Clinical trial NCT03486457
Conditions: Psoriatic Arthritis
Keywords: psoriatic arthritis tofacitinib China
Sponsor: Pfizer
Start date: 2018-08-10; Completion date: 2021-04-28
Enrollment: 204 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a 6 month study investigating the effectiveness and safety of tofacitinib in treating signs and symptoms and improving physical function in Chinese patients with active psoriatic arthritis and had inadequate response to a conventional synthetic disease modifying anti-rheumatic drug. This is a China alone study.

Detailed description:

Arms: arm 1: Tofacitinib 5 mg BID for 6 months arm 2: Placebo for 3 months then tofacitinib 5 mg BID for 3 months
Interventions: intervention 1: Tofacitinib intervention 2: Placebo intervention 3: Tofacitinib
Intervention descriptions: intervention 1: tablets, 5 mg BID x 6 months intervention 2: tablets, to match tofacitinib 5 mg BID x 3 months intervention 3: tablets, 5 mg BID x 3 months

Protocol documents:
Prot_000.pdf: 
Tofacitinib (CP-690,550)
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Final Protocol Amendment 4, 4 June 2020
PFIZER CONFIDENTIAL
Page 1
A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY 
OF THE EFFICACY AND SAFETY OF TOFACITINIB (CP-690,550) IN CHINESE
SUBJECTS WITH ACTIVE PSORIATIC ARTHRITIS AND AN INADEQUATE 
RESPONSE TO AT LEAST ONE CONVENTIONAL SYNTHETIC DMARD
Investigational Product Number:
CP-690,550
Investigational Product Name:
Tofacitinib
Protocol Number:
A3921234
Phase:
3
This document and accompanying materials contain confidential information belonging to Pfizer.  Except as 
otherwise agreed to in writing, by accepting or reviewing these documents, you agree to hold this information in 
confidence and not copy or disclose it to others (except where required by applicable law) or use it for 
unauthorized purposes.  In the event of any actual or suspected breach of this obligation, Pfizer must be 
promptly notified.


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Document History
Document
Version Date
Summary of Changes and Rationale
Amendment 4
4 Jun 2020
1. Sample size increase from approximately 195 to 
approximately 204 to preserve the study power,
which is negatively impacted by the COVID-19
pandemic on the response rates and the rate 
difference of the primary endpoint. (Protocol 
summary, Section 3, Section 5.1, Section 9.1 and 
Section 9.2).
Amendment 3
13 May 2020
1. Exclusion Criteria Section 4.4 number 29 and
Screening Section 6.1: add to evaluate the risk 
factors of venous thromboembolism before 
entering the study.
2. Add checking risk factors for venous 
thromboembolism in every visit (revisions are in 
Schedule of Activities, Section 3, Section 6.2, and 
new Reference #19 added).
3. Add Section 7.5.8 to list the venous 
thromboembolism risk factors that will be checked
every visit and tofacitinib dosing guidance when a 
risk factor is identified.
4. Add confirmed venous thromboembolism into
Section 6.3.2 Discontinuation Criteria.
5. Clarify that the DMARDs prohibition requirement 
ends at last dose in Appendix 3. After last dose of
investigational drug, treatment will be left at the 
discretion of investigators to ensure subjects’
benefit.
6. Clarify that all JAK inhibitors are prohibited in the 
study and require washout as described in 
Appendix 3.
7. Other Inclusion Criteria Section 4.3 - number 2:
make changes based on 2020 WHO guideline and 
China local practice. To be consistent, update the 
chest radiography monitoring requirement
accordingly in SOA and Section 7.5.3.3.
8. Exclusion Criteria Section 4.4 – number 31: clarify 
that patients with previous clinical experience of 
tofacitinib will be excluded to avoid bias.
9. Update Section 4.6.6 Contracepion part per current 


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Version Date
Summary of Changes and Rationale
effective protocol, in which male condom or 
female condom with spermicide are no longer 
considered as highly effective methods. Also add 
clarified requirements that are for background
medications.
10. Incorporate all the revisions addressed in PACLs
dated 31Oct2018, 13Mar2019, 27May2019 and 
01April2020, respectively, as per bullet points
below:

Other Inclusion Criteria Section 4.3 – number 
4: specify the washout requirements for three 
TNFi biosimilar used widely in China. And 
clarify that other biosimilar biologics could 
follow washout requirements of reference 
product after confirming they have same half 
lives.

Correct misleading wording in Section 7.5.7.2 
and Section 4.1.2 and correct some inaccurate
wording of translation in Chinese version.

Section 8.1.4: To clarify requirement of 
differentiate AE reporting and the reporting of
medical history that occurs before study 
intervention.

Add the contingency tactics during Corona 
Virus Disease 2019 into Section 7.7 Corona
Virus Disease 2019.
Amendment 2
20 Aug 2018
1. Sample size is increased to 195 subjects to yield a 
higher power of at least 90%. The enrollment will 
be monitored to cap the proportion of subjects with 
baseline swollen joint count 5 at 40% 
(ie, 78 subjects) to keep study population similar 
to global pivotal study A3921091.
2. Inclusion criteria 4.1.2: the minimum treatment
duration of sulfasalazine is changed to 3 months, 
which is in accordance with clinical practice in 
China.
3. Inclusion criteria 4.3: specify we intend to recruit 
Chinese adult subjects.


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Summary of Changes and Rationale
4. Exclusion criteria 4.4 item 8: wording is updated 
to make this criterion more comprehensive.
5. Update Appendix 3 Prohibited Concomitant 
Medications to include the possible DMARDs 
used in clinical practice.
6. Make clarifications for study visits to avoid
inconsistent understanding.
7. Incorporate all the revisions addressed in PACL 
dated on 26 Feb 2018: 
•
Section 4.4 Exclusion criteria: a change is 
made that 12-lead ECG will be read and 
determined by qualified cardiologist.
•
Correct the identified inconsistencies.
•
Some format adjustments are to make it clear.
8. Update safety part by protocol template.
9. This study is for China registration, so delete US 
IND number and EudraCT number.
Amendment 1
20 November 
2017
1. Regional study is changed to China alone study: 
the study is designed to support PsA registration in 
China.
2. Treatment arm of tofacitinib 10 mg BID is 
removed: based on results of PsA global pivotal 
studies, recommended PsA posology globally is 
tofacitinib 5 mg BID only, the 10 mg BID dose is 
not included as part of the posology in PsA. 
3. Primary endpoint is changed to ACR50 response 
rate at Month 3: ACR50 indicates higher degree of 
improvement with more clinical relevance. Based 
on data of A3921091, with ACR50 as primary 
endpoint makes it possible to detect a statistical 
difference between tofacitinib and placebo with 
adequate power.
 
 
CCI


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Version Date
Summary of Changes and Rationale
 
5. Template update.
Original 
protocol 
11 July 2014
Not applicable (N/A)
This amendment incorporates all revisions to date, including amendments made at the 
request of country health authorities and institutional review boards (IRBs)/ethics committees 
(ECs).
CCI


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TABLE OF CONTENTS
LIST OF TABLES...................................................................................................................11
APPENDICES .........................................................................................................................12
PROTOCOL SUMMARY.......................................................................................................13
1. INTRODUCTION ...............................................................................................................19
1.1. Mechanism of Action/Indication.............................................................................19
1.2. Background and Rationale ......................................................................................19
1.2.1. Mechanism of Action .................................................................................20
1.2.2. Summary of Efficacy..................................................................................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.......................................................................27
2.1. Objectives................................................................................................................27
2.1.1. Primary Objectives .....................................................................................27
2.1.2. Secondary Objectives .................................................................................28
2.2. Endpoints.................................................................................................................28
2.2.1. Primary Endpoint........................................................................................28
2.2.2. Secondary Endpoints ..................................................................................28
2.2.2.1. Secondary Efficacy Endpoints ..................................................28
2.2.2.2. Secondary Physical Function and Health Outcome 
Measures............................................................................................29
2.2.3. Safety Endpoints.........................................................................................29
2.2.4. Other Endpoints..........................................................................................29
2.2.4.1. Other Efficacy Endpoints..........................................................29
2.2.4.2. Other Safety Endpoints .............................................................30
3. STUDY DESIGN.................................................................................................................30
4. SUBJECT ELIGIBILITY CRITERIA.................................................................................31


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4.1. Inclusion Criteria.....................................................................................................32
4.1.1. Active Psoriatic Arthritis............................................................................33
4.1.2. Background DMARDs ...............................................................................34
4.2. PsA Patient Population............................................................................................34
4.3. Other Inclusion Criteria...........................................................................................34
4.4. Exclusion Criteria....................................................................................................36
4.5. Randomization Criteria ...........................................................................................40
4.6. Life Style Guidelines...............................................................................................40
4.6.1. Non-Pharmacologic Interventions..............................................................41
4.6.2. Vaccine Guidelines.....................................................................................41
4.6.2.1. Subject Vaccination...................................................................41
4.6.2.2. Household Contact with Others Vaccinated .............................41
4.6.3. Dietary Supplements...................................................................................41
4.6.4. Fasting Visit Requirements.........................................................................42
4.6.5. Elective Surgery..........................................................................................42
4.6.6. Contraceptive..............................................................................................42
4.7. Sponsor Qualified Medical Personnel.....................................................................44
4.8. Rater Qualifications.................................................................................................45
5. STUDY TREATMENTS.....................................................................................................45
5.1. Allocation to Treatment ..........................................................................................45
5.2. Breaking the Blind ..................................................................................................46
5.3. Subject Compliance.................................................................................................46
5.4. Investigational Product Supplies.............................................................................47
5.4.1. Dosage Form(s) and Packaging..................................................................47
5.4.2. Preparation and Dispensing........................................................................47
5.5. Administration.........................................................................................................47
5.6. Investigational Product Storage ..............................................................................48
5.7. Investigational Product Accountability...................................................................48
5.8. Concomitant Medication(s).....................................................................................49
5.8.1. Stable Background Pain or Other Arthritis Therapy ..................................49
5.8.2. Other Medications ......................................................................................50
5.9. Rescue Therapy.......................................................................................................51


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6. STUDY PROCEDURES .....................................................................................................51
6.1. Screening.................................................................................................................51
6.2. Study Period ............................................................................................................53
6.2.1. Visit 1, Baseline Day 1 ...............................................................................54
6.2.2. Visit 2, Week 2, Day 15..............................................................................56
6.2.3. Visit 3, Month 1, Day 29 ............................................................................57
6.2.4. Visit 4, Month 2, Day 57 ............................................................................58
6.2.5. Visit 5, Month 3, Day 85 ............................................................................59
6.2.6. Visit 6, Month 4, Day 113 ..........................................................................61
6.2.7. Visit 7, Month 6, Day 169 or Early Termination Visit...............................62
6.2.8. Follow-up Visit...........................................................................................63
6.3. Subject Withdrawal.................................................................................................64
6.3.1. Monitoring Criteria.....................................................................................65
6.3.2. Discontinuation Criteria..............................................................................65
7. ASSESSMENTS..................................................................................................................67
7.1. Efficacy Endpoints ..................................................................................................67
7.1.1. ACR Assessments.......................................................................................67
7.1.2. DAS Assessment ........................................................................................67
7.1.3. PsA Response Criteria (PsARC) ................................................................68
7.2. Clinical Evaluation of Rheumatology Endpoints....................................................68
7.2.1. Tender/Painful Joint Count (68).................................................................68
7.2.2. Tender/Painful Joint Count (28).................................................................69
7.2.3. Swollen Joint Count (66)............................................................................69
7.2.4. Swollen Joint Count (28)............................................................................69
7.2.5. Physician’s Global Assessment of Arthritis ...............................................69
7.2.6. Physician’s Global Assessment of Psoriatic Arthritis ................................70
7.2.7. Assessment of Dactylitis.............................................................................70
7.2.8. Assessment of Enthesitis ............................................................................70
7.2.9. C-Reactive Protein (CRP)...........................................................................70
7.3. Clinical Evaluation of Dermatologic Endpoints .....................................................70
7.3.1. Physician’s Global Assessment of Psoriasis (PGA-PsO)...........................70
7.3.2. Psoriasis Area and Severity Index (PASI)..................................................71


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7.3.3. Body Surface Area (BSA) ..........................................................................73
7.3.4. Nail Psoriasis Severity Index (NAPSI) Score ............................................73
7.4. Health Outcome Measures ......................................................................................74
7.4.1. Patient’s Assessment of Arthritis Pain .......................................................74
7.4.2. Patient’s Global Assessment of Arthritis....................................................74
7.4.3. Health Assessment Questionnaire-Disability Index (HAQ-DI) .................74
7.4.4. SF-36 Health Survey (Version 2, Acute)....................................................75
7.4.5. EuroQol EQ-5D Health State Profile .........................................................75
7.4.6. Work Productivity and Activity Impairment – Psoriatic Arthritis 
Questionnaire...................................................................................................75
7.5. Safety.......................................................................................................................75
7.5.1. Vital Signs and Temperature ......................................................................75
7.5.2. Electrocardiogram.......................................................................................76
7.5.3. Tuberculosis Screening...............................................................................76
7.5.3.1. Quantiferon- TB Gold In-Tube Test .......................................76
7.5.3.2. Purified Protein Derivative (PPD) Tuberculin Test ..................77
7.5.3.3. Chest Radiograph (CXR) ..........................................................77
7.5.4. Complete Physical Examination.................................................................77
7.5.5. Targeted Examination.................................................................................77
7.5.6. Weight, Waist and Hips Circumference and Height ..................................78
7.5.7. Clinical Safety Laboratory Tests ................................................................78
7.5.7.1. Hepatitis B and C Virus Testing ...............................................78
7.5.7.2. Pregnancy Testing.....................................................................80
7.5.8. Risk Factor Check for Venous Thromboembolism....................................80
7.6. Cardiovascular and Malignancy Events..................................................................81
7.6.1. Cardiovascular Events ................................................................................81
7.6.2. Malignancy Events .....................................................................................81
7.7. Corona Virus Disease 2019 (COVID-19) ...............................................................82
8. ADVERSE EVENT REPORTING......................................................................................84
8.1. Adverse Events........................................................................................................84
8.1.1. Additional Details On Recording Adverse Event on the CRF ...................85
8.1.2. Eliciting Adverse Event Information..........................................................85


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8.1.3. Withdrawal From the Study Due to Adverse Events (see also the 
Subject Withdrawal section)............................................................................85
8.1.4. Time Period for Collecting AE/SAE Information......................................86
8.1.4.1. Reporting SAEs to Pfizer Safety...............................................86
8.1.4.2. Recording Non-serious AEs and SAEs on the CRF .................86
8.1.5. Causality Assessment .................................................................................86
8.1.6. Sponsor’s Reporting Requirements to Regulatory Authorities ..................87
8.2. Definitions...............................................................................................................87
8.2.1. Adverse Events...........................................................................................87
8.2.2. Abnormal Test Findings .............................................................................88
8.2.3. Serious Adverse Events..............................................................................88
8.2.4. Hospitalization............................................................................................89
8.3. Severity Assessment................................................................................................90
8.4. Special Situations ....................................................................................................90
8.4.1. Protocol-Specified Serious Adverse Events ...............................................90
8.4.2. Potential Cases of Drug-Induced Liver Injury............................................90
8.4.3. Exposure to the Investigational Product During Pregnancy or 
Breastfeeding, and Occupational Exposure.....................................................92
8.4.3.1. Exposure During Pregnancy......................................................92
8.4.3.2. Exposure During Breastfeeding ................................................93
8.4.3.3. Occupational Exposure .............................................................94
8.4.4. Medication Errors .......................................................................................94
8.4.4.1. Medication Errors......................................................................94
8.5. Infections.................................................................................................................95
8.5.1. Serious Infections .......................................................................................95
8.5.2. Treated Infections.......................................................................................95
9. DATA ANALYSIS/STATISTICAL METHODS...............................................................95
9.1. Sample Size Determination.....................................................................................95
9.2. Efficacy Analysis ....................................................................................................96
9.2.1. Analysis of Primary Endpoint of ACR50 Response Rate ..........................96
9.2.2. Analysis of Secondary Endpoints...............................................................96
9.3. Analysis of Other Endpoints ...................................................................................96
9.4. Safety Analysis........................................................................................................96


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9.5. Data Monitoring Committee ...................................................................................97
9.6. Safety Endpoints Adjudication Committees (SEAC) .............................................97
10. QUALITY CONTROL AND QUALITY ASSURANCE.................................................98
11. DATA HANDLING AND RECORD KEEPING .............................................................98
11.1. Case Report Forms/Electronic Data Record .........................................................98
11.2. Record Retention...................................................................................................99
12. ETHICS..............................................................................................................................99
12.1. Institutional Review Board (IRB)/ Ethics Committee (EC)..................................99
12.2. Ethical Conduct of the Study ..............................................................................100
12.3. Subject Information and Consent........................................................................100
12.4. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH 
GCP .........................................................................................................................101
13. DEFINITION OF END OF TRIAL.................................................................................101
14. SPONSOR DISCONTINUATION CRITERIA ..............................................................101
15. PUBLICATION OF STUDY RESULTS........................................................................101
15.1. Communication of Results by Pfizer ..................................................................101
15.2. Publications by Investigators ..............................................................................102
16. REFERENCES ................................................................................................................104
LIST OF TABLES
Table 1.
Component Scoring Criteria for the Physician's Global Assessment 
(PGA-PsO)................................................................................................71
Table 2.
Physician's Global Assessment (PGA-PsO) Score...................................71
Table 3.
Component Scoring Criteria for the Psoriasis Area and Severity 
Index (PASI).............................................................................................72
Table 4.
Psoriasis Area and Severity Index (PASI) Area Score Criteria................72
Table 5.
Psoriasis Area and Severity Index (PASI) Lesions Body Region 
Weighting .................................................................................................73
Table 6.
Clinical Laboratory Testing......................................................................79


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APPENDICES
Appendix 1. Abbreviations....................................................................................................107
Appendix 2. Cockcroft-Gault Calculation.............................................................................110
Appendix 3. Prohibited Concomitant Medications................................................................111
Appendix 4. Approximate Equivalent Morphine Doses of Opioid Analgesics.....................114
Appendix 5. Rescue Therapy.................................................................................................115
Appendix 6. Evaluation of Potentially Malignant Tumors, Suspicious 
Lymphadenopathy, Possible Extranodal Lymphoproliferative 
Disorder (LPD) .......................................................................................117


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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 the 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 received Federal Drug Administration (FDA) 
approval on 6 November 2012 for this indication.  Tofacitinib citrate 5 mg twice daily (BID)
dose was also approved in Japan and Korea, and both tofacitinib citrate 5 mg BID and 10 mg 
BID doses approved in Taiwan.  In China, tofacitinib 5 mg BID was approved on 10 March 
2017, for the indication to treat adult patients with moderately to severely active RA who 
have had inadequate response or intolerance to Methotrexate (MTX).  Efficacy and safety of 
tofacitinib 5 mg BID has been demonstrated in 2 completed Phase 3 studies and 1 ongoing 
long term extension study of PsA.  Data from the Global Phase 3 trials in PsA is under 
review by FDA.
This is a 6 month Phase 3 study designed to evaluate the efficacy and safety of tofacitinib
5 mg BID as a treatment for PsA in Chinese subjects with active PsA who have had an 
inadequate response in their PsA to at least one conventional synthetic disease-modifying 
anti-rheumatic drug (csDMARD).
Objectives:

To compare efficacy of tofacitinib 5 mg BID versus placebo for treatment of 
rheumatological signs and symptoms of PsA in Chinese subjects with active PsA who 
have had an inadequate response to at least one csDMARD.

To compare the safety and tolerability of tofacitinib 5 mg BID versus placebo in 
Chinese subjects with active PsA who have had an inadequate response in PsA to at 
least one csDMARD.

To compare physical function status, health outcome measures and dermatological 
signs and symptoms after administration of tofacitinib 5 mg BID versus placebo in 
Chinese subjects with active PsA who have had an inadequate response in PsA to at
least one csDMARD.


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Study Design:
This is a Phase 3 randomized, 6-month, double-blind, placebo-controlled, parallel group
study designed to evaluate the efficacy and safety of tofacitinib in adult, Chinese subjects 
with active PsA who had an inadequate response in their PsA to at least one csDMARD.  A
total of approximately 204 subjects will be randomized in a 2:1 ratio to one of the following 
two parallel treatment sequences. The enrollment will be monitored to cap the proportion of 
subjects with baseline swollen joint count 5 at approximately 38% (ie, approximately 
78 subjects).
Treatment 
Sequence
Treatment 
Planned Number of 
Randomized Subjects
Sequence A
Tofacitinib 5 mg BID
136
Sequence B
Placebo x 3 Months Tofacitinib 5 mg BID1
68
1. At Month 3, subjects randomized into Treatment Sequence B will receive tofacitinib 5 mg BID in a blinded manner 
through Month 6. 
Primary study endpoint of The American College of Rheumatology’s definition for 
calculating improvement in RA (ACR50) responder rate will be obtained at Month 3.  During 
the study, subjects are required to remain on a stable dose of one csDMARD, 
eg, methotrexate or sulfasalazine and should remain on that dose throughout the study.
Study Treatments:
Subjects are randomized to receive either tofacitinib 5 mg BID or placebo.  At Month 3, all 
subjects receiving placebo will be advanced to tofacitinib 5 mg BID in a blinded manner for
3 months. Investigators, subjects and sponsor will remain blinded through the entire duration 
of the study until database release.
Statistical Methods:
The sample size and power analysis for the primary endpoint are based on the randomization 
of approximately204 subjects in a 2:1 ratio.  The sample size for this study is driven by the 
ACR50 response rate.
On the assumption of a placebo response rate of 9.5% and factoring in the number of subjects
with primary endpoint data missing due to COVID-19 (around 11 subjects as of 29 May 
2020), this sample size of approximately 136 Chinese subjects in the tofacitinib treatment 
arm and 68 subjects in the placebo arm will yield at least 90% power to detect a difference of 
18.5% from placebo in ACR50 response, based on normal approximation (without continuity
correction) at the 2-sided significance level of 5%.


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SCHEDULE OF ACTIVITIES
The Schedule of Activities table provides an overview of the protocol visits and procedures. Refer to STUDY PROCEDURES and
ASSESSMENTS section of the protocol 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.
Visit Identifier and visit windowa
Screening1
Visit 1
Baseline
Day 1
Visit 2
Week 2
(Day 153 
days)
Visit 3
Month 1
(Day 293
days)
Visit 4
Month 2
(Day 577 
days)
Visit 5
Month 3
(Day 857 
days)
Visit 6
Month 4
(Day1137
days)
Visit 7
Month 6
(1697 days)
Early 
Termination
Follow-
up Visit18
Informed Consent
X
PsA Diagnosis, Medical History2
X
Concomitant/Prior Medications
X
X
X
X
X
X
X
X
X
X
Complete Physical Exam3
X
X
X
X
Targeted Physical Exam3
X
X
X
X
X
Vital Signs, Temperature
X
X
X
X
X
X
X
X
X
Waist and Hips Circumference
X
X
X
Height
X
12-Lead ECG
X
X
X
QuantiFERON-TB Gold (or 
Mantoux/PPD Skin Test); Chest 
Radiographs4
X
LABORATORY TESTING19
Hematology5
X
X
X
X
X
X
X
X
X
Hemoglobin A1c (HbA1c)
X
X
X
X
Lymphocyte subset analysis (FACS)
X
X
X
X
Chemistry panel (fasting)6
X
X
X
X
X
X
X
X
X
Lipid Panel (fasting)7
X
X
X
X
X
X
X
Urinalysis8
X
X
X
X
X
X
X
X
Urine pregnancy test (HCG)9
X
X
X
X
X
X
X
X
X
X
C-Reactive Protein (CRP)
X
X
X
X
X
X
X
X
X
HIV serology, HBsAg, HBcAb, 
HCV Ab 
X
Prothrombin time (INR)10
X
Rheumatoid Factor (RF), Cyclic 
Citrullinated Peptide Antibody (CCP)
X


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Visit Identifier and visit windowa
Screening1
Visit 1
Baseline
Day 1
Visit 2
Week 2
(Day 153 
days)
Visit 3
Month 1
(Day 293
days)
Visit 4
Month 2
(Day 577 
days)
Visit 5
Month 3
(Day 857 
days)
Visit 6
Month 4
(Day1137
days)
Visit 7
Month 6
(1697 days)
Early 
Termination
Follow-
up Visit18
Serum follicle stimulating
hormone (FSH)11
X
CLINICAL EVALUATION OF 
RHEUMATOLOGY ENDPOINTS12
Tender/Painful Joint Count, Swollen
Joint Count
X
X
X
X
X
X
X
X
X
Physician’s Global Assessment of 
Arthritis (VAS)
X
X
X
X
X
X
X
X
Physician’s Global Assessment of 
Psoriatic Arthritis (VAS)
X
X
X
X
X
Dactylitis Assessment
X
X
X
X
X
Enthesitis Assessment (Leeds Index)13
X
X
X
X
X
CLINICAL EVALUATION OF 
DERMATOLOGY ENDPOINTS12
Assessment of plaque psoriasis14
X
Physician’s Global Assessment of 
Psoriasis (PGA-PsO)15
X
X
X
X
X
Psoriasis Area and Severity Index 
(PASI); Body Surface Area (BSA)15
X
X
X
X
X
Nail Psoriasis Severity Index (NAPSI)16
X
X
X
X
X
PATIENT REPORTED 
OUTCOMES17
Patient’s Assessment of Arthritis Pain 
(VAS); Patient’s Global Assessment of
Arthritis (VAS); HAQ-DI
X
X
X
X
X
X
X
X
SF-36, EQ-5D
X
X
X
X
X
WPAI-PsA
X
X
X
X
OTHER ACTIVITIES
Contraception check20
X
X
X
X
X
X
X
X
X
Randomization
X
Drug Dispensing
X
X
Dosing diary despensing
X
Drug Accountability; review 
dosing diary
X
X
X
X
X
X
X
Serious and non-serious adverse event 
monitoring
X
X
X
X
X
X
X
X
X
X


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Visit Identifier and visit windowa
Screening1
Visit 1
Baseline
Day 1
Visit 2
Week 2
(Day 153 
days)
Visit 3
Month 1
(Day 293
days)
Visit 4
Month 2
(Day 577 
days)
Visit 5
Month 3
(Day 857 
days)
Visit 6
Month 4
(Day1137
days)
Visit 7
Month 6
(1697 days)
Early 
Termination
Follow-
up Visit18
Risk factor check for venous 
thromboembolism21
X
X
X
X
X
X
X
X
X
X
a.
Day relative to start of study treatment (Day 1).  For the purpose of this protocol, 1 Month is defined as 28 calendar days.
1.
Screening visit occurs within 28 (+10) days prior to Baseline (Day 1) visit.
2.
Psoriatic Arthritis (PsA) diagnosis is based upon Classification Criteria for Psoriatic Arthritis (CASPAR) at screening (see Section 4.1.1).  For study inclusion, subject must 
have had signs and symptoms consistent with PsA diagnosed for at least 6 months.  PsA disease subtype will be collected and documented in eCRF (see Section 6.2).  
Medical history includes cardiovascular (CV) risk factor assessment ie, smoking status, average weekly alcohol consumption, family history of premature coronary heart 
disease (CHD).
3.
Complete physical exam includes weight, general appearance, skin, HEENT (head, eyes, ears, nose and throat), heart, lungs, abdomen, lower extremities, neurologic and 
lymph nodes.  Targeted physical exam consists of weight, examination of heart, lungs, abdomen, lymph nodes and lower extremities.
4.
For subjects with latent tuberculosis infection and treated with preventive anti-tuberculosis therapy during study, chest radiograph should be be monitored per local practice.
5.
Hematology includes RBC, RBC morphology, WBC with differential, hemoglobin, hematocrit, reticulocyte count and platelet count.
6.
Chemistry panel (fasting) 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).
7.
Lipid Panel (fasting) includes: fasting total cholesterol, LDL, HDL, triglycerides.  In addition, apolipoprotein A-1 and B will be measured at baseline, Months 1, 3, 6 (or Early 
Termination) and Follow-Up Visit for eligible subjects. All lipid profile tests will be performed by the central laboratory. 
8.
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).
9.
Urine pregnancy test (human chorionic gonadotrophin, HCG) is required only for women of child-bearing potential; may be repeated more frequently if required by local 
practices, if a menstrual cycle is missed, or if potential pregnancy is otherwise suspected.
10. Prothrombin time (INR) will be performed at Screening and as needed in cases of elevated liver enzymes. 
11. Post-menopausal status may be confirmed at the discretion of investigator by having a serum follicle stimulating hormone (FSH) level within the laboratory’s reference range 
for postmenopausal females as per 4.1 Inclusion Criteria.
12. All rheumatologic and dermatologic evaluations performed at baseline and thereafter will be done by a qualified assessor who is blinded to the subject’s safety data, previous 
efficacy data and treatment randomization. 
13. Enthesitis will be assessed using Leeds Index (Section 7.2.8).
14. For study eligibility, subjects must have active plaque psoriasis at Screening which has been diagnosed or confirmed by a dermatologist or a Sponsor-approved 
rheumatologist.
15. 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. 
16. Nail Psoriasis Severity Index (NAPSI) will be performed on the target finger nail identified at baseline and be followed for duration of the study (Section 7.3.4).


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17. Subject completed questionnaires include: Patient’s Global Assessment of Arthritis (VAS), Patient’s Global Assessment of Arthritis Pain (VAS), Health Assessment 
Questionnaire-Disability Index (HAQ-DI), Short-Form-36 Health Survey (Version 2, Acute) (SF-36), EuroQol 5 Dimensions (EQ5D) and The work productivity and Activity
Impairment – Psoriatic Arthitis Questionnaire (WPAI-PsA).  All patient reported outcomes should be completed prior to any other assessments made at each visit.
18. If a subject discontinues from or completes the study with abnormalities in hematology or clinical chemistry results (as defined in Section 6.3.2), or a subject discontinues 
from study due to an adverse event, a follow-up visit must be performed after the Early Termination study visit within 28 days (+14 days) of last dose of study treatment.  In 
addition, all subjects who complete the study must have a follow-up visit within 28 days (+14 days) of end of study visit. 
19. Testings that are to be done in central lab: hematology, HbA1c, Lymphocyte subset analysis (FACS), Chemistry panel, Lipid Panel, Urinalysis, C-Reactive Protein (CRP),
HIV serology, HBsAg, HBcAb, HCV Ab, Prothrombin time (INR), Rheumatoid Factor (RF), QuantiFERON-TB Gold, FSH testing if needed.
20. Confirm and document that contraception, if assigned, is used consistently and correctly.
21. Per amendment 3, all subjects will be asked at every study visit if they have any newly-developed risk factors for venous thromboembolism as described in Section 7.5.8.


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1. INTRODUCTION
1.1. Mechanism of Action/Indication
Tofacitinib is a highly selective inhibitor of the Janus kinase (JAK) family of kinases that is 
being developed for the treatment of adult, Chinese subjects with active psoriatic arthritis
(PsA) who have had an inadequate response to csDMARD treatment for 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 goals of 
therapy for patients with PsA are: 1) to achieve the lowest possible level of disease activity in 
all disease domains; 2) to optimize functional status, improve quality of life and well-being; 
3) to prevent structural damage to the greatest extent possible; and 4) to avoid or minimize 
complications, both from untreated active disease and from therapy.
While non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids are included in
the 2016 Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA)
guidance,3 these medications are only mildly effective at relieving musculoskeletal signs and
symptoms, and they have safety risks with long-term usage. Despite the relative paucity of
randomized controlled data in PsA trials supporting their efficacy and safety, csDMARDs 
such as MTX are used for treatment of PsA peripheral arthritis, psoriasis, and dactylitis.  
csDMARDs are not recommended by GRAPPA for treatment of enthesitis or axial domains, 
due to lack of evidence for efficacy. Furthermore, their use can be limited by adverse events 
including liver toxicity (methotrexate, leflunomide), hypersensitivity and blood dyscrasias
(sulfasalazine),4 and nephrotoxicity (cyclosporine).5,6,7  Limited or questionable effectiveness 
accompanied with potential toxicity suggest that a large proportion of PsA patients are
inadequately treated with csDMARDs.
The targeted synthetic disease modifying anti-rheumatic drug (tsDMARD) apremilast is a
selective inhibitor of the enzyme phosphodiesterase 4 (PDE4) which was recently approved
for the treatment of PsA.  It has demonstrated mild to modest efficacy on PsA signs and
symptoms, evidenced by lack of statistical significance versus placebo for higher thresholds
of efficacy for peripheral arthritis (eg, American College of Rheumatology criteria
50% improvement [ACR50] and American College of Rheumatology criteria 
70% improvement [ACR70]).  Apremilast also has no PsA structural assessment data, and
its use can be limited by tolerability issues.
Currently 5 tumour necrosis factor inhibitors (TNFi) are approved by the US FDA for use in 
PsA: infliximab, etanercept, adalimumab, golimumab, and certolizumab.8 Within the last
few years, additional biologic disease-modifying anti-rheumatic drugs (bDMARDs) have 
been approved for PsA including ustekinumab (a human mAb interleukin-12 and IL-23
antagonist) and secukinumab (a human mAb interleukin-17A antagonist).  These bDMARD 
therapies have demonstrated statistical significance versus placebo on ACR 20/50/70 
responses; as well as efficacy in other PsA domains.


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TNFi and Apremilast are not approved in China for the treatment of PsA.  There is therefore 
unmet medical need for new disease-modifying anti-rheumatic drugs (DMARDs) in the PsA 
patient population in China where there is no approved biologic/TNFi for PsA and treatment 
alternatives are insufficient. 
This trial will use placebo control in the study design to provide rigorous hypothesis testing
and unequivocal scientific data to evaluate the efficacy and safety profile of tofacitinib in
Chinese PsA patient population.  The placebo control period will be 3 months in duration
which should be adequate time to see effects of active treatment on signs/symptoms of PsA 
and minimize the amount of structural damage incurred.  Subjects who enroll in this study 
should remain on their concomitant non-biologic DMARDs as noted in the 
inclusion/exclusion criteria.  In addition, subjects may be offered an appropriate rescue 
medication (see Appendix 5) during the study if there is an increase in pain.  Finally, if 
subjects do experience an increased or persistent clinical disease activity, they will have the 
option to withdraw from the study at any time.
This Phase 3 study will evaluate the efficacy and safety of tofacitinib, a highly selective 
inhibitor of the JAK family of kinases (including JAK3), for the treatment of active PsA in a 
double-blind, 6-month, placebo-controlled, randomized study in adult, Chinese subjects who 
have had an inadequate response to at least one csDMARD.  Tofacitinib has previously 
demonstrated efficacy and safety in Phase 2 and Phase 3 studies of Rheumatoid Arthritis 
(RA) and 5 mg BID was approved by the FDA 6 November 2012 for treatment of moderate 
to severe RA.  Tofacitinib citrate 5 mg dose was also approved in Japan and Korea, and both 
tofacitinib citrate 5 mg and 10 mg doses approved in Taiwan.  In China, tofacitinib 5 mg BID 
was approved on 10 March 2017, for the indication to treat adult patients with moderately to 
severely active RA who have had inadequate response or intolerance to MTX.  Efficacy and 
safety of tofacitinib 5 mg BID has been demonstrated in 2 completed Phase 3 studies and
1 ongoing long term extension study of PsA.  Data from the Global Phase 3 trials in PsA is 
under review by FDA.
In this study, a similar study design to the global pivotal study A3921091 will be used to 
investigate the safety and efficacy of tofacitinib 5 mg BID in Chinese subjects with active 
PsA.
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 -21.9,10,11  These cytokines are integral to lymphocyte activation, 
proliferation, and function and inhibition of their signaling may thus result in modulation of 
multiple aspects of the 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 


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interferons.  At higher exposures, inhibition of erythropoietin signaling could occur via 
inhibition of JAK2 signaling.  Many of the cytokines that are associated specifically with the 
pathogenesis of PsA (eg, IL-2, IFN-, IL-12, IL-23) are modulated directly by JAK inhibition
with tofacitinib.  Furthermore, tofacitinib has been shown to suppress IL-22 cytokine 
signaling and IL-23 receptor expression and to inhibit T helper 17 (Th17) cell
differentiation.12,13 Tofacitinib suppresses the production of IL-17 by T cells isolated from 
synovium and peripheral blood of RA patients.14  Treatment with tofacitinib dosed at
5 mg BID or 10 mg BID for 52 weeks in RA patients significantly decreased the level of
IL-17 produced by circulating T cells.15
In summary, tofacitinib, via JAK inhibition, was predicted to have robust efficacy in the 
treatment of PsA.  Tofacitinib efficacy has also been demonstrated in RA as well as in 
comorbid diseases frequently seen in PsA such as plaque psoriasis, inflammatory bowel 
disease, with some evidence of efficacy in AS.16,17
1.2.2. Summary of Efficacy
Efficacy of tofacitinib in patients with psoriatic arthritis was demonstrated in two Phase 3 
studies: A3921091 and A3921125.
A3921091 was a randomized, placebo and active comparator controlled, double-blind, 
multi-site Phase 3 study in active PsA subjects who had inadequate response to at least one 
csDMARD.  Of 422 randomized subjects, 406 completed Month 3 visit at which assessments 
of primary endpoints ACR20 and HAQ-DI were done.  Significantly greater improvements 
in ACR20 response rates (5 mg BID vs placebo: 50.5% vs 33.3%, P=0.0102; 10 mg BID vs 
placebo: 60.6 vs 33.3%, P<0.0001) and HAQ-DI (Health Assessment Questionnaire 
Disability Index) (5 mg BID vs placebo: -0.35 vs -0.18, P=0.0062; 10 mg BID vs 
placebo: -0.40 vs -0.18, P=0.0004) were observed for both tofacitinib 5 mg BID and 
10 mg BID versus placebo at Month 3 and were maintained to Month 12.  Tofacitinib 5 and 
10 mg BID demonstrated superiority vs PBO for ACR20 response rate as early as Week 2 
(22.4% and 31.7% vs 5.7%; p<0.001). ACR50 response rates were statistically significantly 
higher in active-treated arms than in the placebo arm at Month 3 during the double-blind 
placebo-controlled period. At Month 3, the ACR50 response rates were 28.04% for 
tofacitinib 5 mg BID, 40.38% for tofacitinib 10 mg BID, 33.02% for adalimumab 40 mg SC 
(subcutaneous) q 2 weeks, and 9.52% for placebo (P values were 0.0004, <0.0001 and 
<0.0001 for tofacitinib 5 mg BID vs Placebo, tofacitinib 10 mg BID vs Placebo and 
Adalimumab vs Placebo).
A3921125 was a randomized, placebo controlled, double-blind, multi-site Phase 3 study in 
active PsA subjects who had inadequate response to at least one TNF inhibitor.  Of the
395 randomized subjects, 394 were treated, 364 (91.6%) completed Month 3 visit at which 
assessments of primary endpoints ACR20 and HAQ-DI were done.  There were significantly 
greater improvements in ACR20 response (5 mg BID vs placebo: 49.6% vs 23.7%, 
P<0.0001; 10 mg BID vs placebo: 47.0% vs 23.7%, P<0.0001) and HAQ-DI (5 mg BID vs 
placebo: -0.39 vs -0.14, P<0.0001; 10 mg BID vs placebo: -0.35 vs -0.14, P=0.0009) for both 
tofacitinib doses compared to placebo at Month 3; improvements were maintained to 
Month 6.  Tofacitinib 5 and 10 mg BID demonstrated superior ACR20 response vs placebo 


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as early as Week 2 (26.7% and 28.8% vs 13.0%; p0.05).  At Month 3, the ACR50 response 
rates were 29.77% for tofacitinib 5 mg BID, 28.03% for tofacitinib 10 mg BID, and 
14.5% for placebo (P values were 0.0025 and 0.0065 for tofacitinib 5 mg BID vs placebo and 
tofacitinib 10 mg BID vs placebo).
1.2.3. Summary of Safety
The clinical development program for tofacitinib includes healthy volunteers and subjects 
with RA, plaque psoriasis, Psoriatic Arthritis, Crohn’s disease, ulcerative colitis, ankylosing 
spondylitis and renal transplants enrolled in Phase 1, 2 and 3 studies.
As of January 2016, over 22,000 patients have received at least 1 study dose of oral 
tofacitinib, in either a randomized clinical study or in a long-term extension (LTE) study.  In 
Phase 1 studies, tofacitinib has been administered to healthy volunteers or subjects in single 
doses ranging from 0.1 to 100 mg and in multiple dose regimens ranging from 5 to 
50 mg BID, as well as 60 mg once daily (QD).
Potential safety risks for subjects treated with tofacitinib are based on the totality of the data
including nonclinical observations, clinical observations, as well as safety risks reported for 
other therapies that may share common pathways with tofacitinib.  These risks include 
serious and other important infections such as opportunistic infections and herpes zoster 
infections, potential for malignancies including lymphoma, and the potential for GI 
perforations.  Laboratory changes associated with, or potentially associated with, tofacitinib 
treatment include decreases in hemoglobin levels and absolute neutrophil counts (ANC), and 
increases in lipids, transaminases, serum creatinine, and creatine kinase (CK); the clinical 
significance of the laboratory changes is uncertain. Although a potential increase risk in 
cardiovascular (CV) events may also be a concern, this is not supported based upon review of 
cardiovascular events in subjects with RA during both short and long-term treatment with 
tofacitinib. However, the number of events reported and resulting wide confidence intervals 
means that a definitive conclusion cannot be made at this time.  The safety profile of 
tofacitinib in both rheumatoid arthritis and psoriasis subject populations is qualitatively
similar. Tofacitinib treatment was well tolerated by subjects participating in the Phase 3 
clinical trials in the PsA development program.  The observed safety findings were consistent 
with those observed in both short and long-term data from the RA and psoriasis (PsO)
development programs and with other drugs used to treat PsA.  No new safety findings were 
identified and the risks associated with tofacitinib treatment can be mitigated or are
manageable via the existing measures employed for the approved indication of RA described 
in the current prescribing information.
Both doses of tofacitinib were well tolerated. In PsA subjects treated with tofacitinib, serious 
infections were few, and did not increase over long-term exposure, with a minimal numerical
dose dependent difference between 5 mg BID and 10 mg BID.  Dose dependent incidence
rates for serious infection events were consistent with those seen in RA and PsO, despite the 
relatively smaller PsA data set. Evidence for dose dependent differences in herpes zoster, 
serious infections, non-melanoma skin cancer, and laboratory abnormalities was identified in 
the RA and in PsO development programs.


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Interpretation of these results and the possible risks associated with the administration of 
tofacitinib are summarized in Investigator's Brochure.
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, especially in China where neither 
TNFi nor other biologics are approved for PsA.
The benefits to individual subjects participating in this study will be the potential control of 
the disease activity by improving signs and symptoms.  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 RA 
subjects who have received tofacitinib, the rate of serious infections is higher in subjects 
65 years of age and older.  Rates of herpes zoster infections in tofacitinib-treated subjects
with RA were increased compared with placebo-treated subjects and historical controls; this 
included an increased risk of herpes zoster infections in Asian RA patients compared with 
non-Asian RA patients. 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.  Infections, anemia 
and neutropenia are all consistent with the pharmacology of tofacitinib as a potent inhibitor 
of JAK3 with cross-over to JAK1 and moderate selectivity for JAK2.  Treatment with 
tofacitinib was associated with increases in levels of low density lipoprotein(LDL) and high 
density lipoprotein (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.  Review of cardiovascular events 
reported in the RA studies suggests that tofacitinib does not appear to increase ocurrence of 
Major Adverse Cardiac Events (MACE) in subjects with RA during both short- and 
long-term treatment.  The long-term implications of these changes for cardiovascular risk are
currently unknown.  Also seen in previous studies were slight increases in measured serum 
creatinine and serum transaminases.  This effect generally returned to baseline 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.  Potential risks that may also be associated with the use 
of tofacitinib include a potential increased risk of lymphoma and lymphoproliferative 
disorders, and other malignancies.  Non-melanoma skin cancers have been reported in RA 
patients treated with tofacitinib and has been assessed as an adverse drug reaction based 
primarily on the review of RA data.


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Cases of gastrointestinal (GI) perforation were observed in RA subjects taking tofacitinib,
often in the setting of diverticulitis.  All affected subjects were taking concomitant 
non-steroidal anti-inflammatory drugs (NSAIDs) and/or corticosteroids that have been
associated with an increased risk of GI tract injury.18  Isolated events of gastrointestinal 
perforation have also been reported in clinical trials in psoriasis and renal transplant subjects.  
These perforations were reported as diverticulitis or perforated diverticulum. In one report, 
the perforation occurred approximately two weeks after discontinuation of study therapy. 
Interstitial lung disease (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. 
In the PsA development program, the serious infection rate was similar between tofacitinib 
doses, as well as between tofacitinib and adalimumab, and similar to the RA and PsO 
development programs.
The incidence rate of malignancy for the PsA program is within range of those observed in 
the RA and PsO programs.  Rates in the RA and PsO long term extension (LTE) studies have 
not changed over time. The incidence rates for malignancies (excluding non-melanoma skin
cancer, NMSC) in tofacitinib treated PsA subjects were found to be within the range of those 
that have been reported in the published PsA literature (including LTE trials) and comparable 
to published rates for other PsA approved therapies. The incidence rate for NMSC for the 
PsA program is within range of those observed in the RA and PsO programs.
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.
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 area under the curve (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 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, Chinese, 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


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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
Completed studies for PsA include: A3921091, a Phase 3, randomized, double-blind,
placebo-controlled, active-controlled study of the efficacy and safety of 2 doses of tofacitinib 
or adalimumab in subjects with active PsA who had an inadequate response to an oral 
csDMARD; and A3921125, a Phase 3, randomized, double-blind, placebo controlled study
of the efficacy and safety of 2 doses of tofacitinib in subjects with active PsA who have had 
an inadequate response to at least one TNF inhibitor, and A3921092, an ongoing long-term, 
open-label extension study of tofacitinib for the treatment of PsA. ACR20 response rates,
HAQ-DI and ACR50 at Month 3 for both tofacitinib 5 mg BID and 10 mg BID were 
significantly superior to placebo in both Study A3921091 and A3921125. The ACR20,
HAQ-DI and ACR50 at Month 3 for the pooled data were consistent with the results of the 
individual study analyses. In Studies A3921091 and A3921125, onset of efficacy as 
measured by ACR20 response was shown at Week 2 (the first post-Baseline assessment) for 
both tofacitinib 5 mg BID and 10 mg BID as demonstrated by a statistically significant 
difference from placebo. In both Studies A3921091 and A3921125, the ACR20 response 
rates and HAQ-DI were maintained or improved for both tofacitinib 5 mg BID and 
10 mg BID from Month 3 through the end of study. Tofacitinib 5 mg BID and 10 mg BID 
response rates at Month 3 for the efficacy endpoints of ACR50 and ACR70 were 
significantly superior to placebo in Study A3921091.  In Study A3921125, ACR50 response 
rates at Month 3 for tofacitinib 5 mg BID and 10 mg BID were also significantly superior to 
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Tofacitinib treatment was well tolerated by subjects participating in the Phase 3 clinical trials 
in the PsA development program.  The observed safety findings were consistent with those 
observed in both short and long-term data from the RA and PsO development programs and 
with other drugs used to treat PsA.  No new safety findings were identified and the risks 
associated with tofacitinib treatment can be mitigated or are manageable via the existing 
measures employed for the approved indication of RA described in the current prescribing 
information. Safety risks identified in the PsA clinical trial program is consistent with 
tofacitinib 5 mg BID RA safety database on both the clinical development program and post
marketing experience.
Study A3921234 is intended to support the indication of tofacitinib 5 mg BID for reducing 
signs and symptoms and improving physical function in adult, Chinese patients with active 
PsA who have had inadequate response to at least one csDMARD.
1.2.7. Dose Selection Rationale
A3921046 was a Phase 3, Randomized, Double-Blind, Placebo-Controlled Study comparing
the efficacy of tofacitinib in doses of 5 mg BID and 10 mg BID versus placebo for the 
treatment of signs and symptoms in patients with active RA who have had an inadequate 
response to a DMARD (traditional or biologic), as measured by ACR20 at Month 6, change 
of HAQ-DI from baseline at Month 3, rate of achieving disease activity score (DAS)28-4 
(erythrocyte sedimentation rate [ESR])<2.6 at Month 6. 795 patients were randomized to 
treatment, and 792 received at least 1 dose of study medication; 651/792 (82.2%) patients 
completed the study.  In this study, China had 218 subjects randomized to treatment and 
216 received at least 1 dose of study medication. Statistical significance of the efficacy 
primary objectives was determined using the step-down procedure.  The ACR20 response 
rates at Month 6 were statistically significantly different for both tofacitinib doses compared
with placebo (tofacitinib 5 mg BID vs placebo, 52.73% vs 31.21%, P<0.0001; tofacitinib 
10 mg BID vs placebo, 58.25% vs 31.21%, P<0.0001).  The differences from placebo for 
mean changes from Baseline in HAQ-DI at Month 3 were also significantly different for both 
tofacitinib doses compared with placebo (tofacitinib 5 mg BID vs placebo, -0.46 vs -0.21, 
P<0.0001; tofacitinib 10 mg BID vs placebo, -0.56 vs -0.21, P<0.0001).  The rate of patients 
achieving a DAS28-4(ESR) <2.6 at Month 6 for tofcitinib 5 mg and 10 mg was also 
significantly different from placebo (tofacitinib 5 mg BID vs placebo, 9.13% vs 2.70%, 
P<0.0038; tofacitinib 10 mg BID vs placebo, 13.33% vs 2.70%, P<0.0001). The ACR50 
response rates at Month 3 and Month 6 were significantly different for both tofacitinib doses 
compared to placebo (at Month 3: tofacitinib 5 mg BID vs placebo, 27.33% vs 9.55%, 
P<0.0001; tofacitinib 10 mg BID vs placebo, 33.98% vs 9.55%, P<0.0001; at Month 6: 
tofacitinib 5 mg BID vs placebo, 33.76% vs 12.74%, P<0.0001; tofacitinib 10 mg BID vs
placebo, 36.57% vs 12.74%, P<0.0001).
A3921174 was a 52-week study evaluating the efficacy and safety of tofacitinib 5 and 
10 mg BID compared to placebo in subjects with moderate to severe chronic plaque psoriasis
in China, Korea, and Taiwan.  266 subjects were randomized to treatment. All of these
266 subjects received at least 1 dose of study medication. At Week 16, tofacitinib 
10 mg BID and 5 mg BID were both superior to placebo for the response of PGA “clear” or 
“almost clear” and the response of Psoriasis Area and Severity Index 75 (PASI75). The 


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proportions of subjects achieving PGA “clear” or “almost clear” and PASI75 responses at 
Week 16 (full analysis set, FAS/nonresponder imputation, NRI) were statistically significant
in the tofacitinib 10 mg BID (75.56% and 81.11%, respectively) and 5 mg BID (52.27% and 
54.55%, respectively) treatment groups compared to the placebo group (19.32% and 
12.50%, respectively) with all p <0.0001.
Tofacitinib 5 mg BID and 10 mg BID both demonstrated as effective doses for the treatment 
of active PsA across the 2 pivotal Phase 3 studies in TNFi-naïve and TNF-IR populations and
across multiple PsA disease domains (peripheral arthritis, skin manifestation, enthesitis, and 
dactylitis).  The observed differences between tofacitinib doses were modest, inconsistent in 
both magnitude and direction, and not considered clinically meaningful.
Tofacitinib treatment was generally well tolerated by PsA subjects participating in the 
Phase 3 clinical trials in the PsA development program.  No new safety findings were
identified. Evidence for dose dependent differences in herpes zoster, serious infection, 
non-melanoma skin cancer, and laboratory abnormalities was identified in the RA and in PsO 
development programs.  Although PsA development program was limited in size, similar 
trends are expected in PsA patients treated with tofacitinib.
Given that in general, the efficacy of tofacitinib 5 BID and 10 mg BID are similar and the 
dose response relationship for certain safety events are established in the larger RA and PsO
programs, the 5 mg BID dose optimizes the risk:benefit profile in the PsA population.
As tofacitinib has demonstrated efficacy and acceptable safety in both Chinese RA and
plaque psoriasis patients, and global PsA pivotal studies has demonstrated efficacy and 
safety, there is rationale to expect that it will be efficacious and acceptably safe in Chinese 
PsA patients. Based on globally recommended posology, tofacitinib 5 mg BID is selected in 
this protocol.  Complete information on 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 Objectives

To compare efficacy of tofacitinib 5 mg BID versus placebo for treatment of 
rheumatological signs and symptoms of PsA in Chinese subjects with active PsA who 
have had an inadequate response to at least one csDMARD.

To compare the safety and tolerability of tofacitinib 5 mg BID versus placebo in 
Chinese subjects with active PsA who have had an inadequate response in PsA to at 
least one csDMARD.


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2.1.2. Secondary Objectives

To compare physical function status after administration of tofacitinib 5 mg BID 
versus placebo in Chinese subjects with active PsA who have had an inadequate 
response in PsA to at least one csDMARD.

To compare the effects of tofacitinib 5 mg BID versus placebo on all health outcomes 
measures in Chinese subjects with active PsA who have had an inadequate response 
to at least one csDMARD.

To compare the efficacy of tofacitinib 5 mg BID versus placebo for the treatment of 
dermatological signs and symptoms of PsA in Chinese subjects who have had an 
inadequate response to at least one csDMARD.
2.2. Endpoints
2.2.1. Primary Endpoint

ACR50 responder rate at Month 3.
2.2.2. Secondary Endpoints
2.2.2.1. Secondary Efficacy Endpoints

ACR20 and ACR70 responder rates at all timepoints;

ACR50 responder rates at all timepoints other than Month 3;

Change from baseline () in ACR response criteria components (HAQ-DI, C-reactive
protein [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;

HAQ-DI response defined as a decrease from Baseline 0.30 for subjects with 
Baseline HAQ-DI 0.30 at all timepoints; HAQ-DI response defined as a decrease
from Baseline 0.35 for subjects with Baseline HAQ-DI 0.35 at all timepoints; 

Psoriatic Arthritis Response Criteria (PsARC) at Month 1, Month 3 and Month 6;

Physician’s Global Assessment of Psoriasis (PGA-PsO) at Month 1, Month 3 and 
Month 6;

PGA-PsO response of clear or almost clear and a 2-step improvement from
Baseline for subjects with Baseline PGA-PsO 2;

PGA-PsO for subjects with Baseline PGA-PsO >0;


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
Psoriasis Area and Severity Index 75 (PASI75) response at Month 1, Month 3 and 
Month 6 for subjects with Baseline psoriatic body surface area (BSA) 3% and 
Baseline PASI >0;

Dactylitis severity score (DSS) at Month 1, Month 3 and Month 6 for subjects with
Baseline DSS >0;

∆DSS;

Resolution of dactylitis defined as a subject achieving DSS=0;

Enthesitis score ([using Leeds enthesitis index (LEI))] at Month 1, Month 3 and 
Month 6 for subjects with Baseline LEI >0;

LEI;

Resolution of enthesitis defined as a subject LEI=0.
2.2.2.2. Secondary Physical Function and Health Outcome Measures
Assessed at baseline, Months 1, 3 and 6:

Short-Form-36 Health Survey (SF-36) Version 2, Acute;

EuroQol 5-Dimension Health State Profile (∆EQ-5D).
2.2.3. Safety Endpoints

Incidence and severity of adverse events.
2.2.4. Other Endpoints
2.2.4.1. Other Efficacy Endpoints

DAS28-3(CRP) at all timepoints;

Physician’s Global Assessment of Psoriatic Arthritis (PGA-PsA) at Month 1, 
Month 3 and Month 6;

%in PASI and PASI clinical sign component scores at Month 1, Month 3 and
Month 6 for subjects with Baseline BSA 3% and Baseline PASI >0;

%BSA at Month 1, Month 3 and Month 6 for subjects with Baseline BSA 0%;

Nail Psoriasis Severity Index (NAPSI) Score at Month 1, Month 3 and Month 6 for 
subjects with Baseline NAPSI >0.


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Health Outcome Measures Assessed at baseline, Months 3 and 6:

Work Productivity and Activity Impairment – Psoriatic Arthritis Questionnaire 
(WPAI-PsA).
2.2.4.2. Other Safety Endpoints

Clinical laboratory tests (eg, clinical chemistry, hematology);

Vital sign measurements (blood pressure, pulse rate and temperature);

Physical examinations;

Electro-cardiogram (ECG) measurements. 
3. STUDY DESIGN
This is a Phase 3 randomized, 6-month, double-blind, placebo-controlled, parallel-group 
study designed to evaluate the efficacy and safety of tofacitinib in adult, Chinese subjects 
with active PsA who had an inadequate response in their PsA to at least one csDMARD. All 
subjects in the study will be evaluated for risk factors for venous thromboembolism.19 See 
Risk Factor Check for VTE in Section 7.5.8 for tofacitinib dosing guidance when a risk 
factor is identified. A total of approximately 204 subjects will be randomized in a 2:1 ratio to 
one of the following two parallel treatment sequences. The enrollment will be monitored to
cap the proportion of subjects with baseline swollen joint count ≤5 at approximately 38% (ie, 
approximately 78 subjects).


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A schematic of the study design is shown below.
*Primary study endpoints of ACR50 will be obtained at Month 3. All subjects randomized to placebo will 
receive tofacitinib 5 mg BID in a blinded manner after Month 3. 
During the study, subjects are required to remain on a stable dose of one csDMARD, 
eg, methotrexate or sulfasalazine, and should remain on that dose throughout the study.
4. SUBJECT ELIGIBILITY CRITERIA
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.
PsA is a chronic inflammatory autoimmune disease characterized by joint inflammation and 
destruction, psoriatic skin lesions, enthesitis, dactylitis and spondylitis.  A subject must meet 
the peripheral arthritis criteria and the ClASsification criteria for Psoriatic ARthritis20
(CASPAR) for enrollment. However, not all of the eligible subjects will have presence of 
other PsA disease manifestations such as psoriasis, enthesitis or dactylitis at baseline.
Subject eligibility should be reviewed and documented by an appropriate member of the 
investigator’s study team before subjects are included in the study.
Randomization
Sequence A: Tofa 5 mg BID (n=136)
Sequence B: Placebo (n=68)
All advance to Tofa 5 mg BID at month 3
Screening
Baseline 
Month 3 
Month 6
-1 month
Visit Schedule


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4.1. Inclusion Criteria
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 legally acceptable representative) has been informed of all pertinent 
aspects of the study.
2. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and 
other study procedures.
3. Female subjects of childbearing potential and at risk for pregnancy must agree to use 
a highly effective method of contraception throughout the study and for at least 
28 days after the last dose of assigned treatment. 
Female subjects of nonchildbearing potential must meet at least one of the following 
criteria:

Have undergone a documented hysterectomy and/or bilateral oophorectomy;

Have medically confirmed ovarian failure; 

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 a serum follicle stimulating hormone 
(FSH) level within the laboratory’s reference range for postmenopausal females. 
All other female subjects (including female subjects with tubal ligations) are
considered to be of childbearing potential.
4. The subject has signs and symptoms consistent with the diagnosis of PsA for at least 
6 months and fulfills ClASsification criteria for Psoriatic ARthritis20 (CASPAR) 
Criteria at screening and has evidence of active arthritis based upon number of 
tender/painful and swollen joints detailed in Section 4.1.1 below. 
5. Ongoing treatment with a stable dose of a csDMARD (eg, methotrexate or
sulfasalazine) (Section 4.1.2 below).
6. Meet all other eligibility criteria described in Sections 4.2, 4.3 and 4.4 below.


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4.1.1. Active Psoriatic Arthritis
To be eligible for participation in this study, a subject must meet the following criteria:
1. To meet the CASPAR criteria, a subject must have inflammatory articular disease 
(joint, spine, or entheseal) with 3 points from the following 5 categories:
a.
Evidence of current psoriasis, a personal history of psoriasis, or a family history
of psoriasis.  Current psoriasis is defined as psoriatic skin or scalp disease present 
today as judged by a rheumatologist or dermatologist.†  A personal history of
psoriasis is defined as a history of psoriasis that may be obtained from a patient, 
family physician, dermatologist, rheumatologist, or other qualified health care 
provider.  A family history of psoriasis is defined as a history of psoriasis in a 
first- or second-degree relative according to patient report.
b. Typical psoriatic nail dystrophy including onycholysis, pitting, and hyperkeratosis 
observed on current physical examination.
c.
A negative test result for the presence of rheumatoid factor by any method except 
latex but preferably by enzyme-linked immunosorbent assay or nephelometry, 
according to the local laboratory reference range.
d. Either current dactylitis, defined as swelling of an entire digit, or a history of 
dactylitis recorded by a rheumatologist.
e.
Radiographic evidence of juxtaarticular new bone formation, appearing as 
ill-defined ossification near joint margins (but excluding osteophyte formation) on 
plain radiographs of the hand or foot.
†Current psoriasis is assigned a score of 2; all other features are assigned a score of 1.
2. The subject must have active arthritis at both screening and baseline, as defined by 
having both:
a.
3 tender/painful joints on motion (out of 68 joints assessed); and;
b. 3 swollen joints (out of 66 joints assessed).
3. The subject must have active plaque psoriasis at Screening which has been diagnosed
or confirmed by a dermatologist or a Sponsor-approved rheumatologist.


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4.1.2. Background DMARDs
All local standard-of-care practices for the administration of permitted background DMARD 
therapy, including laboratory testing, contraceptive requirements, follow-up care and 
contraindications should be performed according to local standards of care throughout the 
study.
Subjects must receive permitted background csDMARDs and should remain on a stable dose 
of one csDMARD throughout the course of 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 5.8).  Subject must 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 g/day.  Minimum duration of therapy 3 months 
and dose stable for 4 weeks prior to first dose of study drug.
4.2. PsA Patient Population

Subjects who had a documented inadequate response to at least one csDMARD due 
to lack of efficacy or toxicity/lack of toleration.

Subjects may have received a TNFi. 
4.3. Other Inclusion Criteria
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the 
study:
1. Subjects must be Chinese adults at least 18 years of age at the Screening visit.
2. No evidence of active or latent or inadequately treated infection with Mycobacterium 
tuberculosis (TB) as defined by all of the following:

A negative QuantiFERON-TB Gold (QFT-G) In-Tube test performed at or within 
3 months prior to a given Screening visit.  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.


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
A chest radiograph taken at or within the 3 months prior to screening without 
changes suggestive of active TB infection as determined (and documented) by a 
qualified radiologist or pulmonologist as per local standard of care.

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 or an acceptable alternative regimen) or active (acceptable
multi-drug regimen) TB infection per local practice, neither a PPD test nor a 
QuantiFERONTB Gold In-Tube(QFT-G) 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 exclusion of close contacts of multi-drug resistant TB,
documentation of an adequate treatment regimen, and prior approval of the 
Sponsor. 
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.  All biologic agents not otherwise mentioned 
(eg, inclusion criteria #4 and exclusion criteria #16) must be discontinued for a 
minimum of 6 months prior to the first dose of study drug. 
4. Subjects must not be receiving TNFi.  Subjects on TNFi must discontinue according 
to the following criteria:

Etanercept and its biosimilar biological products (Enbrel, Yisaipu, Qiangke, 
Anbainuo): 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 first dose of 
study drug;

Other biosimilar biological products could follow the requirements of their
reference product after confirming they have same half lives.


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5. 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.
6. Subjects who are already taking NSAIDs/Cyclooxygenase-2 (COX-2) inhibitors may 
participate in the study provided that the dose is stable for one week prior to first dose 
of study drug.
7. Subjects are to discontinue active psoriasis treatments prior to being enrolled in the 
study.

Biologics: All biologic agents, which includes investigational and marketed 
agents, and are not otherwise mentioned (eg, exclusion criteria #16) must be 
discontinued for a minimum of 6 months prior to first dose of study drug.

Topical treatments that could affect psoriasis, eg, corticosteroids, tars, 
keratolytics, anthralin, vitamin D analogs, and retinoids must be discontinued at
least 2 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.

Ultra-violet B (UVB) (narrowband or broadband) phototherapy must be 
discontinued at least 2 weeks prior to first dose of study drug.  Psoralens + UVA 
phototherapy (PUVA) must be discontinued at least 4 weeks prior to first dose of 
study drug.
4.4. Exclusion Criteria
Subjects with any of the following characteristics/conditions will not be included in the 
study:
1. Currently have non-plaque forms of psoriasis, eg erythrodermic, guttate or pustular, 
with the exception of nail psoriasis, which is allowed.
2. Investigator site staff members directly involved in the conduct of the study 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 study. 


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3. Participation in other interventional studies involving investigational drug(s) 
(Phases 1-4) within 4 weeks before the current study begins and/or during study 
participation.  Participation in any observational studies during study participation is 
permitted. 
4. Pregnant female subjects, breastfeeding female subjects, female subjects of 
child-bearing potential who are unwilling or unable to use a highly effective method 
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.  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 4.6.6). 
5. Blood dyscrasias within 3 months prior to the first dose of study drug including 
confirmed:
a.
Hemoglobin <10 g/dL (<100 g/L); 
b. White blood cell count <3.0 x 109/L (<3000 mm3);
c.
Absolute neutrophil count <1.5 x 109/L (<1500 mm3);
d. Absolute lymphocyte count of <1.0 x 109/L (<1000/mm3); 
e.
Platelet count <100 x 109/L (<100,000/mm3).
6. Estimated Creatinine Clearance <40 ml/min based on Cockcroft-Gault equation 
(Appendix 2).
7. Total bilirubin, aspartate amniotransferase (AST) or alanine aminotransferase (ALT) 
more than 1.5 times the upper limit of normal (ULN) at screening visit.
8. Current or recent history of a severe, progressive or uncontrolled renal, hepatic, 
hematological, gastrointestinal, metabolic (including hypercholesterolemia), 
endocrine, pulmonary, cardiovascular, or neurologic disease.
9. 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.
10. A subject with known immunodeficiency disorder or a first degree relative with a 
hereditary immunodeficiency.


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11. Functional Class IV 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.21
12. History of an infected joint prosthesis at any time, with the prosthesis still in situ.
13. 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.
14. History of recurrent (more than one episode) herpes zoster or disseminated (a single 
episode) herpes zoster or disseminated (a single episode) herpes simplex.
15. History of active infection (including localized infection): 

Requiring hospitalization, parenteral antimicrobial therapy, or as otherwise judged 
clinically significant by the investigator, within the 6 months prior to the first dose 
of study medication;

Requiring oral antimicrobial therapy within 2 weeks prior to the first dose of 
study medication.
16. 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.  Subjects who 
have received rituximab or other selective B-lymphocyte depleting agents (including 
experimental agents) are eligible if they have not received such therapy for at least 
1 year prior to first dose of study drug and have normal CD19/20+ counts by 
fluorescence activated cell sorter (FACS) analysis.
17. 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 4.6.2.  Vaccine Guidelines for further information 
regarding avoidance of household contacts who may be vaccinated).
18. 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.
19. History of alcohol or drug abuse unless in full remission for greater than 6 months 
prior to first dose of study medication.


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20. Screening 12-lead electrocardiogram (ECG) that demonstrates clinically relevant 
abnormalities (as determined by aqualified cardiologist) which may affect subject 
safety (eg, pattern of acute myocardial infarction, acute ischemia or serious 
arrhythmia) or interpretation of study results (eg, continuously paced ventricular 
rhythm or complete left bundle branch block).
21. 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.
22. Significant trauma or surgery procedure within 1 month prior to first dose of study
medication, or any planned elective surgery during the study period. 
23. A subject requiring prohibited concomitant medications (See Appendix 3). 
24. A subject known to be infected with human immunodeficiency virus (HIV), 
hepatitis B virus (HBV) or hepatitis C virus (HCV) or any chronic infection.
25. Hepatitis B surface antigen positive (HBsAg+) is exclusionary; subjects who are 
HBsAg- but Hepatitis B core antibody positive (HBcAb+) must undergo further 
testing and be Hepatitis B surface antibody positive (HBsAb+) to be considered for 
enrollment.
26. Subjects who are HCVAb+ must undergo further testing for HCV RNA and are 
allowed to enroll if negative.
27. 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.
28. A subject that is considered at increased risk for gastrointestinal perforation 
(eg, patient with diverticulitis) by the Investigator or Sponsor.
29. Any factors or clinical characteristics potentially related to the risk of venous 
thromboembolism (see Section 7.5.8, Risk Factor Check for VTE) that may increase 
the risk associated with study participation or investigational product administration 
or may interfere with the interpretation of study results and, in the judgment of the 
investigator, would make the subject inappropriate for entry into this study.
30. Other acute or chronic medical or psychiatric condition including recent (within the 
past year) or active suicidal ideation or behavior 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 the
judgment of the investigator, would make the subject inappropriate for entry into this 
study. 
31. A subject who has previously participated in any study of tofacitinib or has any 
previous clinical experience of tofacitinib.


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32. A subject who, in the opinion of the investigator or Pfizer (or designee), will be 
uncooperative or unable to comply with study procedures.
4.5. Randomization Criteria 
A subject who has signed an informed consent document to participate in the study, has 
undergone all screening procedures, and meets all inclusion and no Exclusion Criteria for 
participation in the study at the baseline visit, may be randomized into this study. Subjects 
will be randomized in a 2:1 ratio to one of the two parallel treatment sequences. A 
centralized computer-generated randomization schedule will be used to assign subjects to the
treatment groups.  Subjects will be assigned a subject identification number in the order of 
their screening for the study. The identifying number will be retained throughout the study.
At Month 3, subjects originally randomized to Treatment Sequence B will be advanced to 
tofacitinib 5 mg BID treatment in a blinded fashion for the remainder of the study.  Study 
blinding will be maintained for all groups throughout the study (see Section 6.2).
4.6. 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).

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.

On study visit days, take prescribed permitted concomitant medication, as needed, 
prior to the study visit, if it can be administered with water only.

Avoid vaccinations with live or attenuated live vaccines and contact with individuals 
who have recently received live or attenuated live vaccines (See Section 4.6.2).

Discontinue and avoid using certain medications and treatments (see Inclusion 
Criteria and list of prohibited medications Appendix 3).

Contact the study site investigator if there are any changes or additions to 
concomitant medications.

Avoid having elective surgery (See Section 4.6.5).

Agree to use acceptable contraceptive methods per Section 4.6.6.


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4.6.1. Non-Pharmacologic Interventions
The subject should continue all non-pharmacological therapies, such as physical therapy, as 
indicated.  However, the subject should avoid changing the type or intensity of therapy or
initiating new therapy until after Month 3, but preferably after Month 6 visit.
4.6.2. Vaccine Guidelines
4.6.2.1. Subject Vaccination
Subjects should be vaccinated appropriately prior to screening for the study. 
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.
4.6.2.2. 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;
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.
4.6.3. 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.


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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.
4.6.4. 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 
(Visit 1), Month 1 (Visit 3), Month 3 (Visit 5), Month 4 (Visit 6), Month 6 (Visit 7), Early 
Termination and Follow-Up Visit (if required).
4.6.5. Elective Surgery
During the course of this study, no elective surgery should be scheduled and will be 
considered a protocol deviation if it occurs. Elective surgery should only be scheduled 
>1 month before study start or delayed to after the study.
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.
4.6.6. Contraceptive 
The investigator or his or her designee, in consultation with the subject, will confirm that the 
subject has selected an appropriate method of contraception for the individual subject and 
his/her partner(s) from the permitted list of contraception methods (see below) and will 
confirm that the subject has been instructed in its consistent and correct use.  At time points 
indicated in the Schedule of Activities, the investigator or designee will inform the subject of 
the need to use highly effective contraception consistently and correctly and document the 
conversation, and the subject’s affirmation, in the subject’s chart (subjects need to affirm 
their consistent and correct use of at least 1 of the selected methods of contraception). In 
addition, the investigator or designee will instruct the subject to call immediately if the 
selected contraception method is discontinued or if pregnancy is known or suspected in the
subject or partner.  
A female subject is eligible to participate if she is not pregnant or breastfeeding, and at least 
1 of the following conditions applies:

Is not a woman of childbearing potential (WOCBP).
OR


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
Is a WOCBP and using a contraceptive method that is highly effective (with a failure 
rate of <1% per year), preferably with low user dependency, as described below 
during the intervention period and for at least 28 days after the last dose of study 
intervention, which corresponds to the time needed to eliminate any study 
intervention(s).  The investigator should evaluate the effectiveness of the 
contraceptive method in relationship to the first dose of study intervention.
The investigator is responsible for review of medical history, menstrual history, and recent 
sexual activity to decrease the risk for inclusion of a woman with an early undetected 
pregnancy.
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 the following:
Highly Effective Methods That Have Low User Dependency 
1. Implantable progestogen-only hormone contraception associated with inhibition of 
ovulation.
2. Intrauterine device (IUD).
3. Intrauterine hormone-releasing system (IUS).
4. Bilateral tubal occlusion.
5. Vasectomized partner.

Vasectomized partner is a highly effective contraceptive method provided that the 
partner is the sole sexual partner of the WOCBP and the absence of sperm has 
been confirmed.  If not, an additional highly effective method of contraception 
should be used.  The spermatogenesis cycle is approximately 90 days.
Highly Effective Methods That Are User Dependent 
6. Combined (estrogen- and progestogen-containing) hormonal contraception associated 
with inhibition of ovulation:

Oral;

Intravaginal;

Transdermal;

Injectable.


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7. Progestogen-only hormone contraception associated with inhibition of ovulation:

Oral;

Injectable.
8. Sexual abstinence:

Sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated 
with the study intervention.  The reliability of sexual abstinence needs to be 
evaluated in relation to the duration of the study and the preferred and usual 
lifestyle of the participant.
No effects of tofacitinib have been seen in male fertility or offspring of dosed males in any 
preclinical studies conducted to date.  However, male subjects who are on background 
medications (including DMARDs) that require male contraceptive precautions according to
the local drug label must do so if they are sexually active with women of child bearing 
potential during the study and after therapy for 3 months or for the duration specified in the 
local drug label.  Subjects who are receiving concomitant drugs (eg, methotrexate) that 
require contraceptive precautions in their labeling should follow the most stringent 
precautions.
4.7. 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 help desk 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 help desk 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 help desk 
number is not intended for use by the subject directly and if a subject calls that number, he or 
she will be directed back to the investigational site.


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4.8. 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 peform 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); and 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.
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).
For this study, the investigational products are Tofacitinib 5 mg tablets and Placebo tablets
that match tofacitinib tablets.
5.1. Allocation to Treatment
Study Treatments:
Subjects are randomized to receive either tofacitinib 5 mg BID or placebo. At Month 3, all 
subjects receiving placebo will be advanced to tofacitinib 5 mg BID in a blinded manner for 
3 months. Investigators, subjects and sponsor will remain blinded through the entire duration 
of the study until database release.
Subjects will be randomized in a 2:1 ratio to one of the following two parallel treatment 
sequences: 

Treatment Sequence A: Tofacitinib 5 mg BID; 

Treatment Sequence B: Placebo Tofacitinib 5 mg BID at Month 3; 
The following medication will be supplied by Pfizer Inc:

Tofacitinib 5 mg tablets;

Placebo tablets that match tofacitinib tablets.


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Treatment Sequence
Treatment
Planned Number of 
Randomized Subjects
Sequence A
Tofacitinib 5 mg BID
136
Sequence B
Placebo x 3 Months Tofacitinib 
5 mg BID1
68
1. At Month 3, subjects randomized into Treatment Sequence B will receive tofacitinib 5 mg BID in a blinded 
manner through Month 6. 
Subjects will be randomized in a 2:1 ratio to Treatment Sequence A or Treatment 
Sequence B.  Assignment to treatment sequence will be accomplished using an automated 
web/telephone randomization system (IVRS).  The IVRS system contains the randomization 
schedule. At the Screening Visit, the investigative site will contact the IVRS (online or by 
telephone call).  The site will enroll the subject into the IVRS by indicating minimal 
information sufficient to distinguish one subject from another (eg, date of birth and gender) 
and receive a unique subject identification number.  At the Baseline/Day 1 (Visit 1), the 
system will associate that subject with the next available treatment on the randomization 
schedule and provide the randomization number. The system will then give the investigative 
site a code which corresponds to study drug that was previously shipped to the site and is in 
the site’s inventory ready to be dispensed.  This code corresponds to the study drug of that 
period in the treatment sequence in which the subject has just been randomized.
The site will call the system on study visit days when study drug is to be dispensed.  The 
randomization schedule will contain sufficient treatment allocations to allow for 
over-enrollment; however when a sufficient number of subjects have enrolled, the
randomization part of the system will be stopped.  The part of the system that supplies codes 
will continue until the last subject randomized has been dispensed the last supply of study 
drug.
5.2. Breaking the Blind
This study will be subject-, investigator-, and Sponsor-blinded.  At the initiation of the study, 
the study site will be instructed on using an automated web/telephone randomization system 
provided by the Sponsor for breaking the blind.  Blinding should only be broken in 
emergency situations for reasons of subject safety.  The Investigator should attempt to
contact Pfizer before breaking the blind.  When the blind for a subject has been broken, the 
reason must be fully documented.
5.3. Subject Compliance
Subject compliance with dosing administration will be verified by accounting of returned 
containers and trial medication at visits Week 2 and Month 1, 2, 3, 4 and 6 or Early 
Termination.  When trial medication is administered at the research facility, it will be 
administered under the supervision of study personnel.
Compliance of the study drug 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. The subjects 
who are determined by investigators or sponsors to be unable to comply with dosage 


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regimen, should be withdrawn.  Subjects who are <80% compliant with dosage regimen for 
any two consecutive visit periods should be withdrawn from the study. 
If the subject overconsumes study drug (>120% of medication, 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 that may potentially impact the safe use of study drug or 
that may result in a serious adverse event.
5.4. Investigational Product Supplies
5.4.1. Dosage Form(s) and Packaging
The Sponsor will provide tofacitinib as 5 mg tablets with corresponding matching placebo 
tablets.  The blinded assignment will consist of one active 5 mg tablet for the 5 mg dose 
sequence or one placebo tablet for the placebo sequence.  Tablets will be supplied in bottles 
as appropriate for the treatment sequence to which the subject is randomized. The subject 
will be instructed to take one tablet from assigned bottle twice daily.  Each bottle will be 
labeled as appropriate for this placebo-controlled, double-blind study.
5.4.2. Preparation and Dispensing
Study drug will be dispensed in bottles.  At each dispensing visit, subjects will receive a 
sufficient quantity of study drug to last until their next scheduled dispensing visit. 
5.5. Administration
The study drug will be labeled in such a manner that the subject and study staff will be 
unable to determine from the dispensed packaging to which treatment sequence the subject is 
assigned.  Each bottle will be labeled with appropriate directions for administration.
Study drug will be dispensed to subjects for self administration after appropriate training and 
specific instructions will be provided. A dosing diary will be provided to the subjects to 
record the administration of study drug.
On the day of a scheduled study visit, the study drug should be taken after completing all the 
study procedures at the clinic.
Tofacitinib tablets and matching placebo for oral administration will be dispensed in bottles 
and may be taken with or without food.  Subjects will swallow the study medication whole,
and will not manipulate or chew the medication prior to swallowing.  Subjects will be 
instructed to take their study drug twice daily (once in the morning and once in the evening 
approximately 12 hours apart) at approximately the same times each day. 
If the investigator deems it necessary to withhold study medication to treat a non-serious 
infection or other medical condition, temporary withholding is permitted for up to 5 days
which should be well documented in medical record and case report form (CRF). If study 
medication interruption exceeding 5 days is required for a medical reason, the investigator 
must contact the Pfizer Study Clinician for approval.


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Temporary withholding of the study medication, as described above, is permitted once during
the study without obtaining prior approval from the Pfizer Study Clinician. Any additional 
request(s) for temporary withholding of study drug require(s) documented approval by the 
Pfizer Study Clinician.
5.6. Investigational Product Storage 
The investigator, or an approved representative, eg, pharmacist, will ensure that all 
investigational 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.  Any storage conditions 
stated in the SRSD will be superseded by the storage conditions stated on the product label.
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 and throughout the study.  Even 
for continuous-monitoring systems, a log or site procedure that ensures active evaluation for 
excursions should be available.  The intent is to ensure that the minimum and maximum 
temperature is checked each business day to confirm that no excursion occurred since the last 
evaluation and to provide the site with the capability to store or view the minimum/maximum 
temperature for all non-working days upon return to normal operations.  The operation of the 
temperature monitoring device and storage unit (for example, refrigerator), as applicable, 
should be regularly inspected to ensure they are 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 the storage 
conditions described in the labeling, as soon as possible.  Deviations from the storage
requirements, including any actions taken, must be documented and reported to Pfizer.
Once an excursion is identified, the investigational product must be quarantined and not used 
until Pfizer provides 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 
including how to report temperature excursions.
5.7. Investigational Product Accountability
The investigator’s site must maintain adequate records documenting the receipt, use, loss, or 
other disposition of the drug supplies. All investigational products will be accounted for 
using a drug accountability form/record.


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To ensure adequate records, all drug 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. 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.
All study drug bottles must be returned to the investigator by the subject and the investigator 
will return the bottles to Pfizer.
5.8. Concomitant Medication(s)
It is important to be aware of, and document, all concomitant medications 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 on 
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.
Medications 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 medications. Medications 
taken after the first dose of study drug has been administered will be documented as 
concomitant medications.  All concomitant medications taken during the study must be 
recorded in the study records with indication (as appropriate), daily dose, administration 
route and start and stop dates of administration. Subjects will be queried about concomitant 
medications 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. 
5.8.1. Stable Background Pain or Other Arthritis Therapy
For csDMARDs which have been discontinued prior to first dose of study drug, the
following minimum washout criteria apply: Methotrexate, Sulfasalazine: must have been 
discontinued for 4 weeks prior to the first dose of study drug.


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Subjects taking permitted csDMARDs (eg, methotrexate (20 mg/week), sulfasalazine
(3 gm/day)), nonsteroidal anti-inflammatory drugs (NSAIDs) including selective 
cyclooxygenase-2 inhibitors (COX-2 inhibitors), and/or corticosteroids (10 mg prednisone 
mg/day) should remain on the same dose regimen throughout the study except if adjustment 
is needed to protect the subject’s safety.  Daily dosages of NSAIDs/COX-2 inhibitors, 
corticosteroids, opioids, and acetaminophen/paracetamol must be stable for 1 week prior to 
first study dose and must remain so during the study treatment period through Month 3 
except if adjustment is needed to protect a subject’s safety.  Daily dosage of NSAIDs/COX-2 
inhibitors, corticosteroids, 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. 
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 4 and Appendix 5).
Intravenous or intramuscular corticosteroids are not allowed during this study either as a 
stable concomitant medication or as rescue medication.  Intra-articular corticosteroids and 
hyaluronate sodium are allowed but only as rescue therapy (See Appendix 5).
5.8.2. Other Medications
Prohibited drugs and dietary supplements must be discontinued at least 30 days or 5 half 
lives (whichever is longer) before the first dose of study drug.  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).  A list of prohibited drugs
with specific discontinuation recommendations is listed in Appendix 3.  Please note that 
certain medications should be discontinued at least 30 days prior to first dose of study drug
based on the half-life of these drugs and amiodarone should be discontinued at least 290 days 
prior to first dose of study drug based on a half-life of 58 days.  All concomitant medication 
taken during the study must be recorded with indication (as required), daily dose,
administration route and start and stop dates of administration.
Traditional Chinese Medicine: Tripterygium wilfordii, or léi gōng téng sometimes called 
thunder god vine but more properly translated thunder duke vine, is a vine used in 
traditional Chinese medicine for treatment arthritis, and is prohibited during the study. 


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5.9. Rescue Therapy
The only medications that are allowed for rescue are listed in Appendix 5.
Increases of acetaminophen/paracetamol and opioids are allowable as rescue medication for 
no more than 10 consecutive days.  Acetaminophen/paracetamol may be added or increased 
to a maximum of 2.6 gm/day.  Opioids may be added or increased to a maximum potency 
equivalent of 30 mg of orally-administered morphine.  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 total acetaminophen/paracetamol dose will exceed 
2.6 gm/day.
Subjects who require rescue 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 may not be dosed with rescue medication during the 24 hours prior to a 
study visit.  Baseline stable use acetaminophen/paracetamol or opioids should NOT be 
discontinued in advance of study visits. 
A maximum of 40 mg methylprednisolone or equivalent of intraarticular corticosteroids will 
be allowed as rescue medication at or after the Month 3 visit; intraarticular corticosteroid 
injections should not be performed within the 4 weeks prior to a study visit.  The total 
allowed intraarticular corticosteroid dose may be divided into separate injections (eg, 20 mg, 
20 mg).  Intra-articular hyaluronate sodium injections may be administered for indications in 
accordance with the local label at or after the Month 3 visit in no more than two joints.  If 
performed at Month 3 visit, intra-articular injections must be given after the assessments are 
completed. 
6. STUDY PROCEDURES
6.1. Screening
All the Days/Months are relative to start of study treatment (Day 1).  For the purpose of this 
protocol, 1 Month is defined as 28 calendar days.
Subjects will be screened within 28 (+10) days prior to administration of study medication to 
confirm that they meet the entrance criteria for the study.  Subjects may not be rescreened 
unless approved by the Sponsor.  Rescreening of subjects will be allowed in a limited number 
of circumstances as determined by the Pfizer Study Clinician (eg, subject requires washout of 
prohibited medications, requires antimicrobial therapy within 2 weeks prior to the first dose 
of study medication, requires emergency surgery) and should be confirmed with the Pfizer 
Study Clinician when rescreening can occur.
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 study.  However, there may be subjects taking a 
prohibited medication who have experienced an ineffectual/suboptimal response or side 
effects and wish to enter the study.  These subjects may require a washout period that extends 
beyond the 4 week screening duration.  For these subjects, written informed consent and a 
unique subject number obtained through the IVRS system must be obtained prior to initiation 
of the washout period.  No other screening activities should be performed at this time.  These 
subjects should return for a Screening Visit within the 4 weeks prior to Baseline/Day 1, at 
which time all screening procedures should be completed.
Subjects are required to fast for at least 9 hours prior to the visit. 
If the Mantoux PPD tuberculin skin test is given, subject must return 48-72 hours post test 
for induration evaluation.
The following procedures will be performed:

Informed consent;

Confirmation of PsA diagnosis: The subject must have a diagnosis of PsA based upon 
the CASPAR Criteria (See Section 4).  PsA disease subtype will be documented in
case report form (CRF);

Medical history: Include history of previous vaccinations, specifically influenza, 
pneumococcal, and zoster.  The medical history should also include 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;

Prior medications: Current and prior Traditional Chinese medicine, Tripterydium 
hypoglaucum (thunder god vine), requires a 4 week washout period prior to first dose 
of study treatment.  Current and prior medications (noting exclusions and required 
DMARD restrictions), including a complete history of all DMARDs (including 
biologics) ever taken with reasons for discontinuation (those taken during the 1 year 
prior to the first dose of study drug should include dose and duration of treatment).  
Complete history of all drugs (including nonprescription drugs, vitamins, and dietary 
supplements), taken within 4 weeks prior to screening procedures; Complete physical 
examination (plus Height): Weight, height, 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;

Vital signs: blood pressure, pulse rate and temperature (tympanic, oral or temporal 
preferred);


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
PsA Disease Activity: Tender/Painful Joint Count (68), Swollen Joint Count (66);

Psoriasis Dermatological Assessment: Active plaque psoriasis;

Risk factor check for venous thromboembolism (see Section 4.4 – Number 30);

Laboratory testing:

Hematology, Urinalysis, Chemistry Panel, HIV Serology, HBsAg, HBcAb, HCV
Ab, C-Reactive Protein (CRP), and Prothrombin time (PT/INR).  Screening lab 
tests may be repeated a single time if the initial result is inconsistent with previous 
documented subject laboratory history;

Urine Pregnancy Test (for women of childbearing potential only);

Serum FSH concentrations (optional, see Section 4.1) for postmenopausal females 
who are not on hormone replacement therapy and with no prior history of
hysterectomy; 

QuantiFERON-Goldor Mantoux PPD tuberculin skin test: Must be performed 
unless previously tested and documented within 3 months of screening visit or 
unless subject has previously received an adequate course of therapy for either
latent or active TB infection.  If the Mantoux PPD tuberculin skin test is done, the 
subject must return 48-72 hours post test for evaluation;

12-lead electrocardiogram;

Radiograph of chest: Unless performed within 3 months of screening visit and review 
documented by radiologist or pulmonologist per local standard of care;

Monitoring of adverse events.
6.2. Study Period
Subjects who have met all the Inclusion Criteria and have no Exclusion Criteria present may 
participate in the study.
Blood collection for laboratory testing requiring a fasting state (at least 9 hours) may be 
taken up to 48 hours following the Baseline/Day 1 visit or up to 48 hours following other 
post-baseline double-blind study period visits as necessary 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. 
Subjects should complete the patient reported outcome (PRO) 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


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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 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.
6.2.1. Visit 1, Baseline Day 1
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 hours following the Baseline/Day 1
visit as necessary to ensure the samples are collected in a fasting state. 
All PROs should be performed before any other study procedures.  These include the 
following: 

Patient’s Assessment of Arthritis Pain (Visual Analog Scale, VAS);

Patient’s Global Assessment of Arthritis (VAS);

HAQ-DI;

SF-36 Version 2 (Acute);

EuroQol 5 Dimensions (EQ-5D);

Work Productivity and Activity Impairment – Psoriatic Arthritis Questionnaires 
(WPAI-PsA).
Procedures that will be performed prior to randomization on Visit 1, Day 1 for baseline 
include:

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), lower extremities (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);

Waist and hips circumference;

Risk factor check for venous thromboembolism (see Section 7.5.8).


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
Laboratory testing: 

Hematology, Chemistry Panel, Hemoglobin A1c (HbA1c), C-Reactive Protein 
(CRP), Rheumatoid Factor (RF), Cyclic Citrullinated Peptide Antibody (CCP), 
Lipid Profile (fasting), Urinalysis; Lymphocyte subset analysis (FACS);

Urine Pregnancy Test (for women of childbearing potential only);

Contraception check: Confirm and document that proper contraception is being used.

Clinical Evaluation of Rheumatology Endpoints (by blinded assessor):

Tender/painful joint counts (68);

Swollen joint counts (66);

Physician’s Global Assessment of Arthritis (VAS);

Assessment of dactylitis using DSS;

Assessment of enthesitis using LEI.

Clinical Evaluation of Dermatology Endpoints (by blinded assessor):

PGA-PsO;

PASI;

BSA;

NAPSI.

Clinical Evaluation of Rheumatology and Dermatology Endpoint (by blinded 
assessor): PGA-PsA (VAS);

Randomization;
Procedures that will be performed after randomization on Visit 1, Day 1 include:

Drug and dosing diary dispensing;

Monitoring of adverse events and concomitant medication;

Observe subject taking the study drug following completion of all the study 
procedures at the clinic with the record logged in the dosing CRF, and also make a 
record of csDMARD taking. 


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6.2.2. Visit 2, Week 2, Day 15
There is a 3 day window for this visit. 
All PROs 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.
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);

Risk factor check for venous thromboembolism (see Section 7.5.8);

Laboratory testing: Urine Pregnancy Test (for women of childbearing potential only), 
CRP;

Contraception check: Confirm and document that proper contraception is being used;

Clinical Evaluation of Rheumatology Endpoints: 

Tender/Painful Joint Counts (68);

Swollen Joint Count (66); 

Physician’s Global Assessment of Arthritis (VAS); 

Monitoring of adverse events and concomitant medications.  Record any 
modifications, deletions or additions;

Dosing diary check and Drug accountability;

Instruct subject to bring the bottles with them to the visit.


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6.2.3. Visit 3, Month 1, Day 29
There is a 3 day window for this visit. 
Subjects are required to fast for at least 9 hours prior to the visit.  Blood collection may 
be taken up to 48 hours following this visit as necessary to ensure samples are collected in a 
fasted state.
All PROs 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);

HAQ-DI;

SF-36;

EQ-5D.
Procedures that will be performed include:

Vital signs: blood pressure, pulse rate and temperature (tympanic, oral or temporal 
preferred);

Risk factor check for venous thromboembolism (see Section 7.5.8);

Laboratory testing: Hematology, Chemistry Panel, CRP, Urinalysis, Lipid Panel 
(fasting), Urine Pregnancy Test (for women of childbearing potential only);

Contraception check: Confirm and document that proper contraception is being used;

Targeted physical examination (weight, examination of heart, lungs, abdomen, 
extremities and lymph nodes).

Clinical Evaluation of Rheumatology Endpoints (by blinded assessor): 

Tender/Painful Joint Counts (68);

Swollen Joint Count (66); 

Physician’s Global Assessment of Arthritis (VAS);

Assessment of of dactylitis using DSS;

Assessment of enthesitis using LEI.


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
Clinical Evaluation of Dermatology Endpoints (by blinded assessor):

PGA-PsO;

PASI;

BSA;

NAPSI.

Clinical Evaluation of Rheumatology and Dermatology Endpoint (by blinded
assessor): PGA-PsA (VAS);

Monitoring of adverse events and concomitant medications.  Record any 
modifications, deletions or additions;

Dosing diary check and Drug accountability;

Instruct subject to bring the bottles with them to the visit.
6.2.4. Visit 4, Month 2, Day 57
There is a 7 day window for this visit. 
Subjects are required to fast for at least 9 hours prior to the visit.  Blood collection may 
be taken up to 48 hours following this visit as necessary to ensure samples are collected in a 
fasted state.
All PROs 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.
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);

Risk factor check for venous thromboembolism (see Section 7.5.8);


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
Laboratory testing: Urinalysis, Hematology, Chemistry panel, CRP, Urine pregnancy 
test (for women of childbearing potential only);

Contraception check: Confirm and document that proper contraception is being used.

Clinical Evaluation of Rheumatology Endpoints: 

Tender/Painful Joint Counts (68);

Swollen Joint Count (66); 

Physician’s Global Assessment of Arthritis (VAS).

Monitoring of adverse events and concomitant medications.  Record any 
modifications, deletions or additions;

Dosing diary check and Drug accountability;

Instruct subject to bring the bottles with them to the visit.
6.2.5. Visit 5, Month 3, Day 85
There is a 7 day window for this visit. 
Subjects are required to fast for at least 9 hours prior to this visit.  Blood collection may 
be taken up to 48 hours following this visit as necessary to ensure samples are collected in a 
fasted state.
All PROS 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;

SF-36 Version 2 (Acute);

EQ-5D;

WPAI-PsA.
Procedures that will be performed include:

Targeted physical examination (weight, examination of heart, lungs, abdomen, lower 
extremities, and lymph nodes);


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
Vital signs: blood pressure, pulse rate and temperature (tympanic, oral or temporal 
preferred);

Risk factor check for venous thromboembolism (see Section 7.5.8);

Laboratory testing: Hematology, Chemistry Panel, CRP, HbA1c, Lipid Panel
(fasting), Urinalysis; Lymphocyte subset analysis (FACS), Urine Pregnancy Test (for 
women of childbearing potential only);

Contraception check: Confirm and document that proper contraception is being used;

Clinical Evaluation of Rheumatology Endpoints (by blinded assessor):

Tender/Painful Joint Counts (68);

Swollen Joint Count (66);

Physician’s Global Assessment of Arthritis (VAS);

Assessment of dactylitis using DSS;

Assessment of enthesitis using LEI.

Clinical Evaluation of Dermatology Endpoints (by blinded assessor):

PGA-PsO;

PASI;

BSA;

NAPSI;

Clinical Evaluation of Rheumatology and Dermatology Endpoint (by blinded 
assessor): PGA-PSA (VAS).

Monitoring of adverse events and concomitant medications.  Record any 
modifications, deletions or additions;

Dosing diary check and Drug accountability;

Drug dispensing;

Instruct subject to bring the bottles with them to the visit.


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6.2.6. Visit 6, Month 4, Day 113
There is a 7 day window for this visit. 
Subjects are required to fast for at least 9 hours prior to the visit.  Blood collection may 
be taken up to 48 hours following this visit as necessary to ensure samples are collected in a 
fasted state.
All PROs must 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);

HAQ-DI.
Procedures that will be performed include:

Vital signs: blood pressure, pulse rate and temperature (tympanic, oral or temporal
preferred);

Risk factor check for venous thromboembolism (see Section 7.5.8);

Laboratory testing: Hematology, Chemistry Panel, CRP, Lipid Panel (fasting), 
Urinalysis, Urine Pregnancy Test (for women of childbearing potential only);

Contraception check: Confirm and document that proper contraception is being used;

Targeted physical examination (weight, examination of heart, lungs, abdomen, lower 
extremities, and lymph nodes).

Clinical Evaluation of Rheumatology Endpoints (by blinded assessor):

Tender/Painful Joint Counts (68);

Swollen Joint Count (66);

Physician’s Global Assessment of Arthritis (VAS).

Monitoring of adverse events and concomitant medications.  Record any 
modifications, deletions or additions;

Dosing diary check and Drug accountability.


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6.2.7. Visit 7, Month 6, Day 169 or Early Termination Visit
There is a 7 day window for the Month 6 visit. 
Subjects are required to fast for at least 9 hours prior to the visit.  Blood collection may 
be taken up to 48 hours following this visit as necessary to ensure samples are collected in a
fasted state.
All PROs 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;

SF-36 Version 2 (Acute);

EQ-5D;

WPAI-PsA.
Procedures that will be performed include:

Vital signs: blood pressure, pulse rate and temperature (tympanic, oral or temporal 
preferred);

Risk factor check for venous thromboembolism (see Section 7.5.8);

Laboratory testing: Hematology, Chemistry Panel, CRP, HbA1c, Lipid Panel 
(fasting), Urinalysis; Lymphocyte subset analysis (FACS), Urine Pregnancy Test (for 
women of childbearing potential only);

Contraception check: Confirm and document that proper contraception is being used;

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;

Waist and hips circumference;

12-lead electrocardiogram.


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
Clinical Evaluation of Rheumatology Endpoints (by blinded assessor):

Tender/Painful Joint Counts (68);

Swollen Joint Count (66);

Physician’s Global Assessment of Arthritis (VAS);

Assessment of dactylitis using DSS;

Assessment of enthesitis using Leed’s Index.

Clinical Evaluation of Dermatology Endpoints (by blinded assessor):

PGA-PsO;

PASI;

BSA;

NAPSI;

Clinical Evaluation of Rheumatology and Dermatology Endpoint (by blinded 
assessor): PGA-PsA,

Monitoring of adverse events and concomitant medications.  Record any 
modifications, deletions or additions;

Dosing diary check and Drug accountability;

Review subject laboratory abnormalities to assess need for potential additional safety 
follow-up. 
6.2.8. Follow-up Visit
Subjects are required to fast for at least 9 hours prior to the visit.  Blood collection may 
be taken up to 48 hours following this visit as necessary to ensure samples are collected in a 
fasted state.
If a subject discontinues from or completes the study with abnormalities in hematology or 
clinical chemistry results which meet criteria as defined in Section 6.3.2, 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 and at least 28 calendar days and up to 42 calendar 
days after last dose of study treatment.  In addition, subjects who complete this study will 
have a follow-up visit at least 28 calendar days and up to 42 calendar days after the last 
administration of investigational product.  The following procedures will be performed:


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
Laboratory testing: Hematology, Chemistry Panel; Lipid Panel (fasting), Urine 
Pregnancy Test (for women of childbearing potential only);

Risk factor check for venous thromboembolism (see Section 7.5.8);

Contraception check: Confirm and document that proper contraception is being used;

Adverse event reporting and concomitant medication 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 (see also the 
Withdrawal From the Study Due to Adverse Events section) 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 
to 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 8.2.1. 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 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 an adverse event (AE) or any abnormality in hematology or clinical 
chemistry results which meet the criteria as defined in Section 6.3.2, a follow-up visit must 
be performed within 28 days (7 days) of last dose of study treatment.  The investigator must 
determine and document the primary reason for subject withdrawal. 


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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. 
6.3.1. 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;

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 the screening and baseline values;

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. 
In case of potential DILI, repeat laboratory tests should be taken within 48 hours of 
awareness.  See Section 8.4.2 Potential Cases of Drug-Induced Liver Injury.
6.3.2. 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 medication for more than 10 consecutive days;

Subjects who are <80% compliant with dosage regimen for any two consecutive visit 
periods should be withdrawn from the study;

Subjects interrupting study drug for more than 14 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 8.4.4);


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
Two sequential absolute neutrophil counts <1.0 × 109/L (<1000/mm3);

Two sequential hemoglobin values <8.0 g/dL (80 g/L) or decreases of >30% from 
baseline value;

Two sequential absolute lymphocyte counts <0.5 × 109/L (<500/mm3);

Two sequential platelet counts <75 × 109/L (<75,000/mm3);

Two sequential AST or ALT elevations 3 × ULN with at least one total bilirubin 
value 2 × ULNl;a

Two sequential AST or ALT elevations 3 × ULN accompanied by signs or 
symptoms consistent with hepatic injury (eg, new onset elevated PT/INR);a

Two sequential AST or ALT elevations >5 × ULN, 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 the screening and 
baseline values;

Two sequential creatine kinase (CK) elevations >10 × ULN, 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; 

Confirmed venous thromboembolism;

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 this section, 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.


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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, which may make it unfeasible to 
perform the test.  In these cases the investigator will take all steps necessary to ensure the 
safety and well being 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 that 
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 will be informed of these incidents in a timely manner.
7.1. Efficacy Endpoints
7.1.1. ACR Assessments
The American College of Rheumatology’s definition for calculating improvement in 
RA (ACR50) is calculated as a 50% improvement in tender and swollen joint counts and
50% improvement in 3 of the 5 remaining ACR-core set measures: patient and physician 
global assessments, pain, disability, and an acute-phase reactant.  Similarly, ACR20 and 
ACR70 are calculated with the respective percent improvement.22  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).
7.1.2. DAS Assessment
The Disease Activity Score (DAS)23 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);


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2. Swollen Joint Count (28);
3. C-Reactive Protein (CRP).
Tender/painful and swollen joint counts used are as described in Sections 7.2.2 and 7.2.4.
7.1.3. PsA Response Criteria (PsARC)
The PsARC24,25 will be calculated 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 PsARC.  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.
7.2. Clinical Evaluation of Rheumatology Endpoints
The PsA subtype for each subject will be documented in the CRF.  PsA subtype will be based 
upon whether or not the disease: is oligoarticular (<5 joints involved), polyarticular (5 joints 
involved), has distal interphalangeal joint involvement, spondylitis (spinal involvement) or is 
characterized by arthritis mutilans (aggressive joint destruction).
All rheumatological evaluations 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 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 blinded 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. 
The 68 joints to be assessed are:

Upper Body: temporomandibular, sternoclavicular, acromioclavicular;


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
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), 
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 blinded joint assessor as described in Section 7.2.1.
7.2.3. Swollen Joint Count (66)
The blinded 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.
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 blinded assessor.
7.2.5. Physician’s Global Assessment of Arthritis
The blinded 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]


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7.2.6. Physician’s Global Assessment of Psoriatic Arthritis
The blinded 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).
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 blinded 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 tenderness, 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 blinded assessor using Leeds Enthesitis 
Index.26  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 (except follow-up) for analysis of CRP using an 
assay by the central laboratory. The investigator and Sponsor will be kept blinded to the 
results of this test at all visits except the Screening Visit.
7.3. Clinical Evaluation of Dermatologic Endpoints
All dermatological evaluations 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 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 1).  
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 2).


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Table 1.
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 2.
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).
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 


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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 is 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 3).
Table 3.
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 4). 
Table 4.
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


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Body Region Weighting: each body region is weighted according to its approximate
percentage of the whole body (Table 5).
Table 5.
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 BSA28 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).  The percent surface area with psoriasis is estimated by means of the handprint
method, where the full palmar hand of the subject (ie, the subject’s fully extended palm, 
fingers and thumb together) represents approximately 1% of the total BSA.  The BSA with 
psoriasis (%) is the sum of the numbers of the handpoints across the 4 body regions.
7.3.4. Nail Psoriasis Severity Index (NAPSI) Score
A target finger nail will be evaluated by the blinded assessor using the NAPSI scale.29  At the 
baseline visit, the worst case fingernail should be chosen and the same nail evaluated 
consistently through the entire study.  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.


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7.4. 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) 
should not be administered.  PRO questionnaires should also be reviewed for potential 
adverse events.
7.4.1. 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]
7.4.2. 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]
7.4.3. 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.30  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. 


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7.4.4. SF-36 Health Survey (Version 2, Acute)
The SF-36 v.2 (Acute)31 is a 36-item generic health status measure.  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 summary scores. 
7.4.5. EuroQol EQ-5D Health State Profile
The EuroQol EQ-5D Health State Profile 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.32  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 PsA and rheumatoid arthritis. 
7.4.6. Work Productivity and Activity Impairment – Psoriatic Arthritis Questionnaire
The work productivity and Activity Impairment – Psoriatic Arthitis Questionnaire33 is a six 
item questionnaire that measures absenteeism (work time missed), presenteesism 
(impairment at work/reduced on –the-job effectiveness), work productivity loss (overall work 
impairment/absenteeism plus presenteeism) and activity impairment.  WPAI-PsA outcomes 
are expressed as impairment percentages, with higher numbers indicating greater impairment 
and less productivity.  The validity and reliability of the WPAI has been well established. 
7.5. Safety
Safety will be assessed by the spontaneous reporting of 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.
7.5.1. Vital Signs and Temperature
Body temperature, blood pressure and pulse rate will be measured at every study visit except 
the follow-up visit.
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.


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
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.
7.5.2. Electrocardiogram
Twelve-lead electrocardiograms (ECGs) will be obtained on all subjects at the Screening and 
the Month 6 (or Early Termination) visit.  All ECGs should be performed after the patient 
has rested quietly for at least 10 minutes.  Screening visit ECG results will be used as a 
screening tool and should be maintained in the subject’s source documentation.  ECGs 
obtained at Month 6 will be compared to Screening ECGs.  Any clinically significant 
changes from the Screening ECG will be recorded as adverse events and evaluated further, as 
clinically warranted.
7.5.3. Tuberculosis Screening
During the Screening period, 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 1).
7.5.3.1. 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.34 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.
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.


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7.5.3.2. 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 using a Mantoux Purified Protein 
Derivative (PPD) test using 5 tuberculin units (5 TU) per 0.1 mL within the 3 months prior to 
a given screening visit at the discretion of the Pfizer Study Clinician.  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 TU is not available, then the PPD may be peformed 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.
7.5.3.3. 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.
For subjects with latent TB infection and treated with preventive anti-TB therapy during 
study, chest radiograph should be be monitored per local practice.
7.5.4. Complete Physical Examination
A standard complete physical examination will be performed at Screening visit, Baseline 
(Visit 1), Month 6 ((Visit 7) or Early Termination).  The following parameters and body 
systems will be examined and any abnormalities described: height (at Screening Visit only), 
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, abdomen (palpation and auscultation), neurologic (mental status, station, 
gait, reflexes, motor and sensory function, coordination) and lymph nodes.  Any clinically 
significant changes from Baseline (Visit 1) should be recorded as adverse events (AEs).
Recommendations for evaluation of emergent lymphadenopathy or other findings suggestive
of lymphoproliferative disorder are provided in Appendix 6.
7.5.5. Targeted Examination
At all other visits except follow-up, an abbreviated physical examination will be performed 
assessing the following: weight, lungs, heart, abdomen, lower extremities and lymph nodes.  
Any clinically significant changes from Baseline (Visit 1) should be recorded as adverse 
events (AEs).


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7.5.6. 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 in centimeters (cm) and 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.
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.
7.5.7. Clinical Safety Laboratory Tests
Blood and urine samples will be collected at the time points identified in the protocol for 
clinical safety laboratory tests (Table 6).  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.
7.5.7.1. Hepatitis B and C Virus Testing
Subjects with known hepatitis B infection will be excluded from the study.  All subjects 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.  At the Screening visit, all subjects 
will be tested for HCV Ab and, if positive, must undergo further testing for HCV RNA and 
allowed to enroll if negative.


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Table 6.
Clinical Laboratory Testing
Laboratory Testing Profile
Tests Included
Laboratory Tests Required at Screening 
Only
QuantiFERON®-TB Gold In-Tube, 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, Prothrombin time (PT/INR);c 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)], Lymphocyte 
subset analysis (FACS) [CD3+ (%, abs), CD3+CD4+ (%, abs), 
CD3+CD8+ (%, abs), CD19+ (%, abs), CD16+/CD56+ (%, 
abs)], platelets 
Hemaglobin A1c (HbA1c).
Chemistry Panel (fasting)
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).
Rheumatoid Factor (RF), Cyclic Citrullinated Peptide Antibody 
(CCP).
Lipid Panel (fasting)
Fasting total cholesterol, HDL, LDL, triglyceride; 
apolipoprotein A-1, B.
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).
Testings that are to be done in central lab: hematology, HbA1c, Lymphocyte subset analysis (FACS), Chemistry panel, 
Lipid Panel, Urinalysis, C-Reactive Protein (CRP), HIV serology, HBsAg, HBcAb, HCV Ab, Prothrombin time (INR), 
Rheumatoid Factor (RF), QuantiFERON-TB Gold, FSH testing if needed.
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.
All subjects will be screened for normal prothrombin time (PT/INR).  PT should also be evaluated to rule out acute 
hepatic injury in cases of hepatic enzyme elevations.
Abnormal test results determined to be caused from laboratory error should not be reported 
as AEs.  Subjects 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.


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7.5.7.2. Pregnancy Testing
All pregnancy tests used in this study, either urine or serum, must have a sensitivity of at 
least 25 mIU/mL and must be performed by a certified laboratory.  For female subjects of 
childbearing potential, 2 negative pregnancy tests are required before receiving 
investigational products (1 negative pregnancy test at screening and 1 at the baseline visit 
immediately before investigational products administration).  Following a negative 
pregnancy test result at screening, appropriate contraception must be commenced and the 
second negative pregnancy test result will then be required at the baseline visit before the 
subject may receive the investigational product. Pregnancy tests will also be repeated at 
every visit and at the end of the study to confirm that the subject has not become pregnant 
during the study. Pregnancy tests will also be done whenever 1 menstrual cycle is missed 
during the active treatment period and when potential pregnancy is otherwise suspected, and
may be repeated if requested by institutional review boards (IRBs)/ethics committees (ECs) 
or if required by local regulations.  In the case of a positive confirmed pregnancy, the subject 
will be withdrawn from administration of investigational product the subject will be 
withdrawn from the study and all necessary follow-up will be conducted.
7.5.8. Risk Factor Check for Venous Thromboembolism
All subjects will undergo a risk factor check at each study visit to check for newly developed
risk factors for venous thromboembolism.19  This information is to be captured in the 
subject’s source file and on the relevant case report form.  
A subject may be at high risk for venous thromboembolism if he/she:

has heart failure or prior myocardial infarction within past 3 months;

has inherited coagulation disorders;

has had venous thromboembolism, either deep venous thrombosis or pulmonary 
embolism;

is taking combined hormonal contraceptives or hormone replacement therapy;

has malignancy (association is strongest with cancers other than non-melanoma skin 
cancers);

is undergoing major surgery or is immobilized.
Additional risk factors for venous thromboembolism, such as age, diabetes, obesity 
(BMI>30 kg/m2), smoking status, hypertension, and first degree family history of VTE
should also be taken into consideration by the investigator and the Sponsor medical monitor 
when evaluating the benefit:risk for each individual subject.
If a subject has one or more of the risk factors for venous thromboembolism listed above, 
investigator judgement based on Exclusion Criteria 30 (Section 4.4) will apply to determine 
whether subject is appropriate for entry into this study.


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If a subject has one or more of the risk factors for venous thromboembolism listed above 
under Amendment 3 and is receiving tofacitinib 5 mg BID, they may remain on tofacitinib 
5 mg BID after careful investigator assessment of benefit:risk.
For subjects who do not have any of the risk factors for venous thromboembolism listed 
above under Amendment 3, he/she will remain on their assigned tofacitinib dose. 
Per Amendment 3, for subjects with suspected venous thromboembolism, treatment with 
tofacitinib should be temporarily withheld while the subject is evaluated.  If venous 
thromboembolism is confirmed, discontinue treatment with tofacitinib and withdraw the 
subject from the study (Section 6.3.2, Discontinuation Criteria).
7.6. Cardiovascular and Malignancy Events
The identification of a cardiovascular event will be made by the study site and communicated 
to Pfizer or designee. Cardiovascular or malignancy events may also be identified by the 
Pfizer Study Team or designee during the review of subject data listings or by site monitors 
during routine monitoring of subject’s study records.  The Pfizer Study Team or designee 
will notify the study site of any cardiovascular events should they identify any ahead of a
study site.
Cardiovascular events should be reported to the Pfizer Study Team or designee according to 
the following reference timepoints:

Report any events that are serious adverse events (SAEs) occurring after the time of 
informed consent;

Report any events that are non-serious adverse events (AEs) occurring after the time
of informed consent.
7.6.1. Cardiovascular Events
Criteria for defining specific cardiovascular events will be provided to investigators in a
separate study manual.  The Pfizer Study Team or designee will provide a listing of specific 
documents needed to support cardiovascular event adjudication (see Section 9.6).  Obtaining 
the documentation will be the responsibility of the study site.  Cardiovascular event 
documentation will include, but is not limited to any of the following: hospital discharge 
summaries, operative reports, clinic notes, ECGs, diagnostic enzymes, results of other 
diagnostic tests, autopsy reports and death certificate information.
7.6.2. Malignancy Events
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 Clinician 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.


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For all biopsies of potentially malignant tumors, suspicious lymphadenopathy, or possible 
extranodal lymphoproliferative disorder (LPD), the study site will 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 for a blinded review by a central pathologist.  
See Appendix 6 for the steps to take in the event of potentially malignant tumors, 
lymphadenopathy or possible extra-nodal lymphoproliferative disorder (LPD) which might 
arise in the course of this study.
Malignancy event samples and documentation will include, but are not limited to any of the 
following: stained and unstained slides for each tissue block, and local pathology report(s). 
7.7. Corona Virus Disease 2019 (COVID-19)
For participants with study visits or procedures impacted by the COVID-19 pandemic, the 
following guidance applies. Once a study participant is able to travel to the study site and the 
study site is operational, these changes outlined this Protocol Section 7.7 will no longer 
apply.

Every effort should be made to follow-up on the safety of the study participant. In 
the event that in-clinic study visits cannot be conducted, remote visits will be 
allowed.

Minimally, phone contact will be required at the scheduled or unscheduled visit when 
an in-clinic visit is not possible due to COVID-19. Video contact can be used if
permitted by local regulations. During the remote visit, the following assessments 
should be performed: 

Review and record any AEs and SAEs since the last contact, including but not 
limited to COVID-19-related events. The AE and SAE reporting process as noted 
in the protocol should be followed. 

Review and record study treatment including compliance and missed doses. If 
allowed by local regulations, photos of remaining tablets can be collected. 
Review and record any changes or new concomitant medications since last 
contact. 

PROs can be mailed via postal services or electronically if allowed and in 
accordance with local regulations to the study participant in advance of remote 
visits and verify they have been completed. These can either be mailed back to
the site or held until a site visit is permissible. PROs cannot be completed by 
phone/video with the study participant. 

Review and verify that contraceptive methods are being followed in those study 
participants that meet requirements for contraception. 

In-clinic dose for the last dose of tofacitinib at the visit 7 can be administered 
during the remote visit and documented in the source. 


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
Missed or partially completed procedures and assessments, based on the Schedule 
of Activities, must be reported as a protocol deviation.

Procedures or tests which are missed due to COVID-19 disruptions should be 
performed at the next available opportunity, even if outside of a protocol-specified 
visit window. 

Protocol-defined laboratory tests may be collected and resulted at an alternative
clinical laboratory facility ONLY if testing at the study site using the central 
laboratory is not possible due to COVID-19 disruptions. 

Local laboratory results or central laboratory results will be needed in order to ship 
study medication to a study participant. This is to ensure no monitoring criteria have 
been met prior to receipt of study medication. Local laboratory results should include 
all assays as required by the protocol except for C-reactive protein as this is a blinded 
assay. If local laboratory results are obtained, your CRA will need to collect the 
laboratory accreditation and laboratory reference ranges electronically or when they 
are back onsite. These local laboratory results will need to be entered in the eCRF 
page.

Women of child-bearing potential will require a negative pregnancy test 
(completed at the site or local laboratory) prior to shipping investigational product
to the study participant.

If courier delivery of the study medication from the study sites is allowable by law 
and local guidance, the study participant must provide verbal consent for providing 
the contact details for shipping purposes. Document the verbal consent in the source 
documents. Tracking records of shipment including temperature monitoring records 
and the chain of custody of the study medication must be kept in the participant’s 
medical records. Investigational product that is dispensed to the study participant via 
courier should correspond to the amount that is dispensed at the specific study visit 
and all dispensing activity should be registered in Impala. 

For study participants that must be discontinued from the study drug and study 
participation due to inability to comply with the protocol visits and procedures within 
the timeframes of the protocol, these discontinuations should be reported as “Other” 
for the Status on both Disposition (End of Treatment and Follow-Up) pages of the 
eCRF and in the “Specify Status” field, enter “COVID-19”. 

If the study participant discontinues due to a COVID-19 infection, record 
COVID-19 infection on the AE page and record the infection details on the 
Treated Infections Details page. The reason for discontinuation from 
investigational product would be “Adverse Event” on the Disposition-End of 
Treatment eCRF page. 


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If the sponsor determines that the impact of COVID-19 on protocol visits and procedures and 
associated timeframe needs to be reported on a case report form (CRF), this will be 
requested. For study medication interruption attributable to logistic restrictions during 
COVID-19, record it in Oral Dosing page as below: enter first day of interruption in 
“Start Date” and last day in “End Date”, enter 0 in “Total Daily Dose”, select Other for 
“Reason for Changed or Missed Dose” and enter COVID-19 in free typing area.
8. ADVERSE EVENT REPORTING
8.1. Adverse Events
The table below summarizes the requirements for recording safety events on the CRF and for 
reporting safety events on the Clinical Trial (CT) Serious Adverse Event (SAE) Report Form 
to Pfizer Safety. These requirements are delineated for 3 types of events: (1) SAEs; 
(2) non-serious adverse events (AEs); and (3) exposure to the investigational product under 
study during pregnancy or breastfeeding, and occupational exposure. 
Safety Event
Recorded on the CRF
Reported on the CT SAE 
Report Form to Pfizer 
Safety Within 24 Hours of 
Awareness
SAE
All
All
Non-serious AE
All
None
Exposure to the 
investigational product 
under study during 
pregnancy or 
breastfeeding, and
occupational exposure
All (regardless of whether 
associated with an AE), 
except occupational
exposure
Exposure during pregnancy, 
exposure via breastfeeding,
occupational exposure
(regardless of whether 
associated with an AE)
All observed or volunteered events regardless of treatment group or suspected causal 
relationship to the investigational product(s) will be reported as described in the following 
paragraphs.
Events listed in the table above that require reporting to Pfizer Safety on the CT SAE Report
Form within 24 hours of awareness of the event by the investigator are to be reported 
regardless of whether the event is determined by the investigator to be related to an 
investigational product under study.  In particular, if the SAE is fatal or life-threatening, 
notification to Pfizer Safety must be made immediately, irrespective of the extent of available 
event information. This time frame also applies to additional new (follow-up) information on 
previously forwarded reports.  In the rare situation that the investigator does not become 
immediately aware of the occurrence of an event, the investigator must report the event 
within 24 hours after learning of it and document the time of his/her first awareness of the 
event.


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For each event, the investigator must pursue and obtain adequate information both to 
determine the outcome and to assess whether it meets the criteria for classification as an SAE 
(see the Serious Adverse Events section below).  In addition, the investigator may be 
requested by Pfizer Safety to obtain specific follow-up information in an expedited fashion.  
This information is more detailed than that recorded on the CRF.  In general, this will include 
a description of the event in sufficient detail to allow for a complete medical assessment of
the case and independent determination of possible causality.  Any information relevant to 
the event, such as concomitant medications and 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 Safety.  Any pertinent additional information must be reported on the CT SAE
Report Form; additional source documents (eg, medical records, CRF, laboratory data) are to
be sent to Pfizer Safety ONLY upon request.
As part of ongoing safety reviews conducted by the sponsor, any non-serious AE that is 
determined by the sponsor to be serious will be reported by the sponsor as an SAE.  To assist 
in the determination of case seriousness, further information may be requested from the 
investigator to provide clarity and understanding of the event in the context of the clinical
study.
8.1.1. Additional Details On Recording Adverse Event on the CRF
All events detailed in the table above will be recorded on the AE page(s) of the CRF.  It
should be noted that the CT SAE Report Form for reporting of SAE information is not the 
same as the AE page of the CRF.  When the same data are collected, the forms must be 
completed in a consistent manner. AEs should be recorded using concise medical 
terminology and the same AE term should be used on both the CRF and the CT SAE Report
Form for reporting of SAE information.
8.1.2. Eliciting Adverse Event Information
The investigator is to record on the CRF all directly observed AEs and all AEs spontaneously
reported by the study subject.  In addition, each study subject will be questioned about the 
occurrence of AEs in a non-leading manner.
8.1.3. Withdrawal From the Study Due to Adverse Events (see also the Subject 
Withdrawal section)
Withdrawal due to AEs should be distinguished from withdrawal due to other causes, 
according to the definition of AE noted below, and recorded on the CRF. 
When a subject withdraws from the study because of an SAE, the SAE must be recorded on 
the CRF and reported, as appropriate, on the CT SAE Report Form, in accordance with the 
Requirements section above.


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8.1.4. Time Period for Collecting AE/SAE Information
The time period for actively eliciting and collecting AEs and SAEs (“active collection 
period”) for each subject begins from the time the subject provides informed consent, which 
is obtained before the subject’s participation in the study (ie, before undergoing any 
study-related procedure and/or receiving investigational product), through and including a 
minimum of 28 calendar days after the last administration of the investigational product.
For subjects who are screen failures, the active collection period ends when screen failure 
status is determined.
Medical occurrences that begin before the start of study intervention but after obtaining 
informed consent will be recorded on the Medical History/Current Medical Conditions
section of the case report form (CRF), not the AE section.
8.1.4.1. Reporting SAEs to Pfizer Safety
All SAEs occurring in a subject during the active collection period are reported to Pfizer 
Safety on the CT SAE Report Form.
SAEs occurring in a subject after the active collection period has ended are reported to Pfizer 
Safety 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 must be reported to Pfizer Safety.
Follow up by the investigator continues throughout and after the active collection period and 
until the event or its sequelae resolve or stabilize at a level acceptable to the investigator, and
Pfizer concurs with that assessment.
8.1.4.2. Recording Non-serious AEs and SAEs on the CRF
During the active collection period, both non-serious AEs and SAEs are recorded on the
CRF.
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.
8.1.5. 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 on the CRF, and report such 
an assessment in accordance with the SAE 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.  If the investigator's causality assessment is “unknown but not 
related” to investigational product, this should be clearly documented on study records. 


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In addition, if the investigator determines that an SAE is associated with study procedures, 
the investigator must record this causal relationship in the source documents and CRF, and 
report such an assessment in the dedicated section of the CT SAE Report Form and in 
accordance with the SAE reporting requirements.
8.1.6. Sponsor’s Reporting Requirements to Regulatory Authorities
AE reporting, including suspected unexpected serious adverse reactions, will be carried out 
in accordance with applicable local regulations.
8.2. Definitions
8.2.1. Adverse Events
An AE is any untoward medical occurrence in a study 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 signs and symptoms;

Changes in physical examination findings;

Hypersensitivity;

Progression/worsening of underlying disease;

Drug abuse;

Drug dependency.
Additionally, AEs may include signs and symptoms resulting from:

Drug overdose;

Drug withdrawal;

Drug misuse; 

Drug interactions;

Extravasation;

Exposure during pregnancy (EDP);

Exposure via breastfeeding;

Medication error;


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
Occupational exposure.
8.2.2. Abnormal Test Findings
Abnormal objective test findings should be recorded as AEs when any of the following 
conditions are met: 

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 (outside of any protocol-specified dose 
adjustments) 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 
recording as an AE.
8.2.3. 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.
Or that is considered to be:

An important medical event.
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.


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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.
8.2.4. 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 is assessed for medical importance.
Hospitalization does not include the following:

Rehabilitation facilities;

Hospice facilities;

Respite care (eg, caregiver relief);

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 
workup of a persistent pretreatment 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;


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
Preplanned 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 noninvasive and invasive procedures, such as surgery, should not 
be reported as SAEs.  However, the medical condition for which the procedure was 
performed should be reported if it meets the definition of an SAE. For example, an acute 
appendicitis that begins during the reporting period should be reported if the SAE 
requirements are met, and the resulting appendectomy should be recorded as treatment of the 
AE.
8.3. Severity Assessment
If required on the AE page of the CRF, 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 
the subject's usual function) but would not be classified as serious unless it met one of the 
criteria for SAEs, listed above.
8.4. Special Situations
8.4.1. Protocol-Specified Serious Adverse Events
There are no protocol-specified SAEs in this study.  All SAEs will be reported to Pfizer
Safety by the investigator as described in previous sections, and will be handled as SAEs in
the safety database.
8.4.2. Potential Cases of Drug-Induced Liver Injury
Humans exposed to a drug who show no sign of liver injury (as determined by elevations in 
transaminases) are termed “tolerators,” while those who show transient liver injury, but adapt
are termed “adaptors.”  In some subjects, transaminase elevations are a harbinger of a more
serious potential outcome.  These subjects fail to adapt and therefore are "susceptible" to 
progressive and serious liver injury, commonly referred to as drug-induced liver injury 
(DILI).  Subjects who experience a transaminase elevation above 3 times the upper limit of
normal (× ULN) should be monitored more frequently to determine if they are an “adaptor” 
or are “susceptible.”
In the majority of DILI cases, elevations in aspartate aminotransferase (AST) and/or alanine 
aminotransferase (ALT) precede total bilirubin (TBili) elevations (>2 × ULN) by several 
days or weeks.  The increase in TBili typically occurs while AST/ALT is/are still elevated 
above 3 × ULN (ie, AST/ALT and TBili values will be elevated within the same lab sample).  


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In rare instances, by the time TBili elevations are detected, AST/ALT values might have 
decreased.  This occurrence is still regarded as a potential DILI.  Therefore, abnormal 
elevations in either AST OR ALT in addition to TBili that meet the criteria outlined below 
are considered potential DILI (assessed per Hy’s law criteria) cases and should always be 
considered important medical events, even before all other possible causes of liver injury 
have been excluded.
The threshold of laboratory abnormalities for a potential DILI case depends on the subject’s 
individual baseline values and underlying conditions.  Subjects who present with the
following laboratory abnormalities should be evaluated further as potential DILI (Hy’s law) 
cases to definitively determine the etiology of the abnormal laboratory values:

Subjects with AST/ALT and TBili baseline values within the normal range who 
subsequently present with AST OR ALT values >3 × ULN AND a TBili value 
>2 × ULN with no evidence of hemolysis and an alkaline phosphatase value
<2 × ULN or not available;

For subjects with baseline AST OR ALT OR TBili values above the ULN, the 
following threshold values are used in the definition mentioned above, as needed, 
depending on which values are above the ULN at baseline:

Preexisting AST or ALT baseline values above the normal range: AST or ALT 
values >2 times the baseline values AND >3 × ULN; or >8 × ULN (whichever is 
smaller).

Preexisting values of TBili above the normal range: TBili level increased from 
baseline value by an amount of at least 1 × ULN or if the value reaches >3 × ULN 
(whichever is smaller).
Rises in AST/ALT and TBili separated by more than a few weeks should be assessed 
individually based on clinical judgment; any case where uncertainty remains as to whether it 
represents a potential Hy’s law case should be reviewed with the sponsor.  
The subject should return to the investigator 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 and TBili, laboratory tests should 
include albumin, creatine kinase (CK), direct and indirect bilirubin, gamma-glutamyl 
transferase (GGT), prothrombin time (PT)/international normalized ratio (INR), total bile 
acids, alkaline phosphatase and acetaminophen drug and/or protein adduct levels.  
Consideration should also be given to drawing a separate tube of clotted blood and an 
anticoagulated tube of blood for further testing, as needed, for further contemporaneous 
analyses at the time of the recognized initial abnormalities to determine etiology.  A detailed 
history, including relevant information, such as review of ethanol, acetaminophen (either by
itself or as a coformulated product in prescription or over-the-counter medications), 


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recreational drug, supplement (herbal) use and consumption, family history, sexual history, 
travel history, history of contact with a jaundiced person, surgery, blood transfusion, history 
of liver or allergic disease, and potential occupational exposure to chemicals, should be 
collected. Further testing for acute hepatitis A, B, C, D, and E infection and liver imaging 
(eg, biliary tract) may be warranted. 
All cases demonstrated on repeat testing as meeting the laboratory criteria of AST/ALT and 
TBili elevation defined above should be considered potential DILI (Hy’s law) cases if no
other reason for the LFT abnormalities has yet been found.  Such potential DILI (Hy’s law)
cases are to be reported as SAEs, irrespective of availability of all the results of the
investigations performed to determine etiology of the LFT abnormalities.
A potential DILI (Hy’s law) case becomes a confirmed case only after all results of
reasonable investigations have been received and have excluded an alternative etiology.
8.4.3. Exposure to the Investigational Product During Pregnancy or Breastfeeding, and 
Occupational Exposure
Exposure to the investigational product under study during pregnancy or breastfeeding and 
occupational exposure are reportable to Pfizer Safety within 24 hours of investigator 
awareness.
8.4.3.1. Exposure During Pregnancy
For both unapproved/unlicensed products and for marketed products, an exposure during 
pregnancy (EDP) occurs if:

A female becomes, or is found to be, pregnant either while receiving or having been 
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).

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 subject or subject’s partner becomes or is found to be pregnant during the subject’s 
treatment with the investigational product, the investigator must report this information to 
Pfizer Safety on the CT SAE Report Form and an 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) to Pfizer Safety 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 


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information submitted should include the anticipated date of delivery (see below for
information related to termination of pregnancy).
Follow-up is conducted to obtain general information on the pregnancy and its outcome for
all EDP reports with an unknown outcome.  The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer Safety 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 a neonatal death]), the 
investigator should follow the procedures for reporting SAEs.
Additional information about pregnancy outcomes that are reported to Pfizer Safety 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 
SAEs when the investigator assesses the infant death as related or possibly related to 
exposure to the investigational product.
Additional information regarding the EDP may be requested by the sponsor.  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 subject with the Pregnant Partner Release of Information Form 
to deliver to his partner.  The investigator must document in the source documents that the 
subject was given the Pregnant Partner Release of Information Form to provide to his
partner.
8.4.3.2. Exposure During Breastfeeding
Scenarios of exposure during breastfeeding must be reported, irrespective of the presence of 
an associated SAE, to Pfizer Safety within 24 hours of the investigator’s awareness, using the 
CT SAE Report Form. An exposure during breastfeeding report is not created when a Pfizer 
drug specifically approved for use in breastfeeding women (eg, vitamins) is administered in 
accord with authorized use.  However, if the infant experiences an SAE associated with such 
a drug’s administration, the SAE is reported together with the exposure during breastfeeding.


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8.4.3.3. Occupational Exposure
An occupational exposure occurs when, during the performance of job duties, a person 
(whether a healthcare professional or otherwise) gets in unplanned direct contact with the 
product, which may or may not lead to the occurrence of an AE.
An occupational exposure is reported to Pfizer Safety within 24 hours of the investigator’s 
awareness, using the CT SAE Report Form, regardless of whether there is an associated
SAE.  Since the information does not pertain to a subject enrolled in the study, the 
information is not recorded on a CRF; however, a copy of the completed CT SAE Report 
Form is maintained in the investigator site file.
8.4.4. Medication Errors
Other exposures to the investigational product under study may occur in clinical trial settings, 
such as medication errors.
Safety Event
Recorded on the CRF
Reported on the CT SAE 
Report Form to Pfizer 
Safety Within 24 Hours of 
Awareness
Medication errors 
All (regardless of whether 
associated with an AE)
Only if associated with an
SAE
8.4.4.1. Medication Errors
Medication errors may result from the administration or consumption of the investigational 
product by the wrong subject, or at the wrong time, or at the wrong dosage strength. 
Medication errors include:

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.
Such medication errors occurring to a study participant are to be captured on the medication 
error page of the CRF, which is a specific version of the AE page.
In the event of a medication dosing error, the sponsor should be notified immediately.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is recorded on the medication error page of the CRF and, if 
applicable, any associated AE(s), serious and non-serious, are recorded on an AE page of the 
CRF.
Medication errors should be reported to Pfizer Safety within 24 hours on a CT SAE Report 
Form only when associated with an SAE.


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8.5. 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.
8.5.1. 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 7.7 on Adverse Event Reporting.
8.5.2. 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 blinded study drug temporarily 
discontinued during antimicrobial therapy in consultation with the Sponsor. This information 
should be noted in the Case Report Form.
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 (SAP), which will be maintained by 
Pfizer.  This document may modify the plans outlined in the protocol; however, any major 
modifications of the primary endpoint definition and/or its analysis will also be reflected in a 
protocol amendment.
9.1. Sample Size Determination
The sample size and power analysis for the primary endpoint are based on the randomization 
of approximately 204 subjects in a 2:1 ratio.  The sample size for this study is driven by the
ACR50 response rate. 
Assuming a placebo response rate of 9.5% and factoring in the number of subjects with 
primary endpoint missing due to COVID-19 (around 11 subjects as of 29 May 2020), a
sample size of approximately 204 Chinese subjects (approximately 136 subjects in the 
tofacitinib treatment arm and 68 subjects in the placebo arm) randomized in a 2:1 ratio to 
tofacitinib and placebo arms will yield at least 90% power to detect a difference of 
18.5% from placebo in ACR50 response rate, based on normal approximation (without 
continuity correction) at the 2-sided 5% significance level.


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9.2. Efficacy Analysis
9.2.1. Analysis of Primary Endpoint of ACR50 Response Rate
The normal approximation to the difference in binomial proportions will be used to test the
difference between tofacitinib 5 mg BID and placebo and to generate 95% confidence 
interval for the difference in response rates. 
Missing values for any reason, eg, due to a subject dropping from the study or due to the 
impact of COVID-19 pandemic will be handled by setting the ACR50 value to 
nonresponsive. The SAP will also specify additional analyses to assess the sensitivity of the
primary analysis to departures from the assumed missing data mechanism.
The analysis will include all randomized subjects who receive at least 1 dose of study drug.
9.2.2. Analysis of Secondary Endpoints
Binary endpoints will be analyzed similarly as for the primary analysis of ACR50.
The HAQ-DI will be analyzed using a repeated measure model that includes the fixed
effects of treatment, visit (Week 2, Months 1, 2, 3, 4 and 6), treatment by visit interaction, 
and baseline value, and an unstructured variance covariance matrix for within-subject 
correlation (an alternative variance covariance matrix will be used if the model does not 
converge under the unstructured variance covariance matrix). Other continuous endpoints 
will be analyzed similarly.
Details of the analysis methods for all the endpoints will be enumerated in the SAP.
9.3. Analysis of Other Endpoints
Other endpoints will be analyzed similarly as for the secondary endpoints.
9.4. Safety Analysis
All the safety data will be summarized descriptively through appropriate data tabulations, 
descriptive statistics, and graphical presentations:

Incidence and severity of adverse events; 

Categorical summary of absolute vital signs and vital sign changes compared to 
baseline by subject;

Incidence of adjudicated safety events;

Serious infections will be summarized separately;

Any safety events that trigger withdrawal of a subject;

Safety laboratory tests will be summarized according to Pfizer standards;


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
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.
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 Endpoints Adjudication Committees (SEAC) 
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 Committtee (OIRC), Malignancy Adjudication 
Committee (MAC), and Hepatic Event Review Committee (HERC).  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 Committee, ILDRC).  
Further information about these committees can be found in their respective charters, 
including specific 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 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 pathologist. If biopsies are not 
available, digital photos of the stained slides for each tissue block, digital image of the slides 
and local pathology report(s) should be submitted.  In some instances, additional expert 
pathology review of submitted samples may be requested external to the central laboratory.  
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described in the Malignancy Histopathology Adjudication charters. Further details on central 
laboratory review of biopsies of suspected malignancies are found in Appendix 6.
10. QUALITY CONTROL AND QUALITY ASSURANCE
Pfizer or its agent will conduct periodic monitoring visits during study conduct 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 are 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 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.
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 


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data contained on the CRFs are true.  Any corrections to entries made in the CRFs or 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 and at Pfizer that clearly identifies those data that 
will be recorded on the CRF, and for which the CRF will stand as the source document.
11.2. Record Retention
To enable evaluations and/or inspections/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, and telephone call reports). The records should 
be retained by the investigator according to the ICH guidelines, 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 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.
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)/ Ethics Committee (EC)
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.


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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.
In addition, the study will be conducted in accordance with the protocol, the ICH guideline 
on GCP, and applicable local regulatory requirements and laws.
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.
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 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.


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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.
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 that 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.
13. DEFINITION OF END OF TRIAL
End of Trial 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/EC, or 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, Pfizer will promptly notify the investigator. After 
notification, the investigator must contact all participating subjects and the hospital pharmacy 
(if applicable) within 180 days.  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 studies on www.clinicaltrials.gov (ClinicalTrials.gov), the European Clinical Trials 
Database (EudraCT), and/or www.pfizer.com, and other public registries in accordance with 
applicable 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.


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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.
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 has no objection to publication by the Investigator of any information collected or 
generated by the investigator, whether or not the results are favorable to the investigational 
drug.  However, to ensure against inadvertent disclosure of confidential information or 
unprotected inventions, the investigator will provide Pfizer an opportunity to review any 
proposed publication or other type of disclosure before it is submitted or otherwise disclosed.
The Investigator will provide manuscripts, abstracts, or the full text of any other intended 
disclosure (poster presentation, invited speaker or guest lecturer presentation, etc.) to Pfizer 
at least 30 days before they are submitted for publication or otherwise disclosed.  If any 
patent action is required to protect intellectual property rights, the investigator agrees to delay 
the disclosure for a period not to exceed an additional 60 days.
The investigator will, on request, remove any previously undisclosed confidential 
information (other than the Study results themselves) before disclosure.


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If the study is part of a multi-centre study, the investigator agrees that the first publication is 
to be a joint publication covering all centers.  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 
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 between 
Pfizer and the institution.  In this section entitled Publications by Investigators, the defined
terms shall have the meanings given to them in the Clinical Study Agreement.


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16. REFERENCES
1.
Gladman DD, Antoni C, et al. Psoriatic arthritis: epidemiology, clinical features, course,
and outcome. Ann Rheum Dis. 2005 Mar;64 Suppl 2:ii14-17.
2.
McHugh NJ. Traditional schemes for treatment of psoriatic arthritis. J Rheumatol. 
Suppl. 2009 Aug; 83:49-51.
3.
Coates LC, Kavanaugh A, Mease PJ, et al. Group for Research and Assessment of 
Psoriasis and Psoriatic Arthritis 2015 Treatment Recommendations for Psoriatic 
Arthritis. Arthritis & Rheumatology 2016; 68(5):1060-71.
4.
Scott DL, Dacre JE.  Adverse reactions to sulfasalazine: the British experience. J 
Rheumatol Suppl 1988;16:17-21.
5.
Madhok R, Torley HI, Capell HA. A study of the longterm efficacy and toxicity of
cyclosporine A in rheumatoid arthritis. J of Rheumatology 1991;18:1485–89.
6.
Schiff MH, Whelton A. Renal toxicity associated with disease-modifying 
anti-rheumatic drugs used for the treatment of rheumatoid arthritis. Semin Arthritis 
Rheum 2000;30:196–208.
7.
Whiting-O’Keefe QE, Fye KH, Sack KD. Methotrexate and histologic hepatic
abnormalities: a meta-analysis. Am J of Med 1991;90:711–16.
8.
Center for Drug Evaluation Research, Summary Review of Otezla, 205437Orig1s000.  
http://www.accessdata.fda.gov/drugsatfdadocs/nda/2014/205437Orig1s000SumR.pdf.
9.
Johnston JA, Bacon CM, Riedy MC, et al. Signaling by IL-2 and related cytokines: 
JAKs, STATs, and relationship to immunodeficiency.  J Leuk Biol. 1996; 60(4):441-52.
10.
Conklyn M, Andresen C, Changelian P et al.  The JAK3 inhibitor CP-690550 
selectively reduces NK and CD8+ cell numbers in cynomolgus monkey blood following 
chronic oral dosing.  J Leuk Biol.  2004; 76(6):1248-55. 
11.
Changelian PS, Moshinsky D, Kuhn CF et al.  The specificity of JAK3 kinase 
inhibitors.  Blood.  2008 Feb 15; 111(4):2155-7.
12.
Ghoreschi K, Jesson MI, Li X, et al. Modulation of innate and adaptive immune 
responses by tofacitinib (CP-690,550). J Immunol 2011;186:4234-43.
13.
Meyer DM, Jesson MI, Li X, et al. Anti-inflammatory activity and neutrophil reductions
mediated by the JAK1/JAK3 inhibitor, CP-690,550, in rat adjuvant-induced arthritis. J 
Inflamm 2010;7:41. 
14.
Maeshima K, Yamaoka K, Kubo S, et al. The JAK inhibitor tofacitinib regulates 
synovitis through inhibition of interferon-γ and interleukin-17 production by human 
CD4+ T cells.  Arthritis Rheum 2012; 64 (6): 1790-98.


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15.
Kubo S, Yamaoka K, Sonomoto K, et al.  Tofacitinib reduces IFN-gamma and IL-17 
production from CD4+ T cells in patients with rheumatoid arthritis. In: American 
College of Rheumatology 75th Annual Scientific Meeting.  Chicago, IL. 2011: Abstr 
1267.
16.
Tak PP, Kalden JR. Advances in rheumatology: new targeted therapeutics. [Review]. 
Arthritis Research & Therapy 2011:13 suppl 1:S5.
17.
Vadasz Z, Rimar D, Toubi E. The New Era of Biological Treatments.  Isr Med Assoc J 
2014;16:793-98.
18.
Curtis JR, Xie F, Chen L et al. The incidence of gastrointestinal perforations among 
rheumatoid arthritis patients. Arthritis Rheum. 2011; 63(2): 346-351.
19.
Konstantinides SV, Meyer G, Becattini C et al. 2019 ESC guidelines for the diagnosis 
and management of acute pulmonary embolism developed in collaboration with the
ERS. Eur Heart J. 2020 Jan 21;41(4):543-603.
20.
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 Aug; 54(8):2665-73.
21.
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.
22.
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.
23.
DAS-score.nl: Disease activity score in rheumatoid arthritis. Available online at: 
http:.// www.das-score.nl/das28/en/.
24.
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 Dec; 39(12):2013-20.
25.
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.
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.


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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 Aug;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.
31.
Ware JE, Kosinski M., Dewey JE.  How to score version two of the SF 36 Health
Survey.  Lincoln, RI: Quality Metric, Incorporated, 2000.
32.
Hurst NP, Kind P, Ruta D, Hunter M, Stubbings A.  Measuring health-related quality of 
life in rheumatoid arthritis: validity, responsiveness and reliability of EuroQol (EQ-5D) 
Br J Rheumatol.  1997; 36 (5):551-9.
33.
Reilly MC, Sbrozek AS, Dukes EM. The validity and reproducibility of a work 
productivity and activity impairment instrument. Pharmacoeconomics 1993;4:353-365.
34.
Guidelines for Using the QuantiFERON-TB Gold Test for Detecting Mycobacterium 
tuberculosis Infection, United States. Online. Available: 
http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5415a4.htm.


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Appendix 1. Abbreviations
This is a list of abbreviations that may or may not be used in the protocol.
Abbreviation
Term
Ab
Antibody
AE
Adverse Event
ACR
American College of Rheumatology
ALT
Alanine Aminotransferase
ANC
Absolute Neutrophil Counts
Anti-CCP
Anti-cyclic citrullinated protein antibody
AST
Aspartate Aminotransferase
AUC
Area Under Curve
BCG
Bacille Calmette Guérin
bDMARD
Biological Disease-Modifying Anti-Rheumatic Drug
BID
Twice daily
BMI
Body Mass Index
BSA
Body surface area
CASPAR
Classification Criteria for Psoriatic Arthritis
CCP
Cyclic Citrullinated Peptide
CDS
Core data sheet
CHD
Coronary Heart Disease
CK
Creatine Kinase
CL/F
Oral Clearance
COVID-19
Corona Virus Disease 2019
COX-2
Cyclooxygenase-2
CRF
Case Report Form
CRP
C-reactive Protein
csDMARD
Conventional Synthetic Disease-Modifying Anti-Rheumatic Drug
CTA
Clinical Trial Application
CV-EAC
Cardiovascular Endpoint Adjudication Committee
CYP
Cytochrome P 
CXR
Chest X-ray
DAS
Disease Activity Score 
DILI
Drug Induced Liver Injury
DIP
Distal interphalangeal
DMARDs
Disease-Modifying Anti-Rheumatic Drugs
DNA
Deoxyribonucleic acid
EC
Ethics committee
ECG
Electrocardiogram
EDMC
External Data Monitoring Committee
EDP
exposure during pregnancy
EQ-5D
The EuroQol EQ-5D Health State Profile
EU
European Union


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Abbreviation
Term
EudraCT
European Clinical Trial Database
FACS
Fluoresence Activated Cell Sorting
FAS
Full analysis set
FDA
Food and Drug Administration
FSH
Follicle Stimulating Hormone
GCP
Good Clinical Practice
GGT
Gamma Glutamyl Transferase
gm
Gram
GRAPPA
Group for Research and Assessment of Psoriasis and Psoriatic Arthritis
HAQ-DI
Health Assessment Questionnaire-Disability Index
HbA1c
Hemoglobin A1c
HBsAg
Hepatitis B surface antigen
HBsAb
Hepatitis B surface antibody
HBcAb
Hepatitis B core antibody
HBV
Hepatitis B virus
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
IEC
Independent Ethics Committee
ILD
Interstitial Lung Disease
IND
Investigational New Drug
INR
international normalized ratio
IP
Interphalangeal
IRB
Institutional Review Board
IRC
Internal Review Committee
IUD
Intrauterine Device
IUS
Interuterine System
IVRS
Interactive Randomization System
JAK
Janus kinase
LDL
Low density Lipoprotein
LEI
Leeds Enthesitis Index
LFT
liver function test
LPD
Lymphoproliferative Disease
LSLV
Last Subject Last Visit
LTE
long term extension 
LTFU
Long-Term Follow-Up
MACE
Major Adverse Cardiac Events
MCP
Metacarpophalangeals
MCTD
Mixed Connective Tissue Disease


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Abbreviation
Term
mg
Milligrams
MTP
Metatarsophalangeal
MTX
Methotrexate
NAPSI
Nail Psoriasis Severity Score
NRI
Nonresponder imputation
NSAIDs
Non-Steroidal Anti-Inflammatory Drugs
PASI
Psoriasis Area Severity Index
PASI75
Psoriasis Area and Severity Index 75
PDE4
Phosphodiesterase 4
PGA-PsO
Physician’s Global Assessment of Psoriasis
PIP
Proximal Interphalangeals
PK
Pharmacokinetics
PPD
Purified Protein Derivative
PRO
Patient Reported Outcome
PsA
Psoriatic Arthritis
PsARC
Psoriatic Arthritis Response Criteria
PsO
Psoriasis
PT
Prothrombin Time
PUVA
Psoralens + UVA phototherapy
Qd
Once Daily
QFT-G
Quantiferon Gold
RA
Rheumatoid Arthritis
RBC
Red Blood Cell
RF
Rheumatoid Factor
RNA
ribonucleic acid
SAE
Serious Adverse Event
SAP
Statistical Analysis Plan
SF-36
36-Item Short-Form Health Survey
SLE
Systemic Lupus Erythematosus
SRSD
Single Reference Safety Document
TB
Tuberculosis
TNFi
Tumour Necrosis Factor Inhibitor
tsDMARD
Targeted Synthetic Disease Modifying Anti-Rheumatic Drug
ULN
Upper Limit of Normal
US
United States
UVB
Ultraviolet B
VAS
Visual Analog Scale
VTE
Venous thromboembolism
WBC
White Blood Cell
WPAI-PsA
Work Productivity and Activity Impairment – Psoriatic Arthritis


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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
All biologic DMARDs are prohibited.  See Section 4.3 regarding washout period for TNFi.  
Other biologic agents are prohibited (eg, ustekinumab or investigational agents) and require a
6 month washout period unless otherwise specified.
The following nonbiologic DMARDs are prohibited before the last dose of investigational 
drug: Leflunomide, azathioprine, cyclosporine, bucillamine, iguratimod, mizoribin, 
tacrolimus, tetracycline (used as a DMARD) and any JAK inhibitor.  All of these prohibited
DMARDs require a 4 week washout period prior to first dose of study treatment.
Leflunomide(Arava) must have been discontinued 8 weeks prior to the first dose of study 
drug if no elimination procedure is followed.  Alternately, it should have been discontinued
with the following elimination procedure at least 4 weeks prior to the first dose of study drug: 
Cholestyramine at a dosage of 8 grams three times daily for at least 24 hours, or activated 
charcoal at a dosage of 50 grams 4-times a day for at least 24 hours.
Traditional Chinese medicine, Tripterydium hypoglaucum (thunder god vine), requires a 
4 week washout period prior to first dose of study treatment. 
All Investigational Drugs not otherwise specified are prohibited and require a 4 week 
(5 half-lives) washout period prior to first dose of study treatment.
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.

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 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
Prohibited are 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.


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
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.
Also prohibited is UVB (narrowband or broadband) phototherapy that must be discontinued 
at least 2 weeks prior to first dose of study drug.  Psoralens + UVA phototherapy (PUVA) 
must be discontinued at least 4 weeks prior to first dose of study drug.


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Appendix 4. 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 5. 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 4) 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 4]) for rescue 
purposes;

Sustained release opioid formulations (eg, OxyContin, MS Contin) and opioids 
with half lives greater than 5 hours (eg, methadone, propoxyphene) 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, propoxyphene; see also Appendix 4) may NOT be 
INCREASED for rescue purposes.


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Intravenous or intramuscular corticosteroids, biologic response modifiers and DMARDs, 
other than methotrexate and sulfasalazine, are not allowed during this study.  Intra-articular 
corticosteroids may be given at or after the Month 3 visit in no more than two joints, in a 
cumulative dose of no more than 40 mg methylprednisolone or its equivalent in any 6 month 
study period.  The total allowed intraarticular corticosteroid dose may be divided into 
separate injections (eg, 20 mg, 20 mg).  Intra-articular hyaluronate sodium injections may be 
administered for indications in accordance with the local label at or after the Month 3 visit in 
no more than two joints in any 6 month study period.  If performed at Month 3 visit, 
intra-articular injections must be given after assessments are completed.  Intra-articular 
corticosteroids should not be administered within 4 weeks prior to a study visit.
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.  In addition, subjects 
should not be dosed with rescue acetaminophen/paracetamol or opioids within 24 hours prior 
to a study visit.  Baseline stable acetaminophen/paracetamol or opioids should NOT be 
discontinued in advance of study visits.
Subjects should not be dosed with any rescue intervention within 24 hours prior to a 
study visit unless medically necessary.


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Appendix 6. 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, 
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.

SAP_001.pdf: 
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Protocol A3921234
A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY 
OF THE EFFICACY AND SAFETY OF TOFACITINIB (CP-690,550) IN CHINESE 
SUBJECTS WITH ACTIVE PSORIATIC ARTHRITIS AND AN INADEQUATE 
RESPONSE TO AT LEAST ONE CONVENTIONAL SYNTHETIC DMARD
Statistical Analysis Plan 
(SAP)
Version:
2
Date:
22-FEB-2021


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TABLE OF CONTENTS 
LIST OF TABLES...........................................................................................................4
LIST OF FIGURES .........................................................................................................4
1. VERSION HISTORY..................................................................................................5
2. INTRODUCTION .......................................................................................................7
2.1. Study Objectives .............................................................................................7
Primary Objectives .............................................................................7
Secondary Objectives .........................................................................8
2.2. Study Design ...................................................................................................8
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS ...................................................................................................9
3.1. Primary Endpoint(s) ........................................................................................9
3.2. Secondary Endpoint(s) ....................................................................................9
Secondary Efficacy Endpoints............................................................9
Secondary Physical Function and Health Outcome Measures .........10
3.3. Other Endpoints.............................................................................................10
Other Efficacy Endpoints .................................................................10
3.4. Baseline Variables.........................................................................................11
Demographic Characteristics............................................................11
Baseline Disease Characteristics ......................................................11
Prior and Baseline Treatments for Psoriatic Arthritis.......................12
3.5. Safety Endpoints ...........................................................................................13
Adverse Events .................................................................................13
Laboratory Data................................................................................14
4. ANALYSIS SETS .....................................................................................................15
4.1. Full Analysis Set ...........................................................................................15
4.2. Per Protocol Analysis Set..............................................................................15
Protocol Deviations Assessed Prior to Randomization ....................16
Protocol Deviations Assessed Post-Randomization.........................16
4.3. Safety Analysis Set........................................................................................17
4.4. Other Analysis Sets .......................................................................................17


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Endpoint Specific Analysis Sets.......................................................17
5. GENERAL METHODOLOGY AND CONVENTIONS..........................................18
5.1. Hypotheses and Decision Rules ....................................................................18
5.2. General Methods ...........................................................................................19
Analyses for Binary Data..................................................................20
Normal Approximation ...................................................20
Generalized Marginal Model for Repeated Measures 
(GMMRM).....................................................................21
Tipping Point Analysis....................................................21
Analyses for Continuous Data..........................................................22
Analyses of Tier-2 Adverse Events ..................................................22
5.3. Methods to Manage Missing Data ................................................................22
6. ANALYSES AND SUMMARIES ............................................................................23
6.1. Primary Endpoint(s) ......................................................................................23
ACR50 Response Rate at Month 3...................................................23
Primary Analysis.............................................................23
Supportive Analyses........................................................24
6.2. Secondary Endpoint(s) ..................................................................................26
Binary Endpoints ..............................................................................26
Continuous Endpoints.......................................................................27
6.3. Other Endpoint(s)..........................................................................................28
6.4. Subset Analyses.............................................................................................29
6.5. Baseline and Other Summaries and Analyses...............................................31
Baseline Summaries..........................................................................31
Prior and Baseline Treatments for Psoriatic Arthritis.......................31
Concomitant DMARD Treatments...................................................31
6.6. Safety Summaries and Analyses ...................................................................31
Adverse Events .................................................................................31
Other Safety Summaries...................................................................32
6.7. Additional Analyses to Address COVID-19 Pandemic Impacts...................33
Additional Supportive Analysis of the Primary Endpoint................33


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Other Summaries and Listings Depicting COVID-19 Pandemic 
Impacts .........................................................................................34
7. INTERIM ANALYSES.............................................................................................34
7.1. Introduction ...................................................................................................34
7.2. Interim Analyses and Summaries..................................................................34
8. REFERENCES ..........................................................................................................35
9. APPENDICES ...........................................................................................................36
LIST OF TABLES
Table 1
Summary of Major Changes in SAP Amendments ......................................5
Table 2
Clinical Laboratory Testing........................................................................14
Table 3
Endpoint Specific Analysis Sets.................................................................17
LIST OF FIGURES
Figure 1
Study Design.................................................................................................8
APPENDICES
Appendix 1. SUMMARY OF EFFICACY ANALYSES..............................................36
Appendix 2. DEFINITION AND USE OF VISIT WINDOWS IN REPORTING .......41
Appendix 3. ENDPOINT DEFINITION AND DATA DERIVATION DETAILS ......43
Appendix 4. STATISTICAL METHODOLOGY DETAILS........................................62


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1. VERSION HISTORY
Table 1
Summary of Major Changes in SAP Amendments
SAP Version
Associated 
Protocol 
Amendment
Change
Rationale
1
(17-APR-2018)
Protocol 
Amendment 1
(20-NOV-2017)
None
Not Applicable
2
(22-FEB-2021)
Protocol 
Amendment 4
(04-JUN-2020)
Sections 2.2 and 5.3: 
Protocol languages 
were updated 
To be consistent with 
protocol amendment 4.
Section 3.4.3: Added 
details for prior 
DMARDs use 
summaries.
To clarify how prior 
DMARDs use will be 
summarized.
Section 4.2.1: Added 
one additional 
criterion for subject 
exclusion from Per-
Protocol analysis set.
To exclude subjects with 
history of or current 
autoimmune rheumatic 
disease or rheumatic 
inflammatory disease other 
than PsA.
Sections 5.2 and 
5.2.1.1: Updated 
method for reporting 
response rate when 
the rate is 0 or 100%.
To clarify the reporting 
method.
Section 6.1.1.2 and 
Appendix 1: 
Sensitivity analysis in 
the per-protocol 
analysis set is 
renamed a supportive 
analysis.
Sensitivity analysis is 
reserved for a different 
statistical method but 
otherwise everything else
(including the analysis set
and missing data handling 
method) stays the same.
Sections 6.2.1 and 
6.2.2: Line graph will 
For TLF reduction.


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only be produced for 
selected endpoints.  
Section 6.4: Updated 
specifications for 
subgroup analysis by 
baseline csDMARD 
use.
To clarify the categories in 
subgroup analysis by baseline 
csDMARD use.
Section 6.6.1: 
Analysis periods for 
AE display were 
updated.
For TLF reduction.
Section 6.7: A new 
section was added for 
additional analyses to 
address COVID-19 
pandemic impacts
To add additional analyses 
addressing COVID-19 
pandemic impacts.
Appendix 2: Added 
clarifications for 
definitions of visit 
windows in reporting.
To clarify visit window 
definition in special cases.
Appendix 3: Added 
details in efficacy 
endpoint calculations
and updated AEs of 
special interest and 
list of DMARDs, 
corrected the waist 
circumference 
threshold.
To make sure data derivation
will be programmed 
correctly.
Appendix 4: Re-
formatted the 
descriptions of tipping 
point analysis into a 
step-by-step format 
and pre-specified the 
number of multiple 
imputations and the 
To make sure tipping point 
analysis will be programmed 
correctly.


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values of MNAR 
adjustment.
Other updates in 
Sections 3.2.1, 3.4, 
4.2, 5.3, 6.2.1, 
Appendix 1 and
Appendix 3.
Minor corrections and 
clarifications for consistency.
2. INTRODUCTION
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 the rationale for 
developing tofacitinib as treatment for PsA.
This is a 6-month Phase 3 study designed to evaluate the efficacy and safety of tofacitinib 5 
mg BID as a treatment for PsA in Chinese subjects with active PsA who have had an
inadequate response in their PsA to at least one conventional synthetic disease-modifying 
anti-rheumatic drug (csDMARD).
This SAP provides the detailed methodology for summary and statistical analyses of the data 
collected in study A3921234. This document may modify the plans outlined in the protocol; 
however, any major modifications of the primary endpoint definition or its analysis will also 
be reflected in a protocol amendment.
2.1. Study Objectives
Primary Objectives

To compare efficacy of tofacitinib 5 mg BID versus placebo for treatment of 
rheumatological signs and symptoms of PsA in Chinese subjects with active PsA who 
have had an inadequate response to at least one csDMARD.

To compare the safety and tolerability of tofacitinib 5 mg BID versus placebo in 
Chinese subjects with active PsA who have had an inadequate response in PsA to at 
least one csDMARD.


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Secondary Objectives

To compare physical function status after administration of tofacitinib 5 mg BID 
versus placebo in Chinese subjects with active PsA who have had an inadequate 
response in PsA to at least one csDMARD.

To compare the effects of tofacitinib 5 mg BID versus placebo on all health outcome
measures in Chinese subjects with active PsA who have had an inadequate response to 
at least one csDMARD.

To compare the efficacy of tofacitinib 5 mg BID versus placebo for the treatment of 
dermatological signs and symptoms of PsA in Chinese subjects who have had an 
inadequate response to at least one csDMARD.
2.2. Study Design
This is a Phase 3, randomized, 6-month, double-blind, placebo-controlled, parallel-group 
study designed to evaluate the efficacy and safety of tofacitinib in adult, Chinese subjects 
with active PsA who had an inadequate response in their PsA to at least one csDMARD. All
subjects in the study will be evaluated for risk factors for venous thromboembolism. A total 
of approximately 204 subjects will be randomized in a 2:1 ratio to one of the following two 
parallel treatment sequences. The enrollment will be monitored to cap the proportion of 
subjects with baseline swollen joint count ≤5 at approximately 38% (i.e., approximately 78 
subjects).
A schematic of the study design is shown in Figure 1.
Figure 1
Study Design


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*Primary study endpoints of ACR50 will be obtained at Month 3. All subjects randomized to placebo 
will receive tofacitinib 5 mg BID in a blinded manner after Month 3.
During the study, subjects are required to remain on a stable dose of one csDMARD, e.g., 
methotrexate or sulfasalazine, and should remain on that dose throughout the study.
3. ENDPOINTS AND BASELINE VARIABLES: DEFINITIONS AND 
CONVENTIONS
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.
3.1. Primary Endpoint(s)

ACR50 responder rate at Month 3.
3.2. Secondary Endpoint(s)
Secondary Efficacy Endpoints

ACR20 and ACR70 responder rates at all timepoints;

ACR50 responder rates at all timepoints other than Month 3 (Note that ACR50
responder rate at Month 3 is already mentioned as the primary endpoint);

Change from baseline (∆) in ACR response criteria components (HAQ-DI, C-reactive 
protein [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;

HAQ-DI response defined as a decrease from baseline ≥0.30 for subjects with 
baseline HAQ-DI ≥0.30 at all timepoints; HAQ-DI response defined as a decrease 
from baseline ≥0.35 for subjects with baseline HAQ-DI ≥0.35 at all timepoints; 

Psoriatic Arthritis Response Criteria (PsARC) at all timepoints;

Physician’s Global Assessment of Psoriasis (PGA-PsO) at Month 1, Month 3 and 
Month 6;
o
PGA-PsO response of clear or almost clear and a ≥2-step improvement from 
baseline for subjects with baseline PGA-PsO ≥2;
o
∆PGA-PsO for subjects with baseline PGA-PsO > 0;

Psoriasis Area and Severity Index 75 (PASI75) response at Month 1, Month 3 and 
Month 6 for subjects with baseline psoriatic body surface area (BSA) ≥3% and 
baseline PASI > 0;


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
Dactylitis severity score (DSS) at Month 1, Month 3 and Month 6 for subjects with 
baseline DSS > 0 (see Appendix 3 Section 12);
o
∆DSS;
o
Resolution of dactylitis defined as a subject achieving DSS = 0;

Enthesitis score [using Leeds enthesitis index (LEI)] at Month 1, Month 3 and 
Month 6 for subjects with baseline LEI > 0 (see Appendix 3 Section 11);
o
∆LEI;
o
Resolution of enthesitis defined as a subject LEI = 0;
Secondary Physical Function and Health Outcome Measures
Assessed at baseline, Months 1, 3 and 6:

Short-Form-36 Health Survey (∆SF-36) Version 2, Acute;
This survey yields 10 endpoints: 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 summary 
scores (PCS and MCS, respectively) (see Appendix 3 Section 6).

EuroQol 5-Dimension Health State Profile – 3 Level Version (∆EQ-5D-3L).
This instrument yields 6 endpoints: scores from the five domains (ΔEQ-5D) and an
EQ-VAS score of the subject’s health state today (ΔEQ-VAS) (see Appendix 3 
Section 7).
3.3. Other Endpoints
Other Efficacy Endpoints

∆DAS28-3(CRP) at all timepoints;

Physician’s Global Assessment of Psoriatic Arthritis (ΔPGA-PsA) at Month 1, Month 
3 and Month 6;

Percent change from baseline (%∆) in PASI and PASI clinical sign component scores 
at Month 1, Month 3 and Month 6 for subjects with baseline BSA ≥3% and baseline
PASI > 0;

%∆BSA at Month 1, Month 3 and Month 6 for subjects with baseline BSA > 0%;

Nail Psoriasis Severity Index (∆NAPSI) Score at Month 1, Month 3 and Month 6 for 
subjects with baseline NAPSI > 0.
This is a score ranging from 0-8 based on 1 targeted nail.


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Health Outcome Measures Assessed at baseline, Months 3 and 6:

Work Productivity and Activity Impairment – Psoriatic Arthritis Questionnaire 
(∆WPAI-PsA).
3.4. Baseline Variables
Demographic Characteristics

Baseline age (2 categorizations: 18-44, 45-64, ≥65 years; 18-44, 45-64, 65-74, 75-84, 
≥85 years; and continuous in years);

Sex (female, male);

Baseline body weight (< 60, ≥60 to 100, > 100 kg; and continuous in kg),

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 in kg/m2);

Screening smoking status (never smoked, former smoker, current smoker); smoking 
duration (years) for former and current smokers.

Alcohol use [never, former, current; continuous (units/week) for subjects who 
consumed any alcohol].
Baseline Disease Characteristics

PsA duration (< 2, ≥2 years; and continuous in years);

Baseline PsA Subtype: (< 5 joints, ≥5 joints);

Screening presence of distal interphalangeal joints involvement (yes, no);

Screening presence of arthritis mutilans (yes, no);

Baseline swollen joint count (66) (continuous);

Baseline tender/painful joint count (68) (continuous);

Baseline HAQ-DI (continuous);

Baseline PGA-PsO (0, 1, 2, 3, 4);

Baseline PGA-PsO (continuous) for those subjects with PGA-PsO > 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 total psoriatic BSA (0, > 0 to < 3, ≥3%);


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
Baseline total psoriatic BSA (continuous) for those with BSA > 0% at baseline,

Number (%) of subjects with baseline PGA-PsO ≥3, PASI ≥12 and BSA ≥10%;

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 enthesitis measured by LEI (yes, no). Yes is defined for those 
subjects with baseline LEI > 0;

Baseline enthesitis index measured by LEI (continuous) for those with LEI > 0 at 
baseline;

Baseline SF-36 (8 domains, physical component score [PCS] and mental component 
score [MCS]);

Baseline EQ-5D-3L (5 domains) and EQ-5D VAS;

Baseline DAS28-3(CRP);

Baseline CRP (≤2.87, > 2.87 mg/L; and continuous in mg/L);

Baseline PGA-PsA;  

Baseline presence of nail psoriasis measured by NAPSI (yes, no). Yes is defined for 
those subjects with baseline NAPSI > 0;

Baseline NAPSI for those with NAPSI>0 at baseline;

Baseline diabetes mellitus (yes, no) (see Appendix 3 Section 14 for definition);

Baseline metabolic syndrome (yes, no) (see Appendix 3 Section 15 for definition);

Baseline cardiovascular risks;

Baseline rheumatoid factor positive (yes, no);

Baseline cyclic citrullinated peptide antibody positive (yes, no);
Prior and Baseline Treatments for Psoriatic Arthritis

Prior oral corticosteroids use (oral only: yes, no);

Baseline oral corticosteroid use (oral only: yes, no), Day 1 predose;

Prior NSAIDs use (yes, no);

Baseline NSAID use (yes, no), Day 1 predose;

Prior Other DMARDs use (yes, no). Other DMARDs are DMARDs other than 
bDMARDs and csDMARDs for primary diagnosis;


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
Number of prior DMARDs experience (1 csDMARD, 2 csDMARDs, ≥3 csDMARDs, 
≥1 bDMARD). This categorization is based on bDMARDs and csDMARDs 
experience, regardless of other DMARDs use. Subjects who were treated with any 
bDMARD or both csDMARDs and bDMARDs will be counted in the “≥1 
bDMARD” category;

Prior csDMARDs experience (yes for csDMARDs only, no). This categorization is 
based on bDMARDs and csDMARDs experience, regardless of other DMARDs use.
3.5. Safety Endpoints

Incidence and severity of adverse events (AEs);

AEs of special interest (see Appendix 3 Section 13);

Clinical laboratory tests (e.g., clinical chemistry, hematology);

Vital sign measurements (blood pressure, pulse rate and temperature);

Physical examinations;

Electro-cardiogram (ECG) measurements. 
Adverse Events
An adverse event is considered treatment emergent relative to a given treatment if:

the event occurs for the first time during the effective duration of treatment and was 
not seen prior to the start of treatment (for example, during the baseline or run-in 
period), or

the event was seen prior to the start of treatment but increased in severity during 
treatment.
Any event occurring after the first day of the treatment will be attributed to the corresponding
treatment period regardless whether the event occurs on- or off-treatment. 
In addition to standard safety displays, a 3-tier approach will be used to summarize AEs. 
Under this approach, AEs are classified into 1 of 3 tiers. Different analyses will be performed 
for different tiers (See Section 6.6.1). 
Tier-1 events: These are pre-specified events of clinical importance. The AEs of special 
interest (see Appendix 3 Section 13) are equivalent to Tier-1 events.
Tier-2 events: These are events that are not tier-1 but are “common”. A MedDRA PT is 
defined as a tier-2 event if occurring in at least 4 subjects in any treatment group.
Tier-3 events: These are events that are neither tier-1 nor tier-2 events.


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The 3 tiers are mutually exclusive. Tier-3 events will be included in standard safety displays 
and not separately displayed in specific Tier-3 tables.
Laboratory Data
Blood and urine samples will be collected at the time points identified in the protocol for 
clinical safety laboratory tests and exploratory biomarkers (Table 2). Unscheduled clinical 
laboratory tests may be performed at any time during the study to assess any perceived safety 
concerns. 
Table 2
Clinical Laboratory Testing
Laboratory Testing Profile
Tests Included
Laboratory Tests Required at
Screening Only
QuantiFERON®-TB Gold In-Tube, 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, Prothrombin time (PT/INR)c; 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 Hemaglobin 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)
Rheumatoid Factor (RF), Cyclic Citrullinated Peptide Antibody
(CCP)
Lipid Panel
Fasting total cholesterol, HDL, LDL, triglyceride;
apolipoprotein A-1, B and other lipoprotein tests potentially
including particle size measurements
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)
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 All subjects will be screened for normal prothrombin time (PT/INR).  PT should also be evaluated to rule out acute hepatic
injury in cases of hepatic enzyme elevations.


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4. ANALYSIS SETS
Below is a description of the analysis sets defined for this study. Note that subjects who are 
screened but not randomized will appear on the subject evaluation table and that subjects 
who are randomized but not treated will appear on the subject evaluation table; this will the 
extent of how much data for these subjects will be reported. If a subject is treated but not 
randomized, then the subject will be excluded from any analyses. A narrative will be 
provided for this subject in the clinical study report (CSR).
Data for all subjects will be assessed to determine if subjects meet the criteria for inclusion in 
each analysis population prior to unblinding and releasing the database and classifications 
will be documented per standard operating procedures.
4.1. Full Analysis Set
The Full Analysis Set (FAS) will include all subjects randomized and who have received at 
least one dose of randomized study drug (tofacitinib or placebo). Subjects will be analyzed in 
the treatment groups as they are randomized regardless of what treatment they received. FAS
is the primary patient population for the primary endpoint.
Continuous and ordered-categorical (analyzed as 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. It is anticipated that there should be little bias due to excluding subjects with no 
baseline since the missingness mechanism is likely to be missing completely at random 
(MCAR) (Rubin, 1987). Excluding a subject with no post-baseline would likely cause a more 
favorable estimate of the mean change from baseline for that endpoint for the treatment 
group in which that subject was assigned (since subjects not responding are more likely to 
drop out prior to a post-baseline measure than those who are responding). However, it is 
anticipated that very few subjects will be excluded for this reason minimizing any potential 
bias.
4.2. Per Protocol Analysis Set 
The Per Protocol (PP) analysis set will be a subset of FAS and will exclude all subjects who 
had a protocol deviation thought to have a material impact on the primary efficacy analysis. 
The PP analysis set will be used in the PP efficacy analysis for the primary endpoint of 
ACR50 at Month 3.
The following sections describe protocol deviations that will lead to subject exclusion from 
the PP analysis set. It is possible that unexpected deviations will arise, becoming known only 
after the study has been active for a long period of time; hence more deviations may be added 
to the list at a later date. As of this writing, the protocol deviations that will define the PP 
analysis set can all be found in Section 4.2.1 and Section 4.2.2 below. 


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Protocol Deviations Assessed Prior to Randomization

Subjects who failed to meet the Classification Criteria for Psoriatic Arthritis 
(CASPAR) diagnostic criteria for PsA at screening. The PsA diagnosis at screening 
will be recorded on the PRIMARY DIAGNOSIS CRF where PSORIATIC 
ARTHRITIS is pre-filled. Subjects who did not have the CRF filled out will be 
considered as having this exclusion criteria met.

Subjects who had < 3 tender/painful joints on motion out of 68 joints assessed or < 
3 swollen joints out of 66 joints assessed at either screening or baseline (i.e., Day 
1 Pre-dose). The “JOINT SWELLING AND TENDERNESS 66/68 – JOINT 
COUNT ASSESSMENT” CRF will be used to check this condition.

Subjects who failed to meet the criterion of “an inadequate response (IR) to at least 
one csDMARD due to lack of efficacy (LOE) and/or toxicity/lack of tolerance (due to 
treatment-related AE)”. csDMARD-IR is defined as those csDMARDs that were 
discontinued due to AE, LOE, or both AE/LOE on or prior to Day 1, or a csDMARD 
that was started prior to Day 1, but was not discontinued and continued beyond Day 1 
regardless of csDMARD dose change. 

Subjects who met the exclusion criterion of “history of or current autoimmune 
rheumatic disease or rheumatic inflammatory disease other than PsA”. The 
“SIGNIFICANT MEDICAL HISTORY” CRF and anti-CCP tested at baseline will be 
used to check this condition. Subjects who were considered to have current 
autoimmune rheumatic disease or rheumatic inflammatory disease other than PsA by 
the investigator and/or the Sponsor will also be excluded.
Protocol Deviations Assessed Post-Randomization

Subject who was randomized but took or received incorrect treatment other than the 
randomized treatment for the entire duration from baseline through Month 3. This 
will be checked manually since there is no CRF for this condition.

Subject who had < 80% compliance with tablet on 2 consecutive visits for the period 
from baseline through Month 3. The study treatment compliances will be calculated 
based on “ORAL DOSING” CRF. Both randomized treatments (i.e., tofacitinib and 
placebo) will be taken into account.

Subject who received rescue medication for PsA on the preceding day or the same 
day of the primary endpoint assessment at Month 3. The rescue medication is 
recorded on “PRIOR AND CONCOMITANT MEDICATIONS : OTHER” CRF in 
the “RESCUE MEDICATIONS” category.


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A list of DMARDs is given in Appendix 3 Section 17. The list will be reviewed and updated 
as new versions of MedDRA dictionary become effective and any updates will be maintained 
in a programming plan.
4.3. Safety Analysis Set
The safety analysis set (SAFETY) will include all subjects who received at least one dose of 
the study drug (tofacitinib or placebo). Subjects will be classified according to the actual 
study treatment received.
4.4. Other Analysis Sets
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.
Table 3
Endpoint Specific Analysis Sets
Instrument/Endpoint
Inclusion
Rationale
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.
∆PGA-PsO
Include subjects with 
baseline PGA-PsO > 0
Baseline PGA-PsO = 0 means no PsO disease at 
baseline.
PGA-PsO responder
(PGA-PsO = 0 or 1 and 
decrease ∆PGA-PsO ≥
2)
Include subjects with 
baseline PGA-PsO ≥2
Restrict baseline PGA-PsO to ≥2 to allow room 
for response.
PASI75
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.
∆DSS
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.
Resolution of dactylitis
(DSS = 0)
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.


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∆Leeds Enthesitis Index
(∆LEI)
Include subjects with
baseline LEI > 0
Baseline LEI = 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.
Resolution of enthesitis
(LEI = 0)
Include subjects with
baseline LEI > 0
Baseline LEI = 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.
%∆in PASI and PASI 
clinical sign component 
scores
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.
%∆BSA
Include subjects with
baseline BSA > 0%
Percent change from baseline cannot be 
calculated if baseline BSA = 0%.
∆NAPSI
Include subjects with
baseline NAPSI > 0
Baseline NAPSI=0 means absence of nail 
psoriasis. Nail psoriasis is not an enrollment 
criterion so it is expected that only a subset of the 
subjects will have nail psoriasis at baseline.
5. GENERAL METHODOLOGY AND CONVENTIONS
5.1. Hypotheses and Decision Rules
This protocol is designed to establish the superiority of tofacitinib 5 mg BID to placebo for 
treatment of rheumatological signs and symptoms of active PsA in subjects who have had an 
inadequate response in PsA to at least one csDMARD.
The null hypothesis is that there is no difference between tofacitinib 5 mg BID and placebo, 
and the alternative hypothesis is that there is a difference between tofacitinib 5 mg BID and 
placebo.
Tofacitinib 5 mg BID will be considered superior to placebo with respect to ACR50 response 
rate at Month 3 if the difference between tofacitinib 5 mg BID and placebo is statistically 
significant at the 2-sided 5% level, i.e., 2-sided p-value ≤0.05.
For endpoints other than the primary (ACR50 response rate at Month 3), this study is not 
statistically powered to test the difference between tofacitinib 5 mg BID and placebo. Thus,
any reported confidence intervals (CIs) and p-values should only be considered nominal.


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5.2. General Methods 
As subjects randomized to treatment group of placebo → tofacitinib 5 mg BID (where → 
means switching to) will advance from placebo to open-label treatment of tofacitinib 5 mg 
BID at Month 3, the treatment label used for reporting visits up to Month 3 will be “Placebo” 
and treatment label for reporting visits after Month 3 through Month 6 will be “Placebo → 
Tofacitinib 5 mg BID”. 
For analyses through Month 3, the following treatment comparison will be made at each time 
point, where applicable:
•
Tofacitinib 5 mg BID vs. Placebo.
For analyses after Month 3 through Month 6, the following treatment comparison will be 
made at each time point,
•
Tofacitinib 5 mg BID vs. Placebo → Tofacitinib 5 mg BID.
The primary efficacy comparison for the primary endpoint of ACR50 will be between 
tofacitinib 5 mg BID and placebo at Month 3. 
Descriptive Summaries:
In general, the data for all continuous endpoints will be summarized by time point and
treatment sequence in tables containing descriptive statistics (n, mean, standard deviation 
(s.d.), standard error (SE) of the mean, minimum, 1st, 2nd (median) and 3rd quartiles and 
maximum) for baseline and change or percent change from baseline for those endpoints
measured at baseline. The data for all binary endpoints will be summarized by treatment 
group and by time point in tables showing descriptive statistics: N, n (i.e., number of 
responders), response rate (%), standard error of the response rate, and 95% confidence 
interval (CI) based on normal approximation. If ݌̂ is the estimated response rate, then the 
95% CI is calculated as 
݌̂ േݖ଴.ଽ଻ହඨ݌̂ሺ1 െ݌̂ሻ
ܰ
,
where ݖ଴.ଽ଻ହis the 97.5th percentile of the standard normal distribution and ܰis the number 
of subjects evaluable for the endpoint at the time point. If the lower bound is calculated to be 
negative, it will be set to 0%; if the upper bound is calculated to be larger than 100%, it will 
be set to 100%. In case when response rate is 0 or 100%, standard error will be reported as 
“NA” and the 95% CI will not be reported. The displays described above for continuous and 
response-type endpoints will only use available data with no imputation. Therefore, the 
calculation of response rates will use the number of evaluable subjects as denominators.


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Analyses for Binary Data
Normal Approximation
The normal approximation for the difference in binomial proportions (such as ACR50 
response rate) can be used to test the superiority of tofacitinib 5 mg BID to placebo at post-
baseline timepoints. The normal approximation to the test statistic for the difference in 
binomial random variables is calculated as
ܼൌ
݌̂௧െ݌̂௖
ට݌̂௧ሺ1 െ݌̂௧ሻ
ܰ௧
൅݌̂௖ሺ1 െ݌̂௖ሻ
ܰ௖
,
where ݌̂ refers to the relative frequency, ܰto the number of observations, the subscript c
refers to the comparator group (e.g., placebo group) and the subscript t refers to the test group 
(e.g., tofacitinib 5 mg BID group) so that test statistics and p-values can be calculated for the
contrast comparing the two treatment groups.
Two-sided 95% confidence intervals will be formed by
݌̂௧െ݌̂௖േݖ଴.ଽ଻ହඨ݌̂௧ሺ1 െ݌̂௧ሻ
ܰ௧
൅݌̂௖ሺ1 െ݌̂௖ሻ
ܰ௖
Two-sided p-value for the test of the 0 difference between tofacitinib 5 mg BID and placebo 
groups will be calculated as
݌ൌ2ሺ1 െΦሺ|ܼ|ሻሻ,
where Φሺ∙ሻis the Gaussian cumulative distribution function.
If there is no (i.e., 0) response or 100% response in any one of the two treatment groups for 
the comparison, e.g., tofacitinib 5 mg BID vs. placebo, when calculating the proportions 
above, 0.5 will be added to the number of responses (i.e., numerator) and 1 will be added to 
the denominator in each treatment corresponding to the pair of comparison for calculating the 
treatment difference, standard error (i.e., ඥݒܽݎሺ݌̂௧െ݌̂௖ሻ), 95% CI and 2-sided p-value 
(Agresti, 2002). Estimated response rates and standard errors will be reported without 
adjustment for both groups. (Note that this adjusted method also applies to the case where the 
response rate is 0% in one treatment group and 100% in the other.)
When response rate of 0% is observed in both treatments or 100% in both treatments in 
comparison, no formal comparison will be performed. Estimated response rate of 0% or 
100% will be reported as observed. Standard error will be reported as NA.
The final results will be expressed in percentages, i.e., (proportions ൈ 100)%.


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Generalized Marginal Model for Repeated Measures (GMMRM)
As a supportive analysis of ACR50, scheduled to be collected multiple times during the first 
3 months of the placebo-controlled period (Week 2, Months 1, 2 and 3) of the study, a 
generalized marginal linear model for repeated measures (GMMRM) will be used. This 
model will have fixed effects for time (discrete), treatment, and time by treatment interaction;
the dependent variable will be logit of the probability of response. Note that the model 
includes fixed effects of treatment, visit, and treatment-by-visit interaction only to ensure the 
estimated response rates and the treatment difference have a population average or marginal 
interpretation. A common AR(1) variance-covariance matrix for both treatment sequences 
will be used to model the variability among observations within a subject. If AR(1) matrix
fails to converge, compound symmetry will be attempted. The parameters of the model will 
be estimated with pseudo-likelihood type methods. Simulations investigating generalized 
linear models (GLM) for correlated binary data indicate good performance as measured by
type I error, confidence interval coverage and bias even in the presence of data that is MAR 
(Liu and Zhan, 2011).
From this model, one can obtain estimate of the probability of response for each treatment 
sequence at each timepoint as well inferential comparisons (odds ratio, CI and p-value) 
between treatment sequences.
In the event that a response rate is 0 or 100% at a particular visit for a treatment sequence that
may lead to convergence issues, data from that visit for both treatment sequences will be
removed from the model fitting in order to overcome any numerical difficulty.
Tipping Point Analysis
A method to analyze the longitudinal binary data measured during the placebo-controlled 
period at Week 2, Months 1, 2 and 3 under the missing not at random (MNAR) assumption is 
called the tipping point analysis. This analysis is used as a supportive analysis for the primary 
endpoint of ACR50 at Month 3. It assesses the robustness of the binary data to potential 
deviations from the missing at random (MAR) assumption for both tofacitinib 5 mg BID and 
placebo groups and it is based on multiple imputation (Yan, Lee and Li, 2009; Ratitch, 
O’Kelly and Tosiello, 2013). 
In this tipping point analysis, a single saturated generalized linear mixed effect model is used 
as the imputation model. The normal approximation of the difference in binomial proportions 
is used for the analysis, which is the same as the method of analyzing response-type endpoint 
at a single time point described in Section 5.2.1.1. The generalized linear mixed effect model 
includes the fixed effects of treatment, visit, treatment-by-visit interaction, and a latent 
subject-level random effect. The logit link is used to model the ACR50 response rate as 
dependent variable for all visits. Estimation of the model parameters is performed under the
Bayesian framework using Markov chain Monte Carlo (MCMC) methods. Only the available 
data without imputation are included in this generalized linear mixed effect model to estimate 
the model parameters.


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Imputation of missing ACR50 response is performed only at Month 3 based on the predictive 
distribution of the generalized linear mixed effect model. Under missing not at random 
(MNAR) assumption, a fixed MNAR quantity (favorable or unfavorable) will be applied to 
the probability of the ACR50 response at Month 3 for subjects with missing response in the 
tofacitinib 5 mg BID group and placebo group independently (i.e., the analysis will be two-
dimensional applied to both tofacitinib 5 mg BID and placebo). A series of fixed quantities 
will be applied to the probability of the ACR50 response at Month 3 for subjects with 
missing response in the tofacitinib 5 mg BID group or placebo group independently to assess 
when the conclusion might change (i.e., tipping). A scenario included in the tipping point 
analysis framework is an analysis under MAR, if there is no fixed quantity applied to the 
mean of the missing response for subjects in the tofacitinib 5 mg BID group and placebo 
group. The Rubin’s rules (Rubin, 1987) will be used to combine the results of multiple 
imputed samples for inference. More detailed descriptions are provided in Appendix 4.
Analyses for Continuous Data
Continuous endpoints will be analyzed by Mixed Model Repeated Measures (MMRM) that 
includes the fixed effects of treatment, visit, treatment by visit interaction, and baseline 
value. An unstructured variance covariance matrix for within-subject correlation (an 
alternative variance covariance matrix will be used if the model does not converge under the 
unstructured variance covariance matrix). Comparison of the two treatment sequences at each 
post-baseline timepoint will be generated from this model (providing 2-sided p-values and 
95% CI). 
Analyses of Tier-2 Adverse Events
Number and percentage of subjects with AEs over the first 3 months will be provided for 
each treatment group. Tier-2 events will be analyzed using asymptotic methods proposed by 
Miettinen and Nurminen (1985). Risk ratios (tofacitinib 5mg BID compared to placebo) and 
2-sided 95% CI will be reported. P-values will not be reported for Tier-2 events.
5.3. Methods to Manage Missing Data
As stated in the protocol, in the primary analysis of the primary endpoint, ACR50 response 
rate at Month 3, missing values for any reason, e.g., due to a subject dropping from the study
or due to the impact of COVID-19 pandemic, will be handled by setting the ACR50 value to 
nonresponsive. Note that this can be viewed as a composite endpoint in the sense that a 
response requires the subject completes a visit of interest, e.g., Month 3, and achieves a 
response per the defined ACR50 response criteria (otherwise it is considered a nonresponse).
This method of handling missing response is known as missing response as non-response 
(MR=NR). This MR=NR approach will be used for all “response-type” endpoints at all 
timepoints except for the supportive analyses using GMMRM (see Section 5.2.1.2) and 
Tipping Point Analysis (see Section 5.2.1.3) for ACR50 up to Month 3. Note that if a subject 


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discontinues from the study at a visit of interest, say Month 3, but the value of the endpoint is 
not missing at Month 3, the value of the endpoint will be used for Month 3.
For a composite “response-type” endpoints (such as ACR50), if values in any of the 
components at a timepoint are missing, the component variables that are not missing will be 
used to determine the response status. If one could not determine the response status in the
presence of missing components at the timepoint, then the composite response-type endpoint 
status is considered as missing and is handled by MR=NR for that timepoint for all of the 
inferential analyses except for the supportive analyses using GMMRM (see Section 5.2.1.2) 
and Tipping Point Analysis (see Section 5.2.1.3) for ACR50 up to Month 3.
Repeated measures data for continuous and ordered-categorical (analyzed as continuous) 
endpoints will be analyzed with MMRM. This model will yield unbiased estimates and valid 
inferences in the presence of data that is MCAR or missing at random (MAR). Given that 
subjects who drop out are scheduled to have an end of study evaluation, the more stringent 
condition of MAR (Rubin, 1987) is believed to be a reasonable assumption. Hence missing 
values will not be imputed in the routine analysis using the repeated measures model. 
For the SF-36, EQ-5D and WPAI-PsA 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, and this missing value will be addressed as specified in the paragraph
above.
In general, missing values in any of the endpoints will not be imputed when summarizing 
these endpoints using descriptive statistics.
For the demographic and baseline characteristics, if a value is missing, a missing category 
will be added to summaries for the categorical variables.
Missing values for safety endpoints will not be imputed.
6. ANALYSES AND SUMMARIES
6.1. Primary Endpoint(s)
ACR50 Response Rate at Month 3
Primary Analysis
Endpoint: ACR50 response rate at Month 3
o
Analysis time points: Month 3
o
Analysis population: FAS


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o
Method of imputation for missing data: MR=NR (specified in Section 5.3)
o
Analysis methodology: The normal approximation to the difference in binomial 
proportions (specified in Section 5.2.1.1) will be used to test the difference between 
tofacitinib 5 mg BID and placebo and to generate 95% CI and p-value for the 
difference in response rates.   
Reporting results:
o
Response rate without imputation: N, frequency and percentage of responders, SE of 
the response rate and 95% CI at Month 3 will be presented by treatment group.
o
Response rate with imputation: N, frequency and percentage of responders, SE of the 
response rate at Month 3 will be presented by treatment group.
o
Response rate difference with imputation: Difference between treatment groups, and 
corresponding SE, 95% CI and p-value at Month 3 will be presented.  
Figures:
o
Line graph of ACR50 response rate (using imputed data) with ± SE will be plotted 
over time for both treatment sequences.
Note that ACR50 response rate at other timepoints will be analyzed by the same approach.
Supportive Analyses
Supportive Analysis 1: The analysis of ACR50 response rate at Month 3 described in Section 
6.1.1.1 will also be conducted on the PP analysis set since the FAS may include instances of 
non-compliance which may diminish the potential efficacy of tofacitinib. This will serve as a 
supportive analysis of the primary endpoint.
Endpoint: ACR50 response rate at Month 3
o
Analysis time points: Month 3
o
Analysis population: PP analysis set
o
Method of imputation for missing data: MR=NR (specified in Section 5.3)
o
Analysis methodology: Normal approximation (specified in Section 5.2.1.1)   
Reporting results:
o
Response rate with imputation: N, frequency and percentage of responders, SE of the 
response rate at Month 3 will be presented by treatment group.
o
Response rate difference with imputation: Difference between treatment groups, and 
corresponding SE, 95% CI and p-value at Month 3 will be presented.


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Supportive Analysis 2: As a supportive analysis for the ACR50 response rate at Month 3, 
GMMRM without imputation for missing data will be applied to the available ACR50 data 
collected at post-baseline visits at Week 2, Months 1, 2 and 3. 
Endpoint: ACR50 response rate
o Analysis time points: Week 2, Months 1, 2 and 3
o Analysis population: FAS
o Method of imputation for missing data: No imputation
o Analysis methodology: GMMRM (specified in Section 5.2.1.2)   
Reporting results:
o Response rate (model-based): N, frequency and percentage of responders, and SE of 
the response rate up to Month 3 will be presented by treatment sequence.
o
Odds ratio: Odds ratio between the two treatment sequences, and corresponding 95% 
CI and p-value at each analysis timepoint will be presented.
Supportive Analysis 3: Another supportive analysis on the ACR50 response rate at Month 3 
is performed to assess the robustness of the data to the departures from the MAR assumption. 
This analysis is called tipping point analysis and its methodology is briefly described in 
Section 5.2.1.3 and further detailed in Appendix 4. 
Endpoint: ACR50 response rate
o
Analysis time points: Week 2, Months 1, 2 and 3
o
Analysis population: FAS
o
Method of imputation for missing data: Multiple imputation
o
Analysis methodology: Tipping point analysis (specified in Section 5.2.1.3 and
Appendix 4)   
Reporting results:
o Response rate (model-based): N, frequency and percentage of responders, and SE of 
the response rate at Month 3 will be presented by treatment sequence, for each pair of
MNAR quantities (favorable or unfavorable) applied to the probability of the ACR50
response at Month 3 for subjects with missing response in the tofacitinib 5 mg BID 
group and placebo group.
o
Response rate difference: Difference between treatment groups, and corresponding 
SE, 95% CI and p-value at Month 3 will be presented, for each pair of MNAR 
quantities (favorable or unfavorable) applied to the probability of the ACR50 


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response at Month 3 for subjects with missing response in the tofacitinib 5 mg BID 
group and placebo group.
6.2. Secondary Endpoint(s)
Binary Endpoints
The analysis and summary methods described in this section apply to all the endpoints below.
Endpoints: ACR20 and ACR70 response rates
o
Analysis time points: All post-baseline timepoints through Month 6
o
Analysis population: FAS
Endpoint: ACR50 response rate
o
Analysis time points: All post-baseline timepoints prior to and after Month 3
o
Analysis population: FAS
Endpoint: ∆HAQ-DI (decrease) ≥0.30 response rate
o
Analysis time points: All post-baseline timepoints through Month 6
o
Analysis population: Subjects in FAS with baseline HAQ-DI ≥0.30
Endpoint: ∆HAQ-DI (decrease) ≥0.35 response rate 
o
Analysis time points: All post-baseline timepoints through Month 6
o
Analysis population: Subjects in FAS with baseline HAQ-DI ≥0.35 
Endpoint: PsARC response rate
o
Analysis time points: All post-baseline timepoints through Month 6
o
Analysis population: FAS
Endpoint: PGA-PsO response (clear or almost clear and a 2-step improvement from 
baseline) rate 
o
Analysis time points: Month 1, Month 3, Month 6
o
Analysis population: Subjects in FAS with baseline PGA-PsO ≥2 
Endpoint: PASI75 response rate
o
Analysis time points: Month 1, Month 3, Month 6
o
Analysis population: Subjects in FAS with baseline BSA ≥3% and baseline PASI > 0
Endpoint: Resolution of dactylitis (achieving DSS = 0)
o
Analysis time points: Month 1, Month 3, Month 6
o
Analysis population: Subjects in FAS with baseline DSS > 0


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Endpoint: Resolution of enthesitis (achieving LEI = 0)
o
Analysis time points: Month 1, Month 3, Month 6
o
Analysis population: Subjects in FAS with baseline LEI > 0
Method of imputation for missing data:  MR=NR (specified in Section 5.3)
Analysis methodology:  Normal approximation (specified in Section 5.2.1.1)   
Reporting results:
o
Response rate without imputation: N, frequency and percentage of responders, SE of 
the response rate, and 95% CI at each analysis timepoint will be presented by 
treatment group.
o
Response rate with imputation: N, frequency and percentage of responders, SE of the 
response rate at each analysis timepoint will be presented by treatment group.
o
Response rate difference with imputation: Difference between treatment groups, and 
corresponding SE, 95% CI and p-value at each analysis timepoint will be presented.   
Figures:
o
For endpoints assessed at more than 3 post-baseline timepoints, line graph of 
response rates (using imputed data) with ± SE will be plotted over time for both 
treatment groups.
Continuous Endpoints
The analysis and summary methods described in this section apply to all the endpoints below.
Endpoints: Change from baseline (∆) in ACR response criteria components (HAQ-DI, C 
reactive protein [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)
o
Analysis time points: All post-baseline timepoints 
o
Analysis population: FAS
Endpoint: ∆PGA-PsO
o
Analysis time points: Month 1, Month 3, Month 6
o
Analysis population: Subjects in FAS with baseline PGA-PsO > 0
Endpoint: ∆DSS
o
Analysis time points: Month 1, Month 3, Month 6
o
Analysis population: Subjects in FAS with baseline DSS > 0


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Endpoint: ∆LEI
o
Analysis time points: Month 1, Month 3, Month 6
o
Analysis population: Subjects in FAS with baseline LEI > 0
Endpoint: ∆SF-36v2
o
Analysis time points: Month 1, Month 3, Month 6
o
Analysis population: FAS
Endpoint: ∆EQ-5D-3L and EQ-VAS
o
Analysis time points: Month 1, Month 3, Month 6
o
Analysis population: FAS
Method of imputation for missing data: No imputation
Analysis methodology: MMRM (specified in Section 5.2.2) 
Reporting results:
o Raw data: N, mean, s.d., SE of the mean, minimum, 1st, 2nd (median) and 3rd quartiles 
and maximum at baseline and post-baseline visits will be presented by treatment 
sequence.
o Change from baseline: N, mean, s.d., SE of the mean, minimum, 1st, 2nd (median) and 
3rd quartiles and maximum will be presented for each analysis time point by treatment 
sequence. The LS means, SE for the LS means, and LS mean of the difference 
between the two treatment sequences with corresponding SE and 95% CI will be 
presented for each analysis timepoint.  
Figures:
o
For endpoints assessed at more than 3 post-baseline timepoints, line graph of LS 
mean change from baseline with ± SE will be plotted over time for both treatment 
sequences.
6.3. Other Endpoint(s)
The following continuous endpoints will be analyzed and reported by methods described in 
Section 6.2.2.
Endpoint: ∆DAS28-3(CRP)
o
Analysis time points: All post-baseline timepoints
o
Analysis population: FAS
Endpoint: ∆PGA-PsA


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o
Analysis time points: Month 1, Month 3, Month 6
o
Analysis population: FAS
Endpoint: %∆in PASI and PASI clinical sign component scores
o
Analysis time points: Month 1, Month 3, Month 6
o
Analysis population: Subjects in FAS with baseline BSA ≥3% and baseline PASI > 0
Endpoint: %∆BSA
o
Analysis time points: Month 1, Month 3, Month 6
o
Analysis population: Subjects in FAS with baseline BSA > 0%
Endpoint: ∆NAPSI
o
Analysis time points: Month 1, Month 3, Month 6
o
Analysis population: Subjects in FAS with baseline NAPSI > 0
Endpoint: ∆WPAI-PsA
o
Analysis time points: Month 3, Month 6
o
Analysis population: FAS
6.4. Subset Analyses 
The primary purpose of the subgroup analyses is to check for consistency of results of the 
primary endpoint of ACR50 response rate at Month 3 across subgroups, i.e., make sure
overall results are not being driven by some subset of subjects. There is no intention to have 
any specific inference within subgroups.
The subgroup comparison will be made on FAS unless stated otherwise. If sample size for a 
category of a subgroup factor is too small, the analysis for that subgroup may not be 
performed.
Endpoint: ACR50 response rate at Month 3
o Analysis time points: Month 3
o Method of imputation for missing data: MR=NR (specified in Section 5.3)
o Analysis methodology: Normal approximation (specified in Section 5.2.1.1) 
Subgroup Analysis will be performed by:
o Gender (female, male),
o Baseline weight (< 60, ≥60 to ≤100, > 100 kg),
o Baseline Body Mass Index (BMI) (< 25, ≥25 to < 30, ≥30 to < 40, and ≥ 40 kg/m2);


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o Age (< 65, ≥65 years),
o PsA disease duration (< 2 years, ≥2 years),
o Baseline PsA subtype (< 5 joints, ≥5 joints) formed based on counting the number of 
joints at baseline that are either swollen (66) or tender/painful (68), i.e., if a joint is 
swollen only, tender/painful only, or both swollen and tender/painful, it is only 
counted as one joint,
o Screening PsA subtype (arthritis mutilans: yes, no),
o Screening PsA subtype (spondylitis: yes, no),
o Baseline CRP (≤2.87, > 2.87 mg/L),
o Baseline PASI (≤ 20, > 20) for subjects with baseline PASI > 0 and BSA ≥ 3%,
o Baseline smoking status (never smoked, former smoker, current smoker),
o Prior bDMARD experience (bDMARD-naive vs bDMARD-experienced),
o Number of prior DMARDs-IR (1 csDMARD-IR, 2 csDMARDs-IR, ≥3 csDMARDs 
IR, ≥1 bDMARD-experienced). Only prior csDMARDs-IR and bDMARD use will 
be used to form the categories (see Appendix 3 Section 16 for prior DMARDs-IR 
definition). Subjects who were treated with any bDMARD or both csDMARDs-IR 
and bDMARDs will be counted in the “≥1 bDMARD-experienced” category,
o Baseline oral corticosteroid use (oral only: yes, no), Day 1 predose,
o Baseline csDMARD use (MTX only, Sulfasalazine only, Other, None), Day 1 
predose.
Reporting results:
o Response rate without imputation: N, frequency and percentage of responders, SE of 
the response rate, and 95% CI at Month 3 will be presented by treatment group for 
each defined category of each subgroup.
o Response rate with imputation: N, frequency and percentage of responders, SE of the 
response rate at Month 3 will be presented by treatment group.
o Response rate difference with imputation: Difference between treatment groups, and 
corresponding SE and 95% CI (no p-value) at Month 3 will be presented for each 
defined category of each subgroup.
Figures:
o
Forest plots of the differences between treatment groups (using imputed data) with 
corresponding 95% CI will be presented. 


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6.5. Baseline and Other Summaries and Analyses
Baseline Summaries
Baseline characteristics will include but may not be limited to the demographic and baseline 
disease characteristics listed in Section 3.4.1 and Section 3.4.2 and will be summarized 
descriptively. For continuous variables, the summary will include N, mean, s.d. 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. In addition to 
displays by treatment groups, the summaries will also be provided for both treatment groups 
combined.
Prior and Baseline Treatments for Psoriatic Arthritis
Prior and baseline treatments for PsA will be characterized by the variables listed in Section 
3.4.3. These variables will be summarized descriptively by frequencies and percentages for 
each treatment group and for both treatment groups combined.
Concomitant DMARD Treatments
Type of concomitant DMARDs use (methotrexate, sulfasalazine, other) will be summarized 
by frequencies and percentages. Subjects who were treated with >1 DMARD(s) will be 
counted in the ‘Other’ category. Concomitant DMARDs use will also be summarized by 
counting each csDMARD regardless of other DMARD use. Frequencies and percentages will 
be provided for each csDMARD. 
These summaries will be presented at two time points: one for Day 1 and the other for Day 1 
through Month 3.
6.6. Safety Summaries and Analyses
All safety data will be summarized descriptively through appropriate data tabulations, 
descriptive statistics, and graphical presentations. AEs, vital signs, 12-lead ECG parameters, 
and laboratory tests will be summarized according to the Clinical Data Interchange Standards 
Consortium (CDISC) and Pfizer Standards (CaPS). All the safety data analyses will be 
performed on the safety analysis set.
Adverse Events
Data related to adverse events will be summarized descriptively through appropriate data 
tabulations, descriptive statistics, and graphical presentations:

Incidence and severity of adverse events;

Incidence of AEs of special interest;


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
Serious infections will be summarized separately;

Any safety events that trigger withdrawal of a subject;

Special attention will be given to the events of anemia.
Adverse events will be reported as treatment-emergent all causality and treatment-emergent 
treatment-related. A treatment-emergent adverse event is any event that has: onset after the 
start of the first dose of study treatment, or onset prior to the first dose of study treatment and 
worsens in severity after the first dose of study treatment. The relationship of adverse event 
to study treatment is assigned by the investigator.
Adverse events will be displayed by two analysis periods: Baseline to Month 3 and Baseline 
to Month 6. Adverse events will be displayed from Baseline to Month 6 by treatment 
sequence groups and from Baseline to Month 3 by treatment groups.
In addition to the AE analyses described above, the AEs (all causality) are classified in 3 tiers
and will be analyzed per the 3-tier approach. Below provides a brief summary.
Analysis of Tier-1 AEs (AEs of special interest) is covered above. 
Tier-2 AEs will be analyzed per Section 5.2.3. No multiplicity adjustment will be used. Both 
tabular form and graphic (e.g., forest plots) display will be provided. They will be sorted by 
System Organ Class (SOC) and preferred terms (PT) within SOC, alphabetically, as well as 
by magnitude in risk ratio.
Tier-3 AEs will not be tabled separately but will be included in the standard AE analyses 
along with all other AEs.
It should be recognized that most studies are not designed to reliably demonstrate a causal 
relationship between the use of a pharmaceutical product and an adverse event or a group of 
adverse events. Except for select events in unique situations, studies do not employ formal 
adjudication procedures for the purpose of event classification. As such, safety analysis is 
generally considered as an exploratory analysis with the potential to generate hypotheses for 
further investigation. The 3-tier approach facilitates this exploratory analysis.
Other Safety Summaries
For laboratory tests, 12-lead ECG parameters and vital signs, summaries include categorical 
tables (e.g., normal, high, low), and descriptive statistics for change from baseline by 
treatment group and visit. For the fluorescence-activated cell sorting (FACS), the endpoints 
to be summarized, which are subsets of lymphocytes and are measured at baseline, Month 3, 
and Month 6/early termination, 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 treatment 
group and visit.


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Demographic parameters will be summarized (as number and percent or mean, standard 
deviation, and range) by treatment group and gender following CaPS.
The number and percent of subjects reporting specific past and present medical histories at 
screening will be summarized by medical history reporting term (from the Medical 
Dictionary for Regulatory Activities (MedDRA)) and treatment group following CaPS.
Clinical findings on any physical examination during the study will be tabulated by treatment 
group following CaPS. 
Previous and concomitant mediation usage by medication type will be tabulated by treatment 
group using the WHO-Drug dictionary following CaPS.
6.7. Additional Analyses to Address COVID-19 Pandemic Impacts
Additional Supportive Analysis of the Primary Endpoint
The analysis of ACR50 response rate at Month 3 described in Section 6.1.1.1 will also be 
conducted by excluding subjects with ACR50 response at Month 3 missing due to COVID-
19 pandemic impact or with ACR50 components collected remotely during COVID-19 
pandemic. This will serve as an additional supportive analysis of the primary endpoint.
Endpoint: ACR50 response rate at Month 3
o
Analysis time points: Month 3
o
Analysis population: FAS excluding subjects impacted by COVID-19 pandemic (i.e., 
excluding subjects with missing or remote Month 3 visit due to COVID-19 pandemic, 
or any PD due to COVID-19 pandemic that had an impact on the primary endpoint)
o
Method of imputation for missing data: MR=NR (specified in Section 5.3)
o
Analysis methodology: Normal approximation (specified in Section 5.2.1.1). 
Reporting results:
o
Response rate with imputation: N, frequency and percentage of responders, SE of the 
response rate at Month 3 will be presented by treatment group.
o
Response rate difference with imputation: Difference between treatment groups, and 
corresponding SE, 95% CI and p-value at Month 3 will be presented.   
o
A listing of subjects who were impacted by COVID-19 pandemic and excluded from 
this additional supportive analysis.


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Other Summaries and Listings Depicting COVID-19 Pandemic Impacts

An anchor date will be used as a start date for COVID-19 pandemic related periods in 
analyses. For China, the date COVID-19 was identified as the causative agent of 
outbreak in Wuhan by the China Center for Disease Control and Prevention (January 
9, 2020) will be used as the anchor date for COVID-19 pandemic.

A summary table showing visits attended both before and after the anchor date will be 
produced. Visit attendance will be based on swollen joint count data.

A summary table of number of subjects with major impact by COVID-19 pandemic, 
which includes:
Subjects who were excluded from the additional supportive analysis in 
Section 6.7.1.
Subjects who withdraw from the study due to COVID-19 pandemic before 
Month 3.

Protocol deviations related to COVID-19 pandemic will be summarized and listed 
separately. Both important and non-important PDs related to COVID-19 pandemic 
will be reported.

A separate summary table solely for subject discontinuations related to COVID-19
pandemic, if any, will be provided.

COVID-19 related AEs, if any, will be reported separately.

A summary table showing AEs reported both before and after the anchor date will be 
produced by treatment group. This summary will consider windows of equal duration 
before and after the anchor date.

Data collected remotely during COVID-19 pandemic for PROs and laboratory tests 
will be marked and footnoted in corresponding listings.
7. INTERIM ANALYSES
There is no interim analysis planned for this study.
7.1. Introduction
Not applicable.
7.2. Interim Analyses and Summaries
Not applicable.


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8. REFERENCES
1. Agresti A. (2002). Categorical Data Analysis, 2nd Edition, New York: John Wiley & 
Sons.
2. 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.
3. Bruce B, Fries JF. The health assessment questionnaire (HAQ). Clinical and
Experimental Rheumatology; 2005, 23 (Supp. 39), S14-S18.
4. 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.
5. Liu, GR and Zhan X Comparisons of methods for analysis of repeated binary responses
with missing data.  Journal of Biopharmaceutical Statistics, 2011, 21: 371-392.
6. Miettinen O and Nurminen M. Comparative analysis of two rates. Statistics in Medicine,
1985, 4: 213-226.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.
7. Rubin DB (1987). Multiple imputation for nonresponse in surveys.  New York:
Wiley.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.
8. Yan X, Lee S, Li N. (2009). Missing data handling methods in medical device clinical 
trials. Journal of Biopharmaceutical Statistics. 19: 1085-1098.
9. Ratitch B, O’Kelly M, Tosiello R. (2013). Missing data in clinical trials: from clinical 
assumptions to statistical analysis using pattern mixture models. Pharmaceutical 
Statistics. 12: 337–347.
10. Madsen, O.R. 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.


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9. APPENDICES 
Appendix 1. SUMMARY OF EFFICACY ANALYSES
Endpoint
Analysis Set
Analysis 
Timepoint
Statistical 
Method
Model
Missing Data 
Imputation
Interpretation
ACR50 Response 
Rate 
FAS
Month 3
Normal 
approximation
MR=NR
Primary
ACR50 Response 
Rate 
PP
Month 3
Normal 
approximation
MR=NR
Supportive
Analysis
ACR50 Response 
Rate 
FAS excluding 
subjects impacted 
by COVID-19
pandemic
Month 3
Normal 
approximation
MR=NR
Supportive
Analysis
ACR50 Response 
Rate 
FAS
Week 2, Months 
1, 2, and 3
GMMRM
Fixed effects: 
treatment, visit, 
treatment*visit
None
Supportive 
Analysis
ACR50 Response 
Rate 
FAS
Week 2, Months 
1, 2, and 3
Tipping point 
analysis
Imputation 
model: Fixed 
effects: 
treatment, visit, 
treatment*visit
Multiple 
Imputation
Supportive 
Analysis
ACR50 Response 
Rate
Each defined 
category of each 
subgroup on FAS 
(see Section 6.4)
Month 3
Normal 
approximation
MR=NR
Subset 
Analysis
ACR50 Response 
Rate
FAS
Week 2, Months 
1, 2, 4 and 6
Normal 
approximation
MR=NR
Secondary 


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ACR20 Response 
Rate 
FAS
Week 2, Months 
1, 2, 3, 4, and 6
Normal 
approximation
MR=NR
Secondary
ACR70 Response 
Rate
FAS
Week 2, Months 
1, 2, 3, 4 and 6
Normal 
approximation
MR=NR
Secondary 
∆HAQ-DI 
(decrease) ≥0.30 
response rate
Subjects in FAS 
with baseline 
HAQ-DI ≥0.30
Week 2, Months 
1, 2, 3, 4 and 6
Normal 
approximation
MR=NR
Secondary 
∆HAQ-DI 
(decrease) ≥0.35 
response rate
Subjects in FAS 
with baseline 
HAQ-DI ≥0.35
Week 2, Months 
1, 2, 3, 4 and 6
Normal 
approximation
MR=NR
Secondary 
PsARC response 
rate
FAS
Week 2, Months 
1, 2, 3, 4 and 6
Normal 
approximation
MR=NR
Secondary 
PGA-PsO 
response rate
Subjects in FAS 
with baseline 
PGA-PsO ≥2
Months 1, 3, 6
Normal 
approximation
MR=NR
Secondary 
PASI75 response 
rate
Subjects in FAS 
with baseline BSA
≥3% and baseline 
PASI > 0
Months 1, 3, 6
Normal 
approximation
MR=NR
Secondary 
Resolution of 
dactylitis
Subjects in FAS 
with baseline DSS
> 0
Months 1, 3, 6
Normal 
approximation
MR=NR
Secondary 
Resolution of 
enthesitis
Subjects in FAS 
with baseline LEI
> 0
Months 1, 3, 6
Normal 
approximation
MR=NR
Secondary 


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∆HAQ-DI
FAS
Week 2, Months 
1, 2, 3, 4 and 6
MMRM
Fixed effects: 
treatment, visit, 
treatment*visit,
baseline value
None
Secondary 
∆CRP
FAS
Week 2, Months 
1, 2, 3, 4 and 6
MMRM
Fixed effects: 
treatment, visit, 
treatment*visit,
baseline value
None
Secondary 
∆in Patient’s 
Assessment of 
Arthritis Pain
FAS
Week 2, Months 
1, 2, 3, 4 and 6
MMRM
Fixed effects: 
treatment, visit, 
treatment*visit,
baseline value
None
Secondary 
∆in Patient’s 
Global 
Assessment of 
Arthritis
FAS
Week 2, Months 
1, 2, 3, 4 and 6
MMRM
Fixed effects: 
treatment, visit, 
treatment*visit,
baseline value
None
Secondary 
∆in Physician’s 
Global 
Assessment of 
Arthritis
FAS
Week 2, Months 
1, 2, 3, 4 and 6
MMRM
Fixed effects: 
treatment, visit, 
treatment*visit,
baseline value
None
Secondary 
∆in swollen joint 
count
FAS
Week 2, Months 
1, 2, 3, 4 and 6
MMRM
Fixed effects: 
treatment, visit, 
treatment*visit,
baseline value
None
Secondary 
∆in tender/painful 
joint count
FAS
Week 2, Months 
1, 2, 3, 4 and 6
MMRM
Fixed effects: 
treatment, visit, 
treatment*visit,
baseline value
None
Secondary 


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∆PGA-PsO
Subjects in FAS 
with baseline 
PGA-PsO > 0
Months 1, 3, 6
MMRM
Fixed effects: 
treatment, visit, 
treatment*visit,
baseline value
None
Secondary 
∆DSS
Subjects in FAS 
with baseline DSS 
> 0
Months 1, 3, 6
MMRM
Fixed effects: 
treatment, visit, 
treatment*visit,
baseline value
None
Secondary 
∆LEI
Subjects in FAS 
with baseline LEI 
> 0
Months 1, 3, 6
MMRM
Fixed effects: 
treatment, visit, 
treatment*visit,
baseline value
None
Secondary 
∆SF-36v2 (10 
endpoints)
FAS
Months 1, 3, 6
MMRM
Fixed effects: 
treatment, visit, 
treatment*visit,
baseline value
None
Secondary 
∆EQ-5D (5 
endpoints) and 
EQ-VAS
FAS
Months 1, 3, 6
MMRM
Fixed effects: 
treatment, visit, 
treatment*visit,
baseline value
None
Secondary 
∆DAS28-3(CRP)
FAS
Week 2, Months 
1, 2, 3, 4 and 6
MMRM
Fixed effects: 
treatment, visit, 
treatment*visit,
baseline value
None
Other
∆PGA-PsA
FAS
Months 1, 3, 6
MMRM
Fixed effects: 
treatment, visit, 
treatment*visit,
baseline value
None
Other


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%∆ in PASI and 
PASI clinical sign 
component scores
Subjects in FAS 
with baseline BSA
≥3% and baseline 
PASI > 0
Months 1, 3, 6
MMRM
Fixed effects: 
treatment, visit, 
treatment*visit,
baseline value
None
Other
%∆BSA
Subjects in FAS 
with baseline BSA
> 0%
Months 1, 3, 6
MMRM
Fixed effects: 
treatment, visit, 
treatment*visit,
baseline value
None
Other
∆NAPSI
Subjects in FAS 
with baseline 
NAPSI > 0
Months 1, 3, 6
MMRM
Fixed effects: 
treatment, visit, 
treatment*visit,
baseline value
None
Other
∆WPAI-PsA
FAS
Month 3 & 
Month 6
MMRM
Fixed effects: 
treatment, visit, 
treatment*visit,
baseline value
None
Other


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Appendix 2. 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. All observations regardless of on- or 
off-treatment will be used. For an endpoint that consists of multiple components, e.g., 
ACR50 and DAS28-3(CRP), the components should be collapsed first in the same visit 
window to derive the endpoint.
If two or more visits/observations fall into the same window, the visit/observation closest to 
the target day will be used in the analyses. If there is a tie, the later visit/observation will be 
used. However, for a subject who discontinues from the study early prior to the Month 6 visit 
and who does not have an observation within the Month 6 visit window, if two or more 
observations fall in the same visit window (i.e., a visit window prior to Month 6), then the 
latest observation (rather than the observation closest to the target day) within this visit 
window will be used in the analysis for that visit window.
Visit Label
Target Day
Definition [Day Window]
Screening
< Day 1
Baseline
Day 1
Last non-missing assessment on or before Day 1 and prior to first 
dose of study drug administration
Week 2
Day 15
Day 2 to Day 21
Month 1
Day 29
Day 22 to Day 42
Month 2
Day 57
Day 43 to Day 70
Month 3
Day 85
Day 71 to [Treatment Switch Day or Day 98, whichever is 
smaller]
Month 4
Day 113
[Treatment Switch Day + 1 or Day 99, whichever is smaller] to 
Day 140
Month 6
Day 169
≥Day 141
Target day is equal to the target week × 7 days + 1 day. A month is 4 weeks or 28 days.
Treatment Switch Day = date of the first dose of treatment switch at month 3 (i.e., treatment switch date – date 
of the first dose + 1). The first dose of the treatment switch at Month 3 will be taken from the first dosing date 
from the Month 4 oral dosing CRF.
All the data collected on the treatment switch day will be counted in ≤ Month 3 except for the AE data.  Any 
new treatment emergent AE occurred on the day of treatment switch will be counted in ≥ Month 4.
Note that the upper limit of the Month 3 visit window and the lower limit of the Month 4 
visit window are defined for each of ALL the subjects in the study since, per the study 
protocol, subjects randomized to the placebo group will receive tofacitinib 5 mg BID in a 
blinded fashion for the remainder of the study. Further details for the Month 3/Month 4 visit 
windows are in order.


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1. If Treatment Switch Day falls between Day 71 and Day 98, then the upper limit of the 
Month 3 visit window is the smaller of Treatment Switch Day or Day 98 and the lower 
limit of the Month 4 visit window is the smaller of Treatment Switch Day + 1 or Day 99;
2. If Treatment Switch Day is < 71, > 98, or missing, the upper limit of the Month 3 visit 
window will be Day 98 and lower limit of the Month 4 visit window will be Day 99.
Effects of Bullets 1 and 2 above are further illustrated as follows.
If Treatment Switch Day is
Missing
< 71
71-98
> 98
Visit label
Month 3
Month 4
Month 3
Month 4
Month 3
Month 4
Month 3
Month 4
Day Window
71 to 98
99 to 140
71 to 98 
99 to 140
from 
[71 to 71]
up to 
[71 to 98]
from 
[72 to 140]
up to 
[99 to 140]
71 to 98
99 to 140
The visit window definitions will be applied to all the endpoints, such as efficacy, PRO, 
safety etc. Note some of the endpoints may not be measured at every visit. For example, 
dactylitis will be assessed at baseline, Months 1, 3, and 6, and visit windows at Week 2, 
Months 2 and 4 will be undefined. In the event that an observation may fall into one of the 
undefined visit windows, that observation will not be used in analysis.


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Appendix 3. ENDPOINT DEFINITION AND DATA DERIVATION DETAILS
1. ACR Assessments
The American College of Rheumatology’s definition for calculating improvement in RA 
(ACR50) is calculated as a ≥50% improvement in tender and swollen joint counts and ≥
50% improvement in 3 of the 5 remaining ACR-core set measures: patient and physician 
global assessments, pain, disability, and an acute-phase reactant. Similarly, ACR20 and 
ACR70 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).
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:

If change from baseline is also equal to 0, then percent change from baseline is set to 
be 0%;

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.
The swollen joint and tender/painful joint counts will be calculated per Section 9 and Section 
10 of Appendix 3.
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 


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mg/dL. The unit for CRP will be mg/dL or mg/L depending on endpoint of interest. The 
normal range for the CRP is ≤2.87 mg/L.
The VAS data will need to be rescaled prior to any calculation (Section 3).
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 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 (i.e., 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 (i.e., 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 
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 reach” 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.


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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.
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 
missing, HAQ-DI score is considered missing, else the HAQ-DI score is computed as the 
average of the non-missing domain scores (Bruce & Fries, 2005). A higher score represents a 
more limited physical functional status/ability.
3. PsA Response Criteria (PsARC)
The PsARC will be calculated 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 PsARC. 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.
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).
Methods for calculating percent change from baseline when baseline value of any component 
is equal to 0 can be found in Appendix 3 Section 1.
If values in any of the components at a timepoint were missing, the component variables that
were not missing were used to determine the response status. It should be noted that since
PsARC response requires no worsening in any measure, a subject with any missing 
components cannot be a responder at that timepoint. If one could not determine the response
status in the presence of missing components at the timepoint, then the PsARC response will 
be considered as missing. Handling of missing values for a subject at timepoint in analyses is 
found in Section 5.3.


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The swollen joint and tender/painful joint counts will be calculated per Section 9 and Section 
10 in Appendix 3.
The VAS data will need to be rescaled prior to any calculation (Section 3).
4. 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. See study protocol for additional details.
PGA-PsO response is defined for a subject who achieves a PGA-PsO score of clear (0) or 
almost clear (1) and a ≥2-step improvement from baseline.
5. Psoriasis Area and Severity Index (PASI)
The Psoriasis Area and Severity Index (PASI) quantifies the severity of a subject’s psoriasis 
based on both lesion severity and the percentage 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. Note: PASI should only be performed if  ≥3% of subject’s BSA is 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 areas of the body: head and neck, upper
limbs, trunk (including axillae and groin), and lower limbs (including buttocks). 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, 
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)


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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. 
6. Short Form 36 (SF-36, version 2, acute)
The SF-36v2 (Acute) is a 36-item generic health status measure. 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 
summary 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.
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.


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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.
The summary component scores are:

Physical Component Summary (PCS).

Mental Component Summary (MCS).
In addition, there is another subscale in the SF-36: 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, 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.
Data Derivation Details to Obtain Scale Scores for SF-36
VARIABLE
DERIVATION
SF-36 PF scale score
rawscore = 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.


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SF-36 RP scale score
rawscore = 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-36 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 8 = reversed 7 as defined above.
If 8 is answered and 7 is missing, set 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-36 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.


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SF-36 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.
SF-36 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.


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SF-36 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-36 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.
SF-36 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=Somewhat worse 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.


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SF-36 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-36 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*- 0.09731)
+ (VT1*.23534))
MCS Summary Scale Score = (raw score*10)+50
Raw score is missing if one of the component scale scores is missing.
7. 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.
8. DAS28-3(CRP)


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The Disease Activity Score (DAS) is a derived measurement with differential weighting 
given to each component. DAS28-3(CRP) will be calculated from measurements made at all 
study visits (Madsen et al., 2011).
The components of the DAS28-3 arthritis assessment are:
1) Tender/Painful Joint Count (28);
2) Swollen Joint Count (28);
3) C-Reactive Protein (CRP in mg/L).
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.
The swollen joint count (28) and tender/painful joint count (28) will be calculated similarly 
as for the swollen joint count (66) and tender/painful joint count (68) per Section 9 and 
Section 10 in Appendix 3.
Any missing component will result in DAS28-3(CRP) as missing. A higher score represents
a more severe disease activity.
9. Swollen Joint Count (66)
Swollen joints are recorded in the CRF page of joint swelling. For each of the 66 joints, 
swelling can be recorded as “Present”, “Absent”, “Not Done”, “Not Applicable” or this joint 
assessment is simply missing. Before calculating the swollen joint count, the following pre-
processing steps for each joint should be performed per Pfizer’s standard:

If a joint receives an intra-articular injection (either at Baseline or post-baseline 
visits), set the joint status to “Present” on or after the date of injection regardless of 
the assessment of the joint recorded on the CRF page.

If there is no associated injection record available, a joint recorded as “Not Done” is 
set to missing.

A joint recorded as “Not Applicable” means that measurement cannot be made and 
this joint is set to missing.
After this pre-processing, a joint assessment that is set to missing is to be imputed by the 
average of the non-missing values of the other joints, with the restriction that the number of 
missing joint assessments cannot exceed 50% of the expected total number of joints 
evaluated for the swollen joint count (i.e., 33, 50% of 66). In that case, the swollen joint 
count is set to missing.


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Explicitly after pre-processing, let

N1=number of joints recorded as “Present”;

N2=number of joints recorded as “Absent”; 

N3=number of joints with missing values.
The total number of joints assessed is N1+ N2+ N3 (i.e., 66). The calculated swollen joint 
count is therefore N1+ N3×( N1/( N1+ N2)) if N1+ N2 > 33; otherwise the swollen joint count 
is set to missing. The calculated swollen joint count will be rounded to a whole number. For 
example, a value of 24.5 is rounded to 25, a value of 24.49 is rounded to 24. Note that if there 
is no missing joint assessment, the swollen joint count will be the number of joints recorded 
as “Present” (i.e., N1).
10. Tender/Painful Joint Count (68)
Tender/painful joints are recorded in the CRF page of joint tender/painful. For each of the 68 
joints, tender/painful can be recorded as “Present”, “Absent”, “Not Done”, “Not Applicable” 
or this joint assessment is simply missing. The tender/painful joint count will be calculated
per Pfizer’s standard similarly as for the swollen joint count (see Appendix 3 Section 9).
11. Leeds Enthesitis Index (LEI) and Resolution of Enthesitis
Six sites, including (right and left): lateral epicondyle humerus, medial femoral condyle and 
Achilles tendon insertion, are assessed for enthesitis. Leeds Enthesitis Index (LEI) is the 
number of sites with presence of enthesitis.
Each of the 6 sites is assessed as “Present”, “Absent”, “Not Done”, “Not Applicable” or 
simply missing. Before calculating the LEI, the pre-processing steps for each site will be 
performed per Pfizer’s standard as follows.

A site recorded as “Not Done” is set to missing.

A site recorded as “Not Applicable” means that measurement cannot be made and 
this site is set to missing.
After this pre-processing, a site assessment that is set to missing is to be imputed by the 
average of the non-missing values of the other sites, with the restriction that the number of 
missing site assessments cannot exceed 50% of the expected total number of sites evaluated 
for the LEI (i.e., 3, 50% of 6). In that case, the LEI is set to missing.
Explicitly after pre-processing, let

N1=number of sites recorded as “Present”;


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•
N2=number of sites recorded as “Absent”; 
•
N3=number of sites with missing values.
The total number of sites assessed is N=N1+ N2+ N3 (i.e., 6). The calculated LEI is therefore 
N1+ N3×( N1/( N1+ N2)) if N1+ N2 > 3; otherwise the LEI is set to missing. The calculated 
LEI will be rounded to a whole number. For example, a value of 4.5 is rounded to 5, a value 
of 4.49 is rounded to 4. Note that if there is no missing site assessment, the LEI will be the 
number of sites recorded as “Present” (i.e., N1).
Resolution of enthesitis is defined as a subject with LEI=0.
12. Dactylitis Severity Score (DSS) and Resolution of Dactylitis
Each of the 20 digits in hands and feet with dactylitis will be evaluated. Dactylitis severity 
will be scored based upon digit tenderness using a scale of 0-3, (0-NONE, 1-MILD, 2-
MODERATE, 3-SEVERE, 8-NOT APPLICABLE, 9-NOT DONE), in each digit of the 
hands and feet. Dactylitis severity score (DSS) is the sum of the severity scores of the 20 
digits (range: 0-60, with a higher score indicating more severe dactylitis).
Before calculating the DSS, the pre-processing steps for each digit will be performed per 
Pfizer’s standard as follows.
•
A digit recorded as “Not Done” is set to missing.
•
A digit recorded as “Not Applicable” means that measurement cannot be made and 
this digit is set to missing.
Let N1 be the number of digits with missing values, and N2 and S be the number of the digits
and the sum of the digit scores assessed as 0-NONE, 1-MILD, 2-MODERATE, OR 3-
SEVERE, respectively, the calculated DSS is: S ൅ܰଵൈ
ௌ
ேమ, if N1<N2; otherwise the DSS is set 
as missing.
The calculated DSS is rounded to the whole number. For example, a value of 24.5 is rounded 
to 25, a value of 24.49 is rounded to 24.
Resolution of dactylitis is defined as a subject with DSS=0.
13. AEs of Special Interest


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
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 deep vein thrombosis (DVT)a

Adjudicated pulmonary embolism (PE)a

Adjudicated venous thromboembolism (VTE)a (i.e., adjudicated DVTa or adjudicated 
PEa)

Arterial thromboembolism (ATE)c

Thromboembolism (TE) (i.e., adjudicated DVTa, adjudicated PEa, or ATEc)

Adjudicated drug-induced liver injury (DILI)a and other hepatic eventsd

Renal eventse

Adjudicated gastrointestinal (GI) perforationsa

Adjudicated interstitial lung disease (ILD)f
Abbreviations: CMQ = Customized MedDRA Queries; 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. CMQs to be included will be specified in the programming plan.
d. Including SMQs: Hepatic failure, fibrosis, and cirrhosis, and other liver damage-related conditions; and 
Hepatitis, non-infectious.
e. Including acute renal failure SMQ.
f. Adjudicated by an internal review committee.
14. Definition of Diabetes Mellitus at Baseline
A subject is considered having diabetes mellitus at baseline, if any of the conditions below is 
met:

subject had a diagnosis of diabetes mellitus recorded on the “SIGNIFICANT 
MEDICAL HISTORY” CRF at screening,

subject received any drug treatment taken on Day 1 recorded on the “PRIOR AND 
CONCOMITANT MEDICATIONS: OTHER” CRF in the “ANTI-DIABETIC 
AGENTS” category,

subject’s HbA1c ≥6.5% at baseline or, if HbA1c is not available, baseline fasting 
plasma glucose ≥126 mg/dL.


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15. 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). 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 (i.e., Day 1) data will be used to derive the metabolic syndrome. 

Any drug treatment taken on Day 1 recorded on the “PRIOR AND CONCOMITANT 
MEDICATIONS: OTHER” CRF in the “ANTI-DIABETIC AGENTS” category will 
be considered having the drug treatment of elevated glucose criterion satisfied.

Any drug treatment taken on Day 1 recorded on the “PRIOR AND CONCOMITANT 
MEDICATIONS: OTHER” CRF in the “ANTI-HYPERTENSION AGENTS” 


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category will be considered having the drug treatment of elevated blood pressure 
criterion satisfied.

Any drug treatment taken on Day 1 recorded on the “PRIOR AND CONCOMITANT 
MEDICATIONS: OTHER” CRF in the “LIPID LOWERING AGENTS” category 
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 China specific 
threshold will be used for this China-alone study.
16. Prior DMARDs-IR
Prior DMARDs-IR count only those DMARDs that resulted in an inadequate response (IR), 
defined as those DMARDS that were discontinued due to AE, LOE or both AE/LOE on or 
prior to Day 1, or a DMARD that was started prior to Day 1, but was not discontinued and 
continued beyond Day 1 regardless of DMARD dose change. Any DMARD that was 
discontinued only due to “Other Reasons” on or before Day 1 will not be considered a 
DMARD IR. If the same one agent (e.g., methotrexate) had multiple dose entries, and if any 
of the doses had AE, LOE or AE/LOE, or the agent continued beyond Day 1 without being 
discontinued, it counts as one DMARD IR.
The prior and the concomitant DMARDs are recorded on the “PRIOR AND 
CONCOMITANT MEDICATIONS – DMARD” CRF.
17. List of DMARDS


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WHO Drug Preferred Term
bDMARD
csDMARD
TNFi
Non-TNFi
ABATACEPT
x
ADALIMUMAB
x
ANAKINRA
x
APREMILAST
x
AZATHIOPRINE
x
CERTOLIZUMAB
x
CERTOLIZUMAB PEGOL
x
CHLOROQUINE
x
CICLOSPORIN
x
ETANERCEPT
x
GOLIMUMAB
x
GUSELKUMAB
x
HYDROXYCHLOROQUINE
x
HYDROXYCHLOROQUINE 
PHOSPHATE
x
INFLIXIMAB
x
IXEKIZUMAB
x
LEFLUNOMIDE
x
METHOTREXATE
x
METHOTREXATE SODIUM
x
RITUXIMAB
x
SECUKINUMAB
x
SULFASALAZINE
x
TOCILIZUMAB
x
USTEKINUMAB
x
TNFi= TNF inhibitor
bDMARD= biologic DMARD
csDMARD= conventional synthetic (i.e., traditional non-biologic) DMARD
A footnote “For analysis purposes, Apremilast (a targeted synthetic DMARD) was grouped 
with the csDMARDs.” will be added to any display where applicable.


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Appendix 4. STATISTICAL METHODOLOGY DETAILS
Tipping Point Analysis for Longitudinal Binary Data
A method to analyze the longitudinal data of a binary endpoint measured during the placebo-
controlled period at Week 2, Months 1, 2 and 3 under the MNAR assumption is called the 
tipping point analysis. This analysis is used as a supportive analysis for the primary endpoint 
of ACR50 at Month 3. It assesses the robustness of the binary data to potential deviations 
from the MAR assumption for both tofacitinib 5 mg BID and placebo groups and it is based 
on multiple imputation (Yan, Lee and Li 2009; Ratitch, O’Kelly and Tosiello, 2013). 
In this tipping point analysis, a single saturated generalized linear mixed effect model is used 
as the imputation model. The normal approximation of the difference in binomial proportions 
is used for the analysis, which is the same as the method of analyzing binary endpoint at a 
single time point described in Section 5.2.1.1. This tipping point analysis will be
implemented in the following steps. 
Step 1: Specification of the imputation model.
The generalized linear mixed effect model includes the fixed effects of treatment, visit, 
treatment-by-visit interaction, and a latent subject-level random effect. The logit link is used 
to model the ACR50 response rate as dependent variable for all visits. Estimation of the 
model parameters is performed under the Bayesian framework using MCMC methods. Only 
the available data without imputation are included in this generalized linear mixed effect 
model to estimate the model parameters. If the binary response is denoted by ܻ௜for subject ݅, 
then the saturated generalized linear mixed effect model for two treatment groups and the 
four post-baseline visits is parameterized as
݈݋݃݅ݐሺߨ௜ሻൌ݈݋݃݅ݐ൫ܲሺܻ௜ൌ1ሻ൯ൌߚ଴൅ߚௗ௢௦௘݀݋ݏ݁൅ߚ௧௜௠௘ଵݐ݅݉݁1 ൅ߚ௧௜௠௘ଶݐ݅݉݁2 ൅ߚ௧௜௠௘ଷݐ݅݉݁3 ൅
ߚ௜௡௧ଵ݀݋ݏ݁∗ݐ݅݉݁1 ൅ߚ௜௡௧ଶ݀݋ݏ݁∗ݐ݅݉݁2 ൅ߚ௜௡௧ଷ݀݋ݏ݁∗ݐ݅݉݁3 ൅߶௜∙
In this model, using reference coding, ݀݋ݏ݁is a dummy variable representing treatment 
assignment. When it is 0, it represents the placebo group; 1 represents tofacitinib 5 mg BID. 
Similarly, ݐ݅݉݁1, ݐ݅݉݁2 and ݐ݅݉݁3 are dummy variables. When all of them are 0, it represents 
Week 2; ݐ݅݉݁1 ൌ1 and all others being 0 represent Month 1; ݐ݅݉݁2 ൌ1 and all others being 0 
represent Month 2; ݐ݅݉݁3 ൌ1 and all others being 0 represent Month 3. Interaction terms 
between the treatment and time point are also included in the model, leading to a saturated 
model. 
Step 2: Estimating the imputation model.
Estimation of the model parameters is performed under the Bayesian framework using 
MCMC methods. All of the ߚ’s are the respective effect parameters and they are all assigned 
the same non-informative prior Normal distribution, ܰሺߤఉൌ0, ߪఉ
ଶൌ9ሻ. The variance of 9 on


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the logit scale ensures this prior is non-informative on the probability scale over its support
of [0, 1]. ߶௜’s are the subject-specific random effects and they are all assigned a common 
prior Normal distribution, ܰሺ0, ߪଶሻ. ߪଶis the common variance and it is further assigned a
weakly informative Inverse-Gamma distribution with shape=1 and scale=1. In this prior 
distribution, the prior 90th percentile for ߪଶis approximately 9. 
Step 3: Imputation of missing response at Month 3.
A single imputation of missing ACR50 response at Month 3 is performed based on the 
predictive distribution of the generalized linear mixed effect model. Inferences at earlier time 
points are not of interest, thus imputation of missing ACR50 at earlier time points will not be 
performed. The following model parameters pertinent to the assessment of treatment 
difference at Month 3: ߚ଴
∗, ߚௗ௢௦௘
∗
, ߚ௧௜௠௘ଷ
∗
, ߚ௜௡௧ଷ
∗
, and ߶௜
∗can be sampled from their posterior 
distributions. Multiply imputed datasets can be generated using multiple samples from the 
MCMC of these parameters. The number of imputations (R) is specified as 100.
Step 4: MNAR parameter (ߜ) and predictive distribution.
For example, for a subject ݅randomized to tofacitinib 5 mg BID with missing ACR50 
response at Month 3, the probability of response of this subject ߨ௜
∗(derived from sampled 
parameters) is subtracted by a fixed MNAR quantity (favorable or unfavorable) of ߜሺെ1 ൏
ߜ൏1ሻto become ߨ௜
௣,
ߨ௜
௣ൌߨ௜
∗െߜ
where ߨ௜
∗ൌ
ୣ୶୮ሺఉబ∗ାఉ೏೚ೞ೐
∗
ାఉ೟೔೘೐య
∗
ାఉ೔೙೟య
∗
ାథ೔
∗ሻ
ଵାୣ୶୮ሺఉబ∗ାఉ೏೚ೞ೐
∗
ାఉ೟೔೘೐య
∗
ାఉ೔೙೟య
∗
ାథ೔
∗ሻ. In the situation when ߨ௜
௣൏0, ߨ௜
௣will be set to 0; 
similarly when ߨ௜
௣൐1, ߨ௜
௣will be set to 1.  For a given ߜ, the missing ACR50 response at 
Month 3 for this subject in the tofacitinib 5mg BID group will be imputed based on Bernoulli 
model with the probability of ߨ௜
௣. This is similarly done for a subject in the placebo group 
with missing ACR50 response. A series of fixed MNAR quantity ߜincluding 0 (i.e., MAR) 
will be applied to both treatment groups. The same series of ߜvalues is used for both 
treatment groups: -0.9, -0.7, -0.5, -0.3, -0.1, 0, 0.1, 0.3, 0.5, 0.7, 0.9. The ߜvalues may be 
adjusted as appropriate. The value of 0 represents MAR assumption, while positive values 
represent unfavorable scenarios (i.e., penalizing the subject’s probability of response) and 
negative values represent favorable scenarios. Once all subjects with missing ACR50 
responses at Month 3 are imputed, this step results in a single complete imputed data set for 
Month 3. 
Step 5: Analysis of complete imputed data set.
Analysis of an imputed data set will produce an estimate as well as standard error of the 
treatment difference applying the normal approximation of the difference in binomial 
proportions. For a given value of MNAR quantity, this is repeated for R=100 times to 
generate R=100 complete imputed data sets and these R=100 sets of estimates are combined 


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using the Rubin’s rules (Rubin, 1987). The analysis method is the same as that used for the 
primary analysis. 
Step 6: Assessment of tipping point.
Steps 4-5 can then be repeated for different values of MNAR quantities ߜto evaluate their 
impact on the treatment difference for subjects with missing ACR50 responses at Month 3 
between tofacitinib 5 mg BID and placebo. The specific implementation (i.e., seed for 
random number generation, burn-in and thinning of the MCMC samples) of this tipping point 
analysis will be pre-specified in the statistical programming plan. Note that there is no need 
to repeat Steps 1-3 for different values of ߜ.