguished from withdrawal due to “lost to 
follow-up” (LTFU).  Every effort should be made to identify and contact subjects who are 
potentially LTFU.  A subject should not be considered a withdrawal due to LTFU until at 
least 3 attempts to contact the subject by multiple methods have been unsuccessful. All 
methods of attempted contact with the subject must be clearly documented (dated and 
initialed) in the subject’s source documents and recorded on appropriate case report form 
(CRF) page. All potential LTFU subjects must be discussed with the Pfizer study team or 
designee prior to assigning LTFU status.


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If a subject discontinues from the study due to any abnormality in hematology or clinical 
chemistry results which meet the criteria as defined in Appendix 4, a follow-up visit must be 
performed within 28 days (7 days) of last dose of study treatment.
If a subject has any clinically significant, treatment-emergent, abnormalities at the conclusion
of the study, the Sponsor (or designated representative) should be notified and every effort
should be made to arrange follow-up evaluations at appropriate intervals to document the
course of the abnormality.  All abnormal laboratory events of clinical significance should be
followed until the laboratory values have returned to normal or baseline levels.
Subjects who require rescue doses of acetaminophen/paracetamol or opioid for more than
10 consecutive days, subjects who require MTX doses higher than the permitted range, 
subjects interrupting study drug for more than 14 consecutive days (see Appendix 4), or 
subjects who are <80% compliant with the dosage regimen for any of the 2 study medications 
for two consecutive visit periods should be withdrawn from the study.
7. ASSESSMENTS
Every effort should be made to ensure that the protocol required tests and procedures are 
completed as described.  However it is anticipated that from time to time there may be 
circumstances, outside of the control of the investigator; that may make it unfeasible to 
perform the test. In these cases the investigator will take all steps necessary to ensure the 
safety and wellbeing of the subject. When a protocol required test cannot be performed the 
investigator will document the reason for this and any corrective and preventive actions 
which he/she has taken to ensure that normal processes are adhered to as soon as possible. 
Single missed assessments, if justified, would not be considered as non-adherence to 
protocol; reason for missed evaluation must be documented.  Two or more consecutively 
missed assessments for any endpoint would be considered non-adherence and be reported. 
The study team should be informed of these incidents in a timely fashion.
7.1. Efficacy Endpoints
All rheumatological and dermatological assessments during the sub-study will be performed 
by qualified, trained assessors who are blinded to the subject’s safety data, previous efficacy 
data and treatment randomization.  To ensure consistency and reduce intra individual 
variability, the same qualified assessor should score all evaluations for a particular 
assessment for a given subject throughout the study.  Please refer to the sub-study Schedule 
of Activities for when assessments are collected.
7.1.1. ACR Components Assessments
The specific components of the ACR Assessments utilized in the sub-study can be found in 
Section 7.1.2 of the main protocol. This efficacy measurement will be made at every study
visit except for the Follow-up visit of the sub-study.


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7.1.2. Disease Activity Score Assessment
The DAS assessment description and components are noted in Section 7.1.3 of the main 
protocol.  This assessment will be made at all study visits except for the Follow-up visit of 
the sub-study.
7.1.3. PsA Response Criteria (PsARC)
Please refer to Section 7.1.4 of the main protocol.  This assessment will be made at all study
visits except for the Follow-up visit of the sub-study.
7.1.4. Minimal Disease Activity Score
Please refer to Section 7.1.8 of the main protocol.
7.1.5. Psoriatic Arthritis Disease Activity Score (PASDAS)
Please refer to Section 7.1.9 of the main protocol.
7.2. Clinical Evaluation of Rheumatology Endpoints
All rheumatological evaluations will be performed by blinded, qualified, trained assessors. 
To ensure consistency and reduce intra-individual variability, the same qualified assessor 
should score all evaluations for a given assessment for a given subject throughout the study.  
Please refer to the sub-study Schedule of Activities for when assessments are collected.
7.2.1. Tender/Painful Joint Count (68)
Please refer to Section 7.2.1 of the main protocol. 
7.2.2. Tender/Painful Joint Count (28)
Please refer to Section 7.2.2 of the main protocol.
7.2.3. Swollen Joint Count (66)
Please refer to Section 7.2.3 of the main protocol.
7.2.4. Swollen Joint Count (28)
Please refer to Section 7.2.4 of the main protocol.
7.2.5. Physician’s Global Assessment of Arthritis
Please refer to Section 7.2.5 of the main protocol. 


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7.2.6. Physician’s Global Assessment of Psoriatic Arthritis
Please refer to Section 7.2.6 of the main protocol. 
7.2.7. Assessment of Dactylitis
Please refer to Section 7.2.7 of the main protocol. 
7.2.8. Assessment of Enthesitis
Please refer to Section 7.2.8 of the main protocol, specifically the LEI assessment.  The LEI 
will be collected at every visit of the sub-study except for the Follow-up visit.
7.2.9. C-Reactive Protein
Blood samples will be collected at each visit for analysis of CRP using an assay analyzed by 
the central laboratory. The test results will be blinded. 
7.3. Clinical Evaluation of Dermatology Endpoints
Please refer to the sub-study Schedule of Activities for when assessments are collected.
7.3.1. Physician’s Global Assessment of Psoriasis (PGA-PsO)
Please refer to Section 7.3.1 of the main protocol. 
7.3.2. Body Surface Area (BSA)
Please refer to Section 7.3.3 of the main protocol. 
7.4. Cardiovascular (CV) Risk Factor Assessment
Please refer to Section 7.4 of the main protocol.  This assessment will be completed at the 
Combined A3921092 Sub-study Switch/Baseline visit and Month 12 or Early Termination 
visit.
7.5. Health Outcome Measures
7.5.1. Patient’s Assessment of Arthritis Pain
Please refer to Section 7.5.1 of the main protocol.
7.5.2. Patient’s Global Assessment of Arthritis
Please refer to Section 7.5.2 of the main protocol.


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7.5.3. HAQ-DI
Please refer to Section 7.5.3 of the main protocol.
7.5.4. Patient’s Global Joint and Skin Assessment (PGJS-VAS)
Please refer to Section 7.5.4 of the main protocol.
7.5.5. Functional Assessment of Chronic Illness Therapy (FACIT-Fatigue Scale)
Please refer to Section 7.5.8 of the main protocol.
7.5.6. SF-36 Health Survey (Version 2, Acute)
Please refer to Section 7.5.9 of the main protocol.
7.5.7. EuroQol EQ-5D Health State Profile
Please refer to Section 7.5.10 of the main protocol.
7.6. Safety
Safety will be assessed by the spontaneous reporting of adverse events (AEs), physical
examinations and clinical laboratory results in all subjects who receive at least one dose of
study drug.  Investigators and Pfizer clinicians will review individual subject data throughout 
the conduct of the study to ensure the subjects’ well-being.
7.6.1. Vital Signs and Temperature
Body temperature, blood pressure and pulse rate will be measured at every study visit except 
Follow-up visit.
Please collect vital signs and temperature as noted in Section 7.6.1 of the main protocol.
7.6.2. Electrocardiogram
Twelve-lead electrocardiograms (ECGs) will be obtained on subjects who enroll into this 
sub-study at a scheduled A3921092 study visit at or after Month 24. All ECGs should be 
performed after the subject has rested quietly for at least 10 minutes.  ECG data will be 
submitted to a central laboratory for measurement. Any clinically significant changes from 
the baseline ECG, will be recorded as adverse events and evaluated further, as clinically 
warranted.
7.6.3. Tuberculosis Screening
Annual TB testing must continue for all applicable countries as described in Section 7.6.3 of
the LTE study A3921092. TB testing will be performed using the QFT for subjects in those 
countries for which TB incidence has been reported at a rate of >50 cases per 


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100,000 persons, eg, Russian Federation and Taiwan [using China incidence rate] (World 
Health Organization, 2016).42  All subjects with positive results must have a chest radiograph 
performed and reviewed by a radiologist or pulmonologist as per local standard of care and
the radiograph must be negative for active TB infection for the subject to continue study
participation. Subjects identified as having latent TB should be treated appropriately; for 
subjects remaining on study during their treatment, the only acceptable regimen is 9 months 
of isoniazid. Note: QFT should not be performed in subjects who had positive result during 
prior testing (screening visit or prior annual visits) and/or previously received adequate 
treatment for TB.
7.6.3.1. QuantiferonTB Gold In-Tube Test
Please refer to Section 7.6.3.1 of the main protocol.
7.6.3.2. Purified Protein Derivative (PPD) Tuberculin Test
Please refer to Section 7.6.3.2 of the main protocol.
7.6.4. Complete Physical Examination
A standard complete physical examination will be performed at the Sub-study 
Switch/Baseline visit (for those subjects who enroll in the sub-study after A3921092 
Month 24 visit, sub-study Month 12 and Early Termination visit. The following parameters
and body systems will be examined and any abnormalities described: height, weight, general
appearance, skin (presence of rash), HEENT (head, ears, eyes, nose, throat), lungs 
(auscultation), heart (auscultation for presence of murmurs, gallops, rubs), lower extremity 
exam (for peripheral edema), abdomen (palpation and auscultation), neurologic (mental 
status, station, gait, reflexes, motor and sensory function, coordination) and lymph nodes.
Any clinically significant changes from Baseline should be recorded as adverse events (AEs).
Recommendations for evaluation of emergent lymphadenopathy or other findings suggestive
of lymphoproliferative disorder are provided in Appendix 8.
7.6.4.1. Targeted Examination
At all other visits, except for the Follow-up visit, an abbreviated physical examination will be 
performed assessing the following: weight, lungs, heart, abdomen, lower extremities (for 
peripheral edema) and lymph nodes. Any clinically significant changes from baseline should 
be recorded as adverse events (AEs). 
7.6.5. Weight, Waist and Hips Circumference and Height
Please refer to Section 7.6.6 of the main protocol.


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7.6.7. Clinical Safety Laboratory Tests
Subjects entering the sub-study will have a new baseline established at the Combined 
Sub-study Switch visit/Baseline visit for laboratory assessments that had previously been 
compared to the baseline of the qualifying study except for assays needed for Hy’s law; 
baseline assessments from the qualifying study will be used.  Blood and urine samples will
be collected at the time points identified in the sub-study protocol. Unscheduled clinical 
laboratory tests may be performed at any time during the study to assess any perceived safety
concerns.
Any laboratory test that is not analyzable should be repeated as soon as possible,
but no later than the next visit.
Sub-Study Table 7.
Clinical Laboratory Testing
Laboratory Testing Profile
Tests Included
Hematology
Hemoglobin, hematocrit, RBC, RBC morphology, reticulocyte (abs); White
blood cell (WBC) count and differential, [neutrophils (%, abs), lymphocytes (%,
abs), monocytes (%, abs), eosinophils (%, abs), basophils (%, abs)], platelets
ChemistryPanel
Urea nitrogen, creatinine, glucose, calcium, sodium, potassium, bicarbonate,
chloride, total protein, total bilirubin, direct bilirubin, indirect bilirubin, alanine
transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase,
gamma-glutamyl transferase (GGT), albumin, creatine kinase (CK)
Lipid Panel
Fasting total cholesterol, HDL, LDL, triglyceride; apolipoprotein A-1, B and
other lipoprotein tests potentially including particle size measurements
TuberculosisScreening
QuantiFERON-TB Gold In-Tubea
Urinalysis
Specific gravity, pH, protein, glucose, ketones, blood, leukocyte esterase.  
Urine hCG pregnancy testing for women of childbearingpotential.
Microscopy and/or culture to be performed if clinically indicated or if urinalysis
results positive (blood, protein or leukocyte esterase/WBC).
Acute Phase Reactants
C-reactive protein (CRP, tested centrally, blinded)
FACS Analysis of Lymphocyte Subsets
CD3(%, abs), CD3+CD4+ (%, abs), CD3+CD8+ (%, abs), CD19+ (%,
abs), CD56+CD16+ (%, abs)
a.
Performed at combined M24/M36 with Screening/Baseline Visit for those subjects in countries which have 
high endemic TB rates and who tested negative at their last QFT.
Abnormal test results determined to be caused from laboratory error should not be reported 
as AEs. Patients who present with clinically significant laboratory findings at the final 
assessment must have a follow-up visit within 28 days 7 days after last dose of study
treatment.  Clinically significant laboratory findings should be followed to resolution or until 
determined by the Investigator to be stabilized.  Repeat tests may be needed to establish this.
7.6.7.1. Pregnancy Testing
Please refer to Section 7.6.7.1 of the main protocol. 


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7.6.8. Events for Adjudication/Review Committee Submission
The Sponsor or designee will provide a listing of specific documents needed to support event 
adjudication by Adjudication/Review Committees (see LTE study A3921092 Section 9.6
Safety Event Adjudication/Review Committees).  Obtaining and submitting the 
documentation will be the responsibility of the study site.  Event documentation will vary
with the event requiring adjudication and may include (but not be limited to): hospital 
discharge summaries, operative report, clinic notes, ECGs, diagnostic tests, pathology
reports, autopsy reports and death certificate information, as applicable.
7.6.9. Triggered Requirements
7.6.9.1. Monitoring Criteria
The following laboratory abnormalities require prompt retesting, ideally within one week:

Any single hemoglobin value that drops >2 g/dL (or 20 g/L) below baseline value of 
the sub-study, if indicated after review by the Pfizer Study Clinician or Investigator.  
Factors that will be considered include stability of hemoglobin values, and their 
relationship to the standard reference range.

Absolute neutrophil count <1.2 x 10
9
cells/L (<1200 cells/ mm3).

Absolute lymphocyte counts <0.5 x 10
9
cells/L (<500 cells/ mm3).

Platelet count <100 x 109 cells/L (<100,000 cells/mm3).

Serum creatinine increase >50% over the baseline value (the first day of the 
sub-study) OR an absolute increase in serum creatinine >0.5 mg/dL (or 44 mol/l), if 
indicated after review by the Pfizer Study Clinician or Investigator.  Factors that will 
be considered include stability of the serum creatinine values, and their relationship to 
the standard reference range.

Any creatine kinase (CK) >5x ULN (repeat laboratory testing should also include 
cardiac troponin).
If the abnormality is confirmed after re-test, follow-up should be discussed with the Sponsor
and frequency of monitoring increased.  Confirmation should be done based upon central 
laboratory results, but local laboratory results will be acceptable, particularly if these may be
done more promptly.
For additional laboratory abnormalities that require prompt retesting, preferably within
48 hours from awareness of the abnormal results, see Section 8.7.2 Potential Cases of 
Drug-Induced Liver Injury.


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7.6.9.2. Discontinuation Criteria
Both study drugs (Tofacitinib and MTX or placebo) will be discontinued and the subject 
withdrawn from the sub-study in the event of any of the following:

Requirement of rescue medications for more than 10 consecutive days.

Serious infections, defined as any infection (viral, bacterial, or fungal) requiring 
parenteral antimicrobial therapy or hospitalization for treatment, or meeting other 
criteria that require the infection to be classified as a serious adverse event (see 
Section 8.7 of the LTE study).

Two sequential absolute neutrophil counts <1.0 x 109 cells/L (<1000 cells/mm
3
).

Two sequential absolute lymphocyte counts <0.5 x 109 cells/L (<500 cells/mm
3
).

Two sequential hemoglobin values <8.0 g/dL (80 g/L) or decreases of >30% from
baseline value (Day 1 of the sub-study).

Two sequential platelet counts <75 x 109 cells/L (<75,000 cells/mm
3
).

Two sequential AST or ALT elevations 3 times the upper limit of normal with at
least one total bilirubin value 2 times the upper limit of normal.
a

Two sequential AST or ALT elevations 3 times the upper limit of normal
accompanied by signs or symptoms consistent with hepatic injury (eg, new onset
elevated PT/INR).
a

Two sequential AST or ALT elevations >5 times the upper limit of normal, regardless
of total bilirubin or accompanying signs or symptoms.a

Two sequential increases in serum creatinine >50% AND an absolute increase in 
serum creatinine >0.5 mg/dL (44 mol/l) over the baseline value (Day 1) in the 
sub-study.

Two sequential creatine kinase (CK) elevations >10 times the upper limit of normal,
unless the causality is known not to be medically serious (eg, exercise or trauma
induced).

A confirmed positive urine pregnancy test in a woman of childbearing potential.

Any opportunistic infection considered significant by investigator or Sponsor.


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
Other serious or severe adverse events, in the opinion of the investigator or Sponsor.  
Whenever possible, the investigator should consult with a member of the Pfizer study 
team before discontinuation of the subject.
If a subject discontinues from the study due to abnormalities in hematology or clinical
chemistry parameters which meet criteria as defined in Appendix 4, a follow-up visit must be
performed within 28 days (7 days) of last dose of study treatment.  For a confirmed increase
in serum creatinine of >50% and >0.5 mg/dL above the baseline value (Day 1) in the 
sub-study, laboratory values will be followed with retesting until the creatinine elevation has 
stabilized (ie, stopped increasing) over at least 3 consecutive tests obtained monthly.
a
In each case, there is a need for additional investigations, such as review of ethanol, recreational drug and
dietary supplement consumption; testing for acute hepatitis A, B or C infection and biliary tract imaging should
be promptly discussed with the Sponsor or designee.
7.7. Exploratory Biomarkers
7.7.1. Lymphocyte Subset Analysis
Fluorescence-activated Cell Sorting (FACS) analysis for lymphocyte subset markers will be 
performed to assess the effects of repeat doses of tofacitinib on T cell (CD4+CD3+, CD8+), 
B cell (CD19+) and NK cell (CD16+CD56+ cell) numbers.  Whole blood samples will be 
collected at Baseline, Month 3, Month 6, Month 9 and Month 12.
7.8. Rater Qualifications
All rheumatological and dermatological assessments in the sub-study will be performed by 
qualified, trained assessors who are blinded to the subject’s safety data, previous efficacy 
data and treatment randomization.  To ensure consistency and reduce intra individual 
variability, the same qualified assessor should score all evaluations for a particular 
assessment for a given subject throughout the study.
8. ADVERSE EVENT REPORTING
Please refer to Section 8 of the LTE A3921092 study. 
9. DATA ANALYSIS/STATISTICAL METHODS
Methodology for summary and statistical analyses of the data collected in this sub-study are 
given here and further detailed in a statistical analysis plan (SAP), which will be dated and 
maintained by Pfizer.  This analysis plan may modify what is outlined in the protocol; 
however, any major modifications of the primary endpoint definitions or their analyses will 
also be reflected in a protocol amendment.


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9.1. Sample Size Determination
This is an estimation study. The primary objective will be met by estimating the effect of 
each treatment and their difference.  A sample size of 90 subjects per group was selected 
such that the 2-sided 95% confidence interval (CI) half-width for the difference in HAQ-DI 
at Month 6 between tofacitinib 5 mg BID + placebo and tofacitinib 5 mg BID + MTX would 
be approximately 0.18 assuming a common standard deviation (SD) of 0.6 for both groups. 
Similarly this sample would yield a 2-sided 95% CI half-width of approximately 0.47 for the 
difference in PASDAS at Month 6 between the 2 treatment groups assuming a common SD 
of 1.6 for both groups.
No adjustment for multiple comparisons will be made in the analyses.  Nominal statistical 
significance will be claimed if the 2-sided p value is ≤0.05.
9.2. Statistical Analyses – General
There will be 2 sets of analyses: one for the A3921092 LTE and the other for the sub-study. 
For the A3921092 LTE:

The safety analysis will include cumulative data from all the subjects and all the data 
(including the data collected in the sub-study). 

The efficacy analysis will include only the data collected in the A3921092 LTE (data 
collected in the sub-study will be excluded from the LTE analysis).
For the sub-study:

The safety analysis will include the data collected in the sub-study only. 

The efficacy analysis will include the data collected in the sub-study only.
The analyses for the A3921092 LTE will be governed by the A3921092 LTE protocol and 
will not be repeated, while the analyses of the sub-study will be detailed in this sub-study 
protocol.
9.3. Efficacy Analysis
The Full Analysis Set (FAS) will include all subjects who were randomized to the sub-study 
and received at least one dose of the sub-study drug (tofacitinib, MTX or placebo).  The 
primary efficacy population for this study is defined by the FAS. 
Continuous endpoints for which change or percent change from baseline is the measure to be 
analyzed, would require that a subject have a baseline value and at least one post-baseline 
value to be included in the FAS for that endpoint.


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For all the efficacy and PRO endpoint analyses, the baseline will be the latest value obtained 
prior to the first dose of the sub-study.
Continuous endpoints collected over multiple visits (eg, HAQ-DI or PASDAS) will be 
analyzed using a Mixed Model for Repeated Measures (MMRM) without imputation for 
missing values on the FAS. Treatment comparison between the 2 groups at each 
post-baseline time point will be generated from this model providing both 2-sided p-value 
and 95% CI.
Binary endpoints (eg, MDA response) will be analyzed using the normal approximation for 
the difference in binomial proportions with missing response as non-response (MR=NR) on 
the FAS. Treatment comparison between the 2 groups at each post-baseline time point will 
be generated providing both 2-sided p-value and 95% CI.
Efficacy will also be assessed for a subset of the subjects who had more severe PsA as 
defined by 5 swollen or tender joints at the baseline of the sub-study, if sample size permits. 
Complete details will be specified in the SAP.
9.3.1. Analysis of Primary Endpoints
There are two primary endpoints in the sub-study: HAQ-DI at Month 6 and ∆PASDAS at 
Month 6. Each primary endpoint will be analyzed using a MMRM without imputation for 
missing values on the FAS.
To assess the impact of missing data due to dropouts, the SAP will also specify additional 
analyses to assess the sensitivity of the primary analysis to departures from the assumed 
missing data mechanism.
9.3.2. Analysis of Secondary and Other Endpoints
Each of the continuous secondary or other efficacy/PRO endpoints listed in Sections 2.2.2
and 2.2.3 of the sub-study will be analyzed using a MMRM without imputation for missing 
values on the FAS.
Each of the binary secondary or other efficacy/PRO endpoints listed in Sections 2.2.2 and 
2.2.3 of the sub-study will be analyzed using the normal approximation for the difference in 
binomial proportions with missing values handled by MR=NR on the FAS.
9.4. Safety Analysis
The safety analysis set (SAFETY) will include all subjects who received at least one dose of 
the sub-study drug (tofacitinib, MTX or placebo).
For the safety analyses, the baseline will be the latest value obtained prior to the first dose of 
the sub-study.


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9.4.1. Analysis of Safety Endpoints
All safety data will be summarized descriptively through appropriate data tabulations, and 
descriptive statistics. 

Incidence and severity of adverse events during treatment.

Incidence of clinical abnormalities and change from baseline in clinical laboratory 
values during treatment.  Special attention will be given to the following safety 
criteria: neutrophil counts, lymphocyte counts, serum creatinine levels, platelet 
counts, transaminase levels, bilirubin levels (and other measures of liver function), 
events of anemia.

Incidence of vital sign (blood pressure and pulse rate) abnormalities and changes 
from baseline in vital sign measurements during treatment.

Incidence of adjudicated safety events.
9.5. Interim Analysis
No formal interim analysis is planned for the sub-study.  However, data-cuts may be 
performed as needed to support tofacitinib regulatory submission.
10. REFERENCES (Sub-Study specific)
41.
Ramiro S, Smolen JS, Landewe R, et al. Pharmacological treatment of psoriatic 
arthritis: a systematic literature review for the 2015 update of the EULAR 
recommendations for the management of psoriatic arthritis. Ann Rheum Dis 2016; 
75:490-498.
42.
Tilling L, Townsend S and David J. Methotrexate and Hepatic Toxicity in Rheumatoid 
Arthritis and Psoriatic Arthritis. Clin Drug Invest 2006; 26 (2): 55-62.
43.
Mease P and Armstrong A. Managing Patients with Psoriatic Disease: The diagnosis 
and pharmacologic treatment of Psoriatic Arthritis in Patients with Psoriasis. Drugs
2014; 74:423-441.
44.
Gossec L, Coates LC et al. Management of psoriatic arthritis in 2016: a comparison of 
EULAR and GRAPPA recommendations. Nat Rev Rheumatol 2016; Dec, 12 (12): 
743-750.
45.
Kingsley G, Kowalczyk A et al. A randomized placebo-controlled trial of methotrexate 
in psoriatic arthritis. Rheum 2012; 51:1368-1377.

SAP_001.pdf: 
Protocol A3921092 (Tofacitinib (CP-690,550)) Statistical Analysis Plan
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Protocol A3921092
A LONG-TERM, OPEN-LABEL EXTENSION STUDY OF TOFACITINIB 
(CP-690,550) FOR THE TREATMENT OF PSORIATIC ARTHRITIS
Statistical Analysis Plan 
(SAP)
(Including SAP for the Methothrexate Withdrawal Sub-Study)
Version:
4.0
Date:
12APR2018 


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TABLE OF CONTENTS
LIST OF TABLES.....................................................................................................................4
APPENDICES ...........................................................................................................................4
1. AMENDMENTS FROM PREVIOUS VERSION(S) ...........................................................6
2. INTRODUCTION .................................................................................................................7
2.1. Study Design .............................................................................................................8
2.2. Study Objectives .......................................................................................................8
3. INTERIM ANALYSES, FINAL ANALYSES AND UNBLINDING..................................9
4. HYPOTHESES AND DECISION RULES...........................................................................9
4.1. Statistical Hypotheses ...............................................................................................9
4.2. Statistical Decision Rules..........................................................................................9
5. ANALYSIS SETS .................................................................................................................9
5.1. Full Analysis Set .......................................................................................................9
5.2. ‘Per Protocol’ Analysis Set .......................................................................................9
5.3. Safety Analysis Set....................................................................................................9
5.4. Other Analysis Sets .................................................................................................10
5.4.1. Endpoint Specific Analysis Sets.................................................................10
5.5. Treatment Misallocations........................................................................................12
5.6. Protocol Deviations.................................................................................................12
6. ENDPOINTS AND COVARIATES ...................................................................................12
6.1. Primary Endpoints...................................................................................................12
6.2. Secondary Endpoints...............................................................................................12
6.3. Other Endpoints.......................................................................................................13
6.4. Covariates................................................................................................................15
7. HANDLING OF MISSING VALUES ................................................................................15
8. STATISTICAL METHODOLOGY AND STATISTICAL ANALYSES ..........................15
8.1. Statistical Methods ..................................................................................................15
8.1.1. Analyses for Continuous Data....................................................................15
8.1.2. Analyses for Categorical Data....................................................................15
8.2. Statistical Analyses .................................................................................................15
8.2.1. Analysis of Primary Endpoints...................................................................16
8.2.2. Analysis of Secondary and Other Efficacy/Health Outcome 
Endpoints .........................................................................................................17


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8.2.3. Analysis of Other Safety Data ....................................................................19
8.3. Baseline and Other Summaries and Analyses.........................................................19
8.3.1. Baseline Summaries....................................................................................19
8.3.2. Prior Drug Treatments for Psoriatic Arthritis.............................................22
8.3.3. Concomitant Drug Treatments for Psoriatic Arthritis ................................23
9. REFERENCES ....................................................................................................................24
10. APPENDICES ...................................................................................................................25
1. INTRODUCTION ...............................................................................................................48
1.1. Study Design ...........................................................................................................48
1.2. Study Objectives .....................................................................................................49
2. INTERIM ANALYSES, FINAL ANALYSES AND UNBLINDING................................49
3. HYPOTHESES AND DECISION RULES.........................................................................49
3.1. Statistical Hypotheses .............................................................................................49
3.2. Statistical Decision Rules........................................................................................49
4. ANALYSIS SETS ...............................................................................................................49
4.1. Full Analysis Set .....................................................................................................49
4.2. ‘Per Protocol’ Analysis Set .....................................................................................50
4.3. Safety Analysis Set..................................................................................................50
4.4. Other Analysis Sets .................................................................................................50
4.4.1. Endpoint Specific Analysis Sets.................................................................50
4.5. Treatment Misallocations........................................................................................50
5. ENDPOINTS AND COVARIATES ...................................................................................51
5.1. Primary Endpoints...................................................................................................51
5.2. Secondary Endpoints...............................................................................................51
5.3. Other Endpoints.......................................................................................................52
5.4. Covariates................................................................................................................52
6. HANDLING OF MISSING VALUES ................................................................................52
7. STATISTICAL METHODOLOGY AND STATISTICAL ANALYSES ..........................52
7.1. Statistical Methods ..................................................................................................53
7.1.1. Analyses for Continuous Data....................................................................53
7.1.2. Analyses for Categorical Data....................................................................53
7.2. Statistical Analyses .................................................................................................54


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7.2.1. Analysis of Primary Endpoints...................................................................54
7.2.2. Analysis of Secondary and Other Efficacy/Health Outcome 
Endpoints .........................................................................................................54
7.2.3. Analysis of Safety Data ..............................................................................55
7.3. Baseline and Other Summaries and Analyses.........................................................55
7.3.1. Baseline Summaries....................................................................................55
7.3.2. Prior Drug Treatments for Psoriatic Arthritis.............................................55
7.3.3. Concomitant Drug Treatments for Psoriatic Arthritis ................................56
7.4. Sub-study Definition and Use of Visit Windows in Reporting...............................56
LIST OF TABLES
Table 1 Endpoint Specific Analysis Sets.................................................................................10
Table 2 AEs of Special Interest ...............................................................................................16
Table 3 Endpoint Specific Analysis Sets.................................................................................50
APPENDICES
Appendix 1. Definition and Use of Visit Windows in Reporting............................................25
Appendix 2. Further Definition of Endpoints..........................................................................27
Appendix 2.1. ACR Assessments............................................................................................27
Appendix 2.2. Health Assessment Questionnaire – Disability Index (HAQ-DI)....................28
Appendix 2.3. DAS 28-3 (CRP) ..............................................................................................29
Appendix 2.4. PsA Response Criteria (PsARC)......................................................................29
Appendix 2.5. PsA Joint Activity Index (PsAJAI)..................................................................30
Appendix 2.6. Disease Activity Index for Reactive Arthritis/Psoriatic Arthritis 
(DAREA/DAPSA)................................................................................................31
Appendix 2.7. Composite Psoriatic Disease Activity Index in Psoriatic Arthritis 
(CPDAI)................................................................................................................31
Appendix 2.8. Minimal Disease Activity (MDA) Response...................................................33
Appendix 2.9. Psoriatic Arthritis Disease Activity Score (PASDAS).....................................34
Appendix 2.10. Psoriasis Area and Severity Index (PASI) .....................................................34
Appendix 2.11. Physician Global Assessment (PGA) of Psoriasis (PGA-PsO)......................35
Appendix 2.12. Dermatology Life Quality Index (DLQI).......................................................35
Appendix 2.13. Itch Severity Item (ISI) ..................................................................................36


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Appendix 2.14. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI).................36
Appendix 2.15. EuroQol-5D Health Questionnaire 3-Level (EQ-5D-3L) ..............................37
Appendix 2.16. Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F).......37
Appendix 2.17. Short Form 36 (SF-36, version 2, acute)........................................................37
Appendix 3. Criteria for Clinical Diagnosis of the Metabolic Syndrome ...............................44
Appendix 4. Definition of Diabetes Mellitus at Baseline........................................................46
Appendix 5. Handling of Joint Count Assessment (Missing Assessment, “NOT 
DONE” and “NOT APPLICABLE”) and Injected Joint......................................47
Appendix 6. Methotrexate Withdrawal Sub-Study..................................................................48


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1. AMENDMENTS FROM PREVIOUS VERSION(S) 
Version 4 (April 12, 2018):
This SAP amendment is mainly updated to reflect the addition of a sub-study. It is based on 
Protocol Amendment 4 dated April 12, 2017.
Version 3 (April 14, 2016):
This SAP amendment occurred after reviews of the data by the external independent Data 
Monitoring Committee, but changes were not based on any recommendations by the DMC.
Appendix 2.1: Updated the method of handling missing components in the evaluation of 
ACR endpoints to a general principle rather than listing out all possible cases of missingness.
Appendix 2.1, Appendix 2.4 & Appendix 2.5: Clarified the evaluation of percent change 
from baseline for the components used in deriving ACR, PsARC, and PsAJAI endpoints 
when the baseline component value is equal to zero.
Appendix 5: Added this section to clarify the handling of tender/painful joint (68) and 
swollen joint (66) assessment that is missing, “NOT DONE” or “NOT APPLICABLE,” as 
well as when a joint receives intra-articular injection at baseline or post-baseline.
Version 2.1 (February 1, 2016):
Appendix 3 and Appendix 4: Clarified drug treatment (other than study drug treatment) taken 
on Day 1 of the qualifying study will be considered as concomitant drug treatment, and taken 
on Day 0 will be considered as prior drug treatment to align with the Pfizer Data Standard for 
reporting drug treatments.
Version 2 (January 30, 2016):
Changes to the original SAP, version 10JUL2013, are summarized below. This SAP 
amendment occurred after reviews of the data by the external independent Data Monitoring 
Committee, but changes were not based on any recommendations by the DMC.

Section 5.4.1, Added the ‘Endpoint Specific Analysis Sets’ section to define analysis 
populations suitable for certain endpoints since disease may not be present at baseline 
as measured by certain endpoints.

Section 6, clarified that VAS will be re-scaled to 100 mm or 10 cm prior to any 
calculation and analysis. 

Section 6.2, added additional details/clarifications for the secondary endpoints.


Protocol A3921092 (Tofacitinib (CP-690,550)) Statistical Analysis Plan
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
Section 6.3, added HAQ-DI response, components of ACR, PASI and its clinical sign 
components and BSA to the other endpoints, and other additional details/clarification 
for the other endpoints.

Section 8.1.2, added normal approximation for construction of confidence interval for 
responder rate.

Section 8.2, added clarification for analysis population.

Section 8.2.2, added analyses for components of ACR, PASI and its clinical sign 
components and BSA, and additional clarifications to analysis populations.

Section 8.3.1, added baseline summaries.

Section 8.3.2, added summaries of prior drug treatment for psoriatic arthritis.

Section 8.3.3, added summaries of concomitant drug treatment for psoriatic arthritis.

Section 9, updated the references. 

Appendix 1, updated visit windows.

Appendix 2, added clarifications and additional details/update for 
definition/calculation of endpoints.
Version 1 (initial version, July 10, 2013):
2. INTRODUCTION
Note: in this document any text taken directly from the protocol is italicized.
Psoriatic arthritis (PsA) is a chronic inflammatory autoimmune disease characterized by 
joint inflammation and destruction, psoriatic skin lesions, enthesitis, dactylitis, spondylitis, 
progressive disability and adverse effects on quality of life.  Tofacitinib (CP-690,550) is a 
potent and selective inhibitor of the Janus Kinase (JAK) family of kinases.  While tofacitinib 
shows nanomolar inhibitory potency against all JAK family kinases in enzymatic assays, it 
shows functional specificity for JAK1 and JAK1/3 over JAK2 in cell-based assays.  The 
broad effects of JAK1/3 inhibition on multiple cytokine pathways provide rationale for 
developing tofacitinib as treatment for PsA.
This Phase 3 study is a long-term extension (LTE) study designed to evaluate the safety and 
tolerability of tofacitinib as a treatment for PsA.
An optional sub-study is included to assess the efficacy, safety and tolerability of tofacitinib 5 
mg BID administered as monotherapy after methotrexate (MTX) withdrawal compared to 
tofacitinib 5 mg BID in combination with MTX. Subjects who have completed at least 24 
months of participation in the long term extension study and are currently receiving 
tofacitinib 5 mg BID in combination with oral methotrexate are eligible to participate. 


Protocol A3921092 (Tofacitinib (CP-690,550)) Statistical Analysis Plan
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The analyses for the LTE study are covered in Sections 2 through 8, while analyses for the 
sub-study are covered in Appendix 6.
2.1. Study Design
This is a Phase 3, long-term, open-label extension study designed to evaluate the safety, 
tolerability and efficacy of tofacitinib in subjects with active PsA.  Subjects with active PsA 
will have previously participated in randomized studies of tofacitinib.  For subjects who are 
completing participation in a randomized study of tofacitinib, the final visit of the qualifying 
study can be combined with screening and baseline visit for this study.  Additional 
assessments and inclusion/exclusion criteria are required for subjects who enroll >14 days 
after completing treatment in their qualifying study.  In this case, a separate screening visit 
to determine subject eligibility is required followed by a baseline visit.
All eligible subjects from qualifying studies A3921091 and A3921125 will receive open-label 
tofacitinib 5 mg BID upon entry into A3921092.  Subjects from A3921091 will receive first 
dose of study medication 1 week after last injection of study medication in that qualifying 
study.  Tofacitinib dose may be increased to 10 mg BID at study visits if, based upon 
investigator’s discretion, subjects receiving tofacitinib 5 mg BID would benefit from a higher 
dose and are not experiencing any tofacitinib-related adverse events, including 
abnormalities in laboratory test results that are judged to be related to tofacitinib.  
Tofacitinib dose may be decreased (ie, 10 mg BID to 5 mg BID) for safety reasons at any 
time.  Treatment duration for subjects participating in the main LTE study is approximately 
3 years (36 standardized 4-week months). Subjects participating in the sub-study may have 
up to an additional 1 year (12 standardized 4-week months) of treatment for a maximum 
potential total of approximately 4 years (48 standardized 4-week months).
At various timepoints in this trial, safety measurements, including physical examination, 
clinical laboratory tests, adverse event monitoring, electrocardiograms (ECGs) and vital 
signs will be performed.  All subjects will be monitored for clinical evidence of PsA response 
to treatment.  Health Outcomes Measures (ie, Patient Reported Outcomes assessments for 
pain, quality of life, physical function, fatigue, work limitations, health care resource 
utilization and health status) will also be performed at various timepoints in this trial.  In 
addition, subjects will be monitored for serious infections, lymphadenopathy and 
lymphoproliferative disorder (LPD).
2.2. Study Objectives
Primary Objectives

To evaluate the long term safety and tolerability of treatment with tofacitinib 
(5 mg BID and 10 mg BID) in adult subjects with active Psoriatic Arthritis (PsA).
Secondary Objectives

To evaluate the long term efficacy of treatment with tofacitinib (5 mg BID and 
10 mg BID) in adult subjects with active Psoriatic Arthritis (PsA).


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3. INTERIM ANALYSES, FINAL ANALYSES AND UNBLINDING
Interim analyses to review safety data along with some efficacy data may be performed.  As 
this is an open-label study with no formal hypothesis testing, there are no issues of protecting 
the Type I error rate.
Data-cuts will be performed as needed to support tofacitinib registration.  Additional data 
reviews may be performed as needed by the study team for safety evaluations or for 
administrative purposes.
This study will use an External Data Monitoring Committee (E-DMC). 
The E-DMC will be responsible for ongoing monitoring of the efficacy and safety of subjects 
in the study according to the Charter.  
Information about the E-DMC can be found in the E-DMC Charter, which outlines the 
operating procedures of the committee, including specific description of the scope of their 
responsibilities, including a plan where communication timelines are defined.
Two final analyses will occur when all subjects finish the study or terminate early, one for 
the main LTE study and the other one for the sub-study.
4. HYPOTHESES AND DECISION RULES
4.1. Statistical Hypotheses
There are no formal hypotheses being tested in this study.
4.2. Statistical Decision Rules
There are no statistical decision rules in this study.
5. ANALYSIS SETS
Below is a description of the Analysis Sets defined for this study.
5.1. Full Analysis Set
The full analysis set (FAS) is defined as all subjects enrolled in this study who were part of a 
prior qualifying study, and who received at least one dose of open-label study medication in 
A3921092.
5.2. ‘Per Protocol’ Analysis Set
There is no Per Protocol Analysis Set defined for this study.
5.3. Safety Analysis Set
The FAS and the Safety Analysis Set are the same. 


Protocol A3921092 (Tofacitinib (CP-690,550)) Statistical Analysis Plan
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5.4. Other Analysis Sets
5.4.1. Endpoint Specific Analysis Sets
Subjects will be excluded from FAS for analyzing a specific endpoint if the criterion for 
inclusion is not met for the endpoint as described in
Table 1.
Table 1 Endpoint Specific Analysis Sets
Instrument/Endpoint
Inclusion
Rationale
PASI75 or PASI
Include subjects with baseline 
BSA≥3% and baseline PASI>0
PASI is not assessed if baseline BSA<3% per the study 
protocol; PASI=0 means absence of psoriasis as measured 
by PASI. 
∆PGA-PsO
Include subjects with baseline 
PGA-PsO>0
PGA-PsO=0 means no PsO disease at baseline as measured 
by PGA.
∆BSA
Include subjects with baseline 
BSA>0%
BSA=0% means no PsO disease at baseline as measured by 
BSA.
HAQ-DI responder 
(decrease ∆HAQ-DI≥0.30)
Include subjects with baseline 
HAQ-DI≥0.30
Restrict baseline HAQ-DI to ≥0.30 to allow room for 
response
HAQ-DI responder 
(decrease ∆HAQ-DI≥0.35)
Include subjects with baseline 
HAQ-DI≥0.35
Restrict baseline HAQ-DI to ≥0.35 to allow room for 
response
Dactylitis presence
Include subjects with baseline 
DSS>0
Baseline DSS=0 means absence of dactylitis. Dactylitis is 
not an enrollment criterion so it is expected that only a 
subset of the subjects will have dactylitis at baseline.
∆DSS
Include subjects with baseline 
dactylitis severity score 
(DSS)>0
Baseline DSS=0 means absence of dactylitis. Dactylitis is 
not an enrollment criterion so it is expected that only a 
subset of the subjects will have dactylitis at baseline.
∆Leeds  Enthesitis Index 
(∆LEI)
Include subjects with baseline 
LEI>0
Baseline LEI score=0 means absence of enthesitis as 
measured by LEI. Enthesitis is not an enrollment criterion 
so it is expected that only a subset of the subjects will have 
enthesitis at baseline.
∆SPARCC Enthesitis 
Index
Include subjects with baseline 
SPARCC Enthesitis Index>0
Baseline SPARCC Enthesitis Index score=0 means absence 
of enthesitis as measured by SPARCC. Enthesitis is not an 
enrollment criterion so it is expected that only a subset of 
the subjects will have enthesitis at baseline.
∆BASDAI
Include subjects with presence 
of spondylitis at screening and 
baseline BASDAI score>0 cm
Absence of spondylitis at screening or baseline BASDAI 
score=0 cm means absence of spondylitis. Spondylitis is 
not an enrollment criterion so it is expected that only a 
subset of the subjects will have spondylitis at baseline.
∆BASDAI
Include subjects with presence 
of spondylitis at screening and 
baseline BASDAI score≥4 cm
Baseline BASDAI score≥4 cm is a more severe disease 
population in spondylitis.
∆CPDAI
Include subjects with baseline 
BSA≥3%
Per the study protocol, PASI should only be performed if 
≥3% of subject’s BSA is affected at baseline.
∆ISI
Include subjects with baseline 
ISI score>0
Baseline ISI score=0 means absence of itching as measured 
by ISI. Itching is not an enrollment criterion so it is 
expected that only a subset of the subjects will have itching 
at baseline.
∆NAPSI
Include subjects with baseline 
NAPSI score>0 on target nail
Baseline NAPSI score=0 means absence of nail psoriasis as 
measured by NAPSI on the target nail. Presence of nail 
psoriasis is not an enrollment criterion so it is expected that 
only a subset of the subjects will have nail psoriasis at 
baseline.


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Abbreviations:  ∆=change from baseline; baseline is the value obtained prior to the first dose of the qualifying study 
A3921091 or A3921125; BASDAI = Bath Ankylosing Spondylitis Disease Activity Index; BSA = body surface area; 
CPDAI = Composite Psoriatic Disease Activity Index; DSS = Dactylitis Severity Score; HAQ-DI = Health Assessment 
Questionnaire - Disability Index; ISI = Itch Severity Item; LEI = Leeds Enthesitis Index; NAPSI = Nail Psoriasis Severity 
Index; PASI = Psoriasis Area and Severity Index; PGA-PsO = Physician’s Global Assessment of Psoriasis; SPARCC = 
Spondyloarthritis Research Consortium of Canada.


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5.5. Treatment Misallocations 
If a subject was:

Admitted to the study but not treated, then the subject will not be reported. 
5.6. Protocol Deviations
No subjects will be excluded from analyses due to protocol deviations.
6. ENDPOINTS AND COVARIATES
Visual analog scale (VAS) data will need to be rescaled prior to any calculation and analysis. 
VAS is recorded on CRF in terms of length at mark (X in mm) and overall length of line (Y 
in mm). The rescaled VAS for use in analysis will be: Z=X/Y × 100 mm or X/Y × 10 cm, 
depending on endpoints or their use in defining other endpoints. 
6.1. Primary Endpoints

Incidence and severity of adverse events.

Incidence of clinical abnormalities and change from baseline (in this and/or prior 
study) in clinical laboratory values during treatment.
6.2. Secondary Endpoints
Change from baseline will be denoted by ∆.

ACR20, ACR50 and ACR70 response rate at all time points (see Appendix 2.1).

∆HAQ-DI score at all time points (see Appendix 2.2).

Psoriatic Arthritis Response Criteria (PsARC) response at all time points (see 
Appendix 2.4). 

Physician’s Global Assessment of Psoriasis (∆PGA-PsO) response at all time points
(see Appendix 2.11).

Psoriasis Area and Severity Index 75 (PASI75) response ie, the proportion of subjects 
achieving at least a 75% reduction in PASI relative to baseline and PASI/PASI 
component scores (%∆PASI and its clinical signs component scores) at all time points
(see Appendix 2.10).

Dactylitis Severity Score (∆DSS) at all time points.
This is the sum of the 20 digit disease severity ratings. A missing score or not 
assessed (ie, NOT DONE with a code of 9 in the CRF) for any digit will result in 
DSS as missing. A score of 8 (ie, not applicable) should be excluded from summing.


Protocol A3921092 (Tofacitinib (CP-690,550)) Statistical Analysis Plan
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
Enthesitis score (using ∆ in Spondyloarthritis Research Consortium of Canada 
(SPARCC) Enthesitis Index and Leeds Enthesitis Index (LEI)) at all time points.
Each score is the number of sites in which enthesitis is present (total number of 
possible sites: 16 sites for SPARCC Enthesitis Index and 6 sites for LEI). A missing 
assessment (ie, no box checked) or not assessed (ie, NOT DONE box checked) for 
any digit will result in the enthesitis score as missing.

Bath Ankylosing Spondylitis Disease Activity Index (∆BASDAI) at all time points (see 
Appendix 2.14).

Physical function/other patient reported outcomes to be assessed at 
Month 1, Month 6 (and every 6 months thereafter): ∆Short-Form 36 (version 2,
Acute); ∆EQ-5D-3L; Functional Assessment of Chronic Illness Therapy-Fatigue 
(∆FACIT-F).
The Short-Form 36 yields 10 endpoints (norm-based): 8 general health domains: 
physical functioning, role limitations due to physical health, bodily pain, general 
health perceptions, vitality, social functioning, role limitations due to emotional 
problems, and mental health.  These domains can also be summarized as physical and 
mental component scores (see Appendix 2.17).
The EQ-5D-3L yields 6 endpoints: an assessment of one’s health status that day
(ΔEQ-VAS) and scores from each of five domains (ΔEQ-5D-3L) (see
Appendix 2.15).
The FACIT-F will have 3 endpoints: ∆FACIT-F total score, ∆FACIT-F experience 
domain score and ∆FACIT-F impact domain score (see Appendix 2.16).
6.3. Other Endpoints

∆DAS28-3 (CRP) at all time points (see Appendix 2.3).

HAQ-DI response, defined as an improvement (ie, a decrease) from baseline of 
≥0.30 and ≥0.35 (2 endpoints) in HAQ-DI scores at all timepoints
(see Appendix 2.2).

ACR response criteria components (∆in following: HAQ-DI, CRP, Patient’s 
Assessment of Arthritis Pain, Patient’s Global Assessment of Arthritis, Physician’s 
Global Assessment of Arthritis, swollen joint count, tender/painful joint count) at all 
time points (see Appendix 2.1). Note that ∆HAQ-DI is covered under Section 6.2 as 
a secondary endpoint already.

Psoriatic Arthritis Joint Activity Index (raw PsAJAI) (see Appendix 2.5), Disease 
Activity Index for Reactive Arthritis/PsA (∆DAREA/DAPSA) (see Appendix 2.6), 
Composite Psoriasis Disease Activity Index (∆CPDAI) (see Appendix 2.7), Psoriatic 
Arthritis Disease Activity Score (∆PASDAS) (see Appendix 2.9), Minimal Disease 


Protocol A3921092 (Tofacitinib (CP-690,550)) Statistical Analysis Plan
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Activity (MDA, yes/no) and their components (yes/no response for each component) 
(see Appendix 2.8) at all time points.

BSA (%∆BSA) at all time points (see Appendix 2.10). 

Presence of dactylitis at all time points.

Nail Psoriasis Severity Index (∆NAPSI) Score at Month 1, Month 6 (and every 
6 months thereafter).
This is a score ranging from 0-8 based on 1 targeted nail.

Itch Severity Item (∆ISI) at Month 1, Month 6 (and every 6 months thereafter)
(see Appendix 2.13).

Patient’s Global Joint and Skin Assessment (∆PGJS-VAS, 3 endpoints) at all time
points.

Ankylosing Spondylitis Quality of Life questionnaire (∆ASQOL) at all time points.
The ASQOL has a total score which is calculated by summing the 18 items.

Physical function/other patient reported outcomes to be assessed at Month 1, Month 6 
(and every 6 months thereafter): Dermatology Life Quality Index (∆DLQI); PsA 
Healthcare Resource Utilization Questionnaire (raw PsA HCRU and ∆PsA HCRU-
Self Rating of Job Performance at Work); Work Limitations Questionnaire (∆WLQ).
A total score for DLQI is computed from 10 questions.
The WLQ is a twenty-five item scale that evaluates the degree to which health 
problems interfere with an ability to perform job roles along four dimensions.  The 
Time Management scale (Question 1) contains five items.  The Physical Demands 
scale (Question 2) contains 6 items.  The Mental/Interpersonal Demands Scale 
(Questions 3 and 4) has nine items.  The Output Demands scale (Question 5) contains 
five items. Scores for each item are: 0 (none of the time), 1, 2, 3 or 4 (all of the time).  
“Does not apply to my job” is treated as missing.  Each of the scale scores are 
computed by averaging the items that comprise the scale, and then multiplying by 25.

Incidence of investigator-reported clinically significant changes in physical 
examination from baseline (in this and/or prior study) during treatment.

Incidence of electrocardiogram (ECG) abnormalities and change from baseline (in 
this and/or prior study) in ECG measurements during treatment.

Incidence of vital sign (blood pressure and pulse rate) abnormalities and changes 
from baseline (in this and/or prior study) in vital sign measurements during treatment.


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6.4. Covariates 
Reporting of the study data will be done with descriptive statistics.  There will be no 
statistical models, and hence no covariates.
7. HANDLING OF MISSING VALUES
For the SF-36v2, ASQOL, DLQL, EQ-5D-3L, BASDAI, WLQ, PsA-HCRU, and FACIT-F 
instruments, rules suggested by the developers of these will be followed in calculating scores 
when individual question/items may be missing.  If these rules are not enough for calculating 
a score, then the endpoint will be considered to have a missing value.  Missing values in any 
of the endpoints will not be imputed when summarizing these endpoints using descriptive 
statistics. See Appendix 2 for additional details for the calculation of endpoints, including 
handling of missing item values in the calculation. 
8. STATISTICAL METHODOLOGY AND STATISTICAL ANALYSES
There will be 2 sets of analyses: one for the A3921092 LTE and the other for the sub-study. 
For the A3921092 LTE, the safety analysis will include cumulative data from all the subjects 
and all the data (including the data collected in the sub-study). The efficacy analysis for the 
LTE will only include the data collected in the A3921092 LTE (the efficacy data collected in 
the sub-study will be excluded from the LTE analysis).
Statistical methods for the sub-study are found in Appendix 6.  
8.1. Statistical Methods 
8.1.1. Analyses for Continuous Data
In general, the data for all continuous endpoints will be summarized by time point in tables 
containing descriptive statistics (N, mean, standard deviation, standard error of the mean, 
minimum, 1st, 2nd (median) and 3rd quartiles and maximum) for baseline and change from 
baseline for those endpoints measured at baseline.  
8.1.2. Analyses for Categorical Data 
The data for all categorical endpoints (including binary) will be summarized by contingency 
tables that show the counts/frequency in the various categories at each time point.  For some 
categorical endpoints, such as the presence or severity of adverse events, contingency or 
frequency tables will consider the data over the entire duration of the study and will not be 
constructed at each time point.  
Normal approximation will be used for the construction of confidence interval (CI) for the 
responder rate over time.  Let N be number of subjects assessed at each visit and n be number 
of responders, and pobs = n/N be the observed responder rate, then the two-sided 95% CI will 
be formed by pobs ±1.96 squared root of [pobs(1pobs )/N]. 
8.2. Statistical Analyses
Tofacitinib dose may be increased to 10 mg BID at study visits based upon investigator’s
discretion.  Also, tofacitinib dose may be decreased (ie, 10 mg BID to 5 mg BID) for safety 


Protocol A3921092 (Tofacitinib (CP-690,550)) Statistical Analysis Plan
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reasons at any time.  Hence changes in the dose are treatment related.  Consequently, 
descriptive statistics will be displayed for just one treatment group: the entire cohort of 
subjects in which tofacitinib is dosed flexibly between 5 mg and 10 mg BID. 
The baseline values for the safety endpoints come from the baseline of the qualifying study
for patients who enroll within 14 days of the last visit of the qualifying study.  For the 
patients whose enrollment are out of 14-day window, their baseline values of the safety 
endpoints will be from the baseline visit of this study, A3921092. The baseline values for all 
the efficacy or health-outcome endpoints come from the baseline of the qualifying study.  In 
addition, as a sensitivity analysis for the ACR response rates and ∆HAQ-DI, the baseline 
value will be the baseline visit for A3921092 for patients whose enrollment is out of 14-day 
window.
All analyses will use FAS (Section 5.1) or FAS with some subjects excluded from analyses 
for certain endpoints (Section 5.4.1) except where indicated otherwise.
8.2.1. Analysis of Primary Endpoints
Safety analysis will include cumulative data from both the main LTE study and sub-study.

Adverse events will be summarized according to Pfizer Data Standards (PDS).

Incidence rate (IR) defined as the number of subjects with an event in the numerator 
divided by the study drug exposure in the denominator (expressed as the number of 
subjects with an event per 100 patient-years) will be calculated for deaths, SAEs, AEs 
leading to discontinuation and AEs of special interest. AEs of special interest include 
but may not be limited in the events listed in Table 2 AEs of Special Interest. The 
event will be counted from subject’s first dose to subject’s last dose of study drug + 
28 days. The denominator is the sum of the time to event or to subject’s last dose of 
study drug + 28 days, whichever is earlier.
Table 2 AEs of Special Interest
Serious infections (SIs)
Herpes zoster (HZ)
Adjudicated opportunistic infections (OIs) excluding tuberculosis (TB)a
Hematologic events (anaemia, neutropenia, lymphopenia, and thrombocytopenia)
Adjudicated malignanciesa
Adjudicated major adverse cardiovascular events (MACE)a,b
Adjudicated drug-induced liver injury (DILI)a and other hepatic eventsc
Renal eventsd
Adjudicated gastrointestinal (GI) perforationsa
Adjudicated interstitial lung disease (ILD)e
Abbreviations: DILI = drug-induced liver injury; GI = gastrointestinal; HZ = herpes zoster; ILD = interstitial lung 
disease; MACE = major adverse cardiovascular events; MedDRA = Medical Dictionary for Regulatory Activities; 
OI = opportunistic infection; SI = serious infection; SMQ = Standardised MedDRA Queries; TB = tuberculosis. 
a.
Adjudicated by Adjudication Committees independent and external to Pfizer.
b.
Components: cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke.
c.
Including SMQs: Hepatic failure, fibrosis, and cirrhosis, and other liver damage-related conditions; and 
Hepatitis, non-infectious.
d.
Including Acute renal failure SMQ.
e.
Adjudicated by an internal review committee.


Protocol A3921092 (Tofacitinib (CP-690,550)) Statistical Analysis Plan
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
Safety laboratory tests will be summarized according to the PDS.

The summaries for laboratory tests include contingency tables (eg, normal, high, 
low), and descriptive statistics for change from baseline by treatment group and visit. 
For the FACS, the endpoints to be summarized, which are subsets of lymphocytes 
and are measured at baseline, and every 3 months beginning at Month 3 visit, are as 
follows: CD3+ (%, abs), CD3+CD4+ (%, abs), CD3+CD8+ (%, abs), CD19+ (%, abs), 
CD16+/CD56+ (%, abs).  Raw values as well as percent change from baseline will be 
summarized with descriptive statistics by visit.
8.2.2. Analysis of Secondary and Other Efficacy/Health Outcome Endpoints
Efficacy analysis will only include the data collected in the main LTE study.
Contingency/frequency tables as described in Section 8.1.2 will summarize:

ACR20, ACR50 and ACR70 response rate at all time points.
In addition, the ACR response rates will be displayed at all time points by the 
qualifying study.  As a sensitivity analysis to using the baseline values from the 
qualifying study for all subjects, one will also provide tables of ACR response rates in 
which baseline is the baseline visit for A3921092 for patients whose enrollment are 
out of 14-day window.

Psoriatic Arthritis Response Criteria (PsARC) response at all timepoints.

Psoriasis Area and Severity Index 75 (PASI75) response, ie, the proportion of 
subjects achieving at least a 75% reduction in PASI relative to baseline for subjects 
with baseline BSA≥3% and baseline PASI>0 (see Section 5.4.1).

Presence of dactylitis at all timepoints for subjects with baseline DSS>0.

HAQ-DI response rates (2 endpoints: (decrease of ≥0.30 and decrease of ≥0.35) at all 
timepoints for subjects with baseline HAQ-DI≥0.30 and HAQ-DI≥0.35, respectively)
(see Section 5.4.1).

Minimal Disease Activity (MDA) at all timepoints.
Descriptive statistics as described in Section 8.1.1 will be tabulated for:

ACR response criteria components (∆ in HAQ-DI, CRP, Patient’s Assessment of 
Arthritis Pain, Patient’s Global Assessment of Arthritis, Physician’s Global 
Assessment of Arthritis, swollen joint count, tender/painful joint count) at all 
timepoints.
In addition, the descriptive statistics for ∆HAQ-DI scores will be displayed at all 
timepoints by the qualifying study.  As a sensitivity analysis to using the baseline 
values from the qualifying study for all subjects, one will also provide tables of 


Protocol A3921092 (Tofacitinib (CP-690,550)) Statistical Analysis Plan
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descriptive statistics in which baseline is the baseline visit for A3921092 for patients
whose enrollment are out of 14-day window.

Physician’s Global Assessment of Psoriasis (∆PGA-PsO) response at all timepoints
for subjects with baseline PGA-PsO>0 (see Section 5.4.1).

PASI and PASI component scores (%∆PASI and its clinical signs component scores) 
at all timepoints for subjects with BSA≥3% and baseline PASI>0 (see Section 5.4.1).

BSA (%∆BSA) at all timepoints for subjects with baseline BSA>0 (see Section 
5.4.1). 

Dactylitis severity score (∆DSS) at all timepoints for subjects with baseline 
DSS>0 (see Section 5.4.1).

Enthesitis score (using ∆ in Spondyloarthritis Research Consortium of Canada 
(SPARCC) Enthesitis Index and Leeds Enthesitis Index) at all timepoints for subjects 
with baseline SPARCC Enthesitis Index>0 and LEI>0, respectively (see Section 
5.4.1).

Bath Ankylosing Spondylitis Disease Activity Index (∆BASDAI) at all timepoints.
Two analysis populations will be used: one for subjects with presence of spondylitis 
at screening and baseline BASDAI score>0 cm, and the other for subjects with 
presence of spondylitis at screening and baseline BASDAI score≥4 cm (see Section 
5.4.1).

∆FACIT-F (3 endpoints: total score, experience score and impact score) at 
Month 1, Month 6 (and every 6 months thereafter).

∆ in components and domains of the Short-Form-36 Health Survey (SF-36) Version 
2, Acute at Month 1, Month 6 (and every 6 months thereafter); for each component 
and domain, only the scaled score should be analyzed (see Appendix 2.17 for 
derivations).

Health status and domains from the EuroQol 5-Dimension Health State Profile 
(∆EQ-5D-3L and ΔEQ-VAS) at Month 1, Month 6 (and every 6 months thereafter).

∆ in DAS28-3 (CRP) at all timepoints.

Psoriatic Arthritis Joint Activity Index (raw PsAJAI), Disease Activity Index for 
Reactive Arthritis/PsA (∆DAREA/DAPSA), Composite Psoriasis Disease Activity 
Index (∆CPDAI), Psoriatic Arthritis Disease Activity Score (∆PASDAS). ∆CPDAI 
will be summarized for subjects with baseline BSA≥3% (see Section 5.4.1).

Nail Psoriasis Severity Index (∆NAPSI) Score at Month 1, Month 6 (and every 
6 months thereafter) for subjects with baseline NAPSI>0 (see Section 5.4.1).


Protocol A3921092 (Tofacitinib (CP-690,550)) Statistical Analysis Plan
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
Itch Severity Item (∆ISI) at Month 1, Month 6 (and every 6 months thereafter) for 
subjects with baseline ISI>0 (see Section 5.4.1).

Patient’s Global Joint and Skin Assessment (∆PGJS-VAS) at all timepoints.

Total score on the Ankylosing Spondylitis Quality of Life questionnaire (∆ASQOL) 
at all timepoints.

Total score for the ∆DLQI and the four scale scores for ∆WLQ at Month 1, Month 6 
(and every 6 months thereafter).

PsA-HCRU (each of the scales) and ∆PsA-HCRU self-rating of job performance at 
work.
8.2.3. Analysis of Other Safety Data
Safety analysis will include cumulative data from both the main LTE study and sub-study.

Vital signs and 12-lead ECG parameters will be summarized according to the PDS. 
This will include summaries with contingency tables (eg, normal, high, low), and 
descriptive statistics for change from baseline by visit.

Demographic parameters will be summarized (as number and percent or mean, 
standard deviation, and range) by gender following the PDS. 

Clinical findings on any physical examination during the study, including 
investigator-reported clinically significant changes in physical examination from 
baseline (in this and/or prior study) during treatment, will be tabulated by following 
the PDS. 

Previous and concomitant mediation usage by medication type will be tabulated using 
the WHO-Drug dictionary following the PDS. 
To help better understand and interpret the observed safety results, registry databases will be 
utilized to construct an appropriate contemporaneous and/or historical control group.
However, such an analysis is outside the scope of this SAP and will include data not only 
from this study but the data from the qualifying studies as well.
8.3. Baseline and Other Summaries and Analyses
8.3.1. Baseline Summaries
Baseline/screening will be the baseline/screening of the qualifying study. Baseline 
characteristics will include but may not be limited to the ones listed below and will be 
summarized descriptively. For continuous variables, the summary will include N, mean, SD 
and range; for binary and categorical variables, the summary will include frequencies and 
percentages. A missing category will be included for those subjects with missing value. 


Protocol A3921092 (Tofacitinib (CP-690,550)) Statistical Analysis Plan
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
Demographic characteristics:

Baseline age (2 categorizations: <18, 18-44, 45-64, ≥65 years; <18, 18-44, 45-64, 
65-74, 75-84, ≥85 years; and continuous);

Sex (female, male);

Race (white, black, Asian, other);

Ethnicity (Hispanic/Latino, non-Hispanic/Latino);

Baseline body weight (<60, ≥60 to ≤100, >100 kg; and continuous),

Baseline height (cm, continuous);

Baseline Body Mass Index (BMI: <18.5, 18.5 to <25, 25 to <30, 30 to <40, and 40 
kg/m2; and continuous);

Geographic region (United States and Canada, Australia and Western Europe, Russia 
and Eastern Europe, Rest of World);

Screening smoking status (never smoked, ex-smoker, smoker);

Alcohol use [yes, no; continuous (units/week) for subjects who consumed any alcohol
(responded Yes)].

Baseline disease characteristics

PsA duration (<2, ≥2 years; and continuous);

Baseline PsA Subtype: (<5 joints, ≥5 joints) formed based on baseline swollen joint 
count (66) or baseline tender/painful joint count (68), ie, count any joint that is either 
swollen or tender/painful;

Baseline PASDAS: (≤3.2, >3.2 to <5.4, ≥5.4; and continuous);

Baseline CPDAI (≤4, >4 to <8, ≥8; and continuous) for subjects with baseline 
BSA≥3%;

Baseline swollen joint count (66) (continuous);

Baseline tender/painful joint count (68) (continuous);

Baseline HAQ-DI (continuous);

Screening presence of distal interphalangeal joints involvement (yes, no);

Screening presence of arthritis mutilans (yes, no);


Protocol A3921092 (Tofacitinib (CP-690,550)) Statistical Analysis Plan
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
Baseline presence of enthesitis measured by SPARCC enthesitis index or LEI (yes, 
no). Yes is defined for those subjects with baseline SPARCC enthesitis index >0 or 
LEI >0;

Baseline presence of enthesitis measured by SPARCC enthesitis index (yes, no). Yes 
is defined for those subjects with baseline SPARCC enthesitis index >0;

Baseline presence of enthesitis measured by LEI (yes, no). Yes is defined for those 
subjects with baseline LEI >0;

Baseline enthesitis index measured by SPARCC enthesitis index (continuous) for 
those subjects with SPARCC enthesitis index >0 at baseline;

Baseline enthesitis index measured by LEI (continuous) for those with LEI >0 at 
baseline;

Baseline presence of dactylitis (yes, no). Yes is defined for those subjects with 
baseline DSS >0;

Baseline DSS (continuous) for those subjects with DSS >0 at baseline;

Baseline presence of spondylitis (yes, no). Yes is defined for those subjects with 
presence of spondylitis at screening and baseline BASDAI >0;

Baseline BASDAI (0, >0 to <4, ≥4) for those subjects with presence of spondylitis at 
screening. BASDAI score ≥4 indicates active disease/suboptimal treatment;

Baseline BASDAI (continuous) for those subjects with presence of spondylitis at 
screening and BASDAI >0 at baseline;

Baseline total psoriatic BSA (0, >0 to <3, ≥3%);

Baseline total psoriatic BSA (continuous) for those with BSA >0% at baseline;

Baseline PASI (0, >0 to ≤20, >20);

Baseline PASI (continuous) for those subjects with BSA≥3% and PASI>0 at baseline;

Baseline PGA-PsO (0, 1, 2, 3, 4);

Baseline PGA-PsO (continuous) for those subjects with PGA-PsO>0 at baseline;

Number (%) of subjects with baseline PGA-PsO≥3, PASI≥12 and BSA≥10%;

Baseline SF-36v2 (8 domains, physical component score [PCS] and mental 
component score [MCS]);


Protocol A3921092 (Tofacitinib (CP-690,550)) Statistical Analysis Plan
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
Baseline FACIT-F (FACIT-F total score, FACIT-F experience score and FACIT-F 
impact score);

Baseline DLQI (<5, ≥5; and continuous);

Baseline CRP (≤2.87, >2.87 mg/L; and continuous);

Baseline diabetes mellitus (yes, no) (see Appendix 4 for definition);

Baseline metabolic syndrome (yes, no) (see Appendix 3 for definition);

Baseline cardiovascular risks per PDS and detailed in the statistical programming 
plan;

Baseline rheumatoid factor positive (yes, no);

Baseline cyclic citrullinated peptide antibody positive (yes, no).
8.3.2. Prior Drug Treatments for Psoriatic Arthritis
Prior drug treatment will include any treatment for PsA prior to the first dose of study 
medication in Study A3921092. It will include the drug treatment prior to the qualifying 
study, the treatment used during the qualifying study (which includes adalimumab but not 
tofacitinib) and any treatment used during the enrollment gap between the qualifying study 
and the Study A3921092. 

Prior DMARDs (disease-modifying antirheumatic drugs) drug treatment (yes, no), 
yes is defined for a subject who used any DMARDs;

Prior bDMARDs (biologic DMARD) drug treatment (yes, no), yes is defined for a 
subject who used any bDMARDs; 

Prior TNFi(Tumor necrosis factors inhibitor) bDMARDs drug treatment (yes, no), 
yes is defined for a subject who used any TNFi bDMARDs;

Prior non-TNFi bDMARDs drug treatment (yes, no), yes is defined for a subject who 
used any non-TNFi bDMARDs; 

Prior csDMARDs drug treatment (yes, no), yes is defined for a subject who used any 
csDMARDs; 

Prior non-DMARDs drug treatment (yes, no), yes is defined for a subject who used 
any non-DMARDs; 

Prior oral corticosteroids use (yes, no);

Prior NSAIDs use (yes, no).


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8.3.3. Concomitant Drug Treatments for Psoriatic Arthritis
Concomitant drug treatment will include any treatment for PsA during Study A3921092. 

DMARDs drug treatment (yes, no);

Non-DMARDs drug treatment (yes, no);

Oral corticosteroids use (yes, no);

NSAIDs use (yes, no);

Joint injection drug use (yes, no).


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9. REFERENCES

Agresti A. Categorical Data Analysis (2nd Edn). Wiley: Hoboken, NJ, 2002.

Alberti KG, Eckel RH, Grundy SM, et al. Harmonizing the metabolic syndrome: a joint 
interim statement of the International Diabetes Federation Task Force on Epidemiology 
and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; 
World Heart Federation; International Atherosclerosis Society; and International 
Association for the Study of Obesity. Circulation, 2009, 120: 1640-1645.

Bruce, B., Fries, J.F. The health assessment questionnaire (HAQ). Clinical and 
Experimental Rheumatology; 2005, 23 (Supp. 39), S14-S18.

Gladman DD, Tom BDMM, Mease PJ and Farewell VT. Informing Response Criteria 
for Psoriatic Arthritis (PsA). II: Further Considerations and a Proposal - The PsA Joint 
Activity Index. J Rheumatol 2010, 37: 2559–2565.

Gottlieb A, Korman NJ, Gordon KB, et al. Guidelines of care for the management of 
psoriasis and psoriatic arthritis: Section 2. Psoriatic arthritis: overview and guidelines of 
care for treatment with an emphasis on the biologics. J Am Acad Dermatol 2008, 58: 
851-64.

Helliwell PS, Fitzgerald O, Fransen J, et al. The development of candidate composite 
disease activity and responder indices for psoriatic arthritis (GRACE project). Ann 
Rheum Dis, 2013, 72: 986–991.

Madsen OR. Is DAS28-CRP with three and four variables interchangeable in individual 
patients selected for biological treatment in daily clinical practice? Clin Rheumatol, 
2011, 30: 1577–1582.

Mumtaz A, Gallagher P, Kirby B, et al. Development of a preliminary composite
disease activity index in psoriatic arthritis. Ann Rheum Dis, 2011, 70: 272-277.

Ramiro S, van Tubergen A, van der Heijde D, van den Bosch F, Dougados M, Landewé 
R. How to deal with missing items in BASDAI and BASFI. Rheumatology, 2014, 53: 
374-376.

Schoels M, Aletaha D, Funovits J, Kavanaugh A, Baker D, Smolen JS. Application of 
the DAREA/DAPSA score for assessment of disease activity in psoriatic arthritis. Ann 
Rheum Dis, 2010, 69: 1441-1447.


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10. APPENDICES 
Appendix 1. Definition and Use of Visit Windows in Reporting
For reporting purposes, the following visit windows will be used for efficacy/PRO variables 
and for any safety displays that display by week/month.  If two or more visits/observations
fall into the same window, the visit/observation closest to the target day should be used in the 
analyses.  If there is a tie, the later visit should be used.  However, if two or more
visits/observations fall in the same window, and the latest visit is the last visit of the study 
due to early termination, then this will be the visit used in the analysis for that visit window.
Per the master visit schedule provided to the investigator sites, a month is defined as 4 weeks 
or 28 days. 
Study day will be calculated as: date of assessment/collection – date of the first dose + 1.
Visit Label
Target 
Day
Definition [Day 
Window] - Lower
Definition [Day Window] - Upper
Screening
Prior to baseline visit
Baseline
The baseline values for the safety endpoints come from the baseline of the 
qualifying study for patients who enroll within 14 days of the last visit of the 
qualifying study.  For the patients whose enrollment are out of 14-day 
window, their baseline values of the safety endpoints will be from the baseline 
visit of this study, A3921092.  
The baseline values for all the efficacy or health-outcome endpoints come 
from the baseline of the qualifying study.
In addition, in the sensitivity analysis for the ACR response rates and 
∆HAQ-DI, the baseline value will be the baseline visit for A3921092 for 
subjects whose enrollment is out of 14-day window.
Day 1 = date of first dose of study treatment taken of study A3921092.
Month 1
29
1*
57
Month 3
85
58
127
Month 6
169
128
211
Month 9
253
212
295
Month 12
337
296
379
Month 15
421
380
463
Month 18
505
464
547
Month 21
589
548
631
Month 24
673
632
715
Month 27
757
716
799
Month 30
841
800
883
Month 33
925
884
967
Month 36
1009
968
1051 (for safety)
≥969 (for efficacy and PRO)
Month 39**
1093
1052
1135
Month 42**
1177
1136
1219
Month 45**
1261
1220
1303
Month 48**
1345
≥1304
*The lower limit of the Month 1 visit window will be Day 2 for safety analysis for subjects who enroll out of 
14-day window of the last visit of the qualifying study.


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**For safety endpoints summarized by visit such as laboratory value and vital signs data at a windowed visit 
only.
Note some of the endpoints may not be measured at every visit. For example, SF-36v2, 
FACIT-F, EQ-5D-3L, PsA-HCRU, WLQ, DLQI, NAPSI and ISI will not be assessed at 
Months 3 per the study protocol and the visit window at Month 3 will be undefined. In the 
event that an observation falls into one of the undefined visit windows, that observation will 
not be used in analysis.
The following categories will be used in the treatment exposure and duration of treatment 
summaries. The duration will be calculated as: date of the last dose – date of the first dose + 
1. Any missed doses/drug holidays will be ignored in the calculation.
Category (days)
1
2-14 (2 weeks)
15-28 (2 weeks-1 month)
29-84 (1-3 months)
85-168 (3-6 months)
169-252 (6-9 months)
253-336 (9-12 months)
337-504 (12-18 months)
505-672 (18-24 months)
673-840 (24-30 months)
841-1008 (30-36 months)
1009-1176 (36-42 months)
≥1177 (42-48 months)


Protocol A3921092 (Tofacitinib (CP-690,550)) Statistical Analysis Plan
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Appendix 2. Further Definition of Endpoints
Appendix 2.1. ACR Assessments
The American College of Rheumatology’s definition for calculating improvement in 
RA (ACR20) is calculated as a ≥20% improvement in tender and swollen joint counts and 
≥20% improvement in 3 of the 5 remaining ACR-core set measures: patient and physician 
global assessments, pain, disability, and an acute-phase reactant.  Similarly, ACR50 and 
70 are calculated with the respective percent improvement.  This efficacy measurement will 
be made at every study visit.  The specific components of the ACR Assessments that will be 
used in this study are:
Tender/Painful Joint count (68);
Swollen Joint Count (66);
Patient’s Assessment of Arthritis Pain (VAS);
Patient’s Global Assessment of Arthritis (VAS);
Physician’s Global Assessment of Arthritis (VAS);
C-Reactive Protein (CRP in mg/L);
Health Assessment Questionnaire – Disability Index (HAQ-DI).
If the value in any of the components at a timepoint is missing, the component variables that 
are not missing will be used to determine the response status.  As a general principle, if there 
are sufficient non-missing components to determine whether the ACR endpoint is a response 
or non-response, then ACR endpoint is not missing, else if the available non-missing 
components are not sufficient to determine the response status of ACR endpoint then it is 
considered missing.
In order to avoid numerical difficulty, if the baseline value of any component is equal to 0, 
the following algorithm will be used in evaluating the percent change from baseline:
1. If change from baseline is also equal to 0, then percent change from baseline is set to 
be 0%;
2. If change from baseline is > 0, then percent change from baseline is set to be 
999999%.
These percentages will be used to derive the ACR endpoints. Change from baseline cannot 
be < 0 since none of the components should have negative value.
Lower limit of quantification (LLOQ) for CRP is 0.020 mg/dL (or 0.200 mg/L). Any CRP 
value below the LLOQ will be reported as “<0.020” in database and will be set to 
0.019 mg/dL (0.190 mg/L) and used in analyses throughout. The unit for CRP will be mg/dL 
or mg/L depending on endpoint of interest. The upper limit of the normal range is 2.87 mg/L.
The VAS data will need to be rescaled prior to any calculation (Section 6).


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Appendix 2.2. Health Assessment Questionnaire – Disability Index (HAQ-DI)
The HAQ-DI assesses the degree of difficulty a subject has experienced during the past week 
in 8 domains of daily living activities: dressing and grooming, arising, eating, walking, 
hygiene, reach, grip, and other activities.  Each activity category or domain consists of 
2-3 items.  For each question in the questionnaire, the level of difficulty is scored from 0 to 
3 with 0 representing “no difficulty,” 1 as “some difficulty,” 2 as “much difficulty,” and 3 as 
“unable to do”.  The domain score for each domain is the maximum (ie, worst) of the scores 
from the items/questions within the domain. If this domain score is 2, no further adjustment 
is needed. If it is < 2 (ie, 0 or 1) but no aids, devices or help from another person is 
indicated, then also no adjustment is needed. However, if it is < 2 and any aid, device or help 
from another person is indicated, then it is further adjusted upward to 2 as described below.
Any activity that requires assistance from another individual or requires the use of an aid or 
an assistive device adjusts to a minimum score of 2 to represent a more limited functional 
status.
Domain
If domain score is either 0 or 1, adjust to 2 
when the following is satisfied.
Dressing and grooming
“Devices used for dressing (button hook, 
zipper pull, long-handled shoe horn, etc)” or 
help from others on “Dressing and 
Grooming” is checked
Arising
“Special or built up chair” or help from 
others on “Arising” is checked.
Eating
“Built up or special utensils” or help from 
others on “Eating” is checked.
Walking
“Cane”, “Walker”, “Crutches”, 
“Wheelchair”, or help form others on 
“Walking” is checked
Hygiene
“Raised toilet seat”, “Bathtub bar”, 
“Long-handled appliances in bathroom”, 
“Bathtub seat” or help from others on 
“Hygiene” is checked.
Reach
“Long-handled appliances for each” or help 
from others on “Reach” is checked
Grip
“Jar opener (for jars previously opened)” or 
help from others on “Gripping or opening 
things” is checked.
Activities
Help from others on “Errands and chores” is 
checked.
Note: For “Other, (specify)”, whether checked or unchecked or 
specifying the other “aids or devices” in this category, is not to be used 
in the adjustment of the domain score.


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For each domain, the domain score will be determined by non-missing scores from the 
questions. A domain score will only be missing if all scores within the domain are missing. 
The HAQ-DI score is the average of all the 8 domain scores. If > 2 domain scores are not 
complete or missing, HAQ-DI score is considered missing, else the HAQ-DI score is 
computed as the average of the non-missing domain scores (Bruce and Fries 2005).3
Change from baseline in HAQ-DI (∆HAQ-DI) will be calculated.
HAQ-DI response will be defined as an improvement (ie, a decrease) from baseline of 
≥0.30 and ≥0.35 (2 endpoints) in HAQ-DI scores.
Appendix 2.3. DAS 28-3 (CRP)
The Disease Activity Score (DAS) is a derived measurement with differential weighting given 
to each component.  DAS 28-3 (CRP) will be calculated from measurements made at all 
visits (Madsen, 2011).7
The components of the DAS 28-3 arthritis assessment are:
Tender/Painful Joint Count (28);
Swollen Joint Count (28);
C-Reactive Protein (CRP in mg/L).
The 28 joint counts include the following joints: shoulders, elbows, wrists, 
metacarpophalangeal joints (MCP), proximal interphalangeal joints (PIP), and knees.
DAS28-3(CRP) = [0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(CRP+1)] * 1.10 + 1.15
where sqrt() refers to the square root, and ln() refers to the natural logarithm. 
Any missing component will result in DAS28-3 (CRP) as missing. A higher score of 
DAS28-3 (CRP) represents a more severe disease activity.
Appendix 2.4. PsA Response Criteria (PsARC)
The PsARC will be collected/derived at all visits in addition to the ACR response criteria.  
The PsARC consists of 4 measurements:
Tender joint count (68); 
Swollen joint count (66); 
Physician’s Global Assessment of Arthritis (VAS); 
Patient’s Global Assessment of Arthritis (VAS). 
The same tender/painful joint count and swollen joint count used for ACR response criteria 
will be applied to the PsA Response Criteria.  In order to be a ‘PsARC responder’, subjects 
must achieve improvement in 2 of 4 measures, one of which must be joint pain or swelling, 
without worsening in any measure.


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Specifically, the PsARC response is defined as improvement in two of the following 
4 criteria, one of which must be joint pain or swelling, without worsening in any measure: 
(1) ≥20% improvement in Physician’s Global Assessment of Arthritis (VAS); 
(2) ≥20% improvement in Patient’s Global Assessment of Arthritis (VAS); 
(3) ≥30% improvement in tender joint count (68); and (4) ≥30% improvement in swollen 
joint count (66) (Gottlieb et al 2008).5
Methods in calculating percent change from baseline when baseline value of any component 
is equal to 0 can be found in Appendix 2.1. 
If values in any of the components at a timepoint are missing, the components that are not 
missing are used to determine the response status. If one could not determine the response 
status in the presence of missing components at the timepoint, then PsARC response will be 
considered as missing. The VAS data will need to be rescaled prior to any calculation 
(Section 6).
Appendix 2.5. PsA Joint Activity Index (PsAJAI)
The PsA Joint Activity Index (PsAJAI) is a weighted sum of ≥30% improvement in the 7 core 
measures of the ACR with weights of 2 given to the joint count measures (JNT, defined below 
defined below), CRP and the physician’s global assessment of disease activity (MDGDA).  
Weights of 1 are given to the remaining ≥30% improvement measures including patient’s 
assessment of arthritis pain (PAIN), patient’s global assessment of Arthritis (PtGDA) and 
HAQ-DI (Gladman et al 2010).4  The values are summed to get a score out of 9 (range 0-9).  
The score is calculated as follows:
PsAJAI= 2 x 30%JNT + 2 x 30%CRP + 2 x 30%MDGDA + 30%PtGDA
+ 30%PAIN + 30%HAQ-DI. 
The formula contains indicator functions. For example, if a subject has a ≥30% improvement 
in CRP, the term “30%↓CRP” will be set to 1 in the above formula; otherwise it is set to 0.
For JNT, “30%JNT” will be set to 1 only if BOTH ≥30% improvement/reduction in 
tender/painful joints (68) AND ≥30% improvement/reduction in swollen joints (66), 
otherwise “30%JNT” will be set to 0.
Methods in calculating percent change from baseline when baseline value of any component 
is equal to 0 can be found in Appendix 2.1.
PsAJAI is set to missing if any of the 7 components (JNT is comprised of tender and swollen 
joint counts) is missing.
The VAS data will need to be rescaled prior to any calculation (Section 6).


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Appendix 2.6. Disease Activity Index for Reactive Arthritis/Psoriatic Arthritis 
(DAREA/DAPSA)
DAREA/DAPSA (Schoels et al 2010)10 is a composite instrument to assess peripheral joint 
involvement that is based upon numerical summation of 5 variables of disease activity:
tender/painful joint count + swollen joint count (using SJC66/ TJC68 assessments), patient’s 
global assessment of Arthritis (PtGA in cm), patient’s assessment of Arthritis Pain (PAIN in 
cm) and CRP (in mg/dL). Since DAREA/DAPSA reflects domains found important in PsA, it 
has been proposed to serve as a Disease Activity Index for Psoriatic Arthritis (DAPSA).  
DAREA/DAPSA is calculated as follows:
DAREA/DAPSA= SJC66 + TJC68 + PtGA + PAIN + CRP.
Any missing component will result in DAREA/DAPSA as missing.
The VAS data will need to be rescaled prior to any calculation (Section 6).
Appendix 2.7. Composite Psoriatic Disease Activity Index in Psoriatic Arthritis 
(CPDAI)
CPDAI (Mumtaz et al 2011)8 is a composite psoriatic disease activity index incorporating 
5 domains including joint disease, skin involvement, enthesitis, dactylitis and spinal disease.  
For dactylitis, a simple dactylitic digit count was applied.  For enthesitis, the Leeds enthesitis 
index (LEI) was used.  For spinal involvement, the Bath Ankylosing Spondylitis Disease 
Activity Index (BASDAI) and the Ankylosing Spondylitis Quality of Life (ASQOL) were used.  
In addition, the Dermatology Quality of Life Index (DLQI) was used as a measure of the 
impact of skin disease.  Using these instruments, and ranges of values based upon literature 
review, disease activity under each domain was graded as none, mild, moderate and severe 
giving a range of attainable CPDAI scores of between 0 and 15. A higher CPDAI score 
indicates a higher disease activity.


Protocol A3921092 (Tofacitinib (CP-690,550)) Statistical Analysis Plan
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Composite Psoriatic Disease Activity Index (CPDAI) score total 0-15
Not 
involved
(0)
Mild
(1)
Moderate
(2)
Severe
(3)
Peripheral 
arthritis
4 Joints (count a joint 
that is swollen and/or
tender); normal 
function (HAQ-DI
≤0.5)*
4 Joints but function 
impaired; or >4 joints, 
normal function
> 4 Joints and function 
impaired
Skin disease
PASI 10 and DLQI 
10
PASI 10 but DLQI 
>10; or PASI >10 but 
DLQI 10
PASI >10 and DLQI > 
10
Enthesitis
3 Sites; normal 
function (HAQ-DI
≤0.5)*
3 Sites but function 
impaired; or >3 sites 
but normal function
>3 Sites and function 
impaired
Dactylitis
3 Digits; normal 
function (HAQ-DI
≤0.5)*
3 Digits but function 
impaired; or >3 digits 
but normal function
>3 Digits and has 
function impaired
Spinal disease
BASDAI 4; normal 
function (ASQoL ≤6)
BASDAI >4 but normal 
function; BASDAI 4 
but function impaired
BASDAI >4 and function 
impaired
*Health assessment questionnaire-disability index (HAQ-DI) only counted if clinical involvement of domain 
(joint/ethesis/dactylitis) present. DLQI or ASQoL only counted if clinical involvement of domain (ie, PASI>0 
or BASDAI>0) present.
Explicitly, each disease dimension will be scored as follows (0=not involved, 1=mild, 
2=moderate, 3=severe). For evaluating peripheral arthritis score (D1 below), if a joint is 
swollen and/or tender, it is only counted once.
D1. Peripheral arthritis scoring
HAQ-DI
Joints (swollen or 
tender)
≤0.5
>0.5
0
0
0
1 to 4
1
2
>4
2
3
D2. Skin disease scoring
DLQI
PASI
≤10
>10
0
0
0
0< to ≤10
1
2
>10
2
3


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D3. Leeds enthesitis scoring
HAQ-DI
Sites
≤0.5
>0.5
0
0
0
1 to 3
1
2
>3
2
3
D4. Dactylitis scoring
HAQ-DI
Digits
≤0.5
>0.5
0
0
0
1 to 3
1
2
>3
2
3
D5. Spinal disease scoring
ASQol
BASDAI
≤6
>6
0
0
0
0< to ≤4
1
2
>4
2
3
CPDAI = D1 + D2 +D3 + D4 + D5.
CPDAI will be set as missing if any of the component score is missing. Per the study 
protocol, PASI should only be performed if ≥3% of subject’s BSA is affected at baseline, 
thus CPDAI will be set as missing and excluded from any analysis for any subject (the entire 
subject) whose baseline BSA is <3%.
Appendix 2.8. Minimal Disease Activity (MDA) Response
A psoriatic arthritis patient is defined as having Minimal Disease Activity (MDA, yes/no) 
when the patient meets 5 of the 7 following criteria: 1) tender/painful joint count 1; 2) 
swollen joint count 1; 3) PASI score 1 or BSA 3%; 4) patient assessment of Arthritis 
Pain (VAS) 15 mm; 5) patient’s global arthritis assessment (VAS) 20 mm; 6) HAQ-DI 
score 0.5; 7) tender entheseal points (using Leeds Enthesitis Index) 1.
If < 5 non-missing component criteria are satisfied and at least one of the remaining 
component criteria is missing, then MDA response is set to be as missing.
The VAS data will need to be rescaled prior to any calculation (Section 6).


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Appendix 2.9. Psoriatic Arthritis Disease Activity Score (PASDAS)
PASDAS (Helliwell et al 2013)6 is a composite PsA disease activity score that includes the 
following components: patient global joint and skin assessment (VAS in mm), physician 
global psoriatic arthritis assessment (VAS in mm), swollen (66 joints) and tender joint counts 
(68 joints), Leeds Enthesitis Index score, tender dactylitic digit score, physical component 
summary score (PCS) of SF-36v2 and CRP (mg/L).
PASDAS=(((0.18 x √Physician global VAS) + (0.159 x √Patient global VAS)
- (0.253x √SF36-PCS) + (0.101 x LN(Swollen joint count + 1))
+ (0.048 x LN(Tender joint count + 1)) 
+ (0.23 x LN(Leeds enthesitis  index score + 1))
+ (0.37 x LN(Tender dactylitis count + 1))
+ (0.102 x LN(CRP + 1)) + 2) x 1.5
where LN() is the natural logarithm. For patient’s global joint and skin assessment (VAS), it 
is obtained only from the first question in the CRF for assessing subject’s global joint and 
skin, “In all the ways in which your PSORIASIS and ARTHRITIS, as a whole, affects you, 
how would you rate the way you felt over the past week?” The physician’s global psoriatic 
arthritis assessment (VAS) is obtained from the CRF at the prompt: “THE SUBJECT’S 
OVERALL PSORIATIC ARTHRITIS AT THIS TIME IS...”. The tender dactylitis digit 
score is the number of digits out of 20 (fingers and toes) where rating of either 2 (digit is 
tender and swollen (active)) or 3 (digit is very swollen and tender or very tender and swollen 
(highly active)) is registered. Any missing component will result in PASDAS as missing. 
The VAS data will need to be rescaled prior to any calculation (Section 6). A higher 
PASDAS score indicates a higher disease activity.
Appendix 2.10. Psoriasis Area and Severity Index (PASI) 
The Psoriasis Area and Severity Index quantifies the severity of a subject’s psoriasis based on
both lesion severity and the percentage of body surface area (BSA) affected.

Lesion severity: The basic characteristics of psoriatic lesions – erythema, induration 
and scaling – provide a means for assessing the severity of lesions.  Assessment of 
these three main signs is performed separately for four areas of the body: head, upper
limbs, trunk, and lower limbs.  Average erythema, induration and scaling are rated for 
each body area according to a 5-point scale: 0, no involvement; 1, slight; 
2, moderate; 3, marked; 4, very marked.

Body surface area involvement (%BSA): The extent (%) to which each of the four
areas of the body is affected by psoriasis is assigned a numerical score according to 
the following area scoring criteria: 0, no involvement; 1, >0 to 9%; 2, 10 to 29%;
3, 30 to 49%; 4, 50 to 69%; 5, 70 to 89%; 6, 90 to 100%.
In each area, the sum of the severity rating scores for erythema, induration and scaling is
multiplied by the score representing the percentage of this area involved by psoriasis,


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multiplied by a weighting factor (head 0.1; upper limbs 0.2; trunk 0.3; lower limbs 0.4).  The 
sum of the numbers obtained for each of the four body areas is the PASI.
PASI = 0.1Ah (Eh + Ih + Sh) + 0.2Au (Eu + Iu + Su) + 0.3At (Et + It + St) + 0.4Al (El + Il + Sl)
Where A = area of involvement score; E = erythema; I =induration; S = scaling; h = head;
u = upper limbs; t = trunk; l = lower limbs.
The PASI score can vary in increments of 0.1 units from 0.0 to 72.0, with higher scores
representing increasing severity of psoriasis.
Each PASI clinical signs component score can be computed as:
PASI_E = 0.1Ah (Eh) + 0.2Au (Eu) + 0.3At (Et) + 0.4Al (El)
PASI_I = 0.1Ah (Ih) + 0.2Au (Iu) + 0.3At (It) + 0.4Al (Il)
PASI_S = 0.1Ah (Sh) + 0.2Au (Su) + 0.3At (St) + 0.4Sl (Sl)
Any missing component will result in PASI as missing. 
BSA (number of handprints; %) will be an endpoint of interest.
Appendix 2.11. Physician Global Assessment (PGA) of Psoriasis (PGA-PsO)
The Physician Global Assessment of Psoriasis is scored on a 5-point scale, reflecting a global
consideration of the erythema, induration and scaling across all psoriatic lesions.  Average
erythema, induration and scaling are rated separately over the whole body according to a 
5-point severity scale, scored as 0 (none), 1, 2, 3, or 4 (most severe).  The severity rating
scores are summed and the average taken – the total average is rounded to the nearest whole 
number score to determine the PGA.
Appendix 2.12. Dermatology Life Quality Index (DLQI) 
The DLQI is a general dermatology questionnaire that consists of 10 items that assess patient 
health-related quality of life (daily activities, personal relationships, symptoms and feelings, 
leisure, work and school, and treatment).  The DLQI is scored such that a higher score 
indicates greater impairment. 
Total raw score = sum (items 1, 2, 3, 4, 5, 6, 7, 8, 9, 10)
The scoring of each question other than Question 7 is:
Very much
is scored 3;
A lot
is scored 2;
A little
is scored 1;
Not at all
is scored 0;


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Not relevant
is scored 0.
For Question 7:
if yes, then scored 3;
if no or not relevant, then scored 0;
if it is answered “no” or “not relevant” but then either “a lot” or “a little’ is checked this is
then scored 2 or 1, respectively.
If a question is unanswered it is scored 0 and the scores are summed and expressed as usual
out of a maximum of 30.  If two or more questions are left unanswered the DLQI is not
scored.
Appendix 2.13. Itch Severity Item (ISI) 
The severity of itching due to psoriasis will be assessed using a single-item, 0 to 
10 horizontal numeric rating scale (NRS).  Subjects will be asked to assess their itch over the 
past 24 hours on the NRS anchored by the terms “no itching” (0) and “worst possible 
itching” (10) at the ends. 
Appendix 2.14. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
The BASDAI score is obtained by computing the mean score for the 2 questions related to 
morning stiffness (questions 5 and 6) and then adding that value to the sum of the scores for 
the first 4 questions and then dividing the total by 5.  This can be written as:
BASDAI=(Q1+Q2+Q3+Q4+(Q5+Q6)/2)/5
The total score will range from 0.0 to 10.0 cm. 
If the answer to either any 1 question is missing, then the BASDAI score will be calculated 
using the remaining non-missing answers.  If >1 answers are missing, then the BASDAI is 
considered as missing (Ramiro, 2014).9
Explicitly, the calculation of BASDAI score for any 1 missing answer is detailed in the table 
below:
Missing Q5 or 
Q6
Missing any one 
of Q1-Q4
Formula
No
Yes
BASDAI=[sum of the 3 non-missing of 
(Q1,Q2,Q3,Q4)+(Q5+Q6)/2]/4
Yes
No
BASDAI=[Q1+Q2+Q3+Q4+(non-missing of Q5 or 
Q6)]/5


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The raw VAS data will need to be rescaled to a 10 cm scale prior to any calculation (Section 
6).
Appendix 2.15. EuroQol-5D Health Questionnaire 3-Level (EQ-5D-3L)
On the EQ-5D (subject version, 3 categories of response per question), 5 dimensions of 
health (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) are 
assessed.  The status of each dimension has three possible responses (no problem in the 
relevant health dimension to severe problems).  
The EQ VAS records the patient’s self-rated health on a vertical visual analogue scale where 
the endpoint is labelled ‘Best imaginable health state’ and ‘Worst imaginable health state’.  
Based on the patient’s mark on the VAS form a score ranging from 0 to 100 mm is recorded. 
The VAS data will need to be rescaled prior to any calculation (Section 6).
Appendix 2.16. Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F)
FACIT-F is a 13 item questionnaire (each item score ranges from 0 to 4). There will be 
3 endpoints derived: ∆FACIT-F total score, ∆FACIT-F experience domain score and 
∆FACIT-F impact domain score. FACIT-F total score (range 0-52) is calculated by 
summing the 13 items. FACIT-F experience domain score (range 0-20) is calculated by 
summing 5 items of Q1 I feel fatigued, Q2 I feel weak all over, Q3 I feel listless (“washed 
out”), Q4 I feel tired and Q7 I have energy, while FACIT-F impact domain score (range 
0-32) is calculated by summing the remaining 8 items. Note that all the scores except Q7 & 
Q8 should be reversed prior to summing for both the total score and the domain scores such 
that higher scores represent better functioning.
All responses are added with equal weight to obtain the total score. In cases where some 
answers are missing, a total score is prorated from the score of the answered items, so long as 
more than 50% of the items (ie, at least 7 of 13 for FACIT-F total score, at least 3 of 5 for 
FACIT-F experience domain score, and at least 5 of 8 for FACIT-F impact domain score) are 
answered.
Appendix 2.17. Short Form 36 (SF-36, version 2, acute)
The SF-36 v.2 (Acute version) is a 36-item generic health status measure.  It measures
8 general health concepts or domains: physical functioning, role physical, bodily pain,
general health, vitality, social functioning, role emotional and mental health.  These domains
can also be summarized as physical and mental component scores.
These 8 domains are as follows:
a.
Physical Functioning (PF).  This score is based on the responses to the 10 items that
compose Question 3 and reflects the degree to which various physical activities have
been limited in the previous week by the subject’s health.


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b. Role-Physical (RP).
This score is based on the responses to the four items that 
compose Question 4 and reflects the relative amount of time that the subject has had
problems with work or other regular daily activities as a result of their physical health
during the previous week.
c.
Bodily Pain (BP).
This score is based on the responses to Questions 7 and 8 and 
reflects bodily pain and its effects on normal work during the previous week.
d. General Health (GH).  This score is based on responses to Question 1 and the four 
items in Question 11 and reflects the subject’s perception of their general health
during the previous week.
e.
Vitality (VT).  This score is based on responses to Question 9 items a, e and g, and 
reflects the subject’s physical energy level relative to time during the previous week.
f.
Social Functioning (SF). This score is based on responses to Questions 6 and reflects
how physical health or emotional problems have interfered with social activities
during the previous week.
g. Role-Emotional (RE).  This score is based on responses to the three items in
Question 5 and reflects the amount of time during the previous week that emotional
problems have interfered with work or regular daily activities.
h. Mental Health (MH). This score is based on responses to Question 9 items b, c, d, f,
and h and reflects various mental/emotional states relative to time during the previous
week.
i.
Health Transition (TR). This score is based on the response to Question 2 and is a 
rating of current general health compared to one week previous.
The summary component scores are:

Physical Component Summary (PCS).

Mental Component Summary (MCS).
The summary component scores, PCS and MCS, are based on a normalized sum of the
8 scale scores PF, RP, BP, GH, VT, SF, RE, and MH.
All domains and summary
components are scored such that a higher score indicates a higher functioning or health level.


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Data Derivation Details to Obtain Scale Scores for SF-36v2
VARIABLE
DERIVATION
SF-36v2 PF scale score
raw score = sum (items 3A, 3B, 3C, 3D, 3E, 3F, 3G, 3H, 3I, 3J)
PF = (raw score -10 ) * 5
PF_Z = (PF – 82.62455) / 24.43176
PF scale score = (PF_Z*10) + 50
When calculating the raw score, if 5 or more of the items are non-missing then
replace any missing values as follows:
Calculate the mean of the answered questions, using the number of answered
questions as the denominator. Substitute the mean for any missing scores.
Otherwise, if less than 5 of the items are non-missing then PF scale score is
missing.
The response scale for each activity ranges from 1 to 3 where 1=limited a lot,
2=limited a little, and 3=not limited at all.
A higher PF scale score indicates better physical functioning.
SF-36v2 RP scale score
raw score = sum (items 4A, 4B, 4C, and 4D )
RP = [(raw score -4)/16] * 100
RP_Z= (RP – 82.65109) / 26.19282
RP scale score = (RP_Z * 10) + 50
When calculating the raw score, if 2 or more of the items are non-missing then
replace any missing values as follows:
Calculate the mean of the answered questions, using the number of answered
questions as the denominator.  Substitute the mean for any missing scores.
Otherwise, if less than 2 of the items are non-missing then RP scale score is
missing.
The response scale for each item ranges from 1 to 5 where 1=All of the time,
2=Most of the time, 3=Some of the time, 4=A little of the time, and 5=None of the
time.
A higher RP scale score indicates better role-physical functioning.


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SF-36v2 BP scale score
raw score = sum (reversed item 7 and reversed item 8)
BP = (raw score -2) * 10
BP_Z = (BP – 73.86999) / 24.00884
BP scale score = (BP_Z * 10) + 50
Reverse direction of Item 7 as follows:
if =1, set to 6; 
if =2, set to 5.4; 
if =3, set to 4.2;
if=4, set to 3.1;
if=5, set to 2.2;
if=6, set to 1.
Reverse direction of item 8 as follows:
if =1 and original value of item 7=1, set to 6;
if =1 and original value of item 7>=2, set to 5;
if=2, set to 4;
if=3, set to 3;
if=4, set to 2;
if=5, set to 1.
If item 7 is answered and item 8 is missing, set reversed 8 = reversed 7 as defined
above.
If 8 is answered and 7 is missing, set reversed 7 as reverse item 8 as 
follows:
if =1, set to 6;
if =2, set to 4.75;
if=3, set to 3.5;
if=4, set to 2.25;
if=5, set to 1.
If 1 or more questions were answered, calculate BP scale score as defined above.
If neither question was answered then BP scale score is missing.
The scale for Question 7, amount of bodily pain, ranges from 1 to 6 where 1=None,
2=Very mild, 3=mild, 4=Moderate, 5=Severe, and 6=Very severe. The scale for
Question 8, the degree to which pain interfered with normal work, ranges from 1 to
5 where 1=Not at all, 2=A little bit, 3=Moderately, 4=Quite a bit, and
5=Extremely.
A higher BP scale score indicates lack of bodily pain.


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SF-36v2 GH scale score
raw score = sum (reversed item 1, item 11A, reversed 11B,
11C and reversed 11D) GH = (raw score -5) * 5
GH_Z = (GH – 70.78372) / 21.28902
GH scale score = (GH_Z * 10) + 50
Reverse direction of Item 1 as follows:
if =1, set to 5;
if =2, set to 4.4; if =3, set to 3.4; if=4, set to 2; if=5, set to 1.
Reverse direction of item 11B and 11D by subtracting score from 6.
When calculating the raw score, if 3 or more of the items are non-missing then
replace any missing values as follows:
Calculate the mean of the answered questions, using the number of answered
questions as the denominator. Substitute the mean for any missing scores.
Otherwise, if less than 3 of the items are non-missing then GH scale score is
missing.
Responses for Question 1, an assessment of self-perceived health status, range 
from 1 to 5 where 1=Excellent, 2=Very good, 3=Good, 4=Fair, and 5=Poor.
Responses for the items in Question 11 range from 1 to 5 where 1=Definitely true,
2=Mostly true, 3=Don’t know, 4=Mostly false, and 5=Definitely false and reflect 
the subject’s perception of their relative health and expectations of their future
health status.  A higher GH scale score indicates better general health perceptions.
SF-36v2 VT scale score
raw score = sum (reversed item 9a, reversed 9e, 9g and 9i)
VT = [(raw score -4)/16] * 100
VT_Z = (VT – 58.41968) / 20.87823
VT scale score = (VT_Z * 10) + 50
Reverse direction of Items 9a and 9e by subtracting score from 6.
When calculating the raw score, if 2 or more of the items are non-missing then
replace any missing values as follows:
Calculate the mean of the answered questions, using the number of answered
questions as the denominator. Substitute the mean for any missing scores.
Otherwise, if less than 2 of the items are non-missing then VT scale score is
missing.
The scale for these items ranges from 1 to 5 where 1=All of the time, 2=Most of
the time, 3=Some of the time, 4=A little of the time, and 5=None of the time. A
higher VT scale score indicates more vitality.


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SF-36v2 SF scale score
raw score = sum (reversed 6 and 10)
SF = [(raw score -2) / 8] * 100
SF_Z = (SF – 85.11568) / 23.24464
SF scale score = (SF_Z * 10) + 50
Reverse direction of score for item 6 by subtracting score from 6.
When calculating the raw score, if 1 of the items is missing then substitute the
missing score with the score on the non- missing item. If both items are missing
then SF scale score is missing.
Responses to Question 6, an assessment of the extent to which health/emotional
problems interfered with social activities, range from 1 to 5 where 1=Not at all, 
2=Slightly, 3=Moderately, 4=Quite a bit, and 5=Extremely.
Responses to
Question 10 reflect the amount of time that health/emotional problems interfered 
with social activities and range from 1 to 5 where 1=All of the time, 2=Most of the
time, 3=Some of the time, 4=A little of the time, and 5=None of the time.  A
higher SF scale score indicates better social functioning.
SF-36v2 RE scale score
raw score = sum (items 5A, 5B, and 5C )
RE = [(raw score -3) / 12] * 100
RE_Z= (RE – 87.50009) / 22.01216
RE scale score = (RE_Z * 10) + 50
When calculating the raw score, if 2 or more of the items are non-missing then
replace any missing values as follows:
Calculate the mean of the answered questions, using the number of answered
questions as the denominator. Substitute the mean for any missing scores.
Otherwise, if less than 2 of the items are non-missing then RE scale score is
missing.
Responses to the items in Question 5 range from 1 to 5 where 1=All of the time,
2=Most of the time, 3=Some of the time, 4=A little of the time, and 5=None of the
time. A higher RE scale score indicates better role-emotional functioning.
SF-36v2 MH scale score
raw score = sum (items 9B, 9C, reversed 9D, 9F and reversed 9H)
MH = (raw score - 5 ) * 5
MH_Z = (MH – 75.76034) / 18.04746
MH scale score = (MH_Z * 10) + 50
Reverse direction of scores for 9D and 9H, by subtracting score from 6.
If 3 or more of the items are non-missing then replace any missing values as
follows:
Calculate the mean of the answered questions, using the number of answered
questions as the denominator. Substitute the mean for any missing scores.
Otherwise, if less than 3 of the items are non-missing then MH scale score is
missing.
The scale for these items ranges from 1 to 5 where 1=All of the time, 2=Most of
the time, 3=Some of the time, 4=A little of the time, and 5=None of the time. A
higher MH scale score indicates better mental health.


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SF-36v2 TR scale score
raw score = item 2
TR scale score = raw score
The scale for this item ranges from 1 to 5 where 1=Much better now than one
week ago, 2=Somewhat better now than one week ago, 3=About the same as one
week ago, 4=Somewhatworse now than one week ago, and 5=Much worse now 
than one week ago. A higher TR scale score indicates worse general health
currently relative to one week previous.
SF-36v2 PCS score
PCS score includes the 8 scales for GH, PF, RP, RE, SF, MH, BP, and VT.
PF1= (PF-82.62455)/24.43176; RP1=(RP-82.65109)/26.19282; 
BP1=(BP-73.86999)/24.00884; GH1 = (GH-70.78372)/21.28902;
VT1= (VT-58.41968)/20.87823; SF1=(SF-85.11568)/23.24464; 
RE1= (RE-87.50009)/22.01216; MH1=(MH-75.76034)/18.04746;
Raw Score = ((GH1*.24954)+(PF1* .42402)+(RP1*.35119)+ 
(RE1*-.19206)+(SF1*-.00753)+(MH1*-.22069)+(BP1*.31754)+ (VT1*.02877))
PCS Summary Scale Score = (raw score *10) + 50
Raw Score is missing if one of the component scale scores is missing.
SF-36v2 MCS score
MCS score includes the 8 scales for GH, PF, RP, RE, SF, MH, BP, and VT.
PF1= (PF-82.62455)/24.43176; RP1=(RP-82.65109)/26.19282; 
BP1=(BP-73.86999)/24.00884; GH1 = (GH-70.78372)/21.28902;
VT1= (VT-58.41968)/20.87823; SF1=(SF-85.11568)/23.24464; 
RE1= (RE-87.50009)/22.01216; MH1=(MH-75.76034)/18.04746;
Raw Score =((GH1*-.01571)+(PF1*-.22999)+(RP1*-.12329)+ 
(RE1*.43407)+(SF1*.26876)+(MH1*.48581)+(BP1*-.09731)+ (VT1*.23534))
MCS Summary Concept Score = (raw score *10) + 50
Raw Score is missing if one of the component scale scores is missing.


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Appendix 3. Criteria for Clinical Diagnosis of the Metabolic Syndrome
Criteria for clinical diagnosis of the metabolic syndrome will be based on the 2009 Joint 
Statement Harmonizing the Metabolic Syndrome (Alberti et al, 2009).1 There are 5 measures 
or risk factors as detailed in Table 1 of the 2009 Joint statement and excerpted below: 
Any 3 abnormal findings out of the 5 measures will qualify a subject for the metabolic 
syndrome. 
The baseline data of qualifying study will be used to derive the metabolic syndrome. 

Any drug treatment taken on Day 0 recorded on the “CONCOMITANT DRUG 
TREATMENT - ANTI-DIABETIC” CRF will be considered having the drug 
treatment of elevated glucose criterion satisfied. 

Any drug treatment taken on Day 0 recorded on the “CONCOMITANT DRUG 
TREATMENT - ANTI-HYPERTENSIVE MEDICATIONS” CRF will be considered 
having the drug treatment of elevated blood pressure criterion satisfied.


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
Any drug treatment taken on Day 0 recorded on the “CONCOMITANT DRUG 
TREATMENT – LIPID LOWERING AGENTS” CRF will be considered having the 
drug treatment of elevated triglycerides criterion satisfied. 

For the HDL-C criterion, only the lab categorical cut points will be considered and 
the drug treatment will not be considered. 

The waist circumference thresholds will be population and country specific per Table 
2 of the 2009 Joint Statement excerpted below. Explicitly, the US specific threshold 
will be used for the subjects enrolled from US, the Canada threshold for the subjects 
enrolled from Canada, the European threshold for the subjects enrolled from Western 
Europe, Eastern Europe and Russia, the Asian (including Japanese) threshold for the 
subjects enrolled from Asia, and Ethnic Central and South American threshold for the 
subjects enrolled from Central and South America.


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Appendix 4. Definition of Diabetes Mellitus at Baseline
A subject is considered having diabetes mellitus at baseline of the qualifying study, if any of 
the conditions below is met:

Subject had a diagnosis of diabetes mellitus recorded on the “CARDIOVASCULAR 
RISK FACTORS” CRF or on the “SIGNIFICANT MEDICAL HISTORY AND 
NON-DRUG ALLERGIES” CRF at screening;

Subject received any drug treatment taken on Day 0 recorded on the 
“CONCOMITANT DRUG TREATMENT - ANTI-DIABETIC” CRF;

Subject’s HbA1c ≥6.5% at baseline or, if HbA1c is not available, baseline fasting 
plasma glucose ≥126 mg/dL.


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Appendix 5. Handling of Joint Count Assessment (Missing Assessment, “NOT DONE” 
and “NOT APPLICABLE”) and Injected Joint
This Section applies to the tender/painful joint (68) and swollen joint (66).
For missing or “NOT DONE” assessment:

A missing painful / tender assessment or one “NOT DONE” at baseline is set to “not 
painful / tender”;

A missing swollen assessment or one “NOT DONE” at baseline is set to “not 
swollen”;

A missing painful / tender assessment or one “NOT DONE” post-baseline is set to 
“painful / tender”;

A missing swollen assessment or one “NOT DONE” at post-baseline is set to 
“swollen”.
For “NOT APPLICABLE” assessment:

A joint marked “NOT APPLICABLE” is not to be counted in the summation of 
swollen and painful / tender joints at baseline and post baseline;

Any new “NOT APPLICABLE” for a joint post baseline is set to “painful / tender” 
and “swollen”. That is, if a joint is assessed, “Present”, “Absent”, “NOT DONE”, or
with missing assessment at baseline, the same joint marked as “NOT APPLICABLE” 
post-baseline will be counted as “painful / tender” and “swollen”.
If a joint received an intra-articular injection (baseline or post-baseline), then set the joint 
status to “painful/tender” and “swollen” on and after the date of injection.


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Appendix 6. Methotrexate Withdrawal Sub-Study
1. INTRODUCTION
The purpose of this sub-study is to assess the efficacy, safety and tolerability of tofacitinib 
5 mg BID administered as monotherapy after methotrexate (MTX) withdrawal compared to 
tofacitinib 5 mg BID continued in combination with MTX in subjects with active PsA. 
Subjects who have completed at least 24 months of participation in the long term extension 
study A3921092 and are currently receiving methotrexate may be included.
Subjects will be randomized to the 2 treatment arms in a 1:1 ratio, one in which they will 
receive open label tofacitinib 5 mg tablets BID and blinded methotrexate capsules (oral dose 
range from 7.5 mg to 20 mg per week) and the second in which they will receive open label 
tofacitinib 5 mg tablets BID and blinded MTX placebo capsules. The sub-study will be 
approximately 12 (standardized 4-week) months in duration and visits will occur at Baseline, 
Months 1, 3, 6, 9 and 12.  The sub-study baseline will occur at the same time as a scheduled 
study visit at or after Month 24 of A3921092.  This visit will be referred to as Sub-study 
Switch Visit or Baseline visit (Sub-study Switch/Baseline visit).
1.1. Study Design
This sub-study within Study A3921092 is a Phase 3, randomized, double-blind, placebo-
controlled, parallel group estimation study designed to assess the efficacy, safety and 
tolerability of tofacitinib 5 mg BID versus tofacitinib 5 mg BID in combination with 
concomitant MTX in subjects with active PsA.  Subjects with active PsA will have previously 
completed at least 24 months of treatment with tofacitinib in Study A3921092 and will be on 
a stable dose of tofacitinib 5 mg BID for at least 3 months prior to the first dose of sub-study 
drug and be on a stable dose of oral MTX at least 4 weeks prior to the first dose of sub-study 
drug.  For subjects who are qualified to enter into the sub-study, the Combined A3921092 
Sub-study Switch/Baseline visit will occur at a scheduled study visit at or after Month 24 of 
A3921092.  There will be no separate Baseline visit for the sub-study.  The visit window will 
remain as in the LTE in which a month is considered 28 days.  Once a subject enters the sub-
study, they will complete their participation in the sub-study portion and be unable to re-
enter the main study.  Subjects may be discontinued from the sub-study at any time during the 
sub-study in the event of deterioration of response as determined by the investigator.
Eligible subjects from study A3921092, will be randomized into A3921092 sub-study in a 1:1 
ratio to tofacitinib 5 mg BID + MTX placebo or tofacitinib 5 mg BID + MTX.  MTX will be 
blinded to the subjects, investigator and the sponsor.  The subjects in the tofacitinib 5 mg 
BID + MTX group will receive blinded MTX capsules (range dose of 7.5-20 mg a week based 
upon the pre-existing dose) and the subjects in the tofacitinib 5 mg BID group will receive 
the matching MTX placebo capsules.  For the duration of the sub-study tofacitinib dose must 
remain stable at 5 mg BID.  The MTX dose and oral route of administration must remain 
stable for the 12 month duration of the sub-study.  All subjects will receive open-label 
tofacitinib 5 mg BID throughout the sub-study without dose increase.  The total number of 
subjects randomized will be approximately 180 with 90 in each treatment group.  Treatment 
duration for subjects participating in this sub-study is approximately 12 months.


Protocol A3921092 (Tofacitinib (CP-690,550)) Statistical Analysis Plan
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At various time points in this trial, safety measurements, including physical examination, 
clinical laboratory tests, adverse event monitoring, electrocardiograms (ECGs) and vital 
signs will be performed.  All subjects will be monitored for clinical evidence of PsA response 
to treatment.  Health Outcomes Measures (ie, Patient Reported Outcomes assessments for 
pain, quality of life, physical function, fatigue and health status) will also be performed at 
various time points in this trial.  In addition, subjects will be monitored for serious infections, 
lymphadenopathy and lymphoproliferative disorder (LPD).
1.2. Study Objectives
Primary Objective

To assess the efficacy of tofacitinib 5 mg BID monotherapy as compared to tofacitinib 
5 mg BID with background MTX in subjects who have received prior treatment of 
tofacitinib in combination with MTX.
Secondary Objective

To assess the safety and tolerability of tofacitinib 5 mg BID monotherapy as 
compared to tofacitinib 5 mg BID with background MTX in subjects who have
received prior treatment of tofacitinib in combination with MTX.
2. INTERIM ANALYSES, FINAL ANALYSES AND UNBLINDING
No formal interim analysis is planned for the sub-study.  However, data-cuts may be 
performed as needed to support tofacitinib regulatory submission.  
This sub-study will use the same External Data Monitoring Committee (E-DMC) as for the 
main LTE study. 
A final analysis will occur when all subjects finish the sub-study or terminate early.
3. HYPOTHESES AND DECISION RULES
3.1. Statistical Hypotheses
There are no formal hypotheses being tested in this sub-study.
3.2. Statistical Decision Rules
There are no statistical decision rules in this sub-study.
4. ANALYSIS SETS
Below is a description of the Analysis Sets defined for this sub-study.
4.1. Full Analysis Set
The full analysis set (FAS) is defined as all subjects who are randomized to the sub-study and 
receive at least one dose of the sub-study drug (tofacitinib, MTX or placebo).  Subjects will 
be analyzed based on treatment randomized.  


Protocol A3921092 (Tofacitinib (CP-690,550)) Statistical Analysis Plan
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4.2. ‘Per Protocol’ Analysis Set
There is no Per Protocol Analysis Set defined for this sub-study.
4.3. Safety Analysis Set
The safety analysis set (SAS) is defined as all subjects who received at least one dose of the 
sub-study drug (tofacitinib, MTX or placebo). Subjects will be analyzed based on treatment 
received.  
4.4. Other Analysis Sets
4.4.1. Endpoint Specific Analysis Sets
Subjects will be excluded from FAS for analyzing a specific endpoint if the criterion for 
inclusion is not met for the endpoint as described in Table 3 Endpoint Specific Analysis 
Sets.
Table 3 Endpoint Specific Analysis Sets
Instrument/Endpoint
Inclusion
Rationale
∆PGA-PsO
Include subjects with baseline 
PGA-PsO>0
PGA-PsO=0 means no PsO disease at baseline as measured 
by PGA.
∆BSA
Include subjects with baseline 
BSA>0
BSA=0 means no PsO disease at baseline as measured by 
BSA.
∆DSS
Include subjects with baseline 
dactylitis severity score 
(DSS)>0
Baseline DSS=0 means absence of dactylitis.  Dactylitis is 
not an enrollment criterion so it is expected that only a 
subset of the subjects will have dactylitis at baseline.
Dactylitis presence
Include subjects with baseline 
DSS>0
Baseline DSS=0 means absence of dactylitis.  Dactylitis is 
not an enrollment criterion so it is expected that only a 
subset of the subjects will have dactylitis at baseline.
∆Leeds  Enthesitis Index 
(∆LEI)
Include subjects with baseline 
LEI>0
Baseline LEI score=0 means absence of enthesitis as 
measured by LEI.  Enthesitis is not an enrollment criterion 
so it is expected that only a subset of the subjects will have 
enthesitis at baseline.
Enthesitis presence
Include subjects with baseline 
LEI>0
Baseline LEI score=0 means absence of enthesitis as 
measured by LEI.  Enthesitis is not an enrollment criterion 
so it is expected that only a subset of the subjects will have 
enthesitis at baseline.
Abbreviations:  ∆=Change from baseline; baseline is the value obtained prior to the first dose of the sub-study; BSA = body 
surface area; DSS = Dactylitis Severity Score; PGA-PsO = Physician’s Global Assessment of Psoriasis.
4.5. Treatment Misallocations
If a subject was:

Randomized but not treated, then the subject will appear on the subject evaluation 
table as randomized but not treated; this is the extent of how much data for this 
subject will be reported.

Treated but not randomized, then by definition the subject will be excluded from the 
FAS and SAFETY analysis sets. A narrative will be provided for this subject in the 
clinical study report (CSR).


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
Randomized but took the incorrect treatment exclusively through the entire duration 
of the study, then the subject will be reported under the randomized treatment group 
for the efficacy analysis but will be reported under the treatment they actually 
received for all safety analyses.

Randomized but took at least one dose of randomized treatment and one dose of 
incorrect treatment, then the subject will be reported under the randomized treatment 
group for the efficacy and safety analyses.
Patient-reported outcomes (PRO) will be considered the same as for efficacy in this regard.
5. ENDPOINTS AND COVARIATES
Visual analog scale (VAS) data will be similarly rescaled prior to any calculation and 
analysis as in the main LTE study. Refer to main LTE study Section 6 for the details. The 
baseline will be the latest value obtained prior to the first dose of the sub-study.
5.1. Primary Endpoints

∆HAQ-DI at 6 months.

∆PASDAS at 6 months.
5.2. Secondary Endpoints

∆HAQ-DI score at all time points except Month 6 (see Appendix 2.2).

∆PASDAS at all time points except Month 6 (see Appendix 2.9).

PsARC response at all time points (see Appendix 2.4). 

∆PGA-PsO at all time points (see Appendix 2.11).

%∆ BSA at all time points (see Appendix 2.10).

∆DSS at all time points.

Dactylitis absence at all time points.

∆ in Enthesitis score (using LEI) at all time points.

Enthesitis absence (using LEI) at all time points.

MDA response at all time points (see Appendix 2.8).

∆ in ACR components (tender/painful joint count (68), swollen joint count (66), 
Physician’s Global Assessment of Arthritis, Patient’s Global Assessment of Arthritis, 
Patient’s Assessment of Arthritis Pain, CRP) at all time points (see Appendix 2.1).


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
Physical function/other patient reported outcomes to be assessed at all time points:
∆Short-Form 36 (version 2, Acute) (see Appendix 2.17); ∆FACIT-F (see
Appendix 2.16); ∆EQ-5D-3L (see Appendix 2.15); EQ-VAS.

Incidence and severity of adverse events.

Incidence of clinical abnormalities and change from baseline (see Appendix 6
Section 5 for baseline definition) in clinical laboratory values during treatment.
5.3. Other Endpoints

∆DAS28-3 (CRP) at all time points (see Appendix 2.3).

MDA component response (yes/no) at all time points.

∆PGJS-VAS at all time points.

Incidence of investigator-reported clinically significant changes in physical 
examination from baseline during treatment.

Incidence of electrocardiogram (ECG) abnormalities and change from baseline in 
ECG measurements during treatment.

Incidence of vital sign (blood pressure and pulse rate) abnormalities and changes 
from baseline in vital sign measurements during treatment.
5.4. Covariates 
Mixed Model for Repeated Measures (MMRM) will be used for analyzing continuous 
efficacy endpoints collected over multiple visits (eg, ∆HAQ-DI or ∆PASDAS).  The baseline 
value will be included in the model as a covariate.
6. HANDLING OF MISSING VALUES
For the SF-36v2, EQ-5D-3L and FACIT-F instruments, the same approaches as for the main 
LTE study will be followed.  Refer to main LTE study Section 7 for the details.  In general, 
missing values will not be imputed. For the binary efficacy endpoints (eg, PsARC Response), 
missing responses will be treated as non-response (MR=NR).
7. STATISTICAL METHODOLOGY AND STATISTICAL ANALYSES
Both the efficacy and safety analysis will base on data collected in the sub-study only unless 
noted otherwise.
There are two treatment groups in the sub-study: Tofacitinib 5 mg BID + MTX placebo and 
Tofacitinib 5 mg BID + MTX.  Subjects will be analyzed and reported by treatment groups.
Efficacy will also be assessed for a subset of the subjects who had more severe PsA as
defined by ≥5 swollen or tender joints at the baseline of the sub-study, if sample size permits.


Protocol A3921092 (Tofacitinib (CP-690,550)) Statistical Analysis Plan
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7.1. Statistical Methods 
7.1.1. Analyses for Continuous Data
For the continuous endpoints, by-visit summary statistics (N, mean, standard deviation, 
standard error of the mean, minimum, 1st, 2nd (median) and 3rd quartiles and maximum) will 
be provided by treatment group for both the original and the change (or for some measures, 
percent change, eg, %∆BSA) from baseline values over 12 months.
In addition, continuous efficacy endpoints collected over multiple visits (eg, ∆HAQ-DI or 
∆PASDAS) will be analyzed using a Mixed Model for Repeated Measures (MMRM) without 
imputation for missing values on the FAS.  The MMRM model will include fixed effects of 
treatment (Tofacitinib + Placebo and Tofacitinib + MTX), visit, treatment by visit interaction, 
and baseline value.  The model will fit a common unstructured variance-covariance matrix 
for both treatment groups.  If the unstructured matrix fails to converge, heterogeneous 
compound symmetry (CSH) will be attempted.  Treatment comparison between the 2 groups 
at each post-baseline time point will be generated from this model providing both 2-sided p-
value and 95% CI.
7.1.2. Analyses for Categorical Data 
The data for all categorical endpoints (including binary) will be summarized by contingency 
tables that show the counts/frequency of the response at each visit by treatment group.  For 
some categorical endpoints, such as the presence or severity of adverse events, contingency 
or frequency tables will consider the data over the entire duration of the study and will not be 
constructed at each time point.  
Two-sided p-value and 95% CI will be generated by normal approximation to the binomial 
distribution approach for the treatment comparison between the 2 groups.  Let 
be number 
of subjects assessed at each visit, 
be number of responders, and 
be the observed 
responder rate.  Use subscript t to refer to the treatment group (Tofacitinib + Placebo) and c 
to refer to the treatment group (Tofacitinib + MTX). Then the normal approximation to the 
2-sided p-value will be calculated as
, 
where Z is Normal (0, 1) distributed.
Two-sided 95% CI will be formed by
.
If there is no (ie, 0) response or 100% response in any of treatments, 0.5 will be added to the 
number of responses and 1 will be added to the denominator in each treatment corresponding 
to the pair of comparison for calculating the treatment difference, standard error, 95% CI and 
2-sided p-value (Agresti, 2002).


Protocol A3921092 (Tofacitinib (CP-690,550)) Statistical Analysis Plan
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When response rate of 0% or 100% is observed in both treatments in comparison, no formal 
comparison will be performed. Estimated response rate of 0% or 100% will be reported as 
observed.
The final results will be expressed in percentages, ie, (proportions x 100)%.
7.2. Statistical Analyses
The primary efficacy analysis will use FAS (Appendix 6 Section 4.1).  Continuous efficacy 
endpoints, for which change or percent change from baseline is the measure to be analyzed, 
would require that a subject have both a baseline value and at least one post-baseline value to 
be included in the FAS.  The safety analysis will use SAS (Appendix 6 Section 4.3).
7.2.1. Analysis of Primary Endpoints
For each of the two primary endpoints in the sub-study: ∆HAQ-DI at Month 6 and 
∆PASDAS at Month 6, a MMRM described in Appendix 6 Section 7.1.1 on the FAS without 
imputation for missing values will be used to estimate the change from baseline at Month 6 
for each treatment group. The treatment comparison between the 2 groups at Month 6 will 
also be generated from this model providing both 2-sided p-value and 95% CI. The analysis 
will include all the data through Month 12. Treatment comparisons between the 2 treatment 
groups at other visits will be made as well from this model.
7.2.2. Analysis of Secondary and Other Efficacy/Health Outcome Endpoints
The MMRM described in Appendix 6 Section 7.1.1 will be used on FAS or endpoint specific 
FAS for:

∆HAQ-DI score at all time points except Month 6 (see Appendix 2.2). Note that this 
will be accomplished by the same MMRM analysis in Appendix 6 Section 7.2.1.

∆PASDAS at all time points except Month 6. Note that this will be accomplished by 
the same MMRM analysis in Appendix 6 Section 7.2.1.

∆PGA-PsO at all time points (see Appendix 2.11).

%∆ BSA at all time points (see Appendix 2.10).

∆DSS at all time points.

∆ in Enthesitis score (using LEI) at all time points.

∆ in ACR components (tender/painful joint count (68), swollen joint count (66), 
Physician’s Global Assessment of Arthritis, Patient’s Global Assessment of Arthritis, 
Patient’s Assessment of Arthritis Pain, CRP) at all time points (see Appendix 2.1).

Physical function/other patient reported outcomes to be assessed at all time points: 
∆Short-Form 36 (version 2, Acute) (see Appendix 2.17); ∆FACIT-F (see
Appendix 2.16); ∆EQ5D (see Appendix 2.15); EQ-VAS.


Protocol A3921092 (Tofacitinib (CP-690,550)) Statistical Analysis Plan
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
∆DAS28-3 (CRP) at all time points (see Appendix 2.3).

∆PGJS-VAS at all time points.
The analysis methods described in Appendix 6 Section 7.1.2 will be used on the FAS or 
endpoint specific FAS for:

PsARC response at all time points (see Appendix 2.4). 

Dactylitis absence at all time points.

Enthesitis absence (using LEI) at all time points.

MDA response at all time points.

MDA component (yes/no) response at all time points.
7.2.3. Analysis of Safety Data

Safety analysis by treatment groups will follow the similar approaches as for the main 
LTE study, except the incidence rate analysis will not be performed in the sub-study. 
Refer to main LTE study Section 8.2.1 Analysis of Primary Endpoints and Section 
8.2.3 Analysis of Safety Data for the details.
7.3. Baseline and Other Summaries and Analyses
7.3.1. Baseline Summaries
Baseline will be from the combined A3921092 Sub-study Switch/Baseline visit unless noted 
otherwise. Baseline characteristics will include but may not be limited to the ones listed 
below and will be summarized similarly as in the main LTE study. Refer to main LTE study 
Section 8.3.1 for more details.

Demographic characteristics include but may not be limited to: Age, Sex, Race (from 
main LTE baseline), Ethnicity (from main LTE baseline), Weight, Height, BMI, 
Geographic Region (from main LTE baseline), Smoking Status, Alcohol Use.

Baseline disease characteristics include but may not be limited to: PsA Duration, PsA 
Subtype, PASDAS, Swollen Joint Count, Tender/Painful Joint Count, HAQ-DI, 
Screening Presence of Distal Interphalangeal Joints Involvement, Screening Presence of 
Arthritis Mutilan, Presence of Enthesitis (LEI), Enthesitis Index (LEI), Presence of 
dactylitis, DSS, BSA, PGA-PsO, SF-36v2 (8 domains and PCS and MCS), FACIT-F
(total score and 2 domains), CRP, Diabetes Mellitus, Metabolic Syndrome, CV Risks per 
PDS, Rheumatoid Factor Positive, Cyclic Citrullinated Peptide Antibody Positive.
7.3.2. Prior Drug Treatments for Psoriatic Arthritis
Prior drug treatment will include any treatment except tofacitinib used during the qualifying 
study, during the enrollment gap between the qualifying study and the main LTE study, and 
the main LTE study for PsA prior to the first dose of study medication in the sub-study.  
Refer to main LTE study Section 8.3.2 for detailed category list of the prior drug treatments. 


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7.3.3. Concomitant Drug Treatments for Psoriatic Arthritis
Concomitant drug treatment will include any treatment for PsA during the sub-study. The 
summary by treatment groups will be similarly as for the main LTE study.  Refer to main 
LTE study Section 8.3.3 for the details.
MTX dose will be summarized by visit.
7.4. Sub-study Definition and Use of Visit Windows in Reporting
The visit windows are similarly defined as for the main LTE study in below table.  The study 
day will be calculated as: date of assessment/collection – date of the first dose in the sub-
study + 1.
If two or more visits/observations fall into the same window, the visit/observation closest to
the target day should be used in the analyses.  If there is a tie, the later visit should be used.  
However, if two or more visits/observations fall in the same window, and the latest visit is 
the last visit of the study due to early termination, then this will be the visit used in the 
analysis for that visit window. Per the master visit schedule provided to the investigator sites, 
a month is defined as 4 weeks or 28 days.
Visit Label
Target 
Day
Definition [Day Window] –
Lower
Definition [Day 
Window] - Upper
Switch/Baseline
1
Day 1 = date of first dose of study treatment taken of sub-study
Prior to first dose of study treatment taken of sub-study
Month 1
29
2
57
Month 3
85
58
127
Month 6
169
128
211
Month 9
253
212
295
Month 12
337
≥296
The following categories will be used in the treatment exposure and duration of treatment 
summaries for tofacitinib. The duration of treatment will be calculated as: date of the last 
dose in the sub-study – date of the first dose in the sub-study + 1. Any missed 
doses/drug holidays will be ignored in the duration calculation. Treatment exposure will be
defined as the number of days that subjects took the study drug (gaps not counted).
Category (days)
1
2-28 (1 month)
29-84 (1-3 months)
85-168 (3-6 months)
169-252 (6-9 months)
≥253 (9-12 months)