Conditions: Ulcerative Colitis
Keywords: Ulcerative colitis open-label long term treatment
Allocation: NON_RANDOMIZED | Intervention model: PARALLEL
Enrollment: 944
Healthy volunteers: no

Brief summary:
This study is an open label, long-term extension study for subjects with moderate to severe ulcerative colitis designed to evaluate long term therapy of CP-690,550.

Detailed description:

Arms:
arm 1: 5 mg BID arm 2: 10 mg BID

Interventions: intervention 1: CP-690,550 intervention 2: CP-690,550
Intervention descriptions: intervention 1: 5 mg tablets, BID, for at least 12 months intervention 2: 10 mg tablets, BID, for at least 12 months

Protocol document:
Prot_000.pdf: 
CP-690,550
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Page 1
CLINICAL PROTOCOL
A MULTI-CENTER, OPEN-LABEL STUDY OF CP-690,550 IN SUBJECTS WITH 
MODERATE TO SEVERE ULCERATIVE COLITIS
Compound:
CP-690,550
Compound Name:
Tofacitinib
US IND Number:
European Clinical Trial Database 
(EudraCT) Number:
2011-004581-14
Protocol Number:
A3921139
Phase:
Phase 3
This document contains confidential information belonging to Pfizer.  Except as otherwise agreed to in writing, 
by accepting or reviewing this document, 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 11
18 June 2019
This global amendment incorporates the 
provisional measures on the restrictions for 
prescriptions of tofacitinib set forth on 17 May 
2019 by the European Medicines Agency’s 
Pharmacovigilance Risk Assessment Committee
(PRAC) in the European Union.
Subjects receiving tofacitinib 10 mg BID who 
are identified as having one or more of the 
contraindicated risk factors for pulmonary 
embolism as described by PRAC will have their 
dose reduced to tofacitinib 5 mg BID.
Any subject identified as having one or more of 
the contraindicated risk factors for pulmonary 
embolism as described by PRAC will not be 
permitted to receive tofacitinib 10 mg BID.  
A risk factor check for pulmonary embolism is
added for each visit beyond Month 36, since at 
the time of this amendment, all subjects have 
crossed the Month 36 study visit.
The following sections have been updated to 
reflect these changes:
Schedule of Activities, Section 3 (Study 
Design), Section 5.5 (ConcomitantMedications),
Section 5.8 (Tofacitinib Dose Adjustment
Guidelines), Section 6.1.8 and Section 6.1.9 
(Study Visit Procedures) and newly added 
Section 7.3.12 (Risk Factor Check for 
Pulmonary Embolism). Appendix 15 
(Abbreviations) was also updated.
Amendment 10
22 October 2018
This amendment specifies the end of the trial 
will be approximately July 2020.  This 2 year 
extension of the study will allow for additional 
collection of long term safety and efficacy data 
in UC patients on tofacitinib.  This trial end date 
has been updated in several sections throughout 
the protocol.
Schedule of Activities footnote 8 was updated to 
clarify that tuberculosis (TB) testing is not 
required at the early termination (ET) visit for 
specific countries that require annual TB testing 
to be performed.
Language related to eligibility criteria for 
enrollment in Study A3921288 has been updated 
to be consistent with the updated study protocol 
for Study A3921288.
Section 5.8 Tofacitinib Dosage Adjustment 


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Guidelines have been revised to provide 
additional clarification for the definition of loss 
of response and flare for subjects who need to 
increase their dose back up to 10 mg BID after 
experiencing a flare on 5 mg BID.
Section 7.3.4 Electrocardiogram (ECG) was 
updated to clarify that ECGs performed at ET 
should be submitted to the central lab. 
Administrative edits, such as updating the name 
of the TB testing performed by the central lab, 
have been made throughout the protocol.
Amendment 9
13 July 2017
This amendment specifies that subjects who 
enroll into Study A3921139 on tofacitinib 
10 mg BID, and who are in stable remission on 
tofacitinib 10 mg BID for at least 6 months may 
have the opportunity to enter Study A3921288 
(A Phase 3b/4, Multi-Center, Double-Blind, 
Randomized, Parallel Group Study of 
Tofacitinib in Subjects with UC in Stable 
Remission) if they meet the eligibility criteria. 
Study A3921288 will evaluate the efficacy and 
safety of tofacitinib in subjects in stable 
remission on 10 mg BID who decrease the dose 
to and remain on 5 mg BID compared to 
subjects who remain on 10 mg BID.  
Section 6.1.5 (Month 12, Early Termination or 
Evaluation Visit for Entry into 
Study A3921288), and Schedule of Activities 
have been revised to include additional 
assessment and information for subjects being 
evaluated for entry into Study A3921288.
Appendix 3 monitoring and discontinuation 
requirements for CK testing have been revised 
for consistency.
Amendment 8
06 August 2015
This amendment specifies the study procedures 
to be performed beyond Month 36. The 
schedule of activities and Section 6 have been 
revised to reflect these procedures.
ECGs and urinalysis beyond Month 36 have 
been removed.
Frequency of collection and the number of 
patient reported outcomes have been reduced 
beyond Month 36.
Addition of exclusion criterion 8 to exclude 
subjects who have evidence of colonic 
malignancy or any dysplasia identified on 
endoscopic exam during study A3921096.
Clarifications to the following sections have 
been made: Section 5.5 (Concomitant 


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Medications), Section 5.7 (Rescue Therapy), and 
Section 5.8 (Tofacitinib Dose Adjustment 
Guidelines).  
Estimated number of subjects to be enrolled has 
been increased.
Annual TB re-testing requirements for specific 
countries have been added (Section 7.3.6).
This amendment also incorporates updates to
Section 7 (Assessments) as well as to standard 
Pfizer protocol text in Section 8 (Adverse Event 
Reporting) and Section 15 (Publication of Study 
Results).
Section 4.5 Sponsor’s Qualified Medical 
Personnel added per Pfizer protocol template.
Additional editorial changes made throughout 
the protocol.
 
 
 
 
 
  
 
 
 
 
Amendment 5
28 September 2012
This amendment updates standard Pfizer 
protocol text, including safety language in 
various sections, including Administration, 
Reproductive Status of Female Subjects and 
Adverse Event Reporting.  
Also included in this amendment are updates to 
the summary of safety section for tofacitinib to 
be consistent with the revised Investigator’s 
Brochure, updates to the secondary study 
endpoints, schedule of activities flowchart, 
prohibited medication list, guidelines for dosage 
adjustment and added guidance on temporary 
withholding of study drug.
 
 
 
Amendment 2
04 January 2012
Added Austria specific requirement of monthly 
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(Country specific: AUSTRIA)
pregnancy testing for females of childbearing 
potential.
 
Original protocol
30 September 2011
N/A
This amendment incorporates all revisions to date, including amendments made at the 
request of country Health Authorities, IRB/ERB, etc.
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PROTOCOL SUMMARY
Indication:
Tofacitinib, also known as tofacitinib citrate or CP-690,550, is being developed for the 
treatment of patients with moderately to severely active ulcerative colitis who have had an 
inadequate response to conventional therapy.
Background and Rationale:
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 heterodimers containing JAK3 
and/or JAK1 with functional selectivity over JAK2 homodimer signaling.  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.  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 IFN.  At higher exposures, inhibition of 
erythropoietin, prolactin and other hormones could occur via inhibition of JAK2 homodimer 
signaling.
The broad effects of JAK1/3 inhibition on multiple cytokine pathways provides the rationale 
for developing tofacitinib as treatment for several diseases in which lymphocyte 
activation/proliferation plays a pathogenic role.  Tofacitinib is being studied as an oral 
treatment for ulcerative colitis (UC), Crohn’s disease, as a disease-modifying anti-rheumatic 
drug (DMARD) for the treatment of RA, as treatment for plaque psoriasis and for the 
prevention of renal allograft rejection.
Objectives and Endpoints:
Primary Objective

To assess the safety and tolerability of long-term tofacitinib therapy in subjects with 
UC.
Secondary Objectives

To evaluate the efficacy of long-term tofacitinib therapy in subjects with UC.

To evaluate the effect of long-term tofacitinib therapy on quality-of-life in subjects 
with UC.
Primary Efficacy Endpoint

As this is an open-label extension study, there will be no primary efficacy endpoint.


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Secondary Efficacy Endpoints

The proportion of subjects in remission at Month 2, Month 12, Month 24 and 
Month 36.  Remission in this study is defined as a Mayo score 2 with no individual 
subscore >1, and rectal bleeding subscore of 0.

The proportion of subjects in clinical remission at Month 2, Month 12, Month 24 and 
Month 36.  Clinical remission in this study is defined as a Mayo score 2 with no 
individual subscore >1. 

The proportion of subjects in partial Mayo score (PMS) remission over time.  PMS 
remission in this study is defined as a partial Mayo score 2 with no individual 
subscore >1.

The proportion of subjects who achieve mucosal healing at Month 2, Month 12, 
Month 24 and Month 36.  Mucosal healing is defined as a Mayo endoscopic subscore 
of 0 or 1.

The proportion of subjects with total score in Inflammatory Bowel Disease 
Questionnaire (IBDQ) 170 over time.
Safety Endpoints

Incidence and severity of adverse events (AEs).

Incidence of serious infections.

Incidence and severity of clinical laboratory abnormalities and change from baseline 
in clinical laboratory values.

Incidence of vital sign abnormalities and change from baseline in vital signs.

Incidence of clinically significant changes in physical examinations from baseline.

Incidence of electrocardiogram (ECG) abnormalities during treatment. 

Summary of adjudicated safety events (eg, cardiovascular, malignancy, opportunistic 
infections).

Proportion of subjects with addition of lipid lowering agents.


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Study Design:
This is a Phase 3, multi-center, open-label study in subjects who have completed or 
demonstrated treatment failure in the maintenance study A3921096, or who were 
non-responders after completing induction studies A3921094 or A3921095.  Approximately 
900 subjects are expected to become eligible for the study.  This study will continue up to 
approximately July 2020. Individual subject duration of participation will vary depending on 
when the subject was enrolled into the study and the end date of approximately July 2020.  
Therefore, the duration of participation for an individual subject may range from
approximately 4 years to more than 7 years. If the study continues beyond year 6 for an 
individual subject, the investigator should continue to follow the same visit schedule and 
study procedures outlined during the study visits of year 4.
Subjects who completed Study A3921096 or had early withdrawal due to treatment failure as 
defined in the A3921096 protocol may be eligible to enroll in this study, A3921139.  In 
addition, subjects who complete induction Study A3921094 or A3921095 and are classified 
as non-responders may be eligible to enroll in this study.  The eligibility of a subject for this 
study will be assessed based on study data collected at Week 8/9 of Study A3921094 or 
A3921095 (for non-responders) or the Week 52/53 visit (for completers) or early termination 
visit (early withdrawals due to treatment failure) of Study A3921096.  The study data 
collected at the Week 8/9 visit for Study A3921094 or A3921095 (for non-responders) or the 
Week 52/53 visit or early termination visit of Study A3921096 will be recorded as the 
baseline data for Study A3921139.
Eligible subjects will be assigned to either tofacitinib 5 mg twice a day (BID) or 10 mg BID 
depending on whether the subject is in remission at baseline of Study A3921139.  Remission
is defined by a total Mayo score 2 with no individual subscore >1, and rectal bleeding 
subscore of 0.  Eligible subjects who are in remission at Week 52 of Study A3921096 will be 
assigned to receive tofacitinib 5 mg BID.  For treatment assignment at baseline, the central 
read assessment of the Mayo endoscopic subscore will be used to determine if a subject is in 
remission.  Subjects who complete Study A3921096 but do not meet the remission definition 
or who are early withdrawals due to treatment failure in Study A3921096 are eligible to 
receive tofacitinib 10 mg BID.  Treatment failure is defined by an increase in Mayo score of 
at least 3 points from baseline value of the maintenance study (A3921096), accompanied by 
an increase in rectal bleeding subscore by at least 1 point, and an increase of endoscopic 
subscore of at least 1 point (yielding an absolute endoscopic subscore of 2) after a minimum 
of 8 weeks of treatment in the maintenance study.  In the scenario where the endoscopic 
subscore is a ‘3’, and the maintenance baseline endoscopic subscore is already a ‘3’ 
(maximum value), then an increase by at least 1 point will not be needed in order to meet 
treatment failure.  However, all other components of the treatment failure criteria will still 
need to be met. Subjects who complete induction studies A3921094 or A3921095 and are 
classified as non-responders are also eligible to receive tofacitinib 10 mg BID.


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Tofacitinib dose can be adjusted from 5 mg BID to 10 mg BID for efficacy and from 
10 mg BID to 5 mg BID after meeting specific laboratory abnormalities or other protocol 
defined criteria regarding efficacy (see Section 5.8 for dose adjustment guidelines).  Dose 
adjustments can only occur after a subject has received at least 8 weeks of treatment in Study 
A3921139.
Subjects who enroll into this study who are on tofacitinib 10 mg BID for at least 
2 consecutive years, and who are in stable remission on tofacitinib 10 mg BID for at least 
6 months may have the opportunity to enter Study A3921288 (A Phase 3b/4, Multi-Center, 
Double-Blind, Randomized, Parallel Group Study of Tofacitinib in Subjects with UC in 
Stable Remission) if they meet the eligibility criteria. Study A3921288 will evaluate the 
efficacy and safety of tofacitinib in subjects in stable remission on 10 mg BID who decrease 
the dose to and remain on 5 mg BID compared to subjects who remain on 10 mg BID. 
Subjects from the induction studies A3921094 or A3921095 (ie, non-responders) who fail to 
demonstrate clinical response at Month 2 of this study will be withdrawn from the study.  
Clinical response is defined by a decrease from the induction study baseline (A3921094 or 
A3921095) Mayo score of at least 3 points and at least 30%, with an accompanying decrease 
in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 
0 or 1.  The endoscopic subscore based on central reading will be used to assess clinical 
response.
All subjects who withdraw early or who complete this open-label study, with the exception 
of those subjects entering Study A3921288, will have a 4-week safety follow-up evaluation 
after the last dose of study medication.
Subjects will be required to remain on stable doses of their concomitant medications for UC
during the study period, with the exception of oral 5-ASA or sulfasalazine and oral 
corticosteroids described in Section 5.5.  Subjects who enter this study on corticosteroids 
(eg, subjects who withdraw from Study A3921096 due to treatment failure or non-responders 
at the end of Study A3921094 or A3921095) will need to continue the steroid tapering 
regimen described in Study A3921096 (see Section 5.5).  If a subject requires rescue therapy 
(see Section 5.7) or undergoes surgery for UC, the subject should be withdrawn from the 
study and appropriate agents should be given at the discretion of the investigator.  If a subject 
discontinues the use of background oral 5-ASA or sulfasalazine during the study and/or has 
the therapy re-initiated, this will not constitute rescue therapy, and the subject will be 
permitted to remain in the study.  
Study Treatments:
Subjects will be assigned to one of two dose groups depending on their remission status at 
baseline of Study A3921139:

Tofacitinib 5 mg BID (subjects in remission).

Tofacitinib 10 mg BID (all other subjects).


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Statistical Methods:
Sample Size Determination
Approximately 900 subjects are expected to become eligible for the study.  Approximately 
460 subjects are expected to enroll from the maintenance Study A3921096 assuming a 
78% rollover rate from the maintenance study.  Approximately 440 subjects are expected to 
enroll from the induction Study A3921094 or A3921095 assuming that 38% of subjects 
enrolled in those studies will not achieve clinical response and will not have improving 
endoscopic subscores after completing induction Study A3921094 or A3921095.
Efficacy Analysis
The primary analysis population will be the Full Analysis Set (FAS) defined as all subjects 
who receive at least 1 dose of study medication.
The primary objective is to assess the safety and tolerability of long-term tofacitinib therapy.  
There will be no primary efficacy endpoint.
Due to the design of the study, there will be no formal hypothesis testing. Descriptive 
summary statistics such as number, percentage for categorical endpoints and mean, standard
deviation, median for continuous endpoints will be summarized by the following four 
subgroups of subjects based on the status at baseline of Study A3921139: 1) in remission 
defined by a total Mayo score 2 with no individual subscore >1, and rectal bleeding 
subscore of 0, 2) treatment failure defined by an increase in Mayo score of at least 3 points 
from baseline value of the maintenance study (A3921096), accompanied by an increase in 
rectal bleeding subscore by at least 1 point, and an increase of endoscopic subscore of at least 
1 point (yielding an absolute endoscopic subscore of 2), 3) all other subjects from 
maintenance study A3921096 neither in remission nor fulfilling the definition of treatment 
failure, and 4) non-responders from induction studies A3921094 or A3921095. 
Safety Analysis
The safety data will be summarized in accordance with Pfizer Data Standards based on the 
safety analysis set defined as all subjects who receive at least 1 dose of study medication.


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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 (Section 6) 
and Assessments (Section 7) for detailed information on each procedure and assessment required for compliance with the protocol.
All study visits during the first year will have a window of 5 days.  The 4-week follow-up evaluation visit and all study visits in 
subsequent years will have a window of 7 days.
This study will continue until approximately July 2020.  Individual subject duration of participation will vary depending on when the 
subject was enrolled into the study and the end date of approximately July 2020.  Therefore, the duration of participation for an 
individual subject may range from approximately 4 years to more than 7 years. Annual schedule of activities are identical from year 4 
and beyond.  For illustration purposes, the Schedule of Activities contains study procedures up to Month 72 (year 6).  If the study 
continues beyond year 6 for an individual subject, the investigator should continue to follow the same visit schedule and study 
procedures outlined during the study visits of year 4.
Schedule of activities for first year:
Study Procedure
Baseline
Open Label Treatment Period
Day 11
Month 1
(5 days)
Month 2
(5 days)
Month 4
(5 days)
Month 6
(5 days)
Month 9
(5 days)
Month 12
(5 days) / 
ET2
Visit Number 
1
2
3
4
5
6
7 or ET2
Informed Consent
X
Medical History3
IND or MNT1
Complete Physical Examination
IND or MNT
X
Targeted Physical Examination4
X
X
X
X
X
Extra-Intestinal Manifestations
IND or MNT
X
Vital Signs5
IND or MNT
X
X
X
X
X
X
12-Lead ECG5
IND or MNT
X
Laboratory
Hematology
IND or MNT
X
X
X
X
X
X
Serum Chemistry
IND or MNT
X
X
X
X
X
X13
Urinalysis6
IND or MNT
X
X
X
X
X
X
Lipid Profile, Fasting
IND or MNT
X
X
X
X
Urine -hCG7
IND or MNT
X
X
X
X
X
X


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Study Procedure
Baseline
Open Label Treatment Period
Day 11
Month 1
(± 5 days)
Month 2
(± 5 days)
Month 4
(± 5 days)
Month 6
(± 5 days)
Month 9
(± 5 days)
Month 12
(± 5 days) / 
ET2
TB Testing/Chest Radiograph, if 
necessary, in Specific Countries8
X
Endoscopic Procedure
Flexible Sigmoidoscopy/
Colonoscopy (if preferred)
IND or MNT
X9
X14
Eligibility Assessment
X
Dose Assignment
X
Study Medication Dispensing
X
X
X
X
X
X
Study Drug Accountability
X
X
X
X
X
X
Ulcerative Colitis Assessments
Bowel Movement Diary Data10
X
X
X
X
X
X
X
Partial Mayo Score
IND or MNT
X
X
X
X
Mayo Score
IND or MNT
X
X
Health Outcome Assessments11
IBDQ
IND or MNT
X
X
X
Adverse Event Assessment
IND or MNT
X
X
X
X
X
X
Concomitant Medication
IND or MNT
X
X
X
X
X
X
1.
The baseline visit of Study A3921139 is the same visit as either the Week 53 visit for subjects who complete Study A3921096 or early termination visit for subjects who are 
treatment failures during Study A3921096, OR is the same visit as the Week 9 visit for subjects who complete Study A3921094 or A3921095 and are deemed to be non-
responders.  All procedures done at Week 52/53 visit or the early termination visit of Study A3921096 or Week 8/9 visit of Study A3921094 or A3921095 for subjects 
enrolled into this study will be used as the baseline data for Study A3921139.  Procedures listed as IND or MNT = Induction Study or Maintenance Study procedures will 
NOT BE REPEATED at baseline of Study A3921139.  Only those procedures marked with a ‘X’ will be performed at the baseline visit.
2.
Subjects who discontinue treatment early from the study will have an early termination (ET) visit and all procedures listed at Month 12/ET will be performed on the last day 
the subject takes the study medication or as soon as possible.  Subjects from the induction studies A3921094 or A3921095 (ie, non-responders) who fail to demonstrate 
clinical response at Month 2 will be withdrawn from the study and will be required to have a modified ET visit consisting of only the following procedures: complete physical 
examination, 12-lead ECG, return all study drug and perform study drug accountability. The Month 12/ET visit will also serve as the Evaluation Visit for Entry into 
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Study A3921288. If, after completion of the evaluation visit for entry into Study A3921288, a subject does not meet eligibility criteria, they should remain in this 
study (A3921139).
3.
Medical history from either the induction studies (A3921094 or A3921095) or the maintenance study (A3921096) will be used for Study A3921139.  Resolved AEs occurring 
in these studies will be captured as part of Baseline Medical History, while ongoing AEs from either A3921094 or A3921095, or A3921096 study will be followed throughout 
Study A3921139.
4.
The targeted physical examination consists of weight, general appearance, and examinations of eyes, mouth, lungs, heart, abdomen, musculoskeletal, extremities, skin and 
lymph nodes.
5.
12-lead ECG and vital sign measurements should be performed before laboratory blood collection and endoscopic procedure, when possible.
6.
Dipstick in all cases; microscopy analysis is indicated if urinalysis is positive for blood, nitrite, leucocyte esterase and/or protein.  Urine culture performed if urinalysis is 
positive for nitrite and/or leucocyte esterase or if clinically indicated.
7.
Urine β-hCG to be performed only for women of childbearing potential.  Pregnancy testing may be performed more frequently per local regulations.
8.
Annual tuberculosis (TB) screening will be conducted using Quantiferon-TB® Gold Plus test (QFT) for subjects in those countries in which TB prevalence has been reported 
at a rate of >50 cases per 100,000 persons (see Section 7.3.6). TB testing is not required at the ET visit.  All subjects with positive results must have chest radiograph 
performed.  Note: QFT should not be performed in subjects who had positive result during prior testing (screening visit in Study A3921094 or A3921095 or prior annual 
visits) and/or previously received adequate treatment for TB.
9.
Flexible sigmoidoscopy/colonoscopy (if preferred) will be performed at Month 2 for all subjects.  The Mayo endoscopic subscore at Month 2 was assessed by both central 
reader and study site investigator prior to implementation of Amendment 8.  After implementation of Amendment 8, the Month 2 Mayo endoscopic subscore will only be 
assessed by site investigator.  All other endoscopies performed in this study will only be read by study site investigator.  Subjects from the induction studies A3921094 or 
A3921095 (ie, non-responders) who fail to demonstrate clinical response at Month 2 of this study will be withdrawn from the study.
10. Bowel movement (BM) diary data will be collected through a phone-based IVRS tool.  Subjects will be instructed in its use at the Baseline visit.  Automatic reminders will be 
generated prior to scheduled visits to remind subjects to start completing the BM diary daily approximately 7 days prior to their next scheduled visit.  Study site staff will also 
contact the subjects 7 days prior to the scheduled visit to ensure compliance.  In addition, subjects should be instructed to start completing the BM diary whenever he/she 
experiences any worsening of UC symptoms anytime during the study.
11. Subjects should complete the self-administered IBDQ, 
 prior to any clinical assessments at the scheduled times noted 
above.  A member of the site staff should be available if a subject requires further instruction and to review the questionnaires for completeness prior to leaving the clinic 
visit.  
 
 
13. For subjects being evaluated for entry into Study A3921288, the serum chemistry panel will include addition of hs-CRP.
14. For subjects being evaluated for entry into Study A3921288, endoscopy (ie, flexible sigmoidoscopy or colonoscopy) will only be performed in subjects who have not had an 
endoscopy performed within the previous 6 months prior to baseline visit of A3921288.  Endoscopic assessment will only be done by local site read.
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Schedule of activities for Years 2 and 3:
Study Procedure
Open Label Treatment Period
Month 15
(±7 days)
Month 18
(±7 days)
Month 21
(±7 days)
Month 24
(±7 days)
Month 27
(±7 days)
Month 30
(±7 days)
Month 33
(±7 days)
Month 36
(±7 days)
Visit Number 
8
9
10
11
12
13
14
15
Complete Physical Examination
X
X
Targeted Physical Examination4
X
X
X
X
X
X
Extra-Intestinal Manifestations
X
X
Vital Signs5
X
X
X
X
X
X
X
X
12-Lead ECG5
X
X
Laboratory
Hematology
X
X
X
X
X
X
X
X
Serum Chemistry
X
X
X
X
X
X
X
X
Urinalysis6
X
X
X
X
X
X
X
X
Lipid Profile, Fasting
X
X
X
X
Urine β-hCG7
X
X
X
X
X
X
X
X
TB Testing/Chest 
Radiograph, if necessary, in 
Specific Countries8
X
X
Endoscopic Procedure
Flexible Sigmoidoscopy/ 
Colonoscopy (if preferred)
X
X
Study Medication Dispensing
X
X
X
X
X
X
X
X
Study Drug Accountability
X
X
X
X
X
X
X
X
Ulcerative Colitis Assessments
Bowel Movement Diary
Data10
X
X
X
X
X
X
X
X
Partial Mayo Score
X
X
X
X
X
X
Mayo Score
X
X
Health Outcome Assessments11
IBDQ
X
X
X
X
Adverse Event Assessment
X
X
X
X
X
X
X
X
Concomitant Medication
X
X
X
X
X
X
X
X
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Study Procedure
Open Label Treatment Period
Month 15
(±7 days)
Month 18
(±7 days)
Month 21
(±7 days)
Month 24
(±7 days)
Month 27
(±7 days)
Month 30
(±7 days)
Month 33
(±7 days)
Month 36
(±7 days)
4.
The targeted physical examination consists of weight, general appearance, and examinations of eyes, mouth, lungs, heart, abdomen, musculoskeletal, extremities, skin and 
lymph nodes.
5.
12-lead ECG and vital sign measurements should be performed before laboratory blood collection and endoscopic procedure, when possible.
6.
Dipstick in all cases; microscopy analysis is indicated if urinalysis is positive for blood, nitrite, leucocyte esterase and/or protein.  Urine culture performed if urinalysis is 
positive for nitrite and/or leucocyte esterase or if clinically indicated.
7.
Urine β-hCG to be performed only for women of childbearing potential. Pregnancy testing may be performed more frequently per local regulations.
8.
Annual TB screening will be conducted using Quantiferon-TB® Gold Plus test (QFT) for subjects in those countries in which TB prevalence has been reported at a rate of 
>50 cases per 100,000 persons (see Section 7.3.6). TB testing is not required at the ET visit.  All subjects with positive results must have chest radiograph performed.  
Note: QFT should not be performed in subjects who had positive result during prior testing (screening visit in Study A3921094 or A3921095 or prior annual visits) and/or 
previously received adequate treatment for TB.
10. Bowel movement (BM) diary data will be collected through a phone-based IVRS tool.  Automatic reminders will be generated prior to scheduled visits to remind subjects 
to start completing the BM diary daily approximately 7 days prior to their next scheduled visit.  Study site staff will also contact the subjects 7 days prior to the scheduled 
visit to ensure compliance.  In addition, subjects should be instructed to start completing the BM diary whenever he/she experiences any worsening of UC symptoms 
anytime during the study.
11. Subjects should complete the self-administered IBDQ, 
 prior to any clinical assessments at the scheduled times noted 
above.  A member of the site staff should be available if a subject requires further instruction and to review the questionnaires for completeness prior to leaving the clinic 
visit. 
 
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Schedule of Activities for Year 4:
Study Procedure
Open-Label Treatment Period
Month 39
(±7 days)
Month 42
(±7 days)
Month 45
(±7 days)
Month 48
(±7 days)
Visit Number
16
17
18
19
Complete Physical Examination
X
Extra-Intestinal Manifestations
X
Vital Signs5
X
X
X
X
Laboratory
Hematology
X
X
X
X
Serum Chemistry
X
X
X
X
Lipid Profile, Fasting
X
X
Urine β-hCG7
X
X
X
X
TB Testing/Chest Radiograph, if 
necessary, in Specific Countries8
X
Ulcerative Colitis Assessments
Bowel Movement Diary Data10
X
X
X
X
Partial Mayo Score
X
X
X
X
Health Outcome Assessments11
IBDQ
X
Study Medication Dispensing
X
X
X
X
Study Drug Accountability
X
X
X
X
Adverse Event Assessment
X
X
X
X
Concomitant Medication
X
X
X
X
Risk Factor Check for Pulmonary Embolism12
X
X
X
X
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Schedule of Activities for Year 5:
Study Procedure
Open-Label Treatment Period
Month 51
(±7 days)
Month 54
(±7 days)
Month 57
(±7 days)
Month 60
(±7 days)
Visit Number
20
21
22
23
Complete Physical Examination
X
Extra-Intestinal Manifestations
X
Vital Signs5
X
X
X
X
Laboratory
Hematology
X
X
X
X
Serum Chemistry
X
X
X
X
Lipid Profile, Fasting
X
X
Urine β-hCG7
X
X
X
X
TB Testing/Chest Radiograph if 
necessary, in Specific Countries8
X
Ulcerative Colitis Assessments
Bowel Movement Diary Data10
X
X
X
X
Partial Mayo Score
X
X
X
X
Health Outcome Assessments11
IBDQ
X
Study Medication Dispensing
X
X
X
X
Study Drug Accountability
X
X
X
X
Adverse Event Assessment
X
X
X
X
Concomitant Medication
X
X
X
X
Risk Factor Check for Pulmonary Embolism12
X
X
X
X
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Schedule of Activities for Year 6:
Study Procedure
Open-Label Treatment Period
Follow-Up Visit
Month 63
(±7 days)
Month 66
(±7 days)
Month 69
(±7 days)
Month 72*
(±7 days)
4 weeks after last dose14
(±7 days)
Visit Number
24
25
26
27
28
Complete Physical Examination
X
Extra-Intestinal Manifestations
X
Vital Signs5
X
X
X
X
X
Laboratory
Hematology
X
X
X
X
X
Serum Chemistry
X
X
X
X
X
Lipid Profile, Fasting
X
X
Urine β-hCG7
X
X
X
X
X
TB Testing/Chest Radiograph, if 
necessary, in Specific Countries8
X
Ulcerative Colitis Assessments
Bowel Movement Diary Data10
X
X
X
X
Partial Mayo Score
X
X
X
X
Health Outcome Assessments11
IBDQ
X
Study Medication Dispensing
X
X
X
X
Study Drug Accountability
X
X
X
X
Adverse Event Assessment
X
X
X
X
X
Concomitant Medication
X
X
X
X
X
Risk Factor Check for Pulmonary Embolism12
X
X
X
X
5.
12-lead ECG and vital sign measurements should be performed before laboratory blood collection and endoscopic procedure, when possible.  NOTE: Weight will be recorded 
along with vital sign measurements during visits where complete or targeted physical examinations are not performed.
7.
Urine β-hCG to be performed only for women of childbearing potential. Pregnancy testing may be performed more frequently per local regulations.
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8.
Annual TB screening will be conducted using Quantiferon-TB® Gold Plus test (QFT) for subjects in those countries in which TB prevalence has been reported at a rate of 
>50 cases per 100,000 persons (see Section 7.3.6). TB testing is not required at the ET visit.  All subjects with positive results must have chest radiograph performed.  Note: 
QFT should not be performed in subjects who had positive result during prior testing (screening visit in Study A3921094 or A3921095 or prior annual visits) and/or 
previously received adequate treatment for TB.
10. Bowel movement (BM) diary data will be collected through a phone-based IVRS tool.  Automatic reminders will be generated prior to scheduled visits to remind subjects to 
start completing the BM diary daily approximately 7 days prior to their next scheduled visit.  Study site staff will also contact the subjects 7 days prior to the scheduled visit to 
ensure compliance.  In addition, subjects should be instructed to start completing the BM diary whenever he/she experiences any worsening of UC symptoms anytime during 
the study.
11. Subjects should complete the self-administered IBDQ, 
 prior to any clinical assessments at the scheduled times noted above.  A member of the site 
staff should be available if a subject requires further instruction and to review the questionnaires for completeness prior to leaving the clinic visit.  
 
.
12. Per Amendment 11, all subjects will be asked at every study visit if they have any newly-developed risk factors for pulmonary embolism as described in 
Section 7.3.12.  At the time of Amendment 11, all subjects have completed the Month 36 study visit and therefore this procedure is only collected at visits beyond 
Month 36 as applicable to each subject’s individual participation.  If a subject has a newly identified risk factor for pulmonary embolism and is receiving tofacitinib 
10 mg BID, they must reduce their dose to tofacitinib 5 mg BID.
14. All subjects are required to have a 4-week follow-up evaluation after the last dose of study medication.
* If the study continues beyond Month 72 for an individual subject, the investigator should continue to follow the same visit schedule and study procedures outlined during the 
study visits of year 4.
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TABLE OF CONTENTS
LIST OF TABLES...................................................................................................................24
LIST OF FIGURES .................................................................................................................24
APPENDICES .........................................................................................................................24
1. INTRODUCTION ...............................................................................................................25
1.1. Indication.................................................................................................................26
1.2. Background and Rationale ......................................................................................26
1.3. Clinical Pharmacokinetics.......................................................................................28
1.4. Rationale of Dose Selection ....................................................................................28
2. STUDY OBJECTIVES AND ENDPOINTS.......................................................................29
2.1. Objectives................................................................................................................29
2.2. Endpoints.................................................................................................................29
3. STUDY DESIGN.................................................................................................................31
4. SUBJECT SELECTION......................................................................................................35
4.1. Inclusion Criteria.....................................................................................................35
4.2. Exclusion Criteria....................................................................................................36
4.3. Randomization Criteria ...........................................................................................37
4.4. Life Style Guidelines...............................................................................................38
4.4.1. Tobacco.......................................................................................................38
4.4.2. Activity .......................................................................................................38
4.4.3. Diet and Dietary Supplements....................................................................38
4.4.4. Vaccination.................................................................................................38
4.4.5. Contraception..............................................................................................39
4.4.5.1. Females of Non-Childbearing Potential....................................39
4.4.5.2. Females of Childbearing Potential ............................................39
4.4.5.3. Pregnancy Testing.....................................................................40
4.4.5.4. Reproductive Status of Male Subjects ......................................40
4.4.5.5. Surgery ......................................................................................40
4.5. Sponsor’s Qualified Medical Personnel..................................................................40
5. STUDY TREATMENTS.....................................................................................................41
5.1. Allocation to Treatment ..........................................................................................41
5.2. Breaking the Blind ..................................................................................................42


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5.3. Drug Supplies..........................................................................................................42
5.3.1. Formulation and Packaging........................................................................42
5.3.2. Preparation and Dispensing........................................................................42
5.3.3. Administration............................................................................................42
5.3.4. Compliance.................................................................................................43
5.4. Drug Storage and Drug Accountability...................................................................43
5.5. Concomitant Medications .......................................................................................44
5.6. Prohibited Concomitant Medications......................................................................46
5.7. Rescue Therapy.......................................................................................................47
5.8. Tofacitinib Dose Adjustment Guidelines................................................................47
5.9. Tofacitinib Temporary Withholding .......................................................................48
6. STUDY PROCEDURES .....................................................................................................49
6.1. Study Period ............................................................................................................49
6.1.1. Baseline (Visit 1)........................................................................................49
6.1.2. Month 1 (5 days, Visit 2)..........................................................................51
6.1.3. Months 2, 4 and 6 (5 days, Visits 3, 4 and 5)...........................................52
6.1.4. Month 9 (5 days, Visit 6)..........................................................................53
6.1.5. Month 12, Early Termination (ET) or Evaluation Visit for Entry into 
Study A3921288 (5 days, Visit 7 or ET).......................................................53
6.1.6. Months 15, 21, 27, and 33 (7 days, Visits 8, 10, 12, and 14)...................55
6.1.7. Months 18, 24, 30 and 36 (7 days, Visits 9, 11, 13, and 15)....................56
6.1.8. Months 39, 42, 45, 51, 54, 57, 63, 66, and 69 (7 days, Visits 16, 17, 
18, 20, 21, 22, 24, 25 and 26) ..........................................................................57
6.1.9. Months 48, 60, and 72 (7 days, Visits 19, 23 and 27)..............................57
6.2. Follow-up Visit (7 days, Visit 28).........................................................................58
6.3. Subject Withdrawal.................................................................................................59
7. ASSESSMENTS..................................................................................................................60
7.1. Ulcerative Colitis Assessments ...............................................................................61
7.1.1. Subject Bowel Movement Diary ................................................................61
7.1.2. Partial Mayo Score .....................................................................................61
7.1.3. Mayo Score.................................................................................................62
7.2. Patient Reported Outcomes.....................................................................................63


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7.2.1. Inflammatory Bowel Disease Questionnaire (IBDQ).................................63
 
7.3. Safety.......................................................................................................................65
7.3.1. Vital Signs ..................................................................................................65
7.3.2. Physical Examinations................................................................................65
7.3.3. Extra-Intestinal Manifestations...................................................................66
7.3.4. Electrocardiogram.......................................................................................66
7.3.5. Clinical Laboratory Tests ...........................................................................66
7.3.6. Annual Tuberculosis Testing......................................................................68
7.3.7. Pregnancy Testing ......................................................................................68
7.3.8. Serum Lipids...............................................................................................69
7.3.9. Creatinine Clearance...................................................................................69
7.3.10. Infections ..................................................................................................69
7.3.11. Cardiovascular, and Malignancy, and Other Safety Events of 
Interest..............................................................................................................70
7.3.12. Risk Factor Check for Pulmonary Embolism...........................................71
8. ADVERSE EVENT REPORTING......................................................................................71
8.1. Adverse Events........................................................................................................71
8.2. Reporting Period .....................................................................................................72
8.3. Definition of an Adverse Event...............................................................................72
8.4. Abnormal Test Findings..........................................................................................73
8.5. Serious Adverse Events...........................................................................................73
8.5.1. Protocol-Specified Serious Adverse Events...............................................74
8.5.2. Potential Cases of Drug-Induced Liver Injury............................................74
8.6. Hospitalization ........................................................................................................75
8.7. Severity Assessment................................................................................................76
8.8. Causality Assessment..............................................................................................77
8.9. Exposure During Pregnancy....................................................................................77
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8.10. Occupational Exposure .........................................................................................78
8.11. Withdrawal Due to Adverse Events (See Also the Section on Subject 
Withdrawal)...............................................................................................................78
8.12. Eliciting Adverse Event Information ....................................................................79
8.13. Reporting Requirements........................................................................................79
8.13.1. Serious Adverse Event Reporting Requirements .....................................79
8.13.2. Non-Serious Adverse Event Reporting Requirements .............................79
8.13.3. Sponsor’s Reporting Requirements to Regulatory Authorities ................79
9. DATA ANALYSIS/STATISTICAL METHODS...............................................................80
9.1. Sample Size Determination.....................................................................................80
9.2. Efficacy Analysis ....................................................................................................80
9.2.1. Analysis of Primary Endpoint ....................................................................80
9.2.2. Analysis of Secondary Endpoints...............................................................80
9.3. Analysis of Health Outcome Assessments..............................................................80
9.4. Safety Analysis........................................................................................................80
9.5. Interim Analysis ......................................................................................................81
9.6. Data Monitoring Committee ...................................................................................81
9.7. Safety Event Adjudication Committees..................................................................81
10. QUALITY CONTROL AND QUALITY ASSURANCE.................................................82
11. DATA HANDLING AND RECORD KEEPING .............................................................82
11.1. Case Report Forms/Electronic Data Record .........................................................82
11.2. Record Retention...................................................................................................83
12. ETHICS..............................................................................................................................83
12.1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC) ............83
12.2. Ethical Conduct of the Study ................................................................................84
12.3. Subject Information and Consent..........................................................................84
12.4. Reporting of Safety Issues and Serious Breaches of the Protocol or ICH 
GCP ...........................................................................................................................84
13. DEFINITION OF END OF TRIAL...................................................................................85
13.1. End of Trial in a Member State.............................................................................85
13.2. End of Trial in all Participating Countries ............................................................85
14. SPONSOR DISCONTINUATION CRITERIA ................................................................85
15. PUBLICATION OF STUDY RESULTS..........................................................................85


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15.1. Communication of Results by Pfizer ....................................................................85
15.2. Publications by Investigators ................................................................................86
16. REFERENCES ..................................................................................................................88
LIST OF TABLES
Table 1
Study Drug Administration...................................................................................42
Table 2.
Concomitant Medications.....................................................................................44
Table 3.
Laboratory Test Parameters..................................................................................67
LIST OF FIGURES
Figure 1.
Study Design.........................................................................................................34
APPENDICES
Appendix 1. Mayo Scoring System* .......................................................................................90
Appendix 2. Prohibited Concomitant Medications..................................................................91
Appendix 3. Guidelines for Monitoring and Discontinuations................................................93
Appendix 4. ECG Values of Potential Clinical Concerns .......................................................95
Appendix 5. Cockcroft-Gault GFR Calculation ......................................................................97
Appendix 6. Evaluation of Potentially Malignant Tumors, Suspicious 
Lymphadenopathy or Possible Extranodal Lymphoproliferative Disorder 
(LPD)....................................................................................................................98
Appendix 7. Evaluation of Gastrointestinal Tract Biopsies ....................................................99
Appendix 8. Recommended Clinical Management of Cholesterol .......................................100
Appendix 9. Quality of Life in Inflammatory Bowel Disease Questionnaire (IBDQ)..........101
Appendix 15. Abbreviations..................................................................................................126
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1. INTRODUCTION
Ulcerative colitis (UC) is a chronic, relapsing, inflammatory disease of the colon 
characterized by alternating episodes of remission and spontaneous relapse.  The prevalence 
has been estimated to range from 37 to 246 cases per 100,000 persons in North America and 
21 to 243 cases per 100,000 persons in Europe.1 It is most commonly diagnosed in late 
adolescence and early adulthood, with the peak incidence occurring between 20-39 years of 
age.2  
Although the precise pathogenesis of UC is presently unknown, the prevailing paradigm is 
dysregulation of the enteric immune response in genetically susceptible individuals.3 Such 
defective immune system leads to upregulation of macrophages and Th2 lymphocytes in UC, 
as a result of inability to appropriately downregulate both innate and adaptive immune
responses to endogenous luminal antigens.  This produces an excess of cytokines, 
interleukins and chemokines, all of which can lead to enhanced inflammation and tissue 
damage.  Evidence has shown that upregulation of some of the common gamma-chain 
cytokines may play a role in the pathogenesis of inflammatory bowel disease (IBD), of which 
the two main forms are UC and Crohn’s disease. 
The hallmark clinical presentations for UC include diarrhea, rectal bleeding, passage of 
mucus, tenesmus, urgency, and abdominal pain. Patients may also experience fatigue, fevers, 
weight loss, and dehydration, particularly in more severe cases. Mortality is not increased in 
UC in general, but the disease may present as life-threatening fulminant colitis.  Most 
patients follow a chronic intermittent course with periods of increased disease activity 
separated by periods of disease remission. After the initial diagnosis, approximately half of 
patients will have active disease at any single point in time and approximately 90% will have 
a disease course characterized by intermittent flares.5
The disease almost universally involves the rectum, extending proximally to involve a 
portion of or the entire colon.  At the time of initial presentation, approximately 45% of 
patients have disease limited to the rectum and sigmoid (proctosigmoiditis), approximately 
35% have disease extending beyond the sigmoid but not involving the entire colon, and 
approximately 20% of patients have pancolitis.5 However, a substantial number of patients 
will experience disease extension over time.6,7
Current therapy for the treatment of UC includes 5-aminosalicylic acid (5-ASA), systemic 
and/or topical steroids, immunosuppressants such as azathioprine/6-mercaptopurine and 
cyclosporine, and tumor-necrosis factor alpha (TNF alpha) blockers.4  However, despite
these treatment options, a significant proportion of UC patients still require colectomy for 
refractory or severe fulminant disease, or in some cases for cancer prevention.5  Although 
patients with UC are often considered to be cured by restorative proctocolectomy, the quality 
of life may be poor and the surgery can be associated with short-term and long-term 
complications, including a decreased female fecundity and the development of pouchitis.11,8  
At present, no current pharmacological therapy is able to provide a cure for UC. The primary 
treatment goal is to induce remission and then to maintain this state.  Therefore, identification 
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This study is designed to evaluate the long term safety and tolerability of tofacitinib in 
patients with moderately to severely active ulcerative colitis who have had an inadequate 
response to conventional therapy.
1.1. Indication
Tofacitinib, also known as tofacitinib citrate or CP-690,550, is being developed for the
treatment of patients with moderately to severely active ulcerative colitis who have had an 
inadequate response to conventional therapy.
1.2. Background and Rationale
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.12  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 heterodimers containing JAK3 
and/or JAK1 with functional selectivity over JAK2 homodimer signaling.13  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.  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 IFN.14  At higher exposures, inhibition of 
erythropoietin, prolactin and other hormones could occur via inhibition of JAK2 homodimer 
signaling.
The broad effects of JAK1/3 inhibition on multiple cytokine pathways provides the rationale 
for developing tofacitinib as treatment for several diseases in which lymphocyte 
activation/proliferation plays a pathogenic role.  Tofacitinib is being studied as an oral 
treatment for UC, Crohn’s disease, as a disease-modifying anti-rheumatic drug (DMARD) 
for the treatment of RA, as treatment for plaque psoriasis and for the prevention of renal 
allograft rejection.
Summary of Efficacy:
Efficacy of tofacitinib in the treatment of UC has been evaluated in one Phase 2 study: 
A3921063.  Efficacy of tofacitinib has also been evaluated in Crohn’s disease, rheumatoid 
arthritis, psoriasis, and renal transplant.  Details of the efficacy results in these patient 
populations can be found in the current version of the tofacitinib Investigator Brochure.
Study A3921063 was a randomized, double-blind, placebo-controlled Phase 2 study 
evaluating the safety and efficacy of tofacitinib in subjects with moderate to severe UC.  In 
this study, 195 subjects with moderate to severe active UC were randomized at a 
1:1:1:2:2 ratio into one of the five treatment groups of tofacitinib 0.5 mg BID, 3 mg BID, 
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The study demonstrated dose-dependent improvements with tofacitinib treatment in clinical 
response (primary endpoint) and clinical remission rates.  Based on protocol-predefined full-
analysis population, the primary endpoint of clinical response (reduction of Mayo score by at 
least 3 points or 30% from baseline with an accompanying decrease in the subscore for rectal 
bleeding of at least 1 point or absolute subscore for rectal bleeding of 0 or 1) at Week 8 was 
achieved in 47.5%, 29.6%, 51.6%, 63.3%, and 80.0% of subjects in the placebo and 
tofacitinib 0.5 mg, 3 mg, 10 mg, and 15 mg BID groups, respectively.  The proportions of 
subjects in clinical remission (total Mayo score of 2 or lower with no individual subscore 
exceeding 1) at Week 8 (secondary endpoint) were 12.2%, 7.4%, 35.5%, 50.0%, and 42.2% 
in the placebo and tofacitinib 0.5 mg, 3 mg, 10 mg, and 15 mg BID treatment groups, 
respectively.  Based on the dose-response model, both 10 mg BID and 15 mg BID doses met 
the protocol-predefined criteria for proof of concept for the primary endpoint. These data 
were further supported by results in other secondary efficacy endpoints including endoscopic 
endpoints and by data in biomarkers and patient-reported outcomes.
Summary of Safety:
The clinical development program for tofacitinib includes healthy volunteers and patients 
with rheumatoid arthritis, psoriasis, ulcerative colitis, Crohn’s disease, dry eye disease, and 
renal transplant recipients enrolled in more than 50 Phase 1, 2, and 3 studies.  In the 
completed Phase 2 study in UC (A3921063), 146 patients with UC received at least one dose 
of tofacitinib (ranging from 0.5 mg BID to 15 mg BID) with 8-week treatment duration.  In 
addition, in the completed Phase 2 study in Crohn’s disease (A3921043), 105 patients with 
Crohn’s disease received at least one dose of tofacitinib (ranging from 1 mg BID to 
15 mg BID) with 4-week treatment duration.  These two studies represent an approximate 
total of 28 patient-years of exposure in IBD (approximately 20 patient-years in UC and 
8 patient-years in Crohn’s disease).
Safety information from the 8-week Phase 2 study in UC (A3921063) is summarized below.
Based on the totality of the clinical data generated thus far, safety findings and potential risks 
that may be associated with the use of tofacitinib include serious and other important 
infections, including tuberculosis and herpes zoster, potential for malignancies including 
lymphoma, and potential for gastrointestinal perforations. Based on nonclinical data, there is 
the potential for tofacitinib to have effects on pregnancy and the fetus.
Laboratory changes observed with the oral use of tofacitinib in humans include decreases in 
neutrophil and lymphocyte counts and hemoglobin levels, increases in serum creatinine, total 
cholesterol, HDL cholesterol, LDL cholesterol, transaminases and creatine kinase. Recovery 
of laboratory changes upon discontinuation of tofacitinib treatment are characteristically 
observed.
In the Phase 2 UC study (A3921063), the overall incidences of AEs were similar between 
tofacitinib-treated and placebo-treated subjects. The most frequently reported AEs were 
colitis ulcerative (worsening of ulcerative colitis) (11.3%) and headache (7.2%).  The 
majority of AEs were mild in severity. Most of the AEs were reported by the investigator as 


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unrelated to study treatment. There were 9 subjects (range 0-4 per treatment group, with 
highest incidence in the placebo group) with permanent discontinuation of study drug due to 
an AE. None of the tofacitinib-treated subjects had a treatment-related discontinuation.  
SAEs were reported in 10 subjects (range 0-4 per treatment group, with highest incidence in 
the placebo group). One subject each in the placebo and tofacitinib 0.5 mg and 3 mg groups
experienced a treatment-related SAE (UC each in placebo and 0.5 mg groups; general 
physical health deterioration in 3 mg group). 
There were no clinically significant changes from baseline at Week 8 in mean neutrophils, 
hemoglobin, hematocrit, serum creatinine, AST and ALT across all dose groups. 
Dose-related increases from baseline at Week 8 in both mean LDL and HDL were observed 
across all dose groups, with the largest increase occurring in the tofacitinib 15 mg group. In 
conclusion, tofacitinib up to the doses of 15 mg BID for study duration of 8 weeks was 
generally well tolerated in subjects with UC, and the overall safety profile was consistent 
with that observed in rheumatoid arthritis and psoriasis.
Complete information for this compound may be found in the Single Reference Safety 
Document (SRSD), which for this study is the Investigator’s Brochure (IB).
1.3. Clinical Pharmacokinetics
The pharmacokinetics of tofacitinib in humans is characterized by rapid absorption and 
elimination, with a time to peak concentration (Tmax) of approximately 0.5 hour and a 
half-life (t1/2) of approximately 3 hours. Steady state pharmacokinetics is predictable from 
single dose data, with no evidence of accumulation.  In general, systemic exposure of 
tofacitinib increases with dose in a dose-proportional manner without regard to duration or 
population. 
The clearance mechanisms for tofacitinib in humans appear to be both non-renal (hepatic 
metabolism) and renal excretion of the parent drug, the former accounting for approximately 
70% of the total clearance. The metabolism of tofacitinib appears to be primarily mediated 
by CYP3A4 with minor contribution from CYP2C19 (based on data from poor metabolizers 
of CYP2C19).
1.4. Rationale of Dose Selection
Study A3921139 is an extension to the Phase 3 placebo-controlled induction studies 
(A3921094 and A3921095) and the maintenance study (A3921096) to provide subjects 
long-term open-label therapy, thus the doses included in this study are supported by the dose 
selection rationale for the maintenance Study A3921096.  
The inclusion of 5 mg BID and 10 mg BID in Study A3921096 is based on the dose-response 
data from the Phase 2 induction Study A3921063, where doses ranging from 0.5 mg BID to 
15 mg BID were evaluated. It is expected that the maintenance effect will be achieved at 
doses not higher than the doses for achieving the induction effect.  Based on the observed
efficacy profile at 10 mg BID after dosing for 8 weeks in Study A3921063, this dose is 
expected to be sufficient to provide maintenance of remission for 12 months.  Although there 
are no data available on persistence of efficacy with tofacitinib treatment beyond 8 weeks in 


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patients with UC, completed randomized-controlled studies in RA ranging from 6 to 
24 weeks in duration showed persistence of efficacy up to 24 weeks.  In addition as a small 
molecule, tofacitinib is not expected to have a loss of response due to immunogenicity once 
efficacy and safety are established in a specific patient. Inclusion of 5 mg BID in Study
A3921096 allows evaluation of a maintenance dose lower than 10 mg BID.  Importantly, 
extensive safety data from the RA program support the choices of 10 mg BID and 5 mg BID 
for this study.
The inclusion of both 5 mg and 10 mg BID in this study will provide long term safety data 
should 5 mg and/or 10 mg BID prove to be effective maintenance doses in Study A3921096.
2. STUDY OBJECTIVES AND ENDPOINTS
2.1. Objectives
Primary objective:

To assess the safety and tolerability of long-term tofacitinib therapy in subjects with 
UC.
Secondary objectives:

To evaluate the efficacy of long-term tofacitinib therapy in subjects with UC.

To evaluate the effect of long-term tofacitinib therapy on quality-of-life in subjects 
with UC.
2.2. Endpoints
Primary efficacy endpoint:

As this is an open-label extension study, there will be no primary efficacy endpoint.
Secondary efficacy endpoints:

The proportion of subjects in remission at Month 2, Month 12, Month 24 and 
Month 36.  Remission in this study is defined as a Mayo score 2 with no individual 
subscore >1, and rectal bleeding subscore of 0.

The proportion of subjects in clinical remission at Month 2, Month 12, Month 24 and 
Month 36.  Clinical remission in this study is defined as a Mayo score 2 with no 
individual subscore >1. 

The proportion of subjects in partial Mayo score (PMS) remission over time.  PMS 
remission in this study is defined as a partial Mayo score 2 with no individual 
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•
The proportion of subjects who achieve mucosal healing at Month 2, Month 12, 
Month 24 and Month 36.  Mucosal healing is defined as a Mayo endoscopic subscore 
of 0 or 1.
•
The proportion of subjects with total score in Inflammatory Bowel Disease 
Questionnaire (IBDQ) ≥170 over time.
Safety endpoints:
•
Incidence and severity of adverse events (AEs).
•
Incidence of serious infections.
•
Incidence and severity of clinical laboratory abnormalities, and change from baseline 
in clinical laboratory values.
•
Incidence of vital sign abnormalities and change from baseline in vital signs.
•
Incidence of clinically significant changes in physical examinations from baseline.
•
Incidence of electrocardiogram (ECG) abnormalities during treatment.
•
Summary of adjudicated safety events (eg, cardiovascular, malignancy, opportunistic 
infections).
•
Proportion of subjects with addition of lipid lowering agents.
  
 
 
 
 
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3. STUDY DESIGN
This is a Phase 3, multi-center, open-label study in subjects who have completed or 
demonstrated treatment failure in the maintenance study A3921096, or who were 
non-responders after completing induction studies A3921094 or A3921095.  Approximately 
900 subjects are expected to become eligible for the study.  This study will continue up to
approximately July 2020.  Individual subject duration of participation will vary depending on 
when the subject was enrolled into the study and the end date of approximately July 2020.  
Therefore, the duration of participation for an individual subject may range from 
approximately 4 years to more than 7 years.  If the study continues beyond Month 72 for an 
individual subject, the investigator should continue to follow the same visit schedule and 
study procedures outlined during the study visits of year 4.
Subjects who completed Study A3921096 or had early withdrawal due to treatment failure as 
defined in the A3921096 protocol may be eligible to enroll in this study, A3921139.  In 
addition, subjects who complete induction Study A3921094 or A3921095 and are classified 
as non-responders may be eligible to enroll in this study.  The eligibility of a subject for this
study will be assessed based on study data collected at Week 8/9 of Study A3921094 or 
A3921095 (for non-responders) or the Week 52/53 visit (for completers) or early termination 
visit (early withdrawals due to treatment failure) of Study A3921096.  The study data 
collected at the Week 8/9 visit for Study A3921094 or A3921095 (for non-responders) or the 
Week 52/53 visit or early termination visit of Study A3921096 will be recorded as the 
baseline data for Study A3921139.
Eligible subjects will be assigned to either tofacitinib 5 mg BID or 10 mg BID depending on 
whether the subject is in remission at baseline of Study A3921139.  Remission is defined by 
a total Mayo score ≤2 with no individual subscore >1, and rectal bleeding subscore of 0.  
Eligible subjects who are in remission at Week 52 of Study A3921096 will be assigned to 
receive tofacitinib 5 mg BID.  For treatment assignment at baseline, the central read
assessment of the Mayo endoscopic subscore will be used to determine if a subject is in 
remission.  Subjects who complete Study A3921096 but do not meet the remission definition 
C
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or who are early withdrawals due to treatment failure in Study A3921096 are eligible to
receive tofacitinib 10 mg BID.  Treatment failure is defined by an increase in Mayo score of 
at least 3 points from baseline value of the maintenance study (A3921096), accompanied by 
an increase in rectal bleeding subscore by at least 1 point, and an increase of endoscopic 
subscore of at least 1 point (yielding an absolute endoscopic subscore of 2) after a minimum 
of 8 weeks of treatment in the maintenance study.  In the scenario where the endoscopic 
subscore is a ‘3’, and the maintenance baseline endoscopic subscore is already a ‘3’ 
(maximum value), then an increase by at least 1 point will not be needed in order to meet 
treatment failure.  However, all other components of the treatment failure criteria will still 
need to be met.  Subjects who complete induction studies A3921094 or A3921095 and are 
classified as non-responders are also eligible to receive tofacitinib 10 mg BID.  
Tofacitinib dose can be adjusted from 5 mg BID to 10 mg BID for efficacy and from 
10 mg BID to 5 mg BID after meeting specific laboratory abnormalities or other protocol 
defined criteria regarding efficacy (see Section 5.8 for dose adjustment guidelines).  Dose 
adjustments can only occur after a subject has received at least 8 weeks of treatment in Study 
A3921139.
Subjects who enroll into this study who are on tofacitinib 10 mg BID for at least 
2 consecutive years, and who are in stable remission on tofacitinib 10 mg BID for at least 
6 months may have the opportunity to enter Study A3921288 (A Phase 3b/4, Multi-Center, 
Double-Blind, Randomized, Parallel Group Study of Tofacitinib in Subjects with UC in 
Stable Remission) if they meet the eligibility criteria.  These subjects must:

Have received tofacitinib 10 mg BID for a minimum of 2 consecutive years in
Study A3921139 (and not have their tofacitinib dose reduced to 5 mg BID due to 
safety or efficacy.

Be in stable remission on tofacitinib 10 mg BID for the 6 month period in 
Study A3921139 up to and including the baseline visit of Study A3921288, defined as 
meeting all of the following criteria:

A partial Mayo score 2, with no individual subscore >1 and a rectal bleeding 
subscore of 0 at each study visit during the 6 month period in Study A3921139 
prior to and at baseline of Study A3921288; AND

At least one assessment of remission based on Mayo score.

Not be receiving any corticosteroids to treat their UC for at least 4 weeks prior to the 
baseline visit of Study A3921288.

Not have any of the risk factors for pulmonary embolism as described in
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Study A3921288 will evaluate the efficacy and safety of tofacitinib in subjects in stable 
remission on 10 mg BID who decrease the dose to and remain on 5 mg BID compared to 
subjects who remain on 10 mg BID.  
Subjects from the induction studies A3921094 or A3921095 (ie, non-responders) who fail to 
demonstrate clinical response at Month 2 of this study will be withdrawn from the study.  
Clinical response is defined by a decrease from the induction study baseline (A3921094 or 
A3921095) Mayo score of at least 3 points and at least 30%, with an accompanying decrease 
in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 
0 or 1.  The endoscopic subscore based on central reading will be used to assess clinical 
response.
All subjects who withdraw early or who complete this open-label study, with the exception 
of those subjects entering Study A3921288, will have a 4-week safety follow-up evaluation 
after the last dose of study medication.
Subjects will be required to remain on stable doses of their concomitant medications for UC
during the study period, with the exception of oral 5-ASA or sulfasalazine and oral 
corticosteroids described in Section 5.5.  Subjects who enter this study on corticosteroids 
(eg, subjects who withdraw from Study A3921096 due to treatment failure or non-responders 
at the end of Study A3921094 or A3921095) will need to continue the steroid tapering 
regimen described in Study A3921096 (see Section 5.5).  If a subject requires rescue therapy 
(see Section 5.7) or undergoes surgery for UC, the subject should be withdrawn from the 
study and appropriate agents should be given at the discretion of the investigator.  If a subject 
discontinues the use of background oral 5-ASA or sulfasalazine and/or has the therapy 
re-initiated during the study, this will not constitute rescue therapy, and the subject will be 
permitted to remain in the study.


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Figure 1.
Study Design
Amendment 11
On 17 May 2019, the European Medicines Agency’s Pharmacovigilance Risk Assessment 
Committee (PRAC) issued interim recommendations on the restrictions for prescriptions of 
tofacitinib.  These interim recommendations on the restrictions for prescriptions of tofacitinib 
state that patients who are at high risk of blood clots in the lungs must not be started on 
tofacitinib 10 mg BID, and that such patients currently taking tofacitinib 10 mg BID for any 
condition must be switched to alternative treatments.  Updated guidance from PRAC will be 
provided to patients and their healthcare professionals in the European Union (EU) once 
PRAC has completed its review of all available data. 
In light of the PRAC interim recommendations in the EU, Study A3921139 will be modified 
globally through protocol Amendment 11, which will involve the following updates:
1. The study investigator or designee will need to review each subject’s medical history 
and study records, including their concomitant medications, to determine whether 
he/she is at high risk for developing pulmonary embolism.  If he/she has any of the 
risk factors listed below and is receiving tofacitinib 10 mg BID, the subject’s 
tofacitinib dose should be reduced to 5 mg BID (see Section 5.8).  
A subject may be at high risk for pulmonary embolism if he/she:

has heart failure;

has inherited coagulation disorders;
Not In Remission
In Remission
Month  0
1            2             4             6          9         12      ~July 2020
Open Label Treatment Period
End of Treatment
4-Week Follow-up
Month 0 = Wk 53 / ET visit 
from Study A3921096, OR 
Wk 9 from Study A3921094 or 
A3921095
Enrollment

Study visits will occur every 3 months after the first year until approximately July 2020.

All subjects will have a 4-week follow-up evaluation after their last dose of study medication.
Tofacitinib 10 mg BID
Tofacitinib 5 mg BID
Follow Up


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
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.
If a subject is identified as meeting any of the above criteria, they will be required to
adjust their dose from 10 mg BID (administered as 2 x 5 mg tablets in the AM and 
2 x 5 mg tablets in the PM) down to 5 mg BID (administered as 1 x 5 mg tablet in the 
AM and 1 x 5 mg tablet in the PM).
2. If a subject is taking tofacitinib 10 mg BID and does not have any of the risk factors 
listed above, he/she will remain on tofacitinib 10 mg BID. 
3. If a subject is taking tofacitinib 5 mg BID, he/she will remain on tofacitinib 
5 mg BID.  However, if a subject has any of the risk factors listed above, he/she will 
not be permitted to increase their dose of tofacitinib to 10 mg BID if he/she 
experiences a flare of their UC disease (see Section 5.8).
4. The study investigator or designee will be required to ask each subject at each study 
visit if he/she has any newly-developed risk factors for pulmonary embolism, and if 
one is identified, the subject will not be permitted to receive tofacitinib 10 mg BID
(see Section 7.3.12).  At the time of Amendment 11, all subjects have reached the 
Month 36 study visit, therefore subjects will undergo the risk factor check at visits 
beyond Month 36 as applicable to their individual participation.
4. SUBJECT SELECTION
This study can fulfill its objectives only if appropriate subjects are enrolled.  The following 
eligibility criteria are designed to select subjects for whom protocol treatment is considered 
appropriate.  All relevant medical and non-medical conditions should be taken into 
consideration when deciding whether this protocol is suitable for a particular subject.
4.1. Inclusion Criteria
Subject eligibility should be reviewed and documented by an appropriately qualified member 
of the investigator’s study team before subjects are included in the study.
Subjects must meet either inclusion criterion number 1 or 2, and all of the other following 
inclusion criteria to be eligible for enrollment into the study:
1. Subjects previously participated in Study A3921096 who either:

completed 52-week maintenance treatment in Study A3921096, or


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•
were early withdrawals from Study A3921096 and met treatment failure criteria 
defined by an increase in Mayo score of at least 3 points from baseline value of 
the maintenance study (A3921096), accompanied by an increase in rectal 
bleeding subscore by at least 1 point, and an increase of endoscopic subscore of at 
least 1 point (yielding an absolute endoscopic subscore of ≥2), after a minimum of 
8 weeks of treatment in the maintenance study.  In the scenario where the 
endoscopic subscore is a ‘3’, and the maintenance baseline endoscopic subscore is 
already a ‘3’ (maximum value), then an increase by at least 1 point will not be 
needed in order to meet treatment failure.  However, all other components of the 
treatment failure criteria will still need to be met.  Note, endoscopic subscores 
based on central reading will be used to assess treatment failure.
2. Subjects who previously participated in the induction Study A3921094 or A3921095 
who:
•
did not demonstrate clinical response after completing 8 weeks of treatment.  
Clinical response is defined by a decrease from baseline in Mayo score of at least 
3 points and at least 30%, with an accompanying decrease in the rectal bleeding 
subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1, and
•
have an endoscopic subscore at Week 8 that is either the same or higher (worse) 
than the endoscopic subscore at Week 0 of Study A3921094 or A3921095.  Note, 
endoscopic subscores based on central reading will be used to determine 
eligibility.
3. Female subjects of childbearing potential must agree to use a highly effective method of 
contraception throughout the study and for at least 4 weeks after the last dose of assigned 
treatment.  Subjects in Canada who are women of childbearing potential and sexually 
active must use two contraceptive methods at the same time: one highly effective 
contraceptive method and one additional effective contraceptive method 
 
.  
4. Women of childbearing potential must have a negative pregnancy test prior to study 
enrollment.
5. Subjects who are willing and able to comply with scheduled visits, treatment plan, 
laboratory tests, bowel movement diary calls, and other study procedures.
6. Evidence of a personally signed and dated informed consent document indicating that the 
subject (or a legal representative) has been informed of all pertinent aspects of the study.
4.2. Exclusion Criteria
Subjects presenting with any of the following will not be included in the study:
1. Subjects who had a major protocol violation in Study A3921094, A3921095 or 
A3921096, as determined by the Sponsor.
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2. Presence of indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis,
or clinical findings suggestive of Crohn’s disease.
3. Subjects who have had surgery for UC or in the opinion of the investigator, are likely to 
require surgery for UC during the study period.
4. Subjects who are expected to receive any prohibited medications, including medications 
that are either moderate to potent CYP3A inducers or inhibitors, during the study period 
as specified in the protocol (see Appendix 2).
5. Subjects who are expected to receive live or attenuated virus vaccination during study 
period and for 6 weeks after last dose of study medication.
6. Women who are pregnant or breastfeeding, or planning to become pregnant during the 
study period.
7. Baseline 12-lead ECG that demonstrates clinically relevant abnormalities which may 
affect subject safety or interpretation of study results (see Appendix 4).
8. Subjects with evidence of colonic malignancy or any dysplasia (eg, “flat dysplasia”; 
polyp) identified on endoscopic exam during Study A3921096.  Subjects with completely 
resected adenomatous polyp(s) outside of (proximal to) the extent of colitis may be 
eligible upon consultation with the sponsor.  Note, pathology report must be reviewed 
prior to subject enrolment.
9. Subjects who, in the opinion of the investigator or Pfizer, will be uncooperative or unable 
to comply with study procedures.
10. Any other severe acute or chronic medical or psychiatric condition or laboratory 
abnormality that may increase the risk associated with study participation or 
investigational product administration or may interfere with the interpretation of study 
results and, in the judgment of the investigator, would make the subject inappropriate for 
entry into this study.
11. Subjects who are investigational site staff members or relatives of those site staff 
members or subjects who are Pfizer employees directly involved in the conduct of the 
trial.
12. Subjects who are or interested in participating in other investigational studies during 
study participation.
4.3. Randomization Criteria
Subjects will not be randomized.  Eligible subjects will be assigned to receive either 
tofacitinib 5 mg BID or 10 mg BID depending on whether the subject is in remission at 
baseline of Study A3921139.  Subjects who are in remission at baseline of Study A3921139 
will be assigned to receive tofacitinib 5 mg BID.  All other subjects will be assigned to 
receive tofacitinib 10 mg BID.  Subjects will be assigned a subject number in the order of 


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their acceptance into the study.  This identifying number will be retained throughout the 
study.
4.4. Life Style Guidelines
4.4.1. Tobacco
Smoking can have an influence on the severity of ulcerative colitis symptoms. For that 
reason, subjects should keep their smoking habits constant throughout the study.  Use of 
nicotine patch should be recorded as a concomitant medication.
4.4.2. Activity
Subjects are encouraged to avoid changing their accustomed exercise levels throughout the 
study.
4.4.3. Diet and Dietary Supplements
Subjects are encouraged to keep their diet habits constant throughout the study. It is 
recommended that subjects avoid consumption of grapefruit juice exceeding 8 ounces 
(~240 mL) total in a day while in the study.  
For the purposes of this protocol, dietary supplements, such as vitamins, minerals, purified 
food substances, and herbals with pharmaceutical properties are considered as concomitant 
medications.  Dietary supplements and herbs are allowed in the study, provided they are 
taken at stable doses prior to the baseline visit if they are started prior to study entry, and not 
associated with known effects on CYP3A that may impact on metabolism of the study 
medication.  Starting dietary supplements or herbs during the study as a new medication is 
permissible as long as they are not listed on the prohibited medication list (see Appendix 2).
4.4.4. Vaccination
Vaccination with live components is prohibited during the study and for 6 weeks after last 
dose of study medication.  Similarly, current routine household contact with individuals who 
have been vaccinated with live vaccine components should be avoided during treatment and 
for 6 weeks following completion of study treatment.  Following vaccination with live 
component vaccines, the virus may be shed in bodily fluids, including stool, and there is a 
potential risk that the virus may be transmitted.
General guidelines suggest that exposure to individuals who have been vaccinated should be 
avoided for the following time periods:
a.
FluMist(intranasal influenza vaccine) for 1 week following vaccination.
b. Attenuated rotavirus vaccine for 10 days following vaccination.
c.
Varicella for 4 weeks following vaccination.
d. Attenuated typhoid fever vaccine for 4 weeks following vaccination.


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e.
Oral polio vaccine for 6 weeks following vaccination.
4.4.5. Contraception
Based on preclinical data, tofacitinib has a potential risk of teratogenicity and early fetal loss. 
Due to this potential risk, women of childbearing potential should not be administered 
tofacitinib until pregnancy is excluded and should use a highly effective method of 
contraception (failure rate <1% when used consistently and correctly) during therapy with 
tofacitinib.
For the purposes of this protocol female subjects must be of non-childbearing potential or 
using adequate contraception, as described below.
4.4.5.1. Females of Non-Childbearing Potential
Female subjects of non-childbearing potential must meet at least one of the following 
criteria:

Postmenopausal females are defined as females over the age of 45 years, who have 
been amenorrheic for at least 12 months with no alternative pathological or 
physiological cause.  Postmenopausal status may be carried forward from Study 
A3921094, A3921095 or A3921096.  If a female has not been confirmed to be 
postmenopausal during Study A3921094, A3921095 or A3921096, then FSH testing 
will be required at baseline in this study.

Females who had a physician-documented hysterectomy and/or bilateral 
oophorectomy.

Females who have medically-confirmed ovarian failure.
All other female subjects will be considered to be of childbearing potential.
4.4.5.2. Females of Childbearing Potential
All female subjects who, in the opinion of the investigator, are biologically capable of having 
children and are sexually active, must agree to use a highly effective method of contraception 
consistently and correctly for the duration of the active treatment period and through the 
4-week follow-up procedures.  The investigator, in consultation with the subject, will select 
the most appropriate method of contraception for the individual subject from the permitted 
list of contraception methods, and instruct the subject in its consistent and correct use.  The 
investigator, at each study visit, will confirm and document consistent and correct use.  In 
addition, the investigator will instruct the subject to call immediately if the selected birth 
control method is discontinued or if pregnancy is known or suspected.  
Highly effective methods of contraception are those that, alone or in combination, result in a 
failure rate of less than 1% per year when used consistently and correctly (ie, perfect use) and 
include:
1. Established use of oral, injected or implanted hormonal methods of contraception.


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2. Correctly placed intrauterine device (IUD) or intrauterine system (IUS).
3. Male condom or female condom used WITH a spermicide (ie, foam, gel, film, cream, 
suppository).
4. Male sterilization with appropriately confirmed absence of sperm in the 
post-vasectomy ejaculate.
5. Bilateral tubal ligation or bilateral salpingectomy.
6. Absolute sexual abstinence, without a second method, may be considered an 
acceptable method at the discretion of the investigator.
 
 
4.4.5.3. Pregnancy Testing
Female subjects of childbearing potential will be tested for urine β-hCG at baseline and at 
each study visit (or more frequently if required by local regulations, if a menstrual cycle is
missed, or if potential pregnancy is otherwise suspected). Urine β-hCG testing will be 
performed at the study site using test kits supplied by the central laboratory using 
methodology with a testing sensitivity at least 25 mIU/mL.  If at any point there is a case of a 
positive urine β-hCG test, the subject will have study drug interrupted and a serum sample 
will be submitted to the central laboratory for β-hCG testing.  If the serum test confirms 
positive, the subject will be withdrawn from the study and all the necessary follow up will be 
conducted as per Section 8.9.  If the serum test is negative, the subject may resume study 
drug.
4.4.5.4. Reproductive Status of Male Subjects
No tofacitinib effects on male fertility or offspring of dosed males have been observed in any 
preclinical studies conducted to date.  Therefore, no specific contraceptive measures are 
required in male subjects during study participation.
4.4.5.5. Surgery
During the course of this study, no elective surgery should be scheduled without first 
consulting with the Pfizer medical monitor.  Investigators should contact the Pfizer medical 
monitor regarding subjects who undergo non-elective surgery to discuss their suitability to 
remain in the study.
4.5. Sponsor’s Qualified Medical Personnel
The contact information for the sponsor's appropriately qualified medical personnel for the 
study is documented in the study contact list located in the investigator site file.
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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 numbers, 
contact information for the investigational site, and contact details for a contact center in the 
event that the investigational site staff cannot be reached to provide advice on a medical 
question or problem originating from another healthcare professional not involved in the 
subject’s participation in the study.  The contact number can also be used by investigational 
staff if they are seeking advice on medical questions or problems; however, it should be used 
only in the event that the established communication pathways between the investigational 
site and the study team are not available. It is therefore intended to augment, but not replace, 
the established communication pathways between the investigational site and the study team 
for advice on medical questions or problems that may arise during the study.  The contact 
number is not intended for use by the subject directly, and if a subject calls that number, he 
or she will be directed back to the investigational site.
5. STUDY TREATMENTS
Subjects will be assigned to one of two dose groups depending on their remission status at 
baseline of Study A3921139:

Tofacitinib 5 mg BID (subjects in remission).

Tofacitinib 10 mg BID (all other subjects).
Remission is defined by a total Mayo score 2 with no individual subscore >1, and rectal 
bleeding subscore of 0.  Central read assessment of the Mayo endoscopic subscore will be 
used to determine if a subject is in remission at baseline.
5.1. Allocation to Treatment
Assignment of subject identification number, study medication, and site drug inventory 
control will be managed by a tele-randomization tool provided by the sponsor.  A manual 
containing complete instructions for web or telephone access and use will be provided to 
each site prior to study start.
At the baseline visit, provided all inclusion/exclusion criteria have been met, the subject will 
be assigned to trial medication via the tele-randomization system.  The investigative site will 
contact the tele-randomization system (online or via a telephone call).  The site will enroll the 
subject into the tele-randomization system by indicating minimal information sufficient to 
distinguish one subject from another (eg, date of birth and initials).
Eligible subjects will be assigned to one of two dose groups by the investigative site,
tofacitinib 5 mg BID or tofacitinib 10 mg BID, depending on their remission status at 
baseline in Study A3921139.
During a successful call, the tele-randomization system will give the investigative site a code 
which corresponds to study medication that has been previously shipped to the site and is in 
the site’s inventory ready to be dispensed. This code corresponds to study medication of the 
dose group to which the subject has just been assigned.


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As this is an open-label study, the investigator’s knowledge of the treatment should not 
influence the decision to enroll a particular subject or affect the order in which subjects are 
enrolled.
5.2. Breaking the Blind
This is an open-label study.  Assignment to tofacitinib will be open to the investigators, 
subjects and the Pfizer study team.
5.3. Drug Supplies
5.3.1. Formulation and Packaging
Tofacitinib will be provided as 5 mg tablets by the sponsor for oral administration.  Tablets 
will be supplied in bottles.  Sufficient study medication will be dispensed at baseline (Visit 1) 
and at each subsequent dispensing visit per the Schedule Of Activities to complete dosing 
until the next scheduled dispensing visit.  The number of bottles dispensed will depend on 
whether the subject is taking 5 mg BID (1 bottle) or 10 mg BID (2 bottles), and the duration 
between the next dispensing study visit.
5.3.2. Preparation and Dispensing
Subjects will be dispensed tofacitinib 5 mg tablets in bottles as allocated by the 
tele-randomization system.  At each dispensing visit, sufficient study medication of 
tofacitinib will be dispensed to complete dosing until the next scheduled visit.  The amount 
of study medication dispensed must be recorded.  At each study visit the subject must return 
all tofacitinib containers and any unused medication will be recorded and documented to 
account for all dispensed study medication. 
5.3.3. Administration
Tofacitinib will be self-administered.  If a subject is assigned to receive tofacitinib 5 mg BID, 
they will be instructed to take 1 tablet in the morning and 1 tablet in the evening, 
approximately 12 hours apart.  If a subject is assigned to receive tofacitinib 10 mg BID, they 
will be instructed to take 2 tablets in the morning and 2 tablets in the evening, approximately 
12 hours apart.  If a tofacitinib dose is missed and the interval to the next scheduled dose is 
less than 6 hours, the missed dose of tofacitinib should not be administered.  Tofacitinib may 
be taken with or without food.
Table 1
Study Drug Administration
Treatment Assignment
AM Dosing
PM Dosing
5 mg BID
1 tablet
1 tablet
10 mg BID
2 tablets
2 tablets
Medication errors may result, in this study, from the administration or consumption of the 
wrong product, by the wrong subject, at the wrong time, or at the wrong dosage strength.
Such medication errors occurring to a study participant are to be captured on the medication 
error CRF, which is a specific version of the adverse event (AE) page, and on the SAE form 


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when appropriate.  In the event of medication dosing error, the sponsor should be notified 
immediately.
Medication errors are reportable irrespective of the presence of an associated AE/SAE, 
including:

Medication errors involving subject exposure to the investigational product.

Potential medication errors or uses outside of what is foreseen in the protocol that do 
or do not involve the participating subject.
Whether or not the medication error is accompanied by an AE, as determined by the 
investigator, the medication error is captured on the medication error version of the AE page
and, if applicable, any associated AE(s) are captured on an AE CRF page.
5.3.4. Compliance
Investigational product compliance will be assessed by the site at each study visit starting at 
the visit after the baseline visit (Visit 2) up to the end of treatment.  Non-compliance is 
defined as taking less than 80% or more than 120% of study drug products as directed by the 
dosing instructions. Subjects are to bring the study drug bottle(s) with any remaining study 
drug and any empty bottle(s) to each visit for review.  The investigator has the discretion to 
withdraw any subject from the study for reasons of non-compliance with the dosing regimen. 
Investigators should indicate on the appropriate CRF page noncompliance with study 
treatment and provide an explanation.  Inventory control of all study medications must be 
rigorously maintained throughout the duration of the study until all medication has been 
accounted for and/or returned to the sponsor. Any discrepancies noted between drug 
dispensing records and the drug inventory must be reported to Pfizer.
5.4. Drug Storage and Drug Accountability
Tofacitinib must be stored at room temperature (15-30C or 59-86F) in a locked area with 
restricted access.  Storage conditions stated in the SRSD, the IB, may be superseded by the 
label storage.
Investigators and site staff are reminded to check temperatures daily for business days and 
ensure that thermometers are working correctly as required for proper storage of 
investigational products.  These include thermometers for both the room storage and 
refrigerator storage.  Any temperature excursions should be reported immediately.  
The investigator or appropriate delegate at the site (eg, pharmacist), will ensure that all study 
drug is stored in a secured area, under recommended storage condition, and in accordance 
with regulatory requirements.


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The investigator must maintain adequate records documenting the receipt, use, loss, or other 
disposition of the investigational product.  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 counting of unused medications returned by the subject at each visit from 
Visit 2 to the end of treatment.  All bottles used to distribute the drug supplies must be 
returned to the investigator by the subject and the investigator will return the bottles to Pfizer.
At the end of trial, Pfizer will provide instructions as to the disposition of any unused 
investigational product.  If Pfizer authorizes destruction at the trial site, the investigator must 
ensure that the materials are destroyed in compliance with applicable environmental 
regulations, institutional policy, and any special instructions provided by Pfizer.  Destruction 
must be adequately documented.
5.5. Concomitant Medications
All subjects will be questioned about concomitant medication use at each study visit.  In 
addition the following concomitant medications that the subject had been taking from the 
study they enrolled from (ie, Study A3921096, Study A3921094 or Study A3921095) and 
will continue to take in this study will be recorded: 
Table 2.
Concomitant Medications
Treatment Type
Information Recorded
Recording Period
Ulcerative colitis (UC)* 
Daily dose, unit, frequency, route, 
start and stop dates
Treatment period
Follow-up period
Oral corticosteroids
Total daily dose, reason for dose 
change, start and stop dates
Treatment period
Follow-up period
Lipid lowering agents
Daily dose, unit, frequency, route, 
start and stop dates
Treatment period
Follow-up period
Anti-hypertension agents
Start and stop dates 
Treatment period
Follow-up period
Anti-diabetic agents
Start and stop dates
Treatment period
Follow-up period
All other treatments+
Indication, start and stop dates
Treatment period
Follow-up period
*
Concomitant treatment for UC must remain at a stable dose (no increase or decrease) during the study 
treatment period, with the exception of oral 5-ASA or sulfasalazine and oral corticosteroids as described 
below.
+
Includes nonprescription drugs, vitamins, and dietary supplements.
The following therapies for the treatment of UC are allowed providing their doses are not
changed (reduced or increased), with the exception of oral 5-ASA or sulfasalazine and oral 
corticosteroids (see below) during the study treatment period: 

Oral 5-ASA or sulfasalazine dose modifications during the study are permitted.

Chronic treatment for ulcerative colitis with antibiotics (eg, metronidazole, rifaximin)
if continued from the preceding study.


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Oral Corticosteroids

Oral corticosteroids are allowed for subjects entering Study A3921139 on oral 
corticosteroids (maximum dose of 25 mg/day of oral prednisone or equivalent) and 
tapering must commence starting the first week of the study.  

The daily dose of oral prednisone or equivalent should be decreased at a rate of 5 mg 
per week until the dose reaches 20 mg/day, then reduce by 2.5 mg to 5.0 mg weekly 
until the dose reaches 0 mg.

For example only, if a subject is receiving oral prednisone 25 mg/day at baseline, the 
subject’s corticosteroid tapering regimen could be as follows:

Baseline/Day 1:
25 mg/day

Week 1 (2 days):20 mg/day

Week 2 (2 days):15 mg/day

Week 3 (2 days):10 mg/day

Week 4 (2 days):7.5 mg/day

Week 5 (2 days):5.0 mg/day

Week 6 (2 days):2.5 mg/day

Week 7 (2 days):0 mg/day

Oral budesonide: the daily dose should be decreased at a rate of 3 mg every 3 weeks 
until discontinuation.

For example only, if a subject is receiving oral budesonide 9 mg/day at baseline, 
the subject’s steroid tapering regimen could be as follows:

Week 1 – 3 (Day 1 – Day 21):
6 mg/day

Week 4 – 6 (Day 22 – Day 42):
3 mg/day

Week 7 and beyond (Day 43):
0 mg/day

If a subject experiences worsening of UC symptoms during the corticosteroid taper or 
symptoms related to chronic corticosteroid therapy that in the opinion of the 
investigator are attributable to the corticosteroid taper, then the investigator may 
instruct the subject to revert back to the preceding dose in the taper schedule (ie, “step
up”).  The signs or symptoms leading to this change (eg, increased stool frequency, 
increased rectal bleeding) must be recorded on the CRF. Study subjects with signs or 


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symptoms attributed to corticosteroid taper are permitted to step up their 
corticosteroid dosage one time during participation in A3921139 and then resume 
corticosteroid taper to achieve steroid-free status.  

If a subject cannot tolerate tapering their corticosteroid dose below 10 mg/day, the 
subject is permitted to remain in the study provided their dose does not exceed 
10 mg/day.  However, efforts should be made to taper corticosteroids completely off.

Re-initiation of oral corticosteroid therapy above 10 mg/day of prednisone or 
equivalent for the treatment of UC, after a subject has achieved steroid-free status 
during either Study A3921096 or A3921139, will be considered rescue therapy and 
the subject should be discontinued from the study.

Initiation of oral corticosteroids during Study A3921139 for the treatment of non-UC 
indications (eg, allergic reaction, asthma, etc) may be permitted and the sponsor 
should be notified.
Subjects receiving tofacitinib 10 mg BID and either concomitant combined hormonal 
contraceptives or hormone replacement therapy must have their tofacitinib dose reduced to 
5 mg BID.
5.6. Prohibited Concomitant Medications
The following medications are prohibited throughout the study (see Appendix 2): 

Azathioprine, 6-mercaptopurine and methotrexate;

Cyclosporine, mycophenolate mofetil/mycophenolic acid and tacrolimus;

Interferon;

Anti-TNF alpha therapy (eg, infliximab, adalimumab, golimumab, or certolizumab);

Intravenous and rectally administered corticosteroids;

Rectally administered 5-ASA;

Natalizumab, vedolizumab, or any other anti-adhesion molecule therapy (including 
investigational agents);

Other investigational or marketed immunosuppressants or biologics with 
immunomodulatory properties;

Leukocyte apheresis including selective lymphocyte, monocyte or granulocyte 
apheresis (eg, Cellsorba) or plasma exchange;


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
Moderate to potent CYP3A inducers or inhibitors listed in Appendix 2 due to 
potential for drug interactions or confounding of data interpretation.
5.7. Rescue Therapy
If a subject requires initiation of a new therapy for UC (including re-initiation of oral 
corticosteroid therapy above 10 mg/day of prednisone or equivalent after a subject has 
achieved steroid-free status during either Study A3921096 or A3921139), the subject should 
be withdrawn from the study and appropriate agents should be given at the discretion of the 
investigator.  If a subject discontinues the use of background oral 5-ASA or sulfasalazine 
during the study and/or has the therapy re-initiated, this will not constitute rescue therapy, 
and the subject will be permitted to remain in the study.
5.8. Tofacitinib Dose Adjustment Guidelines
The maximum tofacitinib dose allowed in this study is 10 mg BID.  Tofacitinib dose 
adjustments (increase or decrease) can only occur after a subject has received at least 
8 weeks of treatment in Study A3921139. 
If a subject receiving tofacitinib 5 mg BID experiences loss of response, defined by an
increase in partial Mayo score of at least 2 points from baseline in the maintenance study 
(A3921096) for two consecutive visits (at least 2 weeks apart), accompanied by an increase
in rectal bleeding subscore by at least 1 point from baseline of the maintenance study 
(A3921096), then the subject could be scheduled for endoscopy to determine if the subject is 
experiencing a flare.  Flare is defined by an increase in Mayo score of at least 3 points from 
baseline value of the maintenance study (A3921096), accompanied by an increase in rectal 
bleeding subscore by at least 1 point, and an increase of endoscopic subscore of at least 
1 point (unless the endoscopic subscore was a ‘3’ at baseline and remains a ‘3’), after a 
minimum of 8 weeks of treatment in Study A3921139.  Once the subject is confirmed to 
meet the definition for flare, documented by site read endoscopy, the investigator may 
increase the tofacitinib dose from 5 mg BID to 10 mg BID provided that the subject does not 
have any of the risk factors for pulmonary embolism.
Subjects receiving tofacitinib 5 mg BID who develop one or more of the risk factors for 
pulmonary embolism during the study will not be permitted to increase their dose to 
tofacitinib 10 mg BID.
Clostridium difficile (C. difficile) toxin testing is recommended for subjects in whom
C. difficile infection is suspected (eg, atypical symptoms or features of their usual UC 
disease course, significantly worsening disease activity assessments from the previous visit, 
and/or the presence of risk factors such as recent antibiotic use or a recent history of 
C. difficile infection).  A full course of C. difficile treatment, as defined by local practice,
must be given to subjects with C. difficile infection to permit their continued participation in 
the study.  Subjects with C. difficile infection that meets serious infection criteria must be 
withdrawn from the study. Stool testing and treatment for other enteric pathogens is at the 
discretion of the investigator.


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For subjects receiving tofacitinib 10 mg BID, the tofacitinib dose may be adjusted to 5 mg 
BID if the subject meets any of the following laboratory criteria after they are repeated and 
confirmed within approximately 7 days:

Any single hemoglobin value that drops >2 g/dL (>20 g/L) below baseline of Study 
A3921139.

Absolute neutrophil count <1.2 x 109/L (<1200/mm3).

Absolute lymphocyte count <0.75 x 109/L (<750/mm3).

Platelet count <100 x 109/L (<100,000/mm3).
In addition, for subjects receiving tofacitinib 10 mg BID, the tofacitinib dose may be adjusted 
to 5 mg BID if the subject is in remission (based on Mayo score) or in PMS remission at 
Month 24 or any visit beyond Month 24, after discussion with the sponsor.  PMS remission is 
defined as a partial Mayo score 2 with no individual subscore >1.  If a subject experiences 
loss of response and flare after the dose reduction from 10 mg BID to 5 mg BID, the dose 
may be increased back to 10 mg BID.  In this situation, loss of response is defined as an 
increase in partial Mayo score of at least 2 points from the time when the subject was in 
remission or PMS remission (ie, when the dose was reduced to 5 mg BID) for two 
consecutive visits (at least 2 weeks apart), accompanied by an increase in rectal bleeding
subscore by at least 1 point from when the subject was in remission or PMS remission.  If 
response is lost, endoscopy should be performed to determine if the subject is experiencing a 
flare.  Flare, in this situation, is defined by an increase in Mayo score of at least 3 points from 
the time when the subject was in remission or PMS remission, accompanied by an increase in 
rectal bleeding subscore by at least 1 point, and an increase of endoscopic subscore of at least 
1 point (unless the endoscopic subscore was a ‘3’ and remains a ‘3’).
Lastly, subjects receiving tofacitinib 10 mg BID and who are identified to have one or more 
of the risk factors for pulmonary embolism will need to reduce their tofacitinib dose to 
5 mg BID.
Tofacitinib dose adjustments should be implemented at a scheduled study visit, unplanned 
study visit, or upon verification of laboratory abnormalities upon repeat testing.  Subjects
who meet the laboratory discontinuation criteria described in Appendix 3 will be withdrawn 
from the study.
5.9. Tofacitinib Temporary Withholding
If the investigator deems it necessary to withhold tofacitinib to treat a non-serious infection 
or other medical condition, temporary withholding is permitted for up to 5 days.  If study 
drug interruption exceeding 5 days is required for a medical reason, the investigator must 
contact the sponsor for approval.


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Temporary withholding of tofacitinib, as described above, is permitted once during the 
study without obtaining prior approval from the sponsor.  Any additional request(s) for 
temporary withholding of study drug require documented approval by the sponsor.
6. STUDY PROCEDURES
6.1. Study Period
6.1.1. Baseline (Visit 1)
The baseline visit will occur on the same day as either the Week 9 visit for those subjects 
enrolling from Study A3921094 or A3921095, or the same day as the Week 53 visit or the 
early termination visit for those subjects enrolling from Study A3921096.
Subject’s eligibility into the study will be evaluated at Baseline of Study A3921139 based on 
remission status, AEs, physical examination, ECG (read by study site), and all 
inclusion/exclusion criteria.
For eligible subjects from Study A3921096, all relevant study information recorded on CRFs 
at Week 52/53 or the early termination visit of Study A3921096 will be used as baseline data 
for Study A3921139.  For eligible subjects from Study A3921094 or Study A3921095, all 
relevant study information recorded on CRFs at Week 8/9 of Study A3921094 or A3921095 
will be used as baseline data for Study A3921139.
To prepare for study participation, subjects will be instructed to continue to follow the Life 
Style Guidelines (see Section 4.4) and Concomitant Medications (see Section 5.5) as they did 
in their previous study.
The study investigator or appropriate delegate at the site will discuss with each subject the 
nature of the study, its requirements, risks and its restrictions.  Written informed consent 
must be obtained prior to performing any protocol-specific procedures.
The following procedures will be recorded:

Informed consent.

Complete medical history.  Medical history from either the induction studies 
(A3921094 or A3921095) or the maintenance study (A3921096) will be used as 
baseline for Study A3921139.  Resolved AEs occurring in these studies will be 
captured as part of Baseline Medical History, while ongoing AEs from either Study 
A3921094 or A3921095, or A3921096 will be followed throughout Study A3921139.
The following procedures will be recorded from either Week 8/9 of Study A3921094 or 
A3921095 or from Week 52/53 or early termination visit of Study A3921096:

UC Assessments (review of Bowel Movement Diary Data, calculation of Mayo score 
and partial Mayo score).


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•
Health Outcome (HO) Assessments (IBDQ, 
 
.
•
Complete physical examination (including weight).
•
Vital signs including temperature.
•
12-lead electrocardiography (ECG).  ECG reading from the study sites will be used to 
determine eligibility.  Central reading will be used for data analysis.  See
Section 7.3.11.
•
Extra-intestinal manifestations.
•
Laboratory blood tests including:
•
Serum chemistry.
•
Hematology.
•
Lipid profile (fasting).
•
Urinalysis.
•
Urine β-hCG for women of childbearing potential.
Eligibility Assessment
•
Review study data collected from Week 8/9 of Study A3921094 or A3921095 to 
assess if a subject is eligible for Study A3921139.  Similarly, review study data 
collected from either Week 52/53 or the early termination visit of Study A3921096 to 
assess eligibility into Study A3921139.  This includes an assessment of all 
inclusion/exclusion criteria.
Entry into Study A3921139
•
Dose assignment based on subject’s remission status (see Section 4.3).
•
Subjects will be reminded of instructions for using the phone-based IVRS tool 
(Bowel Movement Diary).
•
Study medication dispensing.
CCI
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Assessments to be used from Study A3921094, A3921095 or A3921096
•
Adverse event monitoring from either Week 8/9 of the induction studies (A3921094 
or A3921095) or Week 52/53 or early termination visit of the maintenance study 
(A3921096) will be used in Study A3921139.  Resolved AEs occurring in these 
studies will be captured as part of Baseline Medical History, while ongoing AEs from 
either Study A3921094 or A3921095, or A3921096 will be followed throughout 
Study A3921139.  
•
Concomitant medication assessment of current and prior medications including a 
complete history of all drugs (including nonprescription drugs, vitamins, and dietary 
supplements), taken during Study A3921094, A3921095 or A3921096.  Prior 
medications recorded in the study the subject enrolls from will be used for Study 
A3921139.
6.1.2. Month 1 (±5 days, Visit 2)
The following procedures will be performed:
•
UC Assessments (review Bowel Movement Diary Data and calculate partial Mayo 
score, see Section 7.1).
•
Targeted physical examination (including weight, general appearance, and 
examinations of eyes, mouth, lungs, heart, abdomen, musculoskeletal, extremities, 
skin and lymph nodes, see Section 7.3.2).
•
Vital signs including temperature (see Section 7.3.1).
•
Laboratory blood tests (see Section 7.3.5):
•
Hematology.
•
Serum chemistry.
•
Urinalysis (see Section 7.3.5).
•
Urine β-hCG for women of childbearing potential (see Section 7.3.7).
•
Study medication accountability.
•
Adverse event monitoring.
•
Concomitant medication assessment.
C
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6.1.3. Months 2, 4 and 6 (±5 days, Visits 3, 4 and 5)
Visit procedures are identical for all visits, except where noted.
Subjects are required to fast (no food or drink except water) for at least 9 hours prior to these 
visits, as required for fasting lipid profile and fasting glucose sample collection.
The following procedures will be performed:
•
HO Assessments [IBDQ (Months 2 and 6 only),
 
.
•
UC Assessments (review Bowel Movement Diary Data at all visits, calculate partial 
Mayo score (Months 4 and 6 only)).
•
Targeted physical examination (including weight).
•
Vital signs including temperature.
•
Laboratory blood tests:
•
Hematology.
•
Serum chemistry.
•
Lipid profile (fasting).
 
•
Urinalysis.
•
Urine β-hCG for women of childbearing potential.
•
Flexible sigmoidoscopy/colonoscopy (if preferred) (Month 2 only).
•
Calculate Mayo score (Month 2 only).
•
Study medication dispensing and accountability.
•
Adverse event monitoring.
•
Concomitant medication assessment.
CCI
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6.1.4. Month 9 (±5 days, Visit 6)
The following procedures will be performed:
•
UC Assessments (review Bowel Movement Diary Data and calculate partial Mayo 
score).
•
Targeted physical examination (including weight).
•
Vital signs including temperature.
•
Laboratory blood tests:
•
Hematology.
•
Serum chemistry.
•
Urinalysis.
•
Urine β-hCG for women of childbearing potential.
•
Study medication dispensing and accountability.
•
Adverse event monitoring.
•
Concomitant medication assessment.
6.1.5. Month 12, Early Termination (ET) or Evaluation Visit for Entry into Study 
A3921288 (±5 days, Visit 7 or ET)
Subjects are required to fast (no food or drink except water) for at least 9 hours prior to this 
visit, as required for fasting lipid profile and fasting glucose sample collection.
Subjects who discontinue treatment early from the study will have an early termination (ET)
visit and all procedures listed at Month 12/ET will be performed on the last day the subject 
takes the study medication or as soon as possible.
Subjects undergoing evaluation for entry into Study A3921288 will have all procedures listed 
at Month 12/ET.  Please refer to Section 3, Study Design for eligibility criteria for 
Study A3921288.  If, after completion of the evaluation visit for entry into Study A3921288, 
a subject does not meet eligibility criteria, they should remain in this study (A3921139).
C
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•
HO Assessments (IBDQ, 
.
•
UC Assessments (review Bowel Movement Diary Data).
•
Complete physical examination (including weight).
•
Assessment of extra-intestinal manifestations (see Section 7.3.3).
•
Vital signs including temperature.
•
12-lead ECG.
•
Laboratory blood tests:
•
Hematology.
•
Serum chemistry.  For subjects being evaluated for entry into 
Study A3921288, the serum chemistry panel will include addition of high 
sensitivity C reactive protein (hs-CRP).  
•
Lipid profile (fasting).
•
Tuberculosis (TB) testing (QFT) for subjects in specific countries (see 
Section 7.3.6).  All subjects with a positive result must have a chest radiograph 
performed. (NOTE: TB testing is not required at the ET visit).
•
Urinalysis.
•
Urine β-hCG for women of childbearing potential.
•
Flexible sigmoidoscopy/colonoscopy (if preferred).  For subjects being evaluated 
for entry into Study A3921288, endoscopy (ie., flexible sigmoidoscopy or 
colonoscopy) will only be performed for subjects who have not had an endoscopy 
performed within the previous 6 months prior to baseline visit of 
Study A3921288.  Endoscopic assessment will only be done by local site read.
•
Calculate Mayo score.
•
Study medication dispensing and accountability.
•
Adverse event monitoring.
•
Concomitant medication assessment.
CCI
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Subjects who enroll from induction studies A3921094 or A3921095 (ie, non-responders) who 
fail to demonstrate clinical response at Month 2 will be withdrawn from the study and will be 
required to have a modified ET visit consisting of only the following procedures:
•
Complete physical examination (including weight).
•
12-lead ECG.
•
Return study medication and perform study medication accountability.
6.1.6. Months 15, 21, 27, and 33 (±7 days, Visits 8, 10, 12, and 14)
Visit procedures are identical for all visits.
The following procedures will be performed:
•
UC Assessments (review Bowel Movement Diary Data and calculate partial Mayo 
score).
•
Targeted physical examination (including weight).
•
Vital signs including temperature.
•
Laboratory blood tests:
•
Hematology.
•
Serum chemistry.
•
Urinalysis.
•
Urine β-hCG for women of childbearing potential.
•
Study medication dispensing and accountability.
•
Adverse event monitoring.
•
Concomitant medication assessment.
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6.1.7. Months 18, 24, 30 and 36 (±7 days, Visits 9, 11, 13, and 15)
Visit procedures are identical for all visits, except where noted.
Subjects are required to fast (no food or drink except water) for at least 9 hours prior to these 
visits, as required for fasting lipid profile and fasting glucose sample collection.
The following procedures will be performed:
•
HO Assessments (IBDQ, 
.
•
UC Assessments (review Bowel Movement Diary Data at all visits, calculate partial 
Mayo score (Months 18 and 30 only)).
•
Targeted physical examination, including weight (Months 18 and 30 only).
•
Complete physical examination, including weight (Months 24 and 36 only).
•
Assessment of extra-intestinal manifestations (Months 24 and 36 only).
•
Vital signs including temperature.
•
12-lead ECG (Months 24 and 36 only).
•
Laboratory blood tests:
•
Hematology.
•
Serum chemistry.
•
Lipid profile (fasting).
•
TB testing (QFT) for subjects in specific countries.  All subjects with a positive 
result must have a chest radiograph performed (Months 24 and 36 only).
•
Urinalysis.
•
Urine β-hCG for women of childbearing potential.
•
Flexible sigmoidoscopy/colonoscopy (if preferred) (Months 24 and 36 only).
•
Calculate Mayo score (Months 24 and 36 only).
•
Study medication dispensing and accountability.
•
Adverse event monitoring.
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•
Concomitant medication assessment.
6.1.8. Months 39, 42, 45, 51, 54, 57, 63, 66, and 69 (±7 days, Visits 16, 17, 18, 20, 21, 22, 
24, 25 and 26)
Visit procedures are identical for all visits, except where noted.
Subjects are required to fast (no food or drink except water) for at least 9 hours prior to the 
visits indicated below, as required for fasting lipid profile and fasting glucose sample 
collection.
The following procedures will be performed:
•
UC Assessments (review Bowel Movement Diary Data and calculate partial Mayo 
score).
•
Vital signs including temperature and weight.
•
Laboratory blood tests:
•
Hematology.
•
Serum chemistry.
•
Lipid profile (fasting) (Months 42, 54, and 66 only).
•
Urine β-hCG for women of childbearing potential.
•
Study medication dispensing and accountability.
•
Adverse event monitoring.
•
Concomitant medication assessment.
•
Risk factor check for pulmonary embolism (see Section 7.3.12).
6.1.9. Months 48, 60, and 72 (±7 days, Visits 19, 23 and 27)
Visit procedures are identical for all visits.
Subjects are required to fast (no food or drink except water) for at least 9 hours prior to these 
visits, as required for fasting lipid profile and fasting glucose sample collection.
The following procedures will be performed:
•
HO Assessments (IBDQ, 
.
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•
UC Assessments (review Bowel Movement Diary Data and calculate partial Mayo 
score).
•
Complete physical examination, including weight.
•
Assessment of extra-intestinal manifestations.
•
Vital signs including temperature.
•
Laboratory blood tests:
•
Hematology.
•
Serum chemistry.
•
Lipid profile (fasting).
•
TB testing (QFT) for subjects in specific countries.  All subjects with a positive 
result must have a chest radiograph performed.
•
Urine β-hCG for women of childbearing potential.
•
Study medication dispensing and accountability (study medication will be dispensed 
at Month 72 for those subjects who participate beyond Month 72).
•
Adverse event monitoring.
•
Concomitant medication assessment.
•
Risk factor check for pulmonary embolism (see Section 7.3.12).
6.2. Follow-up Visit (±7 days, Visit 28)
This follow-up visit is to occur 4 weeks (±7 days) after the last dose of study medication is 
administered. 
The following procedures will be performed:
•
Vital signs including temperature and weight.
•
Laboratory blood tests:
•
Hematology.
•
Serum chemistry.
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
Urine -hCG for women of childbearing potential.

Adverse event monitoring.

Concomitant medication assessment.
6.3. Subject Withdrawal
Should a subject withdraw from active treatment, the subject should complete the procedures 
listed at the Month 12/ET Visit.  After completing the procedures for the early withdrawal 
visit, the subject should return for a safety evaluation to occur approximately 4 weeks after 
discontinuing study medication as per the follow-up visit.
Subjects will be withdrawn from the study if any of the following occurs during the study 
treatment period:

If a subject who enrolled from the induction studies A3921094 or A3921095 
(ie, non-responders) fails to demonstrate clinical response at Month 2.  Clinical 
response is defined by a decrease from the induction study baseline (A3921094 or 
A3921095) Mayo score of at least 3 points and at least 30%, with an accompanying 
decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal 
bleeding subscore of 0 or 1.  The endoscopic subscore based on central reading will 
be used to assess clinical response.

If rescue therapy is initiated for UC with the exception of oral 5-ASA or 
sulfasalazine.  Rescue therapy includes re-initiation of oral corticosteroid therapy 
above 10 mg/day of prednisone or equivalent after a subject has achieved steroid-free 
status during either Study A3921096 or A3921139.

If a subject undergoes surgery for UC.

If a subject remains on oral corticosteroids exceeding 15 mg/day of prednisone or 
equivalent after Month 3.
A subject may be withdrawn from the study for any of the safety concerns as listed in 
Appendix 3.
Subjects who develop a serious infection during the study, defined as any infection (viral, 
bacterial, and fungal) requiring hospitalization or parenteral antimicrobials or being classified 
as a serious adverse event should be withdrawn from the study (see Section 7.3.10).
All abnormal laboratory events of clinical significance should be followed until the 
laboratory values have returned to normal or baseline levels (see Appendix 3).  Subjects who 
meet the discontinuation criteria described in Appendix 3 will be withdrawn from the study.


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If a subject has any clinically significant, study-related abnormalities at the conclusion of the 
study, the Pfizer medical monitor (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 abnormalities.
The reason for a subject discontinuing from the study will be recorded in the Case Report 
Form (CRF).  A discontinuation occurs when a subject ceases participation in the study, 
regardless of the circumstances, prior to completion of the protocol.  The investigator must 
determine the primary reason for discontinuation.  Withdrawal due to adverse event should 
be distinguished from withdrawal due to insufficient response.  The early withdrawal
evaluation required by the protocol (see Month 12/ET visit procedures) will be performed at 
the time of study discontinuation, or as soon as possible thereafter.  The investigator will 
record the reason for study discontinuation, provide or arrange for appropriate follow-up (if 
required) for each such subject, and document the course of the subject’s condition.
Subjects may withdraw from the study at any time at their own request, or they may be 
withdrawn at any time at the discretion of the investigator or sponsor for safety or behavioral 
reasons, or the inability of the subject to comply with the protocol required schedule of study 
visits or procedures at a given study site.  If a subject does not return for a scheduled visit, 
every effort should be made to contact the subject.  In any circumstance, every effort should 
be made to document subject outcome, if possible.  The investigator should inquire about the 
reason for withdrawal, request the subject to return all unused investigational product(s), 
request the subject to return for a final visit, if applicable, and follow-up with the subject 
regarding any unresolved adverse events (AEs).
In accordance with due diligence requirements, if a subject fails to return for scheduled 
visit(s), the site shall record information concerning attempts to contact the subject in the 
subject source documents, including method of contact (eg, letter, phone call) and date of 
each attempted contact.  It is recommended that the investigational site makes two phone 
calls to the subject who missed the visit, documenting each call in the source documents.  A 
third contact attempt is a certified letter to the subject, and this letter and the response 
received become part of the source documents.  When a site has made at least 3 attempts to 
contact the subject, the subject is considered lost to follow up (LTFU).  Subject’s status shall 
be designated LTFU in the CRF and in the study monitoring report.
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.
7. ASSESSMENTS
Every effort should be made to ensure that the protocol required tests and procedures are 
completed as described. However it is anticipated that from time to time there may be 
circumstances, outside of the control of the investigator, that may make it unfeasible to 
perform the test. In these cases the investigator will take all steps necessary to ensure the 
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investigator will document the reason for this and any corrective and preventive actions 
which he/she has taken to ensure that normal processes are adhered to as soon as possible.
The study team will be informed of these incidents in a timely fashion.
7.1. Ulcerative Colitis Assessments
7.1.1. Subject Bowel Movement Diary
Subjects will use a phone-based interactive voice recording system (IVRS) tool to record 
their bowel movement data throughout the study.  Subjects will be instructed in its use at the 
Baseline visit.  This information should be entered daily approximately 7 days prior to their 
study visit AND any time during the study that the subject experiences a worsening of UC 
symptoms.  Automatic reminders will be sent to the subject before their scheduled visit to 
remind them to record their bowel movement data.  Also, as an additional reminder the site 
personnel will call the subject 7 days before their next scheduled visit to prompt them to 
complete their stool data in the phone-based tool.
The phone-based IVRS tool will be provided at baseline for subjects to record the following 
information during the study:

‘Normal’ number of stools per day (when not having a flare and will only be asked at 
baseline of induction study).

Number of toilet visits for bowel movements (per day).

Presence of blood in the stools (if any).

Description of blood in the stools (if any).
7.1.2. Partial Mayo Score
A partial Mayo score (PMS) is an instrument designed to measure disease activity of 
ulcerative colitis without endoscopy.  Partial Mayo score ranges from 0 to 9 points.  It 
consists of 3 subscores, each graded from 0 to 3 with higher scores indicating more severe 
disease.

stool frequency (0-3);

rectal bleeding (0-3);

physician global assessment (PGA) (0-3).
The partial Mayo score (PMS) will be assessed prior to the administration of study 
medication at each specified study visit (see Schedule Of Activities).  Partial Mayo score of 
2 or less with no individual subscore >1, is defined as PMS remission, and reduction of PMS 
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The PMS will be calculated based on the subject’s diary data recorded over the 3 prior 
consecutive days.  The physician’s global assessment (PGA) acknowledges the three other
criteria, the patient’s recollection of abdominal discomfort and general sense of wellbeing, 
and other observations, such as physical findings and the patient’s performance status.
7.1.3. Mayo Score
The Mayo score is an instrument designed to measure disease activity of ulcerative colitis.  
Mayo score ranges from 0 to 12 points. It consists of 4 subscores, each graded from 0 to 3 
with higher scores indicating more severe disease (see Appendix 1).

Stool frequency (0-3).

Rectal bleeding (0-3).

Findings of flexible sigmoidoscopy (0-3).

Physician global assessment (PGA) (0-3).
Mayo score is assessed at Month 2, at the following annual study visits (Months 12, 24 and 
36), and at the early withdrawal/early termination visit per the Schedule Of Activities.
The endoscopic finding at Month 2 will be read by both central reader and site investigators 
prior to Amendment 8.  The endoscopic subscore read by central reader will be used to 
calculate the Mayo score at Month 2 and determine clinical response until implementation of 
Amendment 8.  After implementation of Amendment 8, Month 2 endoscopic subscore will 
be locally read by study site investigator.  The endoscopic subscore at all other applicable 
visits will be read by study site investigator before and after Amendment 8.
Calculation of the Mayo score requires an assessment of the subject’s stool frequency and 
quantification of the amount of blood in the stool.  The subject will use the phone-based 
IVRS tool to record this information. Mayo score will be calculated based on the subject’s 
BM diary data recorded over the 3 prior consecutive days.
The mucosal appearance during the sigmoidoscopic portion of endoscopic examination will 
be assessed for the Mayo endoscopic subscore, based on the scoring system provided in the 
protocol (see Appendix 1).
The PGA acknowledges the three other criteria, the patient’s recollection of abdominal 
discomfort and general sense of wellbeing, and other observations, such as physical findings 
and the patient’s performance status.  The endoscopic subscore and the PGA must be 
performed by a physician qualified to perform endoscopy, and it is recommended that the 
same physician performs all such assessments for a particular subject throughout the study, 
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7.2. Patient Reported Outcomes
Paper diary will be used to record various patient reported outcomes (PRO) assessments 
during the study.  PRO assessments collected during the study will be presented in separate 
tables, figures, and data listings, and will be reviewed in the final study report. 
It is important to note that the PRO measurements are collected and evaluated in a different 
manner than the observed or volunteered adverse events.  Given these differences, no attempt 
will be made to resolve any apparent discrepancies between observed or volunteered adverse 
events and PRO data collected from subjects.  Adverse event incidence rates will not be 
calculated from these solicited data but rather from the information recorded on the AE pages 
on the CRF.
 
 
 
To be completed during study visits:
The following PROs will be completed as specified in the Schedule Of Activities.  Subjects 
should be encouraged to complete the PROs at the clinic at the beginning of the study visit
prior to any clinical assessments.  A member of the staff should be available if a subject 
requires further instruction and to review the PRO questionnaires for completeness prior to 
leaving the clinic.
•
Inflammatory Bowel Disease Questionnaire (IBDQ) (see Appendix 9).
 
7.2.1. Inflammatory Bowel Disease Questionnaire (IBDQ)
IBDQ Questionnaire is a psychometrically validated PRO instrument for measuring the 
disease-specific quality of life in subjects with Inflammatory Bowel Disease, including 
ulcerative colitis.  The IBDQ comprises 32-items, which are grouped into 4 dimensions: 
bowel function, emotional status, systemic symptoms and social function.10  The 4 domains 
are scored as follows:
•
Bowel symptoms: 10 to 70.
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•
Systemic symptoms: 5 to 35.
•
Emotional function: 12 to 84.
•
Social function: 5 to 35.
The total IBDQ score ranges from 32 to 224.  For the total score and each domain, a higher 
score indicates better quality of life.  A score of ≥170 corresponds to clinical remission and 
an increase of at least 16 points is considered to indicate a clinically meaningful 
improvement.
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7.3. Safety
Safety will be assessed by vital signs, physical examinations, ECGs, clinical laboratory tests 
and the spontaneous reporting of AEs, in all subjects who received at least 1 dose of study 
medication.  Unscheduled safety assessments may be performed at any time during the study 
to assess any perceived safety concerns.  Investigators and Pfizer Clinicians will review 
individual subject data throughout the conduct of the study to ensure subjects’ well-being.
Subject safety monitoring and discontinuation guidelines are provided in Appendix 3.
7.3.1. Vital Signs
As a guideline, blood pressure should be measured in the subject’s dominant arm and 
recorded to the nearest mmHg. The same arm should be used throughout the study, when 
possible. All blood pressure in this study should be measured with the subject in the sitting 
position after resting for at least 5 minutes, when possible.
The use of automated devices for measuring blood pressure and pulse rate are acceptable, 
although, when done manually, pulse rate will be measured in the brachial/radial artery for at 
least 30 seconds. When the timing of these measurements coincides with a blood collection, 
blood pressure and pulse rate should be obtained first.
Temperature will be collected as either oral, axillary or tympanic temperature, but the same 
method should be used throughout the study.
7.3.2. Physical Examinations
A complete physical examination will be performed at each specified visit according to the
Schedule Of Activities.  The following parameters and body systems will be examined and 
any abnormalities described: weight, general appearance, head, ears, eyes, nose, mouth, 
throat, thyroid, skin (presence of rash), lungs (auscultation), heart (auscultation for presence 
of murmurs, gallops, rubs, peripheral edema), abdominal (palpation and auscultation), 
perianal, musculoskeletal, extremities, neurologic (mental status, gait, reflexes, motor and 
sensory function, coordination) and lymph nodes.
Targeted physical examination will be performed at each specified visit according to the
Schedule Of Activities.  The following will be assessed: weight, general appearance, eyes, 
mouth, lungs, heart, abdomen, musculoskeletal, extremities, skin and lymph nodes.
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Recommendations for evaluation of emergent lymphadenopathy or other findings suggestive
of lymphoproliferative disorder are provided in Appendix 6.
7.3.3. Extra-Intestinal Manifestations
Assessment of the following extra-intestinal manifestations will be obtained on all subjects at 
specified visits according to the Schedule Of Activities: peripheral arthritis, sacroiliitis, 
ankylosing spondylitis, myopathy, pyoderma gangrenosum, erythema nodosum, scleritis, 
episcleritis, uveitis, iritis, oral ulcer/stomatitis, and thromboembolic disorder.  
7.3.4. Electrocardiogram
Twelve (12) lead ECGs will be obtained on all subjects at specified visits according to the
Schedule Of Activities. All scheduled ECGs should be performed after the subject has rested 
quietly for at least 10 minutes in a supine position, when possible.
The ECG results from Week 8 of Study A3921094 or A3921095, or from Week 52 or the 
early termination visit of Study A3921096 will be used to evaluate subject’s eligibility for 
Study A3921139 and serve as the baseline for Study A3921139.  The ECG results should be 
maintained in the subject’s source documentation. ECG data will be submitted to a central 
laboratory for measurement through Month 36 and at early termination.  Any clinically 
significant changes from the baseline ECG should be recorded as AEs and evaluated further, 
as clinically warranted.
The list of ECG values of potential clinical concern is listed in Appendix 4.
7.3.5. Clinical Laboratory Tests
Blood and urine samples will be collected at each specified visit according to the Schedule 
Of Activities.  Unscheduled clinical labs may be obtained at any time during the study to 
assess any perceived safety concerns or in accordance with the guidelines for subject safety 
monitoring and discontinuation (see Appendix 3).  Clinically significant abnormal findings 
should be recorded as AEs per Section 8.4.


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The following laboratory tests will be performed during the study:
Table 3.
Laboratory Test Parameters
Hematology
Serum Chemistry
Urinalysis
Others
Hemoglobin
Blood urea nitrogen
Specific gravity
Follicle stimulating hormone 
(FSH)2
Hematocrit
Creatinine
pH
β-hCG urine pregnancy test1
Reticulocyte
Glucose (fasting)4
Color
Lipid profile (fasting)2
Platelet count
Glucose (non-fasting)5
Glucose
Total cholesterol
White blood cell 
(WBC) count
Calcium
Nitrite
    Low density lipoprotein 
cholesterol (LDL-C)3
Neutrophils (abs, %)
Sodium
Blood
    High density lipoprotein 
cholesterol (HDL-C)
Eosinophils (abs, %)
Potassium
Leucocyte 
esterase
   Triglycerides3
Monocytes (abs, %)
Chloride
Protein
Basophils (abs, %)
Total carbon dioxide (CO2) 
or bicarbonate
Microscopy1
Lymphocytes (abs, %)
Aspartate aminotransferase  
(AST)
hs-CRP
Red blood cell (RBC) 
count
Alanine aminotransferase 
(ALT)
Mean corpuscular 
volume (MCV)
Total bilirubin
Mean corpuscular 
hemoglobin (MCH)
Direct bilirubin
Red cell distribution 
width (RDW)
Indirect bilirubin
Alkaline phosphatase
Gamma-glutamine 
transferase (GGT)
Total protein
Albumin
Lactate dehydrogenase 
(LDH)
Uric acid
Creatine kinase (CK)/ 
creatine phosphokinase 
(CPK)
1.
Dipstick in all cases; microscopy analysis is indicated if urinalysis is positive for blood, nitrite, leucocyte esterase 
and/or protein; Urine culture performed if urinalysis is positive for nitrite and/or leucocyte esterase or if clinically 
indicated. 
2.
Follicle stimulating hormone (FSH) to confirm postmenopausal status at baseline visit only if postmenopausal 
status has not been confirmed in Studies A3921094, A3921095 or A3921096.
1.
Urine testing performed with a sensitivity of at least 25 mIU/mL at the study site using test kits supplied by the 
central laboratory at baseline and at all study visits for females of childbearing potential.
2.
Fasting lipid profile will be obtained according to the Schedule Of Activities.
3.
If triglycerides >400 mg/dl, LDL-C will be determined by direct measurement.
4.
Fasting glucose will be measured at study visits when fasting lipid profile is obtained according to the Schedule Of 
Activities.
5.
Non-fasting glucose will be measured at all other study visits according to the Schedule Of Activities.
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10. Serum chemistry panel will include addition of hs-CRP only for those subjects being evaluated for entry into 
Study A3921288.
Clinically significant abnormal findings should be recorded as AEs if they meet any of the 
following criteria:
•
Test result is associated with accompanying symptom, and/or
•
Test result requires additional diagnostic testing or medical/surgical intervention, 
and/or
•
Test result leads to a change in study dosing or discontinuation from the study, 
significant additional concomitant drug treatment, or other therapy, and/or
•
Test result is considered to be an adverse event by the Investigator or sponsor.
Abnormal test results determined to be caused from laboratory error should not be reported 
as AEs.  Clinically significant laboratory findings at the final assessment should be followed 
to resolution or until determined by the Investigator to be stabilized.  Repeat tests may be 
indicated.
7.3.6. Annual Tuberculosis Testing
Annual tuberculosis (TB) testing will be conducted using Quantiferon-TB® Gold Plus test 
(QFT) for subjects in those countries in which TB prevalence has been reported at a rate of 
>50 cases per 100,000 persons (eg, Brazil, Latvia, Romania, Russia, Ukraine, South Africa, 
and South Korea, based on World Health Organization, 2015 
http://www.who.int/tb/country/data/profiles/en/index.html).  All subjects with positive results 
must have a chest radiograph performed and the radiograph must be negative for active TB 
infection for the subject to continue study participation.  Subjects identified as having latent 
TB (positive QFT and negative chest radiograph for active TB) should be treated 
appropriately; for subjects remaining on study during their treatment, the only acceptable 
regimen is 9 months of isoniazid. Subjects can continue to take tofacitinib without 
interruption while receiving treatment for latent TB.  Note: QFT should not be performed in 
subjects who had a positive result during prior testing (screening visit in Study A3921094 or 
A3921095 or prior annual visits) and/or previously received adequate treatment for TB.
7.3.7. Pregnancy Testing
For female subjects of childbearing potential, a urine β-hCG pregnancy test, with sensitivity 
of at least 25 mIU/mL, will be performed at baseline (Visit 1), before investigational product 
administration.  A negative urine β-hCG test result is required before the subject may receive 
the investigational product.  Urine β-hCG tests will also be done whenever one menstrual 
cycle is missed during the active treatment period (or when potential pregnancy is otherwise 
suspected), repeated at all study visits and at the end of the study to confirm the subject has 
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not become pregnant during the study.  Pregnancy tests may also be repeated as per request 
of IRB/IECs or if required by local regulations.
If at any point there is a case of a positive urine β-hCG test, the subject will have study drug 
interrupted and a serum sample submitted to the central laboratory for β-hCG testing.  If the 
serum test confirms positive, the subject will be withdrawn from the study and all the 
necessary follow up will be conducted as per Section 8.9.  If the serum test is negative, the 
subject may resume study drug.  It is essential to make sure that female study subjects use 
acceptable birth control (see Section 4.4.5.2 and 
) from 
the time of the first dose of study medication until completion of follow-up procedures.
In Austria, if the interval between study visits exceeds one month, female subjects of 
childbearing potential should have a pregnancy test performed each month between study 
visits and results reported to the investigational site to be entered into the subject’s study 
record.
7.3.8. Serum Lipids
Total cholesterol, LDL-cholesterol, direct HDL-cholesterol and triglycerides will be 
measured during the study at specific study visits according to the Schedule Of Activities
requiring subjects to fast at least 9 hours prior to sample collection.  See Appendix 8 for 
recommended clinical management of cholesterol.
7.3.9. Creatinine Clearance
A commonly used surrogate marker for actual creatinine clearance is the Cockcroft-Gault 
formula (see Appendix 5), which employs creatinine measurements and a subject’s weight to 
calculate the clearance. Cockcroft-Gault GFR calculation will be done as part of clinical 
laboratory tests from baseline (Visit 1) through follow-up.
7.3.10. Infections
Subjects will be monitored for development of infection. Infections will be classified as 
either treated or non-treated infections. All treated infections occurring during the study 
should be cultured if feasible and the results (eg, any identified organisms or absence of 
growth) recorded in the CRF.
Treated infections are infections that:
•
Require antimicrobial therapy by any route of administration or;
•
Require any surgical intervention (eg, incision and drainage).
Treated infections will be further classified as serious or non-serious. Serious infections are 
treated infections that:
•
Require parenteral antimicrobial therapy or;
•
Require hospitalization for treatment or;
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
Meet other criteria that require the infection to be classified as a serious adverse event 
(SAE).
A subject who experiences a serious infection should be discontinued from the study.  A 
serious infection should be reported as a SAE and should be listed as the reason for 
discontinuation in the CRF. All serious infections occurring during the study should undergo 
appropriate laboratory investigations, including culture, and the results (eg, any identified 
organisms or absence of growth) recorded in the CRF.
Subjects who experience non-serious infections that require treatment may have their study 
drug temporarily discontinued during treatment (see Section 5.9).  Temporary 
discontinuation of study drug should be recorded in the CRF.
Clostridium difficile (C. difficile) toxin testing is recommended for subjects in whom
C. difficile infection is suspected (eg, atypical symptoms or features of their usual UC 
disease course, significantly worsening disease activity assessments from the previous visit, 
and/or the presence of risk factors such as recent antibiotic use or a recent history of 
C. difficile infection).  A full course of C. difficile treatment, as defined by local practice,
must be given to subjects with C. difficile infection to permit their continued participation in 
the study.  Subjects with C. difficile infection that meets serious infection criteria must be 
withdrawn from the study. Stool testing and treatment for other enteric pathogens is at the 
discretion of the investigator.
7.3.11. Cardiovascular, and Malignancy, and Other Safety Events of Interest
The identification of a cardiovascular, malignancy, or other safety events of interest can be 
identified by the study site and communicated to Pfizer or designee. These safety 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 study records.
Criteria for defining specific cardiovascular, cerebrovascular and peripheral vascular 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 by the Cardiovascular Event Adjudication Committee (CV-EAC; see
Section 9.7).  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.
When there is a decision to biopsy a potentially malignant tumour, lymph node, or other 
tissue, the investigator and/or consultant(s) should contact Pfizer or designee to discuss the 
issue and any decisions as soon as possible.  For all biopsies of potentially malignant 
tumours, 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 tumours, lymphadenopathy or possible extra-nodal LPD 


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which might arise in the course of this study.  See Appendix 7 for the steps to take when
gastrointestinal tract biopsies are obtained.
7.3.12. Risk Factor Check for Pulmonary Embolism
All subjects will undergo a risk factor check at each study visit to check for newly-developed 
risk factors for pulmonary embolism.  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 pulmonary embolism if he/she:

has heart failure;

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.
If a subject has any of the risk factors listed above and is receiving tofacitinib 10 mg BID, the 
subject’s tofacitinib dose should be reduced to 5 mg BID.  If a subject has any 
newly-developed risk factors for pulmonary embolism identified during the study, they will 
not be permitted to receive tofacitinib 10 mg BID.
Lastly, if a subject has any of the risk factors listed above, the subject will not be eligible to 
enroll in Study A3921288.  
8. ADVERSE EVENT REPORTING
8.1. Adverse Events
All observed or volunteered AEs regardless of treatment group or suspected causal 
relationship to the investigational product(s) will be reported as described in the following 
sections. 
For all AEs, the investigator must pursue and obtain information adequate both to determine 
the outcome of the AE and to assess whether it meets the criteria for classification as an SAE
requiring immediate notification to Pfizer or its designated representative.  For all AEs, 
sufficient information should be obtained by the investigator to determine the causality of the 
AE.  The investigator is required to assess causality.  Follow-up by the investigator may be 
required until the event or its sequelae resolve or stabilize at a level acceptable to the 
investigator, and Pfizer concurs with that assessment.


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As part of ongoing safety reviews conducted by the Sponsor, any non-serious adverse event 
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.  
8.2. Reporting Period
For SAEs, the active reporting period to Pfizer or its designated representative begins from 
the time that the subject provides informed consent, which is obtained prior to the subject’s 
participation in the study, ie, prior to undergoing any study-related procedure and/or 
receiving investigational product, through and including 28 calendar days after the last 
administration of the investigational product.  SAEs occurring to a subject after the active 
reporting period has ended should be reported to the sponsor if the investigator becomes 
aware of them; at a minimum, all SAEs that the investigator believes have at least a 
reasonable possibility of being related to investigational product are to be reported to the 
sponsor.

AEs (serious and non-serious) should be recorded on the CRF from the time the 
subject has taken at least 1 dose of investigational product through the subject’s last
visit.  
8.3. Definition of an Adverse Event
An AE is any untoward medical occurrence in a clinical investigation subject administered a 
product or medical device; the event need not necessarily have a causal relationship with the 
treatment or usage.  Examples of AEs include but are not limited to:  

Abnormal test findings;

Clinically significant symptoms and signs;

Changes in physical examination findings;

Hypersensitivity;

Progression/worsening of underlying disease;

Drug abuse;

Drug dependency.
Additionally, they may include the signs or symptoms resulting from:

Drug overdose;

Drug withdrawal;


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
Drug misuse; 

Drug interactions;

Extravasation;

Exposure during pregnancy (EDP);

Exposure via breastfeeding;

Medication error;

Occupational exposure.
8.4. Abnormal Test Findings
The criteria for determining whether an abnormal objective test finding should be reported as 
an AE are as follows: 

Test result is associated with accompanying symptoms, and/or

Test result requires additional diagnostic testing or medical/surgical intervention, 
and/or

Test result leads to a change in study dosing, outside of those permitted by the 
protocol, or discontinuation from the study, significant additional concomitant drug 
treatment, or other therapy, and/or

Test result is considered to be an AE by the investigator or sponsor.
Merely repeating an abnormal test, in the absence of any of the above conditions, does not 
constitute an AE.  Any abnormal test result that is determined to be an error does not require 
reporting as an AE.
8.5. 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.


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Medical and scientific judgment is exercised in determining whether an event is an important 
medical event.  An important medical event may not be immediately life-threatening and/or 
result in death or hospitalization.  However, if it is determined that the event may jeopardize 
the subject or may require intervention to prevent one of the other AE outcomes, the 
important medical event should be reported as serious.
Examples of such events are intensive treatment in an emergency room or at home for 
allergic bronchospasm; blood dyscrasias or convulsions that do not result in hospitalization; 
or development of drug dependency or drug abuse.
8.5.1. Protocol-Specified Serious Adverse Events 
There are no protocol-specified SAEs in this study.  All SAEs will be reported by the 
investigator as described in previous sections, and will be handled as SAEs in the safety 
database (see the section on Serious Adverse Event Reporting Requirements).
8.5.2. Potential Cases of Drug-Induced Liver Injury 
Abnormal values in aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) 
levels concurrent with abnormal elevations in total bilirubin level that meet the criteria 
outlined below in the absence of other causes of liver injury are considered potential cases of 
drug-induced liver injury (potential Hy’s law cases) and should always be considered 
important medical events.  
The threshold of laboratory abnormalities for a potential case of drug-induced liver injury 
depends on the subject’s individual baseline values and underlying conditions. Subjects who 
present with the following laboratory abnormalities should be evaluated further to 
definitively determine the etiology of the abnormal laboratory values:

Subjects with AST or ALT and total bilirubin baseline values within the normal range
who subsequently present with AST or ALT values 3 times the upper limit of 
normal (× ULN) concurrent with a total bilirubin 2 × ULN with no evidence of 
hemolysis and an alkaline phosphatase 2 × ULN or not available.

For subjects with preexisting ALT OR AST OR total bilirubin values above the 
upper limit of normal, the following threshold values should be used in the definition 
mentioned above:

For subjects with pre-existing AST or ALT baseline values above the normal 
range: AST or ALT values 2 times the baseline values and 3 × ULN, or 
8 × ULN (whichever is smaller).


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


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


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


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Follow-up is conducted to obtain general information on the pregnancy and its outcome for 
all EDP reports with an unknown outcome.  The investigator will follow the pregnancy until 
completion (or until pregnancy termination) and notify Pfizer of the outcome as a follow up 
to the initial EDP supplemental form.  In the case of a live birth, the structural integrity of the 
neonate can be assessed at the time of birth.  In the event of a termination, the reason(s) for 
termination should be specified and, if clinically possible, the structural integrity of the 
terminated fetus should be assessed by gross visual inspection (unless pre-procedure test 
findings are conclusive for a congenital anomaly and the findings are reported).
If the outcome of the pregnancy meets the criteria for an SAE (ie, ectopic pregnancy, 
spontaneous abortion, intrauterine fetile 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 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 investigational product.
Additional information regarding the EDP may be requested by the investigator.  Further 
follow-up of birth outcomes will be handled on a case-by-case basis (eg, follow-up on 
preterm infants to identify developmental delays). In the case of paternal exposure, the 
investigator will provide the study subject with the Pregnant Partner Release of Information 
Form to deliver to his partner. The Investigator must document in the source documents that 
the subject was given the Pregnant Partner Release of Information Form to provide to his 
partner.
8.10. 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 the drug safety unit within 24 hours of the 
investigator’s awareness, using the SAE report form, regardless of whether there is an 
associated AE/SAE.  Since the information does not pertain to a subject enrolled in the study, 
the information is not reported on a CRF; however, a copy of the completed SAE report form 
is maintained in the investigator site file.
8.11. Withdrawal Due to Adverse Events (See Also the Section on Subject Withdrawal)
Withdrawal due to AEs should be distinguished from withdrawal due to other causes, 
according to the definition of AE noted earlier, and recorded on the appropriate AE CRF 
page.  


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


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9. DATA ANALYSIS/STATISTICAL METHODS
Detailed methodology for summary and statistical analyses of the data collected in this study 
will be documented in a Statistical Analysis Plan, which will be maintained by the sponsor.  
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
Approximately 900 subjects are expected to become eligible for the study.  Approximately 
460 subjects are expected to enroll from the maintenance Study A3921096 assuming a 
78% rollover rate from the maintenance study.  Approximately 440 subjects are expected to 
enroll from the induction Study A3921094 or A3921095 assuming that 38% of subjects 
enrolled in those studies will not achieve clinical response and will not have improving 
endoscopic subscores after completing induction Study A3921094 or A3921095.
9.2. Efficacy Analysis
The primary analysis population will be the Full Analysis Set (FAS) defined as all subjects 
who receive at least 1 dose of study medication.
9.2.1. Analysis of Primary Endpoint
The primary objective is to assess the safety and tolerability of long-term tofacitinib therapy.  
There will be no primary efficacy endpoint.
9.2.2. Analysis of Secondary Endpoints
Due to the design of the study, there will be no formal hypothesis testing. Descriptive 
summary statistics such as number, percentage for categorical endpoints and mean, standard
deviation, median for continuous endpoints will be summarized by the following four
subgroups of subjects based on the status at baseline of Study A3921139: 1) in remission 
defined by a total Mayo score 2 with no individual subscore >1, and rectal bleeding 
subscore of 0, 2) treatment failure defined by an increase in Mayo score of at least 3 points 
from baseline value of the maintenance study (A3921096), accompanied by an increase in 
rectal bleeding subscore by at least 1 point, and an increase of endoscopic subscore of at least 
1 point (yielding an absolute endoscopic subscore of 2), 3) all other subjects from 
maintenance study A3921096 neither in remission nor fulfilling the definition of treatment 
failure, and 4) non-responders from induction studies A3921094 or A3921095.
9.3. Analysis of Health Outcome Assessments
These endpoints will be analyzed using the same approach as the secondary endpoints.
9.4. Safety Analysis
The safety data will be summarized in accordance with Pfizer Data Standards based on the 
safety analysis set defined as all subjects who receive at least 1 dose of study medication.


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9.5. Interim Analysis
As this is an open-label and uncontrolled study, interim analyses may be performed for study 
monitoring for internal decision making, application for approval or due to regulatory
requests. There are no issues of protecting the Type I error rate as no hypothesis testing will 
be conducted.  
9.6. Data Monitoring Committee
An independent Data Safety Monitoring Board (DSMB), a group of experts external to 
Pfizer, will review accumulating safety data from this study on an ongoing basis. Review of 
efficacy data may occur as part of any risk-benefit assessment deemed the responsibility of 
this committee. Based on these reviews, the DSMB will have the capacity to make 
recommendations to Pfizer that might impact the future conduct of the trial. The DSMB will 
have access to unblinded treatment information during the clinical trial. The management 
and process of this committee will be in accordance with Pfizer’s Standard Operating 
Procedures and will be documented in the DSMB Charter. The DSMB members will all be 
individuals who are independent of Pfizer.
A DSMB Liaison will be appointed; this is an individual who represents Pfizer to coordinate 
communications and facilitates access to Pfizer’s resources, but is not involved in the study 
design, study management, site management, data accrual, or study analysis. Records of 
DSMB meetings, interactions with Pfizer contacts, assessments and recommendations and 
materials reviewed will be maintained and kept proprietary and confidential by the DSMB. 
Further information about the DSMB can be found in the DSMB 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.
The DSMB 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 DSMB 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.
9.7. Safety Event Adjudication Committees
To help assess specific safety events in this and other studies for the tofacitinib 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), Malignancy Adjudication 
Committee (MAC), Opportunistic Infection Review Committee (OIRC), Hepatic Event 
Review Committee (HERC) and Gastrointestinal Perforation Review Committee (GIPRC).  
Further information about these committees can be found in the respective charters, including 
specific descriptions of the scope of their responsibilities, and the processes and definitions 
used to review and assess specific safety events.


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In addition to the event adjudication or review committees described above, all biopsies of 
potentially malignant tumors, suspicious lymphadenopathy, or possible extranodal 
lymphoproliferative disorder, and all bowel biopsies containing dysplasia or malignancy, 
should be submitted to the central laboratory for review by central laboratory pathologists. 
In some instances, additional expert pathology review of submitted samples may be 
performed.  Description of the scope of review and the processes used to obtain and assess 
biopsies is described in the Histopathology Review for Potential Malignancy charter. 
In addition to these external committees, an internal committee of medically qualified Pfizer 
personnel with expertise in the assessment and diagnosis of respiratory disease will review 
and categorize potential events of interstitial lung disease (Interstitial Lung Disease Review 
Committee, ILDRC).
Additional safety event adjudication or review committees may be established to harmonize 
and standardize selected safety event assessments.  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.
10. QUALITY CONTROL AND QUALITY ASSURANCE
During study conduct, Pfizer or its agent will conduct periodic monitoring visits to ensure 
that the protocol and Good Clinical Practices (GCPs) are being followed.  The monitors may 
review source documents to confirm that the data recorded on CRFs is accurate.  The 
investigator and institution will allow Pfizer monitors or its agents and appropriate regulatory 
authorities direct access to source documents to perform this verification.
The study site may be subject to review by the Institutional Review Board (IRB)/Independent 
Ethics Committee (IEC), 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.
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, 


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consistent, legible, timely (contemporaneous), enduring and available when required.  The 
CRFs must be signed by the investigator or by an authorized staff member to attest that the 
data contained on the CRFs is true. Any corrections to entries made in the CRFs, source 
documents must be dated, initialed and explained (if necessary) and should not obscure the 
original entry. 
In most cases, the source documents are the hospital's or the physician's subject chart.  In 
these cases data collected on the CRFs must match the data in those charts. 
In some cases, the CRF, or part of the CRF, may also serve as source documents.  In these 
cases, a document should be available at the investigator’s site as well as at Pfizer and clearly 
identify those data that will be recorded in the CRF, and for which the CRF will stand as the 
source document.
11.2. Record Retention
To enable evaluations and/or audits from regulatory authorities or Pfizer, the investigator 
agrees to keep records, including the identity of all participating subjects (sufficient 
information to link records, eg, CRFs and hospital records), all original signed informed 
consent documents, copies of all CRFs, safety reporting forms, source documents, and 
detailed records of treatment disposition, and adequate documentation of relevant 
correspondence (eg, letters, meeting minutes, telephone calls reports).  The records should be 
retained by the investigator according to International Conference on Harmonisation (ICH), 
local regulations, or as specified in the Clinical Study Agreement (CSA), whichever is 
longer.
If the investigator becomes unable for any reason to continue to retain study records for the 
required period (eg, retirement, relocation), Pfizer should be prospectively notified.  The 
study records must be transferred to a designee acceptable to Pfizer, such as another 
investigator, another institution, or to an independent third party arranged by Pfizer. 
Investigator records must be kept for a minimum of 15 years after completion or 
discontinuation of the study or for longer if required by applicable local regulations.
The investigator must obtain Pfizer's written permission before disposing of any records, 
even if retention requirements have been met. 
12. ETHICS
12.1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC)
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, informed consent documents, and other relevant documents, eg,
recruitment advertisements, if applicable, from the IRB/IEC.  All correspondence with the 
IRB/IEC should be retained in the Investigator File.  Copies of IRB/IEC approvals should be 
forwarded to Pfizer.


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The only circumstance in which an amendment may be initiated prior to IRB/IEC approval is 
where the change is necessary to eliminate apparent immediate hazards to the subjects.  In 
that event, the investigator must notify the IRB/IEC and Pfizer in writing immediately after 
the implementation.
12.2. Ethical Conduct of the Study
The study will be conducted in accordance with legal and regulatory requirements, as well as 
the general principles set forth in the International Ethical Guidelines for Biomedical 
Research Involving Human Subjects (Council for International Organizations of Medical 
Sciences 2002), Guidelines for GCP (ICH 1996), and the Declaration of Helsinki (World 
Medical Association 1996, 2008). 
In addition, the study will be conducted in accordance with the protocol, the International 
Conference on Harmonization guideline on Good Clinical Practice, 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 
on any sponsor forms, reports, publications, or in any other disclosures, except where
required by laws.
Subject names, address, birth date and other identifiable data will be replaced by a numerical 
code consisting of a numbering system provided by Pfizer in order to de-identify the trial 
subject. In case of data transfer, Pfizer will maintain high standards of confidentiality and 
protection of subject personal data.
The informed consent document must be in compliance with ICH GCP, local regulatory 
requirements, and legal requirements.
The informed consent document used in this study, and any changes made during the course 
of the study, must be prospectively approved by both the IRB/IEC and Pfizer before use.
The investigator must ensure that each study subject, or his/her legal representative, is fully 
informed about the nature and objectives of the study and possible.
The investigator, or a person designated by the investigator, will obtain written informed 
consent from each subject or the subject's legal 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 
Competent Authority in any area of the World, or if the investigator is aware of any new 
information which might influence the evaluation of the benefits and risks of the 
investigational product, Pfizer should be informed immediately.  


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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
13.1. End of Trial in a Member State
End of Trial in a Member State of the European Union is defined as the time at which it is 
deemed that sufficient subjects have been recruited and completed the study as stated in the 
regulatory application (ie, Clinical Trial Application (CTA)) and ethics application in the 
Member State.  Poor recruitment (recruiting less than the anticipated number in the CTA) by 
a Member State is not a reason for premature termination but is considered a normal 
conclusion to the study in that Member State.
13.2. End of Trial in all Participating Countries
End of Trial in all participating countries is defined as last subject last visit.
14. SPONSOR DISCONTINUATION CRITERIA
Premature termination of this study may occur because of a regulatory authority decision, 
change in opinion of the IRB/IEC, drug safety problems, or at the discretion of Pfizer.  In 
addition, Pfizer retains the right to discontinue development of tofacitinib at any time.
If a study is prematurely terminated or discontinued, Pfizer will promptly notify the 
investigator.  After notification, the investigator must contact all participating subjects and 
the hospital pharmacy (if applicable) within 1 week.  As directed by Pfizer, all study 
materials must be collected and all CRFs completed to the greatest extent possible.
15. PUBLICATION OF STUDY RESULTS
15.1. Communication of Results by Pfizer
Pfizer fulfills its commitment to publicly disclose clinical trial results through posting the 
results of 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.
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 for studies in 


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adult populations or within 6 months of the primary completion date for studies in pediatric 
populations.
Primary completion date 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 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 primary completion date for studies in adult populations or within 6 months of the 
primary completion date for studies in pediatric populations.
www.pfizer.com
Pfizer posts Public Disclosure Synopses (clinical study report synopses in which any data 
that could be used to identify individual patients has been removed) on www.pfizer.com for 
Pfizer-sponsored interventional studies at the same time the US Basic Results document is 
posted to www.clinicaltrials.gov.
15.2. Publications by Investigators
Pfizer supports the exercise of academic freedom and has no objection to publication by 
principal investigator of the results of the study based on information collected or generated 
by principal investigator, whether or not the results are favorable to the Pfizer product. 
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 of the results of the study (collectively, “Publication”)
before it is submitted or otherwise disclosed.
The investigator will provide any publication to Pfizer at least 30 days before 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 before disclosure except for any study- or Pfizer product-related information 
necessary to the appropriate scientific presentation or understanding of the study results.
If the study is part of a multi-centre study, the investigator agrees that the first publication is 
to be a joint publication covering all study sites, and that any subsequent publications by the  
principal investigator will reference that primary publication. However, if a joint manuscript 
has not been submitted for publication within 12 months of completion or termination of the 
study at all participating sites, the investigator is free to publish separately, subject to the 
other requirements of this section.


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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 CSA between Pfizer and the 
institution.  In this section entitled Publications by Investigators, the defined terms shall have 
the meanings given to them in the CSA.
If there is any conflict between the CSA and any Attachments to it, the terms of the CSA 
control.  If there is any conflict between this protocol and the CSA, this protocol will control 
as to any issue regarding treatment of study subjects, and the CSA will control as to all other 
issues.


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16. REFERENCES
1.
Loftus EV Jr. Clinical epidemiology of inflammatory bowel disease: incidence, 
prevalence and environmental influences.  Gastroenterol 2004; 126:1504-17.
2.
Loftus CG, Loftus EV, Harmsen WS et al Update on the incidence and prevalence of 
Crohn’s disease and ulcerative colitis in Olmsted County, Minnesota, 1940-2000. 
Inflamm Bowel Dis 2007; 13:254-61.
3.
Abraham C, Cho JH. Inflammatory bowel disease. N Engl J Med 2009; 361:2066-78.
4.
Kornbluth A, Sachar DB. Ulcerative Colitis Practice Guidelines in Adults: American 
College of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol 2010; 
105:501-23.
5.
Langholz E, Munkholm P, Davidsen M, et al. Course of ulcerative colitis: analysis of 
changes in disease activity over years. Gastroenterol 1994; 107:3-11.
6.
Ayres RC, Gillen CD, Walmsley RS, and et al Progression of ulcerative 
proctosigmoiditis: incidence and factors influencing progression. Eur J Gastroenterol 
Hepatol 1996; 8(6):555-8.
7.
Powell-Tuck J, Ritchie JK, and Lennard-Jones JE. The prognosis of idiopathic proctitis. 
Scand J Gastroenterol 1977; 12:727-732.
8.
Ørding Olsen K, Juul S, Berndtsson I, Oresland T, Laurberg S. Ulcerative colitis: 
female fecundity before diagnosis, during disease, and after surgery compared with a 
population sample. Gastroenterol 2002; 122(1):15-9.
9.
Schroeder KW, Tremaine WJ, Ilstrup DM.  Coated oral 5-aminosalicylic acid therapy 
for mildly to moderately active ulcerative colitis: a randomized study.  N Engl J Med 
1987; 317:1625-9.
10.
Irvine EJ, Feagan B, Rochon J, Archambault A, Fedorak RN, Groll A, Kinnear D, Saibil 
F, McDonald JW.  Quality of life: a valid and reliable measure of therapeutic efficacy in 
the treatment of IBD.  Canadian Crohn’s Relapse Prevention Trial Study Group.  
Gastroenterol 1994; 106:287-296.
11.
Fazio VW, Ziv Y, Church JM, Oakley JR, Lavery IC, Milsom JW, Schroeder TK. Ileal 
pouch-anal anastomoses complications and function in 1005 patients. Ann Surg 1995;  
222:120-127.
12.
Karaman MW, Herrgard S, Treiber DK, et al. A quantitative analysis of kinase inhibitor 
selectivity. Nat Biotechnol 2008; 26:127-32.


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13.
Meyer DM, Jesson MI. 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.
Murray PJ. The JAK-STAT signaling pathway: input and output integration. J Immunol 
2007; 178(5):2623-9.


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Appendix 1. Mayo Scoring System*
Stool frequency†:
0 = Normal no. of stools for this patient
1 = 1 to 2 stools more than normal
2 = 3 to 4 stools more than normal
3 = 5 or more stools more than normal
Subscore, 0 to 3
Rectal bleeding‡:
0 = No blood seen
1 = Streaks of blood with stool less than half the time
2 = Obvious blood with stool most of the time
3 = Blood alone passes
Subscore, 0 to 3
Findings on endoscopy:
0 = Normal or inactive disease
1 = Mild disease (erythema, decreased vascular pattern)
2 = Moderate disease (marked erythema, absent vascular pattern, any friability, erosions)
3 = Severe disease (spontaneous bleeding, ulceration)
Subscore, 0 to 3
Physician’s global assessment§:
0 = Normal
1 = Mild disease
2 = Moderate disease
3 = Severe disease
Subscore, 0 to 3
*
The Mayo score ranges from 0 to 12, with higher scores indicating more severe disease.9
†
Each patient serves as his or her own control to establish the degree of abnormality of the stool frequency.  
Normal number of bowel movements represents the number of bowel movements when not having a flare.
‡
The daily bleeding score represents the most severe bleeding of the day.
§
The physician’s global assessment acknowledges the three other criteria, the patient’s recollection of 
abdominal discomfort and general sense of wellbeing, and other observations, such as physical findings and 
the patient’s performance status.


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Appendix 2. Prohibited Concomitant Medications
This is not an all inclusive list. Study personnel should stay current and consult with their 
pharmacy to exclude all concomitant medications that are either moderate to potent CYP3A 
inhibitors or inducers.
Moderate to Potent CYP3A 
Inhibitors
Moderate to Potent CYP3A 
Inducers
Other Prohibited 
Medications
Amprenavir
Avasimibe#
Azathioprine
Amiodarone
Bosentan
6-Mercaptopurine
Aprepitant
Barbiturates
Methotrexate
Atazanavir
Carbamazepine#
Cyclosporine
Boceprevir
Efavirenz
Mycophenolate mofetil 
/mycophenolic acid
Casopitant
Etravirine
Tacrolimus
Cimetidine
Mitotane#
Interferon
Ciprofloxacin
Modafinil
Infliximab
Clarithromycin#
Nafcillin
Adalimumab
Certolizumab
Cobicistat#
Phenobarbital#
Golimumab
Conivaptan#
Phenytoin#
Corticosteroids IV or PR
Darunavir
Rifabutin#
5-ASA PR
Rifampin#
Natalizumab, vedolizumab, 
and other anti-adhesion 
molecule therapy (including 
investigational agents)
Diethyldithiocarbamate
St. John’s Wort#
Leukocyte apheresis including 
selective lymphocyte,  
monocyte or granulocyte 
apheresis (eg, Cellsorba) or 
plasma exchange
Diltiazem
Other immunosuppressants 
Dronedarone
Talviraline
Other biologics with 
immunomodulatory properties
Elvitegravir#
Erythromycin
Fluconazole
Fluvoxamine
Imatinib
Indinavir#
Itraconazole#
Ketoconazole#
Lopinavir#
Mibefradil#
Mifepristone (RU486)
Nefazodone#
Nelfinavir#
Norfloxacin
Posaconazole#
Ritonavir#
Saquinavir#
Schisandra sphenanthera


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Telaprevir
Telithromycin#
Tipranavir#
Tofisopam
Troleandomycin#
Verapamil
Voriconazole#
# Notated as potent inhibitors or inducers
It is recommended that subjects avoid consumption of grapefruit juice exceeding 8 ounces 
(~240 mL) total in a day while in the study.
In a situation where appropriate medical care of a subject requires the use of a 
prohibited CYP3A inhibitor or inducer: Potent inhibitors and inducers of CYP3A are not 
permitted in the study EXCEPT in emergency situations requiring no more than one day of 
administration.  Note: Mitotane (half-life of 18-159 days) is not permitted for any duration 
due to its long half-life.  Subjects may be initiated on moderate inhibitors (except 
amiodarone) and moderate inducers (shown above), as required, if the total duration of 
treatment lasts less than or equal to 7 days.  If a subject requires multiple courses of treatment 
with a prohibited medication as described above, the investigator should contact the sponsor 
to discuss the suitability of the subject to remain in the study.  Topical (including skin or 
mucous membranes) application of antibacterial and antifungal medications is permitted.


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Appendix 3. Guidelines for Monitoring and Discontinuations
The following laboratory abnormalities require monitoring and re-testing ideally within 
3-5 days:
•
Absolute neutrophil count <1.2 x 109/L (<1200/mm3).
•
Absolute lymphocyte count <0.5 x 109/L (<500/mm3).
•
Any single hemoglobin value <8.0 g/dL, or any decrease in hemoglobin >2.0 g/dL 
from baseline.
•
Platelet count <100 x 109/L (<100,000/mm3).
•
An increase in serum creatinine of >50% from the baseline value; OR an absolute 
increase in serum creatinine >0.5 mg/dL (>44.2 umol/L) from baseline value.
•
Any single AST and/or ALT elevation ≥3 times the upper limit of normal (repeat 
laboratory testing should include albumin, creatine kinase, total bilirubin, direct and 
indirect bilirubin, GGT, PT [prothrombin time] with INR [international normalized 
ratio], and alkaline phosphatase), regardless of the total bilirubin. (Please note that 
3 times the upper limit of normal increases in ALT, AST need confirmation on 
separate blood draw before undertaking thorough evaluation for liver injury).
•
Any creatine kinase (CK) >10 times the upper limit of normal (repeat laboratory 
testing should also include cardiac troponin).
•
For women of child-bearing potential with any positive urine β-hCG test, the subject 
will have study drug interrupted and a serum sample submitted to the central 
laboratory for β-hCG testing.
Additional individual subject safety monitoring in addition to these guidelines is at the 
discretion of the investigator and dependent on any perceived safety concerns. Unscheduled 
laboratory testing through the central laboratory may be obtained at any time during the study 
to assess such concerns, and a subject may be withdrawn at any time at the discretion of the 
investigator.
Treatment with tofacitinib will be discontinued and the subject withdrawn from this 
study for:
•
Serious infections defined as any infection (viral, bacterial, and fungal) requiring 
parenteral antimicrobial therapy, hospitalization for treatment, or meeting other 
criteria that require the infection to be classified as serious adverse event.
•
Two sequential absolute neutrophil counts <0.75 x 109/L (<750/mm3).
C
C


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•
Two sequential absolute lymphocyte counts <0.5 x 109/L (<500/mm3).
•
Two sequential hemoglobin <8.0 g/dL or a decrease of >30% from baseline.
•
Two sequential platelet counts <75 x 109/L (<75,000/ mm3).
•
Two sequential increases in serum creatinine >50% over the baseline value AND an 
absolute increase in serum creatinine >0.5 mg/dL (>44.2 umol/L).
•
Two sequential AST or ALT elevation ≥3 times the upper limit of normal with at 
least one total bilirubin value ≥2 times the upper limit of normal.a
•
Two sequential AST or ALT elevation ≥3 times the upper limit of normal 
accompanied by signs or symptoms consistent with hepatic injury.a
•
Two sequential AST or ALT elevation ≥5 times the upper limit of normal, regardless 
of total bilirubin or accompanying signs or symptoms.a
•
Two sequential CK elevations >10 times the upper limit of normal, unless the 
causality is known not to be medically serious (eg, exercise induced).
•
Female subjects found to be pregnant during the study.
•
Initiation of a new treatment for UC.
•
Surgery for UC.
•
Other serious or severe AEs, after consultation with the Pfizer medical monitor or 
designee.
 
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 Pfizer medical monitor or designee.
C
C
I


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Appendix 4. ECG Values of Potential Clinical Concerns
Rhythms/Patterns of Potential Clinical Concern (Adverse Effects)

Marked Sinus Bradycardia (rate <35 bpm) lasting >10 minutes.

New PR interval prolongation >280 ms. 

New prolongation of QRS duration to >120 ms or by >40 ms or by 50% when 
baseline 100 ms.

New prolongation of QTcF (Fridericia correction) to >480 ms or by 60 ms.

New Onset Atrial Flutter or Fibrillation, with controlled ventricular response rate: 
ie, rate <120 bpm.

New Onset Type I Second Degree (Wenckebach) AV Block of >30 seconds duration.

Frequent Premature Ventricular Complexes (PVCs), Ventricular Bigeminy, Triplets 
or short intervals (<30 seconds) of consecutive ventricular complexes.
Adverse Experiences

QTcF (Fridericia correction) prolongation >500 ms.

New ST-T changes suggestive of myocardial ischaemia.

New Onset Left Bundle Branch Block (QRS>120 ms).

Symptomatic Marked Sinus Bradycardia (rate <40 bpm).

Sinus Pause >3 seconds without an escape beat.

Atrial Flutter or Fibrillation, with rapid ventricular response rate: rapid = rate 
>120 bpm.

Sustained Supraventricular Tachycardia (rate >120 bpm) (‘sustained’ = short duration 
with relevant symptoms or lasting >1 minute).

Ventricular Rhythms >30 seconds duration, including idioventricular rhythm (rate 
<40 bpm), accelerated idioventricular rhythm (40< x<100) and 
monomorphic/polymorphic ventricular tachycardia >100 bpm (such as Torsades de 
pointes).

Type II Second Degree (Mobitz) AV Block.

Complete (third degree) Heart Block.


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Serious Adverse Experiences

Change in pattern suggestive of new or indeterminate age myocardial infarction.

Sustained Ventricular Tachyarrhythmias (>30 seconds duration).

Second or third degree AV block requiring pacemaker placement.

Sinus pauses requiring pacemaker placement.

Atrial flutter or fibrillation with rapid ventricular response requiring cardioversion.

Ventricular Fibrillation/Flutter.

At the discretion of the investigator, any arrhythmia classified as an adverse 
experience.


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Appendix 5. Cockcroft-Gault GFR Calculation
Cockcroft-Gault GFR = ([M] or [F]) x (140 – Age) x BW / (72 x Creatinine)
Units or Value
GFR
=
Glomerular Filtration Rate
mL/min
M
=
Male
1
F
=
Female
0.85
Age
=
Age
Years
BW
=
Body Weight
Kg
Creatinine
=
Serum Creatinine
mg/dL
When serum creatinine is expressed as mol/L the appropriate formula is: 
Cockcroft-Gault GFR = ([M] or [F]) x (140 – Age) x BW / (0.814 x Creatinine)


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Appendix 6. Evaluation of Potentially Malignant Tumors, Suspicious 
Lymphadenopathy or Possible Extranodal Lymphoproliferative Disorder (LPD)
The following steps should be taken in the event of suspicious lymphadenopathy or possible 
extranodal lymphoproliferative disorder (LPD) which might arise in the course of this or 
other studies of Pfizer’s experimental immunosuppressive drugs. 
Any new cases or worsening cases of existing lymphadenopathy need to be discussed with 
Pfizer study team first. In addition, when there is a decision to biopsy a suspicious lymph 
node, the investigator and/or consultants should discuss the issue and any decisions as soon 
as possible with Pfizer study team. 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 study biopsy procedures instructions 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 of potentially malignant tumors, suspicious lymphadenopathy, or possible 
extranodal lymphoproliferative disorder (LPD), 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. Should the 
central pathologist make a diagnosis that is not essentially similar to the local pathologist’s 
diagnosis, the site will be notified and provided with an opportunity to consult with the 
central pathologist. Translation during this consultation, if needed, will be provided by the 
staff of the Pfizer Clinical Country Office (CCO) or designee.


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Appendix 7. Evaluation of Gastrointestinal Tract Biopsies
For gastrointestinal tract biopsies, obtained from any gastrointestinal endoscopic procedure 
performed during the study because of a clinical suspicion of malignancy (even if the local 
pathologist reading is negative for dysplasia or malignancy) OR gastrointestinal tract 
biopsies obtained during the study for any reason that show the findings or suspicion of
dysplasia or malignancy, the original slides will need to be sent for central pathologist over 
read in addition to the local pathologist’s diagnosis.


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Appendix 8. Recommended Clinical Management of Cholesterol
Safety monitoring of a subject’s lipid panel results is recommended to include an assessment
of individual subject risk for cardiovascular disease. Management of lipid levels should be
determined on an individual subject level due to the individualized nature of cholesterol
treatment recommendations. The Third Report of the Expert Panel on Detection, Evaluation,
and Treatment of High Blood Cholesterol in Adults (ATP III, National Cholesterol Education
Program 2002) provides guiding principles for the intensity of lipid lowering therapy based 
on an individual’s absolute risk for coronary heart disease (CHD). ATP III guidelines and/or 
other relevant local practices and guidelines should be used to determine if any lipid lowering 
intervention is required for a subject. Such assessments should occur throughout the study, 
in light of the observed increases in lipid levels in previous clinical trials with tofacitinib. As 
appropriate, lipid management decisions may be considered in collaboration with the 
subject’s primary care physician or general practitioner.
A copy of the complete ATP III guidelines will be provided to each study site for reference.


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Appendix 9. Quality of Life in Inflammatory Bowel Disease Questionnaire (IBDQ)
This questionnaire is designed to find out how you have been feeling during the last 2 weeks.
You will be asked about symptoms you have been having as a result of your inflammatory 
bowel disease, the way you have been feeling in general, and how your mood has been.
1. How frequent have your bowel movements been during the last two weeks? Please 
indicate how frequent your bowel movements have been during the last 2 weeks by 
picking one of the options from:
1. BOWEL MOVEMENTS AS OR MORE FREQUENT THAN THEY HAVE 
EVER BEEN
2. EXTREMELY FREQUENT
3. VERY FREQUENT
4. MODERATE INCREASE IN FREQUENCY OF BOWEL MOVEMENTS
5. SOME INCREASE IN FREQUENCY OF BOWEL MOVEMENTS
6. SLIGHT INCREASE IN FREQUENCY OF BOWEL MOVEMENTS
7. NORMAL, NO INCREASE IN FREQUENCY OF BOWEL MOVEMENTS
2. How often has the feeling of fatigue or of being tired and worn out been a problem for 
you during the last 2 weeks? Please indicate how often the feeling of fatigue or tiredness 
has been a problem for you during the last 2 weeks by picking one of the options from:
1. ALL OF THE TIME
2. MOST OF THE TIME
3. A GOOD BIT OF THE TIME
4. SOME OF THE TIME
5. A LITTLE OF THE TIME
6. HARDLY ANY OF THE TIME
7. NONE OF THE TIME


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3. How often during the last 2 weeks have you felt frustrated, impatient, or restless? Please 
choose an option from:
1. ALL OF THE TIME
2. MOST OF THE TIME
3. A GOOD BIT OF THE TIME
4. SOME OF THE TIME
5. A LITTLE OF THE TIME
6. HARDLY ANY OF THE TIME
7. NONE OF THE TIME
4. How often during the last 2 weeks have you been unable to attend school or do your work 
because of your bowel problem? Please choose an option from:
1. ALL OF THE TIME
2. MOST OF THE TIME
3. A GOOD BIT OF THE TIME
4. SOME OF THE TIME
5. A LITTLE OF THE TIME
6. HARDLY ANY OF THE TIME
7. NONE OF THE TIME
5. How much of the time during the last 2 weeks have your bowel movements been loose? 
Please choose an option from:
1. ALL OF THE TIME
2. MOST OF THE TIME
3. A GOOD BIT OF THE TIME
4. SOME OF THE TIME
5. A LITTLE OF THE TIME
6. HARDLY ANY OF THE TIME
7. NONE OF THE TIME


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6. How much energy have you had during the last 2 weeks? Please choose an option from:
1. NO ENERGY AT ALL
2. VERY LITTLE ENERGY
3. A LITTLE ENERGY
4. SOME ENERGY
5. A MODERATE AMOUNT OF ENERGY
6. A LOT OF ENERGY
7. FULL OF ENERGY
7. How often during the last 2 weeks did you feel worried about the possibility of needing to 
have surgery because of your bowel problem? Please choose an option from:
1. ALL OF THE TIME
2. MOST OF THE TIME
3. A GOOD BIT OF THE TIME
4. SOME OF THE TIME
5. A LITTLE OF THE TIME
6. HARDLY ANY OF THE TIME
7. NONE OF THE TIME
8. How often during the last 2 weeks have you had to delay or cancel a social engagement 
because of your bowel problem? Please choose an option from:
1. ALL OF THE TIME
2. MOST OF THE TIME
3. A GOOD BIT OF THE TIME
4. SOME OF THE TIME
5. A LITTLE OF THE TIME
6. HARDLY ANY OF THE TIME
7. NONE OF THE TIME


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9. How often during the last 2 weeks have you been troubled by cramps in your abdomen? 
Please choose an option from:
1. ALL OF THE TIME
2. MOST OF THE TIME
3. A GOOD BIT OF THE TIME
4. SOME OF THE TIME
5. A LITTLE OF THE TIME
6. HARDLY ANY OF THE TIME
7. NONE OF THE TIME
10. How often during the last 2 weeks have you felt generally unwell? Please choose an 
option from:
1. ALL OF THE TIME
2. MOST OF THE TIME
3. A GOOD BIT OF THE TIME
4. SOME OF THE TIME
5. A LITTLE OF THE TIME
6. HARDLY ANY OF THE TIME
7. NONE OF THE TIME
11. How often during the last 2 weeks have you been troubled because of fear of not finding 
a washroom? Please choose an option from:
1. ALL OF THE TIME
2. MOST OF THE TIME
3. A GOOD BIT OF THE TIME
4. SOME OF THE TIME
5. A LITTLE OF THE TIME
6. HARDLY ANY OF THE TIME
7. NONE OF THE TIME


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12. How much difficulty have you had, as a result of your bowel problems, doing leisure or 
sports activities you would have liked to have done during the last 2 weeks? Please 
choose an option from:
1. A GREAT DEAL OF DIFFICULTY; ACTIVITIES MADE IMPOSSIBLE
2. A LOT OF DIFFICULTY
3. A FAIR BIT OF DIFFICULTY
4. SOME DIFFICULTY
5. A LITTLE DIFFICULTY
6. HARDLY ANY DIFFICULTY
7. NO DIFFICULTY; THE BOWEL PROBLEMS DID NOT LIMIT SPORTS OR 
LEISURE ACTIVITIES
13. How often during the last 2 weeks have you been troubled by pain in the abdomen? 
Please choose an option from:
1. ALL OF THE TIME
2. MOST OF THE TIME
3. A GOOD BIT OF THE TIME
4. SOME OF THE TIME
5. A LITTLE OF THE TIME
6. HARDLY ANY OF THE TIME
7. NONE OF THE TIME
14. How often during the last 2 weeks have you had problems getting a good night’s sleep, or 
been troubled by waking up during the night? Please choose an option from:
1. ALL OF THE TIME
2. MOST OF THE TIME
3. A GOOD BIT OF THE TIME
4. SOME OF THE TIME
5. A LITTLE OF THE TIME
6. HARDLY ANY OF THE TIME
7. NONE OF THE TIME


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15. How often during the last 2 weeks have you felt depressed or discouraged? Please 
choose an option from:
1. ALL OF THE TIME
2. MOST OF THE TIME
3. A GOOD BIT OF THE TIME
4. SOME OF THE TIME
5. A LITTLE OF THE TIME
6. HARDLY ANY OF THE TIME
7. NONE OF THE TIME
16. How often during the last 2 weeks have you had to avoid attending events where there 
was no washroom close at hand? Please choose an option from:
1. ALL OF THE TIME
2. MOST OF THE TIME
3. A GOOD BIT OF THE TIME
4. SOME OF THE TIME
5. A LITTLE OF THE TIME
6. HARDLY ANY OF THE TIME
7. NONE OF THE TIME
17. Overall, in the last 2 weeks, how much of a problem have you had with passing large 
amounts of gas? Please choose an option from:
1. A MAJOR PROBLEM
2. A BIG PROBLEM
3. A SIGNIFICANT PROBLEM
4. SOME TROUBLE
5. A LITTLE TROUBLE
6. HARDLY ANY TROUBLE
7. NO TROUBLE


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18. Overall, in the last 2 weeks, how much a problem have you had maintaining or getting to, 
the weight you would like to be at? Please choose an option from:
1. A MAJOR PROBLEM
2. A BIG PROBLEM
3. A SIGNIFICANT PROBLEM
4. SOME TROUBLE
5. A LITTLE TROUBLE
6. HARDLY ANY TROUBLE
7. NO TROUBLE
19. Many patients with bowel problems often have worries and anxieties related to their 
illness. These include worries about getting cancer, worries about never feeling any 
better, and worries about having a relapse. In general, how often during the last 2 weeks 
have you felt worried or anxious? Please choose an option from:
1. ALL OF THE TIME
2. MOST OF THE TIME
3. A GOOD BIT OF THE TIME
4. SOME OF THE TIME
5. A LITTLE OF THE TIME
6. HARDLY ANY OF THE TIME
7. NONE OF THE TIME
20. How much of the time during the last 2 weeks have you been troubled by a feeling of 
abdominal bloating? Please choose an option from:
1. ALL OF THE TIME
2. MOST OF THE TIME
3. A GOOD BIT OF THE TIME
4. SOME OF THE TIME
5. A LITTLE OF THE TIME
6. HARDLY ANY OF THE TIME
7. NONE OF THE TIME


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21. How often during the last 2 weeks have you felt relaxed and free of tension? Please 
choose an option from:
1. NONE OF THE TIME
2. A LITTLE OF THE TIME
3. SOME OF THE TIME
4. A GOOD BIT OF THE TIME
5. MOST OF THE TIME
6. ALMOST ALL OF THE TIME
7. ALL OF THE TIME
22. How much of the time during the last 2 weeks have you had a problem with rectal 
bleeding with your bowel movements? Please choose an option from:
1. ALL OF THE TIME
2. MOST OF THE TIME
3. A GOOD BIT OF THE TIME
4. SOME OF THE TIME
5. A LITTLE OF THE TIME
6. HARDLY ANY OF THE TIME
7. NONE OF THE TIME
23. How much of the time during the last 2 weeks have you felt embarrassed as a result of 
your bowel problem? Please choose an option from:
1. ALL OF THE TIME
2. MOST OF THE TIME
3. A GOOD BIT OF THE TIME
4. SOME OF THE TIME
5. A LITTLE OF THE TIME
6. HARDLY ANY OF THE TIME
7. NONE OF THE TIME


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24. How much of the time during the last 2 weeks have you been troubled by a feeling of 
having to go to the bathroom even though your bowels were empty? Please choose an 
option from
1. ALL OF THE TIME
2. MOST OF THE TIME
3. A GOOD BIT OF THE TIME
4. SOME OF THE TIME
5. A LITTLE OF THE TIME
6. HARDLY ANY OF THE TIME
7. NONE OF THE TIME
25. How much of the time during the last 2 weeks have you felt tearful or upset? Please 
choose an option from:
1. ALL OF THE TIME
2. MOST OF THE TIME
3. A GOOD BIT OF THE TIME
4. SOME OF THE TIME
5. A LITTLE OF THE TIME
6. HARDLY ANY OF THE TIME
7. NONE OF THE TIME
26. How much of the time during the last 2 weeks have you been troubled by accidental 
soiling of your underpants? Please choose an option from:
1. ALL OF THE TIME
2. MOST OF THE TIME
3. A GOOD BIT OF THE TIME
4. SOME OF THE TIME
5. A LITTLE OF THE TIME
6. HARDLY ANY OF THE TIME
7. NONE OF THE TIME


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27. How much of the time during the last 2 weeks have you felt angry as a result of your 
bowel problem? Please choose an option from:
1. ALL OF THE TIME
2. MOST OF THE TIME
3. A GOOD BIT OF THE TIME
4. SOME OF THE TIME
5. A LITTLE OF THE TIME
6. HARDLY ANY OF THE TIME
7. NONE OF THE TIME
28. To what extent has your bowel problem limited sexual activity during the last 2 weeks? 
Please choose an option from:
1. NO SEX AS A RESULT OF BOWEL DISEASE
2. MAJOR LIMITATION AS A RESULT OF BOWEL DISEASE
3. MODERATE LIMITATION AS A RESULT OF BOWEL DISEASE
4. SOME LIMITATION AS A RESULT OF BOWEL DISEASE
5. A LITTLE LIMITATION AS A RESULT OF BOWEL DISEASE
6. HARDLY ANY LIMITATION AS A RESULT OF BOWEL DISEASE
7. NO LIMITATION AS A RESULT OF BOWEL DISEASE
29. How much of the time during the last 2 weeks have you been troubled by nausea or 
feeling sick to your stomach? Please choose an option from:
1. ALL OF THE TIME
2. MOST OF THE TIME
3. A GOOD BIT OF THE TIME
4. SOME OF THE TIME
5. A LITTLE OF THE TIME
6. HARDLY ANY OF THE TIME
7. NONE OF THE TIME


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30. How much of the time during the last 2 weeks have you felt irritable? Please choose an 
option from:
1. ALL OF THE TIME
2. MOST OF THE TIME
3. A GOOD BIT OF THE TIME
4. SOME OF THE TIME
5. A LITTLE OF THE TIME
6. HARDLY ANY OF THE TIME
7. NONE OF THE TIME
31. How often during the past 2 weeks have you felt a lack of understanding from others? 
Please choose an option from:
1. ALL OF THE TIME
2. MOST OF THE TIME
3. A GOOD BIT OF THE TIME
4. SOME OF THE TIME
5. A LITTLE OF THE TIME
6. HARDLY ANY OF THE TIME
7. NONE OF THE TIME
32. How satisfied, happy, or pleased have you been with your personal life during the past 
2 weeks? Please choose one of the following options from:
1. VERY DISSATISFIED, UNHAPPY MOST OF THE TIME
2. GENERALLY DISSATISFIED, UNHAPPY
3. SOMEWHAT DISSATISFIED, UNHAPPY
4. GENERALLY SATISFIED, PLEASED
5. SATISFIED MOST OF THE TIME, HAPPY
6. VERY SATISFIED MOST OF THE TIME, HAPPY
7. EXTREMELY SATISFIED, COULD NOT HAVE BEEN MORE HAPPY OR 
PLEASED


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Appendix 15. Abbreviations
Abbreviation
Term
AE
adverse event
AV
atrialventricular
5-ASA
5- aminosalicylic acid
ALT
alanine aminotransferase
AST 
aspartate aminotransferase
β-hCG
beta human chorionic gonadotropin
BID
twice a day
bpm
beats per minute
BUN
blood urea nitrogen
BW
body weight
CD
cluster determinant
CHD
coronary heart disease
CK
creatine kinase
CO2
carbon dioxide
CP-690,550
compound 690,550
CPK
creatine phosphokinase
CRF
case report form
CSA
Clinical Study Agreement
CT
computerized tomography
CYP3A
cytochrome P450, family 3, subfamily A
CV-SEAC
Cardiovascular Safety Endpoint Adjudication Committee
DMARD
disease modifying anti-rheumatic drug
DNA
Deoxyribonucleic acid
DSMB
Data Safety Monitoring Committee
ECG
electrocardiogram
EDP
exposure during pregnancy
ET
early termination
EudraCT
European Clinical Trials Database
FMA
First Market Approval
PRO
Patient Reported Outcomes
EU
European Union
FAS
full analysis set
GCP
good clinical practice
GGT
gamma-glutamyl transferase
g/dL
grams per deciliter
GFR
glomerular filtration rate
HDL-C
high density lipoprotein cholesterol
HO
health outcomes
hs-CRP
high sensitivity C reactive protein
IBD
inflammatory bowel disease
IBDQ
Inflammatory Bowel Disease Questionnaire
ICH
International Conference on Harmonization
IEC
Independent Ethics Committee
IFN γ
interferon γ (gamma)
IL-6
Interleukin 6
INR
international normalized ratio
IRB
Institutional Review Board
IUD
intrauterine device
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Abbreviation
Term
IV
intravenous
IVRS
Interactive Voice Recording System
JAK
janus kinase
kg
kilograms
LDH
lactate dehydrogenase
LDL-C
low density lipoprotein cholesterol 
LFT
liver function test
LPD
lymphoproliferative disorder 
LTFU
lost to follow up
6-MP
6-mercaptopurine
MCV
mean corpuscular volume
MCH
mean corpuscular hemoglobin
MRI
magnetic resonance image
mL
milliliters
mg
milligrams
NK
natural killer
μmol
micromoles
pH
potential of hydrogen
PhRMA
Pharmaceutical Research and Manufactures of America
PMS
partial Mayo score
PR
per rectum
PRAC
Pharmacovigilance Risk Assessment Committee
PT
prothrombin time
PVCs
premature ventricular complexes
QTc 
corrected QT interval
RA
rheumatoid arthritis
RBC
red blood cell
RDW
red cell distribution
SAE
serious adverse event
SRSD
Single Reference Safety Document
t½ 
half-life
TB
tuberculosis
Tmax
time to maximum plasma concentration
TNF alpha
tumor necrosis factor alpha
UC
ulcerative colitis
ULN
upper limit of normal
US
United States
WBC
white blood cell
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SAP_001.pdf: 
Protocol A3921139 (CP-690,550)
Statistical Analysis Plan v3.0
PFIZER CONFIDENTIAL
Page 1
PROTOCOL A3921139
A MULTI-CENTER OPEN-LABEL STUDY OF CP-690,550 IN SUBJECTS WITH 
MODERATE TO SEVERE ULCERATIVE COLITIS
STATISTICAL ANALYSIS PLAN
(SAP)
Version
Date
1.0
1 February 2012
 
UK)
2.0
29 June 2016
3.0
12 August 2020
P
P
PPD
PPD
PPD
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TABLE OF CONTENTS
LIST OF FIGURES ...................................................................................................................3
APPENDICES ...........................................................................................................................3
1. AMENDMENTS FROM PREVIOUS VERSION(S) ...........................................................4
2. INTRODUCTION .................................................................................................................4
2.1. Study Design .............................................................................................................5
2.2. Study Objectives .......................................................................................................7
3. INTERIM ANALYSES, FINAL ANALYSES AND UNBLINDING..................................8
4. HYPOTHESES AND DECISION RULES...........................................................................8
4.1. Statistical Hypotheses ...............................................................................................8
4.2. Statistical decision rules............................................................................................8
4.2.1. Sample Size Rationale..................................................................................8
5. ANALYSIS SETS .................................................................................................................9
5.1. Full Analysis Set .......................................................................................................9
5.2. Safety Analysis Set....................................................................................................9
5.3. Other Analysis Sets ...................................................................................................9
5.4. Treatment Misallocations........................................................................................10
5.5. Protocol Deviations.................................................................................................10
6. ENDPOINTS AND COVARIATES ...................................................................................10
6.1. Efficacy Endpoints ..................................................................................................10
6.1.1. Primary Endpoint........................................................................................11
6.1.2. Secondary Endpoints ..................................................................................11
6.2. Safety Endpoints .....................................................................................................11
6.3. Other Endpoints.......................................................................................................12
6.3.1. Patient Reported Outcome (PRO) Endpoints .............................................12
6.4. Covariates................................................................................................................12
7. HANDLING OF MISSING VALUES ................................................................................13
7.1. Efficacy Endpoints ..................................................................................................13
 
7.2. PRO Endpoints........................................................................................................15
7.3. Safety Data Endpoints.............................................................................................15
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8. STATISTICAL METHODOLOGY AND STATISTCAL ANALYSES............................15
8.1. Statistical Methods ..................................................................................................15
8.2. Statistical Analyses .................................................................................................15
8.2.1. Demographic and Baseline Characteristics ................................................15
8.2.2. Primary Analysis ........................................................................................15
8.2.3. Secondary 
 Efficacy Analyses ..........................................15
8.2.4. Safety Analyses ..........................................................................................17
8.2.5. Analyses of Patient reported Outcome (PRO) Endpoints...........................17
9. APPENDICES .....................................................................................................................18
LIST OF FIGURES
Figure 1. Study Design ..............................................................................................................7
APPENDICES
Appendix 1. Definition of Analysis Visit Windows................................................................18
Appendix 2.1. Mayo Scoring System for Assessment of Ulcerative Colitis Activity.............20
Appendix 2.2.1. Inflammatory Bowel Disease Questionnaire (IBDQ)...................................21
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1. AMENDMENTS FROM PREVIOUS VERSION(S) 
This document is Version 3 of the statistical analysis plan (SAP) for Protocol A3921139
based on protocol Amendment 11. Although this study used a Data Monitoring Committee 
(DMC), no changes were based on any result from DMC review.  
Major changes from Version 2 to Version 3 include:
•
Section 2 was updated based on the protocol Amendments 9, 10 and 11.
•
Section 5.5 was updated to mention protocol deviations related to COVID-19.
•
Section 6.2 was updated to include incidence rates for adverse events of special 
interest.
•
Section 7.1 was updated to include approach for handling subjects that moved to 
Study A3921288 (Riveting) or Japan post-marketing surveillance study, or 
discontinued due to regulatory approval in Japan, or had dose escalation.
•
Section 8.2.4 was updated to include listing of subjects with dose reduction due to 
pulmonary embolism (PE) risk factors and analyses for incidence rates.
Major changes from Version 1 to Version 2 include:
•
Section 2 and Section 4.2.1 were updated based on the protocol Amendment 8. 
•
Section 5.3 was updated to add subpopulations.
•
Section 7 was updated to add the non-responder imputation (NRI) for binary 
endpoints, and last observation carried forward (LOCF) for continuous endpoints. 
•
Section 8.2 was updated to include details of data summaries to be done in each 
subpopulation.
•
Appendix 1 was updated for definition and use of visit windows.
2. INTRODUCTION
The purpose of this document is to provide further details about the statistical analysis 
methods specified in the protocol. 
Ulcerative colitis (UC) is a chronic, relapsing, inflammatory disease of the colon 
characterized by alternating episodes of remission and spontaneous relapse.  The prevalence 
has been estimated to range from 37 to 246 cases per 100,000 persons in North America and 
21 to 243 cases per 100,000 persons in Europe. It is most commonly diagnosed in late 
adolescence and early adulthood, with the peak incidence occurring between 20-39 years of 
age. 
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Current therapy for the treatment of UC includes 5-aminosalicylic acid (5-ASA), systemic 
and/or topical steroids, immunosuppressants such as azathioprine/6-mercaptopurine and 
cyclosporine, and tumor-necrosis factor alpha (TNFα) blockers. However, despite these 
treatment options, a significant proportion of UC patients still require colectomy for 
refractory or severe fulminant disease, or in some cases for cancer prevention.  Although 
patients with UC are often considered to be cured by restorative proctocolectomy, the quality 
of life may be poor and the surgery can be associated with short-term and long-term 
complications, including a decreased female fecundity and the development of pouchitis.  At 
present, no current pharmacological therapy is able to provide a cure for UC.  The primary 
treatment goal is to induce remission and then to maintain this state.  Therefore, identification 
of new effective therapies is an important area of research.
This study is designed to evaluate the long term safety and tolerability of tofacitinib in 
patients with moderately to severely active ulcerative colitis who have had an inadequate 
response to conventional therapy.
2.1. Study Design
This is a Phase 3, multi-center, open-label study in subjects who have completed or 
demonstrated treatment failure in the maintenance study A3921096, or who were 
non-responders after completing 8 weeks of treatment in the induction Study A3921094 or 
A3921095.  Approximately 900 subjects are expected to become eligible for the study.  This 
study will continue up to approximately July 2020. Individual subject duration of 
participation will vary depending on when the subject was enrolled into the study and the 
study end date. Therefore, the duration of participation for an individual subject may range 
from approximately 4 years to more than 7 years. If the study continues beyond Month 72 
for an individual subject, the investigator should continue to follow the same visit schedule 
and study procedures outlined during the study visits of year 4. 
Subjects who completed Study A3921096 or had early withdrawal due to treatment failure as 
defined in the A3921096 protocol are eligible to enroll in this study, A3921139. In addition, 
subjects who complete 8 weeks of treatment in Study A3921094 or A3921095 and are 
classified as non-responders are eligible to enroll in this study. The eligibility of a subject for 
this study will be assessed based on study data collected at Week 8/9 of Study A3921094 or 
A3921095 (for non-responders) or the Week 52/53 visit (for completers) or early termination 
visit (early withdrawals due to treatment failure) of Study A3921096.  The study data 
collected at the Week 8/9 visit for Study A3921094 or A3921095 (for non-responders) or the 
Week 52/53 visit or early termination visit of Study A3921096 will be recorded as the 
baseline data for Study A3921139.
Eligible subjects will be assigned to either tofacitinib 5 mg BID or 10 mg BID depending on 
whether the subject is in remission at baseline of Study A3921139. Remission is defined by 
a total Mayo score 2 with no individual subscore >1, and rectal bleeding subscore of 0.  
Eligible subjects who are in remission at Week 52 of Study A3921096 will be assigned to 
receive tofacitinib 5 mg BID.  For treatment assignment, the central read assessment of the 
Mayo endoscopic subscores will be used to determine if a subject is in remission.  Subjects 
who complete Study A3921096 but do not meet the remission definition or who are early 


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withdrawals due to treatment failure in Study A3921096 are eligible to receive 
tofacitinib10 mg BID.  Treatment failure is defined by an increase in Mayo score of at least 
3 points from the baseline value of the maintenance study (A3921096), accompanied by an 
increase in rectal bleeding subscore by at least 1 point, and an increase of endoscopic 
subscore of at least 1 point (yielding an absolute endoscopic subscore of 2) after a minimum 
of 8 weeks of treatment in the maintenance study.  In the scenario where the endoscopic 
subscore is a ‘3’, and the maintenance baseline endoscopic subscore is already a ‘3’ 
(maximum value), then an increase by at least 1 point will not be needed in order to meet 
treatment failure. However, all other components of the treatment failure criteria will still 
need to be met. Subjects who complete induction Study A3921094 or A3921095 and are 
classified as non-responders are also eligible to receive tofacitinib 10 mg BID. 
Tofacitinib dose can be adjusted from 5 mg BID to 10 mg BID for efficacy and from 10 mg 
BID to 5 mg BID after meeting specific laboratory abnormalities or other protocol defined 
criteria regarding efficacy. Dose adjustments can only occur after a subject has received at 
least 8 weeks of treatment in Study A3921139.
Subjects from the induction Study A3921094 or A3921095 (ie, non-responders) who fail to 
demonstrate clinical response at Month 2 of this study will be withdrawn from the study.  
Clinical response is defined by a decrease from the induction study baseline (A3921094 or 
A3921095) Mayo score of at least 3 points and at least 30%, with an accompanying decrease 
in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 
0 or 1.  The endoscopic subscore based on central reading will be used to assess clinical 
response.
Subjects who enroll into this study, who are on tofacitinib 10 mg BID for at least 2 
consecutive years, and who are in stable remission on tofacitinib 10 mg BID for at least 6 
months may have the opportunity to enter Study A3921288 (A Phase 3b/4, Multi-Center,
Double-Blind, Randomized, Parallel Group Study of Tofacitinib in Subjects with UC in 
Stable Remission) if they meet the eligibility criteria. These subjects must:

Have received tofacitinib 10 mg BID for a minimum of 2 consecutive years in Study 
A3921139 (and not have their tofacitinib dose reduced to 5 mg BID due to safety or 
efficacy.

Be in stable remission on tofacitinib 10 mg BID for the 6 month period in Study 
A3921139 up to and including the baseline visit of Study A3921288, defined as
meeting all the following criteria:

A partial Mayo score <=2, with no individual subscore >1 and a rectal bleeding
subscore of 0 at each study visit during the 6 month period in Study A3921139
prior to and at baseline of Study A3921288; AND

At least one assessment of remission based on Mayo score.

Not be receiving any corticosteroids to treat their UC for at least 4 weeks prior to the
baseline visit of Study A3921288.


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Study A3921288 will evaluate the efficacy and safety of tofacitinib in subjects in stable
remission on 10 mg BID who decrease the dose to and remain on 5 mg BID compared to
subjects who remain on 10 mg BID.
All subjects who withdraw early or who complete this open-label study, with the exception
of those subjects entering Study A3921288, will have a 4-week safety follow-up evaluation 
after the last dose of study medication.
Subjects will be required to remain on stable doses of their concomitant medications for UC 
during the study period.  Subjects who enter this study on corticosteroids (eg, subjects who 
withdraw from Study A3921096 due to treatment failure or non-responders at the end of 
Study A3921094 or A3921095) will need to continue the steroid tapering regimen described 
in Study A3921096.  If a subject requires rescue therapy or undergoes surgery, the subject 
should be withdrawn from the study and appropriate agents should be given at the discretion 
of the investigator.
Per protocol Amendment 11, Version 18 June 2019, the study investigator or designee will 
be required to ask each subject at each study visit if he/she has any newly-developed risk 
factors for PE, and if one is identified, the subject will need to have their tofacitinib dose 
adjusted to 5 mg BID if they are taking open label 10 mg BID. 
Figure 1. Study Design
2.2. Study Objectives 
Primary objective:


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
To assess the safety and tolerability of long-term tofacitinib therapy in subjects with 
UC.
Secondary objectives:

To evaluate the efficacy of long-term tofacitinib therapy in subjects with UC.

To evaluate the effect of long-term tofacitinib therapy on quality-of-life in subjects 
with UC.
3. INTERIM ANALYSES, FINAL ANALYSES AND UNBLINDING 
This is an open-label study. Assignment to tofacitinib will be open to the investigators, 
patients and the Pfizer study team.  There will be no need for unblinding. Knowledge of 
open-label treatment assignment will not unblind the treatment assignment in the previous 
double-blinded studies (A3921094, A3921095, or A3921096).
Interim analyses may be performed for study monitoring for internal decision making, 
application for approval or due to regulatory requests.  An independent Data Safety 
Monitoring Board (DSMB), a group of experts external to Pfizer, will review accumulating 
safety data from this study on an ongoing basis.  Review of efficacy data may occur as part 
of any risk-benefit assessment deemed the responsibility of this committee.  Based on these 
reviews, the DSMB will have the capacity to make recommendations to Pfizer that might 
impact the future conduct of the trial.  The DSMB will have access to treatment information 
during the clinical trial.  The management and process of this committee will be in 
accordance with Pfizer’s Standard Operating Procedures and will be documented in the 
DSMB Charter.  The DSMB members will all be individuals who are independent of Pfizer.
The final analysis will be performed after the official release of the database.
4. HYPOTHESES AND DECISION RULES
4.1. Statistical Hypotheses
No formal hypotheses are to be tested.
4.2. Statistical decision rules
4.2.1. Sample Size Rationale 
Approximately 900 subjects are expected to become eligible for the study. Approximately
460 subjects are expected to enroll from the maintenance Study A3921096 assuming a
78% rollover rate from the maintenance study. Approximately 440 subjects are expected to
enroll from the induction Study A3921094 or A3921095 assuming that 38% of subjects
enrolled in those studies will not achieve clinical response and will not have improving
endoscopic subscores after completing induction Study A3921094 or A3921095.


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5. ANALYSIS SETS
5.1. Full Analysis Set
The Full Analysis Set (FAS) is defined as all subjects who receive at least 1 dose of study 
medication in this study.
5.2. Safety Analysis Set
The FAS and the Safety Analysis Set (SAS) are the same.
5.3. Other Analysis Sets
The following subpopulations that are subsets of the FAS population will be used to 
summarize the efficacy data:

Maintenance remission subpopulation:  Subjects that completed the maintenance 
Study A3921096 in remission. Remission is defined by a total Mayo score 2 with 
no individual subscore >1, and rectal bleeding subscore of 0.

Maintenance treatment failure subpopulation: Subjects that were treatment 
failures or dropped out due to lack of efficacy from the maintenance Study A3921096
and received tofacitinib 10 mg BID or placebo from induction Study A3921094 or 
A3921095. Treatment failure was defined by an increase in Mayo score of at least 
3 points from the baseline value of Study A3921096, accompanied by an increase in 
rectal bleeding subscore by at least 1 point, and an increase of endoscopic subscore of 
at least 1 point yielding an absolute endoscopic subscore of ≥2. In the scenario where 
the endoscopic subscore is a ‘3’, and the maintenance baseline endoscopic subscore is 
already a ‘3’ (maximum value), then an increase by at least 1 point will not be needed 
in order to meet treatment failure. Subjects that completed the maintenance Study 
A3921096 and fulfilled the definition of treatment failure are included in this 
subpopulation. 

Other maintenance completers subpopulation: All other completed subjects from 
maintenance Study A3921096, that is, those subjects who were neither in remission 
nor fulfilled the definition of treatment failure.

Induction Non-responder subpopulation: Subjects who were enrolled from 
induction Study A3921094 or A3921095 directly but did not achieve clinical 
response and received tofacitinib 10 mg BID or placebo in the induction studies. 
Please notice that some subjects may not be included in any of the subpopulations, such as 
those in maintenance treatment failure but received tofacitinib 15 mg BID in the induction
studies, or those who were enrolled from induction studies directly (in error) but were in 
clinical response. A listing of subjects that do not meet any of the subpopulation categories 
will be generated.  Central read endoscopic subscore was used in defining these 
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The analysis described in this SAP may be repeated on the specific country and/or region 
subpopulation sets in order to meet country-specific regulatory requirements.  The 
subpopulation sets will be the subjects in analysis sets defined in this section who have 
enrolled from sites in the specific country and/or region.
5.4. Treatment Misallocations 
If a subject was enrolled into the study but did not receive any study drug then the subject
will be excluded from all the analyses.
5.5. Protocol Deviations
A full list of protocol deviations for the study report will be compiled prior to database 
closure including protocol deviations related to COVID-19. Per-protocol analysis set is not 
defined. All analyses will be performed for FAS population and its subpopulations.  
6. ENDPOINTS AND COVARIATES
Measurement will be collected/derived at visits specified in the protocol.  The details of visit 
windows are defined in Appendix 1.  Unless specifically stated otherwise, the baseline value 
is defined as the last non-missing measurement collected prior to the first administration of 
study medication in this study, A3921139, at Day 1.
6.1. Efficacy Endpoints
Efficacy endpoints will be based upon the Mayo score and partial Mayo score. The Mayo 
score is an instrument designed to measure disease activity of ulcerative colitis. Mayo score 
ranges from 0 to 12 points. It consists of 4 subscores, each graded from 0 to 3 with higher 
scores indicating more severe disease.

Stool frequency (0-3);

Rectal bleeding (0-3);

Findings of flexible sigmoidoscopy (0-3);

Physician global assessment (PGA) (0-3).
A partial Mayo score (PMS) is an instrument designed to measure disease activity of UC
without endoscopy. Partial Mayo score ranges from 0 to 9 points.
An endoscopy will be performed at Baseline, Month 2, at annual study visits (Months 12, 
24 and 36), and at the early withdrawal/early termination visit. The endoscopic subscores at 
all applicable visits will be read by study site investigator. However, at Month 2 visit, the 
endoscopic score will be read by both central reader and site investigators prior to 
Amendment 8. After implementation of Amendment 8, the Month 2 endoscopic subscore 
will be read by study site investigator only.  The endpoints that require the endoscopic 
subscore component will be derived based on local-read endoscopic subscores, as well as 
central-read endoscopic subscores, if available.


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Further information on the Mayo score is given in Appendix 2.1. 
6.1.1. Primary Endpoint
As this is an open-label extension study, there is no primary efficacy endpoint. 
6.1.2. Secondary Endpoints
•
Remission.  Remission in this study is defined as a Mayo score ≤2 with no individual 
subscore >1, and rectal bleeding subscore of 0. 
•
Clinical remission. Clinical remission in this study is defined as a Mayo score ≤2
with no individual subscore >1.
•
Partial Mayo score (PMS) remission.  PMS remission in this study is defined as a 
partial Mayo score ≤2 with no individual subscore >1.
•
Mucosal healing.  Mucosal healing is defined as a Mayo endoscopic subscore of 0 or 
1.
 
 
 
  
6.2. Safety Endpoints
•
Incidence and severity of adverse events.
•
Incidence of serious infections.
•
Incidence and severity of clinical laboratory abnormalities, and change from baseline 
in clinical laboratory values.
•
Incidence of vital sign abnormalities and change from baseline in vital signs.
•
Incidence of clinically significant changes in physical examinations from baseline.
•
Incidence of electrocardiogram (ECG) abnormalities during treatment.
•
Summary of adjudicated safety events (eg, cardiovascular, malignancy, opportunistic
infections, hepatic events).
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•
Proportion of subjects with addition of lipid lowering agents.
•
Proportion of subjects whose dose is decreased to 5 mg BID from 10 mg BID. 
 
 
6.3. Other Endpoints 
6.3.1. Patient Reported Outcome (PRO) Endpoints 
Section 7.2 of the protocol gives details on the IBDQ, 
 
 
•
IBDQ remission, defined as total score in Inflammatory Bowel Disease Questionnaire 
(IBDQ) ≥170 over time.
•
The scores and change from Baseline (of Study A3921139) in total IBDQ score and 
domains (Bowel Symptoms, Systemic Symptoms, Emotional Function and Social 
Function) over time.
 
 
 
 
 
 
 
 
6.4. Covariates
•
None.
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7. HANDLING OF MISSING VALUES
7.1. Efficacy Endpoints
For binary efficacy endpoints (Remission, Clinical remission, Mucosal healing, 
PMS remission, Clinical response) derived from Mayo subscores (site-read endoscopic 
subscore was used), data will be summarized based on the observed-case data and non-
responder imputation and last observation carried forward imputation (NRI-LOCF). The 
NRI-LOCF approach is described as the following:  

For subjects who discontinued from the study, other than those who moved to Study 
A3921288 or to the Japan post-marketing surveillance study, or due to regulatory 
approval in Japan, NRI will be used for missing data up to the visit (using the lower 
bound of visit window as defined in Appendix 1) they would have reached if they had 
stayed at the study. The missing data before time of discontinuation will be imputed 
as non-responders.

For ongoing subjects (for interim analyses only), they will be included in the 
summary tables only up to visits with non-missing data in the dataset for the interim 
report. For subjects with intermittent missing data, they will be treated as non-
responders. Otherwise no imputation for missing data will be applied since it’s hard 
to separate the true missing data from being late for the scheduled visit. 

For completed subjects, they will be included in the summary tables only up to the 
completion visit. Missing data before the completion will be imputed using the NRI 
approach.

For subjects who discontinued from the study and moved to Study A3921288 or to 
the Japan post-marketing surveillance study, or due to regulatory approval in Japan,
LOCF will be used up to the visit (using the lower bound of visit window as defined 
in Appendix 1) they would have reached if they had stayed in the study. The missing 
data before time of discontinuation will be imputed as non-responders. This approach 
will likely overestimate the proportions of subjects who achieve the binary endpoints 
since it is assumed that the response status remains after subjects moved to Study 
A3921288 or the Japan post-marketing surveillance study. 
For continuous endpoints total Mayo score and Partial Mayo score, data will be summarized 
based on the observed-case data and LOCF. The LOCF approach is described as the 
following:  

For subjects who discontinued from the study, other than moved to Study A3921288
or to the Japan post-marketing surveillance study, or due to regulatory approval in 
Japan, LOCF approach will be used for missing data up to the visit (using the lower
bound of visit window as defined in Appendix 1) they would have reached if they had 
stayed in the study. Any missing data before time of discontinuation will be imputed 
using LOCF. 


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•
For ongoing subjects (for interim analyses only), they will be included in the 
summary tables only up to visits that are included in the dataset for the interim report.
For intermittent missing data, LOCF approach will be applied. Otherwise no 
imputation for missing data will be applied since it’s hard to separate the true missing 
data from being late for the scheduled visit. 
•
For completed subjects, they will be included in the summary tables only up to the 
completion visit. Missing data before the completion will be imputed using LOCF
approach.
•
For subjects who discontinued from the study and moved to Study A3921288 or to 
the Japan post-marketing surveillance study, or due to regulatory approval in Japan,
LOCF approach will be used after the time of discontinuation up to the visit (using 
the lower bound of visit window as defined in Appendix 1) they would have reached 
if they had stayed in the study. Any missing data before time of discontinuation will 
be imputed using LOCF. 
To implement LOCF, individual components were carried forward first, then the endpoints 
were derived using the imputed components.  
The central read endoscopic subscore was only assessed at baseline and Month 2 visit for 
subjects who enrolled prior to protocol Amendment 8. For subpopulations other than 
induction non-responder subpopulation, the endpoints using central-read endoscopic 
subscore as a component will be summarized based on observed data only. No NRI or 
LOCF imputation will be applied.  However, for induction non-responder subpopulation, 
subjects were expected to complete Month 2 visit prior to implementation of protocol 
Amendment 8, endpoints using central-read endoscopic subscore as a component will be 
summarized based on both NRI for binary endpoints (or LOCF for continuous endpoints),
and observed data for Month 2.
 
 
 
 
 
 
 
 
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7.2. PRO Endpoints
For the PRO endpoints based on IBDQ, 
 rules suggested by the 
developers of the questionnaires will be followed in calculating the endpoints with any 
missing items.  If these rules are not sufficient to impute the missing values, then the missing 
values will be handled as following:
•
For IBDQ binary endpoints IBDQ remission and deterioration (worsening) in IBDQ 
bowel symptom domain, they will be handled in the same way as binary efficacy 
endpoints as specified in section 7.1 for missing data and data after the dose 
escalation. 
•
For IBDQ, 
 continuous endpoints, they will be handled in the 
same way as continuous efficacy endpoints as specified in section 7.1 for missing 
data and data after the dose escalation.  
  
7.3. Safety Data Endpoints
Safety data will be summarized based on observed-case data. Missing data will not be 
imputed.
8. STATISTICAL METHODOLOGY AND STATISTCAL ANALYSES
8.1. Statistical Methods 
As no formal statistical tests will be conducted, there will be no need to report p-values.  
Descriptive summary statistics such as number, percentage for categorical endpoints and 
mean, standard deviation, median for continuous endpoints will be presented, along with 
some graphical representations using the FAS as defined in Section 5.1.
8.2. Statistical Analyses 
8.2.1. Demographic and Baseline Characteristics
Demographics and baseline characteristics will be summarized for the FAS and 
subpopulations as detailed in Section 5.3 for overall and by initial dose assignment. 
8.2.2. Primary Analysis
The primary analysis is the analysis of safety. See Section 8.2.3 below.
8.2.3. Secondary 
 Efficacy Analyses
All efficacy endpoints are considered as secondary
. Descriptive summary 
statistics will be reported at scheduled visits in FAS, and subpopulations: maintenance 
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remission subpopulation, maintenance treatment failure subpopulation, other maintenance
completers subpopulation, and induction non-responder subpopulation. However, the 
endpoints of proportion of subjects with dose increase from tofacitinib 5 mg BID to 10 mg 
BID will be summarized for maintenance remission subpopulation only.  
For FAS or each subpopulation, the data will be summarized based on the following table:
Efficacy Analysis 
Population/Subpopulation 
Treatment group (the 
default is the assigned
dose for initial 
assignment in 
A3921139)
By group
FAS
Overall
Tofacitinib 5 mg BID
Tofacitinib 10 mg 
BID
Overall
Maintenance Remission 
subpopulation
Tofacitinib 5 mg BID
Overall
By maintenance treatment (4 groups: 
10 mg, 5 mg, placebo, 5mg+10mg)
Maintenance Treatment 
Failure subpopulation
Tofacitinib 10 mg
BID
Overall
By dose combination received in 
induction and maintenance (6 groups)
and a 7th group of 
Tofacitinib 10 mg in induction and 
Tofacitinib 5 mg + placebo in 
maintenance
Other Maintenance
Completers subpopulation
Tofacitinib 10 mg
BID
Overall
By maintenance treatment (4 groups: 
tofacitinib 10 mg, Tofacitinib 5 mg, 
placebo, Tofacitinib 10 mg and 5 mg 
combined)
Induction Non-responder 
subpopulation
Tofacitinib 10 mg
BID
Overall
By Induction treatment (Tofacitinib 10 
mg, Placebo) 
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8.2.4. Safety Analyses
The primary analysis is the analysis of safety.
That is, all safety data will be summarized descriptively by initial treatment group and 
combined Tofacitinib group of A3921139 in the safety analysis set. The adverse event data 
will be summarized for entire treatment duration.
A listing of subjects with dose reduction due to PE risk factors will be provided.  
Incidence Rates (IR) of Adverse Events of Special Interest will be provided. Confidence 
intervals (95%) will be computed using exact Poisson method.
In general, IR will be calculated only for discrete (0/1) endpoints determined by adverse 
event data for events of special interest only. The numerator will be the number of unique 
subjects with a treatment emergent event as defined above during the interval from the first 
dose in Study A3921139 to last dose of tofacitinib + 28 days at risk period. The denominator 
of the incidence rate is person time accruing from the subject’s first dose of tofacitinib in 
Study A3921139 to last dose of tofacitinib + 28 days, or to the date of the first event, 
whichever occurs earlier. For a subject who died, the time will be the minimum of (the date 
of the last dose + 28 days, or death date).
However, for mortality, malignancies (excluding NMSC and NMSC) and MACE related 
endpoints, all events regardless of their onset within 28 days or beyond after the last dose of 
tofacitinib will be included.
The concept of 28 days is applied to subjects without events that discontinued or completed 
the study. For ongoing subjects, 28 days will not be added to the exposure. 
8.2.5. Analyses of Patient reported Outcome (PRO) Endpoints
Descriptive summary statistics will be reported at scheduled visits in FAS, and four 
subpopulations; Maintenance Remission, Maintenance Failure, Other Maintenance 
Completers, and Induction Non-responders using the same methods as for the efficacy 
endpoints for IBDQ  
.
 
 
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9. APPENDICES
Appendix 1. Definition of Analysis Visit Windows 
Analysis visit windows will be used for efficacy variables, and for any safety displays that 
display by visit.
Visit Label
Target Day
Analysis Visit window
Baseline
Day 1
Up to Day 1
Month 1
Day 30
Days 2-45
Month 2
Day 60
Days 46-90
Month 4
Day 120
Days 91-150
Month 6
Day 180
Days 151-225
Month 9
Day 270
Days 226-315
Month 12
Day 360
Days 316-405
Month 15
Day 450
Days 406-495
Month 18
Day 540
Days 496-585
Month 21
Day 630
Days 586-675
Month 24
Day 720
Days 676-765
Month 27
Day 810
Days 766-855
Month 30
Day 900
Days 856-945
Month 33
Day 990
Days 946-1035
Month 36
Day 1080
Days1036-1125
Month 39
Day 1170
Days 1126-1215
Month 42
Day 1260
Days 1216-1305
Month 45
Day 1350
Days 1306-1395
Month 48
Day 1440
Days 1396-1485
Month 51
Day 1530
Days 1486-1575
Month 54
Day 1620
Days 1576-1665
Month 57
Day 1710
Days 1666-1755
Month 60
Day 1800
Days 1756-1845
Month 63
Day 1890
Days 1846-1935
Month 66
Day 1980
Days 1936-2025
Month 69
Day 2070
Days 2026-2115
Month 72
Day 2160
Day 2116-2205
Month 75
Day 2250
Days 2206-2295
Month 78
Day 2340
Days 2296-2385
Month 81
Day 2430
Days 2386-2475
Month ≥84
Day 2520
Days ≥2476
If more than one observation from the same subject falls into the same window, the value 
closest to the target day will be used as the observation for that analysis visit. All
observations will, however, be included in the listings. 


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For efficacy endpoints derived based on total Mayo score we will use the same windows 
from the above table although total Mayo score was not assessed at each visit.
Some PRO data or laboratory data were not scheduled to be assessed at each visit. In this 
case, the unscheduled ‘windowed’ visit will be moved to the next scheduled windowed visit 
for analysis and reporting. 


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Appendix 2. Further Definition of Endpoints
Appendix 2.1. Mayo Scoring System for Assessment of Ulcerative Colitis Activity
The Mayo Score ranges from 0 to 12, with higher scores indicating more severe disease. It 
consists of 4 subscores. Each sub-score ranges from 0 to 3. The 4 components of the Mayo 
Score are:
Stool Frequency:
0 = Normal no. of stools for this patient. 
1 = 1 to 2 stools more than normal. 
2 = 3 to 4 stools more than normal. 
3 = 5 or more stools more than normal. 
Rectal Bleeding: 
0 = No blood seen. 
1 = Streaks of blood with stool less than half the time. 
2 = Obvious blood with stool most of the time. 
3 = Blood alone passes. 
Findings on Endoscopy: 
0 = Normal or inactive disease. 
1 = Mild disease (erythema, decreased vascular pattern). 
2 = Moderate disease (marked erythema, lack of vascular pattern, any friability, 
erosions). 
3 = Severe disease (spontaneous bleeding, ulceration).
Physician’s Global Assessment: 
0 = Normal. 
1 = Mild disease. 
2 = Moderate disease. 
3 = Severe disease.
The subject’s stool diary information will be captured by an interactive voice response 
system (IVRS) connected through the phone system.  Subjects will report stool frequency 
and the most severe bleeding of the day for rectal bleeding subscore daily at least 
5 consecutive days prior to each study visit during the study. Stool frequency subscore will 
be calculated based on the average number (rounded to an integer) of stools over the prior 3 
days minus the normal number of stools per day reported by the subject.  The rectal bleeding 
subscore is the average number (rounded to an integer) of the 3 days prior to the study visit.
 
 
 
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Appendix 2.2.1. Inflammatory Bowel Disease Questionnaire (IBDQ)
The Inflammatory Bowel Disease Questionnaire (IBDQ) is a psychometrically validated 
patient reported outcome (PRO) instrument for measuring the disease-specific quality of life 
in subjects with IBD.  The IBDQ consists of 32 items with scores ranging from 1 to 7 with 
1 being the worst possible response and 7 being the best possible response.
The following endpoints will be derived based on the collected responses.  In each instance, 
the change from Baseline values will be evaluated:
•
IBDQ Total Score.
•
IBDQ Domain Scores:
•
Bowel Symptoms;
•
Emotional Function;
•
Systemic Symptoms;
•
Social Function.
The Bowel Symptoms Domain score is calculated as the sum of the scores for questions 1, 5, 
9, 13, 17, 20, 22, 24, 26 and 29 (Range 10-70).
The Emotional Function Domain score is calculated as the sum of the score for questions 3,
7, 11, 15, 19, 21, 23, 25, 27, 30, 31 and 32 (Range 12-84).
The Systemic Symptoms Domain score is calculated as the sum of the scores for questions 2, 
6, 10, 14 and 18 (Range 5-35).
The Social Function Domain score is calculated as the sum of the scores for questions 4, 8, 
12, 16 and 28 (Range 5-35).
The total IBDQ score is calculated as the sum of scores for questions 1 to 32 (Range 32-224) 
with a higher score indicating a better quality of life.  Scores of patients with clinical 
remission usually range from 170 to 190.
 
 
 
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Protocol A3921139 (CP-690,550)
Statistical Analysis Plan v3.0
PFIZER CONFIDENTIAL
Page 28
CCI


Protocol A3921139 (CP-690,550)
Statistical Analysis Plan v3.0
PFIZER CONFIDENTIAL
Page 29
CCI


Protocol A3921139 (CP-690,550)
Statistical Analysis Plan v3.0
PFIZER CONFIDENTIAL
Page 30
CCI


Protocol A3921139 (CP-690,550)
Statistical Analysis Plan v3.0
PFIZER CONFIDENTIAL
Page 31
CCI


Protocol A3921139 (CP-690,550)
Statistical Analysis Plan v3.0
PFIZER CONFIDENTIAL
Page 32
CCI