Public Disclosure Synopsis
Protocol A3921086 – 14 July 2017 – Final

PFIZER INC.
These results are supplied for informational purposes only.
Prescribing decisions should be made based on the approved package insert.
GENERIC DRUG NAME AND/OR COMPOUND NUMBER: Tofacitinib / CP-690,550
PROTOCOL NO.: A3921086
PROTOCOL TITLE: A Open-Label Extension Study of CP-690,550 as Maintenance
Therapy in Patients with Crohn’s Disease
Study Center(s):This study was conducted at 57 sites: 1 site each in Austria, the Czech Republic, Greece, andSouth Africa; 2 sites each in Bulgaria, France, the Netherlands, the Republic of Korea, andthe Ukraine; 3 sites each in Australia, Canada, Germany, Israel, and Spain; 5 sites each in
Hungary and Japan; and 18 sites in the United States.

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Study Initiation Date and Primary Completion or Final Completion Dates: Study
Initiation Date: 23 April 2012; Final Completion Date: 25 July 2016
Phase of Development: Phase 2b
Study Objective(s):Primary Objective:
The primary objective of the study was to assess the safety and tolerability of long-term
open-label (OL) tofacitinib (CP-690,550) therapy in subjects with Crohn’s Disease (CD).
Secondary Objectives:•

To evaluate the effect of OL tofacitinib maintenance therapy on clinical remission in
subjects with CD•

To evaluate the effect of OL tofacitinib maintenance therapy on quality of life in subjects
with CD•To evaluate the effect of OL tofacitinib maintenance therapy on biomarkers as measured
by C-reactive protein (CRP) and fecal calprotectin (FEC).

METHODS
Study Design:This was a Phase 2b, multicenter, OL extension study in subjects with CD who completed
the double-blind maintenance treatment in Study A3921084 or withdrew early due toStudy A3921084 treatment failure. This study consisted of a 48-week OL treatment period
followed by a 4-week safety follow-up. The eligibility of a subject for Study A3921086 wasassessed based on study data collected at the Week 26 or Early Termination (ET) visit ofPage 1

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Protocol A3921086 – 14 July 2017 – Final

Study A3921084. The study data collected at the Week 26 visit or ET visit ofStudy A3921084 was recorded as the baseline data for Study A3921086.
Eligible subjects were assigned to either tofacitinib 5 mg twice daily (BID) or 10 mg BID
depending on the subject’s clinical remission status at the end of the Study A3921084
treatment visit. Restrictions on the use of prohibited concomitant medications wereapplicable throughout the study. All subjects who either withdrew early or completed the OL
study were asked to return to the study site for a safety follow-up visit approximately
4 weeks after the last dose of study drug.

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A schedule of study activities is provided in Table 1.

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Protocol A3921086 – 14 July 2017 – Final

Table 1.

Schedule of Activities

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Study Procedure

Visit Number
Informed consent
Medical historyd
Concomitant medication
Complete physical examination
Targeted physical examinatione
Vital signs, including height, weight andtemperaturef
12-lead ECGf
Assessment of inclusion/exclusion criteria(Pseudo)randomization/study treatment
assignmentg
AEs
Study drug dispensing
Study drug accountability
Laboratory
Hematologyh
Blood chemistryh
Lipid profile, fasting
Urinalysis
Urine pregnancy testi
Biomarker Analysis
hsCRP
Fecal calprotectinj
CD assessments

A3921084
Week 26/
A3921086
Baseline
Day 1aVisit 1
X
X
X
X
X

Open-Label Treatment Period

Week 8

Week 16

Week 24

Week 36

Visit 2(±5 days)

Visit 3(±5 days)

Visit 4(±5 days)

Visit 5(±5 days)

X

X

X

X

X
X

X
X

X
X

X
X

X
X
X
X
X

Follow-up

Week 48b(End ofTreatment/
Early
Termination)
Visit 6(±5 days)Week 52c(End of
Study/Followup)
Visit 7(±7 days)

X
X

X

X

X
X

X

X
X
X

X
X
X

X
X
X

X
X
X

X

X
X
X
X
X

X
X
X
X
X

X
X
X
X
X

X
X
X
X
X

X
X
X
X
X

X
X
X
X
X

X
X
X
X
X

X
X

X
X

X
X

X
X

X
X

X
X

X
X

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X

X

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Protocol A3921086 – 14 July 2017 – Final

Table 1.

Schedule of Activities

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Study Procedure

Visit Number

A3921084
Week 26/
A3921086
Baseline
Day 1aVisit 1Open-Label Treatment Period

Week 8

Week 16

Week 24

Week 36

Visit 2(±5 days)
X
X

Visit 3(±5 days)
X
X

Visit 4(±5 days)
X
X

Visit 5(±5 days)
X
X

Follow-up

Week 48b(End ofTreatment/
Early
Termination)
Visit 6(±5 days)
X
X

Week 52c(End of
Study/Followup)
Visit 7(±7 days)
X
X

Subject diariesk
X
CDAIl
X
Patient-Reported Outcome Assessments
IBDQ
X
X
X
X
PRTI
X
SF-36
X
X
X
EQ-5D/VAS
X
X
X
Abbreviations: AE = adverse event; CD = Crohn’s Disease; CDAI = Crohn’s Disease Activity Index; ECG = electrocardiogram; EQ-5D = EuroQOL 5
Dimensions questionnaire; hsCRP = high-sensitivity C-reactive protein; IBDQ = Inflammatory Bowel Disease Questionnaire; PRTI = Patient-Reported
Treatment Impact; SF-36 = 36-Item Short Form Health Survey; VAS = visual analog scale.
a.
b.
c.
d.

e.
f.
g.
h.

For eligible subjects who completed the double-blind treatment of Study A3921084 or fulfilled Study A3921084 treatment failure criteria and consent forStudy A3921086, their Week 26/Visit 6 data from Study A3921084 served as their baseline visit data for Study A3921086.
If a subject discontinued early from the open-label therapy, study procedures were to be completed as per End of Treatment/Early Termination schedule.
This visit could have been scheduled on the last day the subject took study drug or as soon as possible thereafter.
All subjects participating in the open-label extension study were asked to return to the clinic for the End of Study/Follow-up Visit.
Medical history for Study A3921084 was to be brought forward to Study A3921086. Resolved AEs occurring in Study A3921084 were captured as partof the medical history for Study A3921086. Ongoing AEs from Study A3921084 were brought forward to Study A3921086 and were followed as
appropriate.
The targeted physical examination was performed at Week 8, 16, 24, 36 and Follow-up Visit (Week 52) assessing the following: general appearance, eyes,mouth, heart, lungs, abdomen, perineal, musculoskeletal ,extremities, skin and lymph nodes.
12-lead ECG along with vital signs were to be performed before laboratory blood collections. Height was measured as part of vital signs at the baseline
visit only.
(Pseudo) randomization number was generated and subjects were assigned to open-label study treatment.
Baseline hematology, blood chemistry, and laboratory AEs at baseline were obtained from the results of the Week 26/Visit 6 laboratory results ofPage 4

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Protocol A3921086 – 14 July 2017 – Final

Table 1.

Schedule of Activities

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Study Procedure

Visit Number

i

j.

k.
l.

A3921084
Week 26/
A3921086
Baseline
Day 1aVisit 1Open-Label Treatment Period

Week 8

Week 16

Week 24

Week 36

Visit 2(±5 days)

Visit 3(±5 days)

Visit 4(±5 days)

Visit 5(±5 days)

Follow-up

Week 48b(End ofTreatment/
Early
Termination)
Visit 6(±5 days)Week 52c(End of
Study/Followup)
Visit 7(±7 days)

Study A3921084.
Urine pregnancy testing (human chorionic gonadotropin) was required only for women of childbearing potential; testing could have been repeated more
frequently if required by local practices, if a menstrual cycle was missed, or if potential pregnancy was otherwise suspected. Urine pregnancy testing was
performed (using methodology with a testing sensitivity of at least 25 mIU/mL) at the study site using test assays supplied by the central laboratory.
Labeled stool containers and plastic bags were provided to the subjects at the preceding visit so they could bring a refrigerated or frozen stool specimen
with them at that visit. While it was preferred to provide a fresh specimen, it would not have interfered with testing if the stool was immediately
refrigerated or frozen. If the subject failed to bring in the stool specimen, they were to stay at the site and provide it the day of the visit if at all possible orat the earliest possible time.
To be consistent in diary recording, study site staff were asked to place a telephone call approximately 10 days prior to each scheduled visit to remind
subjects to start entering diary data continuously.
Subjects were assigned to open-label study treatment based on the CDAI score calculated using the Study A3921084 Week 20 hematocrit result. When
the Study A3921084 Week 26 hematocrit result became available, the Investigator or designate was required to recalculate CDAI score in order to aid theassessment of subject’s Crohn’s disease progress.

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Protocol A3921086 – 14 July 2017 – Final

Number of Subjects (Planned and Analyzed):
All subjects who completed Study A3921084 or withdrew early due to Study A3921084
protocol-specified treatment failure criteria were eligible for the A3921086 OL study. It was
expected that approximately 108 subjects would enroll in Study A3921084 and estimated that
40% of subjects would have dropped out from Study A3921084. It was expected thatapproximately 85 subjects in Study A3921084 would be enrolled in the A3921086 OL
extension study. The estimated number of subjects included the number of subjects who
withdrew early but met Study A3921084 treatment failure criteria.

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Diagnosis and Main Criteria for Inclusion and Exclusion:
Eligible subjects were expected to meet the following and all other qualifying criteria:
Subjects who completed the 26-week maintenance treatment of Study A3921084 or subjects
who withdrew early due to Study A3921084 treatment failure according to prespecified
criteria; women of childbearing potential who tested negative for pregnancy prior to study
enrolment; sexually active females of childbearing potential were required to use adequate
contraceptive methods during the study period and until completion of the follow-up
procedures. No specific contraceptive measures were required in male subjects during study
participation. Subjects in Canada who were women of childbearing potential and sexuallyactive had to use 2 contraceptive methods at the same time: a highly effective contraceptive
method and an additional effective contraceptive method; subjects who were willing and able
to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures;and evidence of a personally signed and dated informed consent document indicating that the
subject (or a legal representative) had been informed of all pertinent aspects of the study.
Study Treatment:
Eligible subjects were assigned to either tofacitinib 5 mg BID or 10 mg BID depending on
the subject’s clinical remission status at the end of the Study A3921084 treatment visit.
Eligible subjects who were in clinical remission (Crohn’s Disease Activity Index [CDAI]<150) at Week 26 of Study A3921084 were assigned to tofacitinib 5 mg BID. Eligible
subjects who were not in clinical remission (CDAI ≥150) were assigned to receive tofacitinib
10 mg BID. There was a single study treatment dose adjustment allowed, at the discretion of
the Investigator, from 5 mg BID to 10 mg BID or from 10 mg BID to 5 mg BID, after the
initial 8 weeks of fixed OL treatment and for the remaining treatment period.
The first dose of study drug was to occur approximately 12 hours after the last dose of
Study A3921084 medication. Tofacitinib tablets were dispensed in bottles. Subjects
receiving tofacitinib 5 mg BID were instructed to take 1 tablet from their bottle in themorning and 1 tablet from their bottle in the evening, approximately 12 hours apart. Subjects
receiving tofacitinib 10 mg BID were instructed to take 1 tablet from each of the 2 bottles in
the morning and 1 tablet from each of the 2 bottles in the evening, approximately 12 hours
apart. Tofacitinib could be administered with or without food.
Tofacitinib was not made available to subjects at the end of study treatment.

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Protocol A3921086 – 14 July 2017 – Final

Efficacy, Pharmacodynamic, and Outcomes Research Endpoints:
Primary Efficacy Endpoint
There was no primary efficacy endpoint.
Secondary Efficacy Endpoints
All efficacy endpoints were secondary endpoints and were exploratory. Sustained clinicalremission was defined as being in clinical remission (CDAI score <150) at both Week 24 andWeek 48.

090177e18c5cd567\Approved\Approved On: 19-Jul-2017 09:47 (GMT)The secondary efficacy endpoints included:•

The proportion of all enrolled subjects in clinical remission and sustained clinicalremission at Week 48•

The proportions of subjects in clinical remission and sustained clinical remission among
subjects in clinical remission at the A3921086 study baseline•

Proportion of subjects in clinical remission (CDAI score <150) and sustained clinicalremission among subjects in clinical response (CDAI-100 response from Study
A3921083 baseline) or clinical remission at Study A3921086 baseline. CDAI-100
response from Study A3921083 baseline was defined as a decrease of at least 100 points
in CDAI score from Study A3921083 baseline•

The median time to relapse among subjects in clinical remission (CDAI score <150) atbaseline. Relapse was defined as an increase in CDAI of >100 points from the baseline
and an absolute CDAI score of >220 points•

CDAI scores over time and change from baseline in CDAI scores•

The 8 CDAI component scores over time:
1. Number of liquid or very soft stools
2. Abdominal pain
3. General well-being
4. CD related signs and symptoms
5. Use of anti-diarrheals (Y/N)
6. Abdominal mass
7. Hematocrit
8. Body weight

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Protocol A3921086 – 14 July 2017 – Final•

The proportion of subjects achieving a steroid-free clinical remission at Week 48 among
subjects on steroids at baseline•

Corticosteroid use over time•

Proportion of subjects switching from 5 mg BID to 10 mg BID and from 10 mg BID to
5 mg BID after the initial assignment at Day 1

The CDAI is a validated instrument to measure disease activity and the response to treatment
in CD studies, and clinical remission or clinical response as measured by CDAI has beenused as a primary endpoint in multiple pivotal trials in the CD indication. Scores range from0 to approximately 600. An electronic CDAI diary was provided to the subjects at baseline(Visit 1) in order for them to record the number of liquid or very soft stools, the intensity of
abdominal pain, and general well-being. Subjects were requested to complete the daily diary
for at least 7 days prior to each study clinic visit. The information extracted was used for
calculation of the CDAI score, taking into account the continuous 7 days’ data recorded prior
to each study clinic visit.

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Pharmacodynamic (Biomarker) Evaluations
Biomarker endpoints, serum CRP and FEC over time and change from baseline in CRP and
FEC, were measured throughout the study at protocol-specified times and analyzed by acentral laboratory. FEC was obtained from stool samples, and high sensitivity CRP (hsCRP)
was obtained from serum samples.
Patient-Reported Outcomes (PRO) Research Endpoints
PRO endpoints were:•Absolute scores and change from baseline in Inflammatory Bowel Disease Questionnaire(IBDQ) total score and domain scores (Bowel Symptoms, Systemic Symptoms,
Emotional Function and Social Function) over time•

The proportion of subjects with IBDQ total score ≥170 at Week 48 (clinical remission)•

The absolute scores for the Patient-Reported Treatment Impact (PRTI) assessment at
Week 48•

The absolute scores and change from baseline in the 36-Item Short Form Health Survey(SF-36), version 2, acute (physical and mental component summary scores, and 8 domainscores) over time•

The absolute scores and change from baseline in EuroQOL 5 Dimensions Questionnaire(EQ-5D) and visual analog scale (VAS) over time•

The number of subjects hospitalized and the total length of hospitalizations related to CD

PRO measurements were collected and evaluated in a different manner than the observed or
volunteered adverse events (AEs). Given these differences, no attempt was made to resolve
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Protocol A3921086 – 14 July 2017 – Final

any apparent discrepancies between observed or volunteered AEs and PRO data collectedfrom subjects.
The IBDQ is a psychometrically validated PRO instrument with 32 items (grouped into
4 domains: bowel function, emotional status, systemic symptoms and social function) for
measuring the disease-specific quality of life in subjects with inflammatory bowel disease,including CD. Total possible IBDQ scores ranged from 32 to 224. For each domain, ahigher score indicated a better quality of life. An IBDQ total score ≥170 indicates clinicalremission.

090177e18c5cd567\Approved\Approved On: 19-Jul-2017 09:47 (GMT)At the Week 48 or ET visit, subjects completed the PRTI at the clinic prior to any procedures
being performed or the administration of study drug. The inflammatory bowel disease PRTI
survey is a validated instrument completed by the subject designed to assess their preference,
willingness to use and satisfaction with therapy. The PRTI questionnaire comprises 3
individual questions (subject satisfaction with study treatment, subject preference for study
drug over prior treatment, and subject willingness to re-use the study treatment again), eachof which was scored on a 5-point Likert scale.
The SF-36 (version 2 with a 1-week recall) is a widely used general health statusquestionnaire that assesses 8 domains of functional health and well-being. On the specifiedstudy visit days, subjects completed the SF-36 at the clinic prior to any procedures being
performed or the administration of study drug.
The EQ-5D and VAS is a standardized instrument completed by the subject designed toassess impact on quality of life in 5 domains (including mobility, self-care, usual activities,
pain/discomfort, and anxiety/depression) and 1 question on the subject’s current health state“today”. The VAS records the respondent’s self-rated health on a scale from 0 (worst
imaginable health state) to 100 (best imaginable health state). On the specified study visit
days, subjects completed the EQ-5D/VAS at the clinic prior to any procedures being
performed or the administration of study drug.
Safety Evaluations:
Safety endpoints in this study were:•

Incidence and severity of AEs•

Incidence and severity of clinical laboratory abnormalities, and change from baseline inclinical laboratory values•

Incidence of clinically significant changes in physical examination from baseline•

Incidence of vital sign abnormalities and changes from baseline in vital sign measures•

Incidence of electrocardiogram (ECG) abnormalities and change from baseline in ECG
measurements during treatment

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Protocol A3921086 – 14 July 2017 – Final•

Summary of adjudicated clinical safety endpoints of special interest (major adverse
cardiovascular events, hepatic injury, opportunistic infection, malignancy,
gastrointestinal [GI] perforation, and interstitial lung disease [ILD])•

Summary of malignancies confirmed by central laboratory pathologist over-read ofbiopsies

090177e18c5cd567\Approved\Approved On: 19-Jul-2017 09:47 (GMT)An AE was defined as any untoward medical event in a clinical investigation subject
administered a product or medical device, whether or not the event had a causal relationshipwith the treatment or usage. Examples of AEs included, but were not limited to, abnormal
test findings, clinically significant symptoms and signs, changes in physical examination
findings, hypersensitivity, progression/worsening of underlying disease, drug abuse, and drug
dependency. AEs could also include signs or symptoms resulting from drug overdose, drug
withdrawal, drug misuse, drug interactions, extravasation, exposure during pregnancy,
exposure via breast feeding, and medication errors.
A serious AE (SAE) was defined as an untoward medical event at any dose that resulted indeath, was life-threatening (immediate risk of death), required inpatient hospitalization or
prolongation of existing hospitalization, resulted in persistent or significant
disability/incapacity (substantial disruption of the ability to conduct normal life functions), or
resulted in a congenital anomaly/birth defect.
As part of safety data collection, the study closely monitored serious infections, defined as
any infection (viral, bacterial, and fungal) requiring hospitalization or parenteral
antimicrobials. Subjects were monitored for the development of conditions that increased therisk of infection and the risk of the development of infection. A subject who experienced aserious infection was discontinued from the study and the serious infection was reported as
an SAE.
The Investigator was required to assess the causality of all AEs (both serious andnonserious), record the causal relationship in the case report form (CRF), as appropriate, andreport the assessment in accordance with SAE reporting requirements as applicable. In
addition, if the Investigator determined an SAE was associated with study procedures, theInvestigator recorded this causal relationship in the source documents and CRF, asappropriate, and reported this assessment in accordance with SAE reporting requirements asapplicable.
To help assess specific safety events in this and other studies in the tofacitinib program,adjudication committees, including a Cardiovascular Endpoint Adjudication Committee,
Malignancy Adjudication Committee, Opportunistic Infection Review Committee, Hepatic
Event Review Committee, and GI Perforation Review Committee, were established toharmonize and standardize selected safety event assessment. All biopsies of potentiallymalignant tumors, suspicious lymphadenopathy, or possible extranodal lymphoproliferative
disorder, and all bowel biopsies containing suspicious dysplasia or malignancy were also to
be submitted to the central laboratory for review by central laboratory pathologists. In
addition to these external committees, an internal committee of medically qualified Pfizer

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Protocol A3921086 – 14 July 2017 – Final

personnel with expertise in the assessment and diagnosis of respiratory disease, the ILD
Review Committee, were to review and categorize potential events of ILD.
Statistical Methods:
The Full Analysis Set (FAS) was defined as all subjects enrolled in this OL extension study
and was the primary analysis set. No protocol deviations were used to define a per-protocol
analysis set. All analyses were performed for the FAS. The Safety Analysis Set (SAS) was
defined as all subjects who received at least 1 dose of study drug and was consistent with the
FAS, as all enrolled subjects received a minimum of 1 dose of study drug.
Descriptive summary statistics were calculated based on all subjects and the initialassignment of dose groups. If a treatment different from the initial assigned treatment was
taken on Day 1, the actual treatment taken was used. All summaries were obtained based on
the observed data. Missing data were not imputed.

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There was no primary efficacy endpoint. All efficacy endpoints were exploratory. CDAI
was measured at baseline, Weeks 8, 16, 24, 36, 48, and 52 (follow-up) and was calculated
based on the hematocrit measured at the same visits. Sustained clinical remission was
defined as being in clinical remission (CDAI score <150) at both Week 24 and Week 48.
Summary statistics such as number of subjects, proportions, 95% 2-sided confidence
intervals (CIs) for binary endpoints and number of subjects, means, median, minimum,
maximum, and 95% CIs for continuous endpoints including changes from baseline, werereported by study visit.
Kaplan-Meier estimates and the median time for the time to relapse among subjects inclinical remission at baseline were also summarized.
The 8 CDAI component scores were descriptively summarized. Six component scores (thenumber of liquid or very soft stools, the intensity of abdominal pain, general well-being, theoccurrence of extraintestinal symptoms or signs, hematocrit and body weight) were alltreated as continuous data and the observed scores and changes from baseline weresummarized. The other 2 component scores (the need for antidiarrheal drugs and thepresence of abdominal mass) were treated as categorical variables and the frequency andpercentage of subjects in each category was summarized.
PRO Analyses: IBDQ was assessed at baseline, Week 8, Week 24, Week 48, and Week
48/ET. The IBDQ total score and the 4 IBDQ domain scores were summarized as observed
scores and changes from baseline. The IBDQ derived binary response endpoint at Week 48
was descriptively summarized as frequencies and percentages.
The categorical PRTI data collected at Week 48/ET was descriptively summarized using
frequencies and percentages.
SF-36 was assessed at baseline, Week 24, Week 48, and Week 48/ET. The 2 component
summaries (physical and mental component scores) and the 8 domain scores weresummarized as observed scores and changes from baseline. The additional SF-36

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Health-Transition score is a 5-point ordered categorical endpoint. This was summarized as
number of subjects and percent per category.
The EQ-5D was assessed at baseline, Week 24, Week 48, and Week 48/ET. The EQ-5D
utility index score and the EQ-5D VAS score were summarized as observed scores andchanges from baseline. The 5 EQ-5D domain scores are all scored on a 3-point scale. The
number of subjects in each category was summarized as number of subjects and percent per
category.
Other Evaluations: Demographics and baseline characteristics were summarized by the
initial assignment dose group as well as the combined group. For continuous variables suchas age; number of subjects meeting the criteria (n), mean, median, standard deviation (SD),minimum, and maximum were reported. For categorical variables such as gender, thefrequency and the percentage in each category was reported. The summaries were performed
for the FAS population.

090177e18c5cd567\Approved\Approved On: 19-Jul-2017 09:47 (GMT)The number of subjects and length of hospitalizations were also descriptively summarizedusing mean and median.
Pharmacodynamic (Biomarker) Analyses: The biomarker endpoints; hsCRP (mg/L) andFEC (mg/kg), were measured at baseline (Day 1) and Weeks 8, 16, 24, 36, 48 and 52(follow-up). Concentrations were summarized descriptively by dose group assigned atbaseline as well as the combined group. Summaries included both the median and geometricmean concentrations. Changes from baseline were summarized as medians and the
back-transformed results from the log-transformed change gave the estimates of the relativechanges from baseline. Values below any limits of quantification were replaced; otherwise
missing data were not imputed. The summaries were performed for the FAS population.
Safety: Long-term safety evaluation was the primary objective of this study.
AEs, vital signs, ECGs, laboratory tests data, and adjudicated events were summarized.
Treatment-emergent AEs were tabulated by body system and by preferred term (PT). The
proportion of AEs as reported was presented for the combined group as well as by the initialassignment of dose group.
In addition, significant infections, defined as any infection (viral, bacterial, and fungal)
requiring hospitalization or parenteral antimicrobials were summarized. The proportion of
AEs as reported, was presented for the combined group as well as by the initial assignment ofdose group.
A 3-tier approach classified AEs into 1 of 3 tiers. Tier-1 events were prespecified events ofclinical importance that were maintained in a list in the product’s safety review plan; this list
could have been updated as more was understood about the drug. Tier-2 events were not
Tier-1 events but were “common.” A Medical Dictionary for Regulatory Activities PT was
defined as a Tier-2 event if there were at least 4 subjects with the same event in any group.
Tier-3 events were events that were neither Tier-1 nor Tier-2 events. The analysis of AEs
under this 3-tier approach was considered exploratory. There was no adjustment for multiple
comparisons or stratification factors in the analyses. The proportions of Tier-1 and Tier-2

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AEs observed in each group were presented along with the point estimates and associated
95% CIs of the risk difference between the 2 active treatments.
RESULTS
Subject Disposition and Demography:
There were 150 subjects assigned to study treatment (Table 2). Of the 150 subjects treated,
88 subjects (43 subjects in the tofacitinib 5 mg BID group and 45 subjects in the tofacitinib
10 mg BID group) completed the study.
All assigned subjects (n=150) were included in the FAS population, which was used as theprimary analysis population, and in the SAS population used for the safety analyses.

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Table 2.

Subject Evaluation Groups
Tofacitinib 5 mg
BID

Tofacitinib 10 mg
BID

Total

Number (%) of subjects
Assigned to study treatment
TreatedCompleted
Discontinued

62
62
43 (69.4)
19 (30.6)

88
88
45 (51.1)
43 (48.9)150
150
88 (58.7)
62 (41.3)

Analyzed for Efficacy:
Full Analysis Set

62 (100.0)

88 (100.0)

150 (100.0)

88 (100.0)
88 (100.0)
88 (100.0)

150 (100.0)
150 (100.0)
150 (100.0)

Analyzed for Safety:
Adverse events
62 (100.0)
Laboratory data
62 (100.0)
Safety Analysis Set
62 (100.0)
Subjects were analyzed as per their initial dose assignment.
Abbreviation: BID = twice daily.

There were 19 subjects who discontinued from the study in the tofacitinib 5 mg BID groupand 43 subjects who discontinued the study in the tofacitinib 10 mg BID group. The reasonsfor discontinuation from study are provided in Table 3.

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Table 3.

Discontinuations from Study

Number (%) of subjects
Discontinuations
Related to Study Drug
Adverse event
Insufficient clinical response
Not Related to Study Drug
Adverse event
Does not meet entrance criteria
Lost to follow-up
No longer willing to participate in study
Other
Protocol violation

Tofacitinib 5 mg
BID
62

Tofacitinib 10 mg
BID
88

Total

8 (12.9)2 (3.2)6 (9.7)32 (36.4)
5 (5.7)27 (30.7)

40 (26.7)
7 (4.7)33 (22.0)

11 (17.7)
1 (1.6)
1 (1.6)2 (3.2)3 (4.8)1 (1.6)3 (4.8)11 (12.5)5 (5.7)0
1 (1.1)4 (4.5)0
1 (1.1)22 (14.7)
6 (4.0)1 (0.7)3 (2.0)7 (4.7)1 (0.7)4 (2.7)150

090177e18c5cd567\Approved\Approved On: 19-Jul-2017 09:47 (GMT)

Total
19 (30.6)
43 (48.9)
62 (41.3)
Subjects were analyzed as per their initial dose assignment.
The ‘Other’ reason was that the subject in the tofacitinib 5 mg BID group was unable to return for thefollow-up visit.
Abbreviation: BID = twice daily.

The mean age of subjects across treatment groups in this study was 39.4 years(SD 12.1 years), and ages ranged from 18 to 67 years. Most subjects (80.0%) were white.
There were no notable differences in demographic characteristics between the 2 groups(Table 4).

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090177e18c5cd567\Approved\Approved On: 19-Jul-2017 09:47 (GMT)

Table 4.

Demographic Characteristics

Tofacitinib 5 mg BID Tofacitinib 10 mg BID
Total
Number (%) of subjects
62
88
150
Gender, n
Male
32
47
79
Female30
4171
Age (years):
<18
0
0
0
18-44
37 (59.7)
64 (72.7)
101 (67.3)
45-64
24 (38.7)
23 (26.1)
47 (31.3)
1
(1.6)
1
(1.1)
2 (1.3)≥65
Mean (SD)
41.0 (12.6)
38.2 (11.6)
39.4 (12.1)
Range
18-67
19-66
18-67
Race:
White
49 (79.0)
71 (80.7)
120 (80.0)
Black
2 (3.2)
1 (1.1)3 (2.0)Asian
11 (17.7)
14 (15.9)25 (16.7)
Other
0
2 (2.3)2 (1.3)Weight (kg):N
62 (100.0)
88 (100.0)
150 (100.0)
Mean (SD)75.5 (19.2)
71.2 (20.3)
73.0 (19.9)
Range
49.8-167.6
45.3-141.8
45.3-167.6
Body Mass Index(kg/m2):
N
62 (100.0)
88 (100.0)
150 (100.0)
Mean (SD)25.9 (5.5)
24.5 (6.0)
25.1 (5.8)
Range
15.0-46.2
16.0-50.4
15.0-50.4
Height (cm):N
62 (100.0)
88 (100.0)
150 (100.0)
Mean (SD)
170.3 (9.2)
170.0 (10.3)
170.1 (9.9)
Range
154.9-190.5
150.0-205.0
150.0-205.0
Abbreviations: BID = twice daily; N = number of subjects; n = number of subjects meeting the criteria;
SD = standard deviation.
Subjects were analyzed as per their initial dose assignment.

Efficacy Results:
Clinical Remission and Sustained Clinical Remission at Week 48
At baseline, the number of subjects who met clinical remission criteria based on recalculatedbaseline CDAI scores was 61/62 subjects in the tofacitinib 5 mg BID group (98.4%) and
4/88 subjects in the tofacitinib 10 mg BID group (4.6%). Baseline CDAI scores wererecalculated using baseline hematocrit results received after treatment assignment wasdetermined. Therefore, 1 subject in the tofacitinib 5 mg BID group and 4 subjects in thetofacitinib 10 mg BID group had remission status that did not correspond to their initial doseassignment.
For subjects in the tofacitinib 5 mg BID group, a slight decrease in the proportion of subjects
remaining in the study who met clinical remission criteria was observed at Week 8(41/54 subjects, 75.9%) with the observed rate remaining fairly similar over time with
29/33 subjects (87.9%) in clinical remission at Week 48. Notably for subjects in thetofacitinib 10 mg BID group, who were intended to be, by protocol design, those who entered
the study not in remission, the proportion of subjects remaining in the study at a given study

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visit who met clinical remission generally increased at each study visit, with 55.6%(20/36 subjects) at Week 48 in remission.
The proportion of subjects who met sustained clinical remission was 75.0% for the tofacitinib
5 mg BID group and 34.3% for the tofacitinib 10 mg BID group (Table 5).
Table 5.

Proportion of Subjects Who Met Clinical Remission Criteria by Week, andSustained Clinical Remission Criteria (FAS)
Observed

090177e18c5cd567\Approved\Approved On: 19-Jul-2017 09:47 (GMT)NnRate (%)

95%a CI

Baseline
Tofacitinib 5 mg BID
62
61
98.39
91.34, 99.96
Tofacitinib 10 mg BID
88
4
4.55
1.25, 11.23
Total
150
65
43.33
35.27, 51.66
Week 8
Tofacitinib 5 mg BID
54
41
75.93
62.36, 86.51
Tofacitinib 10 mg BID
75
28
37.33
26.43, 49.27
Total
129
69
53.49
44.50, 62.31
Week 16
Tofacitinib 5 mg BID
53
45
84.91
72.41, 93.25
Tofacitinib 10 mg BID
66
23
34.85
23.53, 47.58
Total
119
68
57.14
47.75, 66.17
Week 24
Tofacitinib 5 mg BID
49
41
83.67
70.34, 92.68
Tofacitinib 10 mg BID
59
27
45.76
32.72, 59.25
Total
108
68
62.96
53.14, 72.06
Week 36
Tofacitinib 5 mg BID
41
37
90.24
76.87, 97.28
Tofacitinib 10 mg BID
48
24
50.00
35.23, 64.77
Total
89
61
68.54
57.83, 77.97
Week 48
Tofacitinib 5 mg BID
33
29
87.88
71.80, 96.60
Tofacitinib 10 mg BID
36
20
55.56
38.10, 72.06
Total
69
49
71.01
58.84, 81.31
Follow-up
Tofacitinib 5 mg BID
38
25
65.79
48.65, 80.37
Tofacitinib 10 mg BID
43
19
44.19
29.08, 60.12
Total
81
44
54.32
42.87, 65.44
Sustained Clinical Remission
Tofacitinib 5 mg BID
32
24
75.00
56.60, 88.54
Tofacitinib 10 mg BID
35
12
34.29
19.13, 52.21
Total
67
36
53.73
41.12, 66.00
Subjects were analyzed as per their initial dose assignment.
Clinical remission was defined as CDAI <150. Sustained clinical remission was defined as being in clinicalremission at both Week 24 and Week 48.
Abbreviations: BID = twice daily; CDAI = Crohn’s Disease Activity Index; CI = confidence interval;
FAS = Full Analysis Set; N=number of subjects with non-missing data (at Week 24 and Week 48 for sustained
clinical remission); n = number of subjects meeting the binary endpoint criteria.
a. 95% Clopper-Pearson exact CI reported for the proportions.

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Protocol A3921086 – 14 July 2017 – Final

Clinical Remission and Sustained Clinical Remission Among Subjects in ClinicalRemission at Baseline of the OL Study
Among subjects in clinical remission at baseline who remained in the study at a given time
point, the proportion of subjects who met clinical remission in the tofacitinib 5 mg BID
group decreased slightly at Week 8 with 40/53 (75.5%) subjects but remained fairly similar
at each subsequent time point, with 28/32 (87.5%) subjects at Week 48 (Table 6).

090177e18c5cd567\Approved\Approved On: 19-Jul-2017 09:47 (GMT)The proportion of subjects with sustained clinical remission among subjects in clinicalremission at baseline was 77.4% for subjects in the tofacitinib 5 mg BID group(24/31 subjects) and 33.3% (1/3 subjects) in the tofacitinib 10 mg BID group.

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Protocol A3921086 – 14 July 2017 – Final

Table 6.

Proportion of Subjects Who Met Clinical Remission Criteria by Week
Among Subjects in Clinical Remission at A3921086 Baseline (FAS)
Observed

090177e18c5cd567\Approved\Approved On: 19-Jul-2017 09:47 (GMT)NnRate (%)

95%a CI

Baseline
Tofacitinib 5 mg BID
61
61
100.0094.13, 100.00
Tofacitinib 10 mg BID
4
4100.0039.76, 100.00
Total
65
65
100.0094.48, 100.00
Week 8
Tofacitinib 5 mg BID
53
40
75.47
61.72, 86.24
Tofacitinib 10 mg BID
4
2
50.00
6.76, 93.24
Total
57
42
73.68
60.34, 84.46
Week 16
Tofacitinib 5 mg BID
52
44
84.62
71.92, 93.12
Tofacitinib 10 mg BID
4
3
75.00
19.41, 99.37
Total
56
47
83.93
71.67, 92.38
Week 24
Tofacitinib 5 mg BID
48
41
85.42
72.24, 93.93
Tofacitinib 10 mg BID
4
1
25.00
0.63, 80.59
Total
52
42
80.77
67.47, 90.37
Week 36
Tofacitinib 5 mg BID
40
37
92.50
79.61, 98.43
Tofacitinib 10 mg BID
3
1
33.33
0.84, 90.57
Total
43
38
88.37
74.92, 96.11
Week 48
Tofacitinib 5 mg BID
32
28
87.50
71.01, 96.49
Tofacitinib 10 mg BID
3
3100.0029.24, 100.00
Total
35
31
88.57
73.26, 96.80
Follow-up
Tofacitinib 5 mg BID
37
24
64.86
47.46, 79.79
Tofacitinib 10 mg BID
3
1
33.33
0.84, 90.57
Total
40
25
62.50
45.80, 77.27
Sustained Clinical Remission
Tofacitinib 5 mg BID
31
24
77.42
58.90, 90.41
Tofacitinib 10 mg BID
3
1
33.33
0.84, 90.57
Total
34
25
73.53
55.64, 87.12
Subjects were analyzed as per their initial dose assignment.
Clinical remission was defined as CDAI <150
Abbreviations: BID = twice daily; CDAI = Crohn’s Disease Activity Index; CI = confidence interval;
FAS = Full Analysis Set; N=number of subjects with non-missing data (at Week 24 and Week 48 for sustained
clinical remission); n = number of subjects meeting the binary endpoint criteria.
a. 95% Clopper-Pearson exact CI reported for the proportions.

Clinical Remission and Sustained Clinical Remission Among Subjects in Clinical
Response or Clinical Remission at Baseline of the OL Study
Clinical response-100 was defined as a CDAI score decrease of at least 100 points from the
Study A3921083 baseline. At baseline, the proportion of subjects who met clinical responseor clinical remission criteria was 98.4% for subjects in the tofacitinib 5 mg BID group(61/62 subjects) and 17.4% in the tofacitinib 10 mg BID group (4/23 subjects; Table 7).

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For subjects in the tofacitinib 5 mg BID group, a decrease in the proportion of subjects who
met clinical remission criteria among those in clinical response or clinical remission atbaseline was observed at Week 8 (41/54 subjects, 75.9%) but the observed proportion
remained fairly consistent over time from Week 16 with 87.9% (29/33) of subjects in clinicalremission at Week 48. A slight increase from baseline in the number of subjects in clinicalremission was observed at each time point among those in clinical response or clinicalremission at baseline for subjects in the tofacitinib 10 mg BID group, although the number ofsubjects meeting the criteria remained low (≤7).

090177e18c5cd567\Approved\Approved On: 19-Jul-2017 09:47 (GMT)

Among subjects in clinical response or clinical remission at baseline of this study, theproportion of subjects who met sustained clinical remission was 75.0% for subjects in thetofacitinib 5 mg BID group (24/32 subjects) and 30.0% for subjects in the tofacitinib 10 mg
BID group (3/10 subjects).

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Protocol A3921086 – 14 July 2017 – Final

Table 7.

Proportion of Subjects Who Met Clinical Remission Criteria by Week
Among Subjects in Clinical Response or Clinical Remission at A3921086
Baseline (FAS)
Observed

090177e18c5cd567\Approved\Approved On: 19-Jul-2017 09:47 (GMT)NnRate (%)

95%a CI

Baseline
Tofacitinib 5 mg BID
62
61
98.39
91.34, 99.96
Tofacitinib 10 mg BID
23
4
17.39
4.95, 38.78
Total
85
65
76.47
66.03, 85.00
Week 8
Tofacitinib 5 mg BID
54
41
75.93
62.36, 86.51
Tofacitinib 10 mg BID
20
7
35.00
15.39, 59.22
Total
74
48
64.86
52.89, 75.61
Week 16
Tofacitinib 5 mg BID
53
45
84.91
72.41, 93.25
Tofacitinib 10 mg BID
19
7
36.84
16.29, 61.64
Total
72
52
72.22
60.41, 82.14
Week 24
Tofacitinib 5 mg BID
49
41
83.67
70.34, 92.68
Tofacitinib 10 mg BID
16
7
43.75
19.75, 70.12
Total
65
48
73.85
61.46, 83.97
Week 36
Tofacitinib 5 mg BID
41
37
90.24
76.87, 97.28
Tofacitinib 10 mg BID
13
5
38.46
13.86, 68.42
Total
54
42
77.78
64.40, 87.96
Week 48
Tofacitinib 5 mg BID
33
29
87.88
71.80, 96.60
Tofacitinib 10 mg BID
10
5
50.00
18.71, 81.29
Total
43
34
79.07
63.96, 89.96
Follow-up
Tofacitinib 5 mg BID
38
25
65.79
48.65, 80.37
Tofacitinib 10 mg BID
12
5
41.67
15.17, 72.33
Total
50
30
60.00
45.18, 73.59
Sustained Clinical Remission
Tofacitinib 5 mg BID
32
24
75.00
56.60, 88.54
Tofacitinib 10 mg BID
10
3
30.00
6.67, 65.25
Total
42
27
64.29
48.03, 78.45
Subjects were analyzed as per their initial dose assignment.
Clinical remission was defined as CDAI <150. Clinical response was defined as CDAI-100 response from
Study A3921083 baseline. Sustained clinical remission was defined as being in clinical remission at both
Week 24 and Week 48.
Abbreviations: BID = twice daily; CDAI = Crohn’s Disease Activity Index; CI = confidence interval;
FAS = Full Analysis Set; N = number of subjects with non-missing data (at Week 24 and Week 48 for sustained
clinical remission); n = number of subjects meeting the binary endpoint criteria.
a. 95% Clopper-Pearson exact CI reported for the proportions.

Time to Relapse
Relapse was defined as increase in CDAI of >100 points from baseline and an absolute
CDAI score of >220 points. For subjects in the tofacitinib 5 mg BID group, the estimatedrelapse rate among subjects in clinical remission at baseline gradually increased over time
and was greatest at Week 48 (24.7%; 95% CI: 17.21%, 32.89%). For subjects in the

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Protocol A3921086 – 14 July 2017 – Final

tofacitinib 10 mg BID group, of whom only 4 subjects were in remission at baseline, there
was no notable change from Week 16 to 36 (Table 8). The estimated median time to relapse
was 366 days.
Table 8.

090177e18c5cd567\Approved\Approved On: 19-Jul-2017 09:47 (GMT)

VisitTime to Relapse Among Subjects in Clinical Remission at Baseline (FAS)
Treatment

Cumulative
Number of
EventsNumber of
Estimated Rate (%)
Subjects
Ratea
SE
95% CIb
Remaining at
Lower
Upper
Risk
Baseline Tofacitinib 5 mg BID
061
Tofacitinib 10 mg BID
0
4
Week 8
Tofacitinib 5 mg BID
4
55
6.78
3.27
3.38
11.78
Tofacitinib 10 mg BID
0
4
Week 16 Tofacitinib 5 mg BID
7
51
11.86
4.21
7.15
17.87
Tofacitinib 10 mg BID
1
3
25.00
21.65
4.56
53.66
Week 24 Tofacitinib 5 mg BID
9
46
15.46
4.75
9.98
22.05
Tofacitinib 10 mg BID
1
3
25.00
21.65
4.56
53.66
Week 36 Tofacitinib 5 mg BID
12
38
21.42
5.52
14.82
28.83
Tofacitinib 10 mg BID
1
3
25.00
21.65
4.56
53.66
Week 48 Tofacitinib 5 mg BID
13
7
24.69
6.18
17.21
32.89
Tofacitinib 10 mg BID
10
Subjects were analyzed as per their initial dose assignment.
Relapse was defined as increase in CDAI of >100 points from the baseline and an absolute CDAI score of>220 points.
Subjects who dropped out due to lack of efficacy were treated as a relapse event with an event time at the timeof drop out.
The actual days were used as the event time or censored time. The number of events/subjects at risk and event
rate at each post baseline visit was estimated from the scheduled visit target day + 10 days.
Abbreviations: BID = twice daily; CI = confidence interval; FAS = Full Analysis Set; SE = standard error.
a. Estimated from the Kaplan-Meier curveb. Calculated from the product-limit method / Calculated from the log[-log(x-<year, month> survival
probability)] using a normal approximation and back transformation

CDAI Scores Over Time and CDAI Score Changes from Baseline
Mean (SD) baseline CDAI scores were 77.13 (43.22) for subjects in the tofacitinib 5 mg BID
group (subjects in remission) and 291.19 (95.78) for subjects in the tofacitinib 10 mg BID
group (subjects not in remission).
For subjects in the tofacitinib 5 mg BID group, mean CDAI scores increased from baseline at
Weeks 8, 16, and 24 with the highest mean score and greatest mean increase from baseline
observed at Week 8 (mean [SD] 105.39 [75.82]; mean [SD] change from baseline:
26.96 [62.68]). A decrease in mean CDAI scores was subsequently observed from Weeks 36
to 48, returning to near baseline scores with a mean (SD) CDAI score of 73.91 (70.23) at
Week 48.
In the tofacitinib 10 mg BID group, the mean CDAI scores at Week 8 through Week 48 forsubjects who still remained in the study decreased over 100 points from baseline (Table 9).

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Protocol A3921086 – 14 July 2017 – Final

Table 9.

Descriptive Statistics of Observed CDAI Score and Change From Baseline CDAI Score by Week (FAS)

090177e18c5cd567\Approved\Approved On: 19-Jul-2017 09:47 (GMT)

N

n

Mean

Observed Data
SDMedian

Min

n

Mean

Change from Baseline
SD
MedianMin

Max
Baseline
Tofacitinib 5 mg BID
62
62
77.13
43.22
83.00
-2
156
Tofacitinib 10 mg BID
88
88291.1995.78
270.00
138
551
Total
150
150
202.71131.56190.50-2
551
Week 8
Tofacitinib 5 mg BID
62
54
105.3975.82
106.00
-10
313
54
26.96
62.68
10.00
-82
185
Tofacitinib 10 mg BID
8875
176.9682.39
163.0011
410
75-114.31 112.44-96.00
-445
96
Total
150
129
147.0086.95
143.00-10410
129-55.17 117.61-25.00-445
185
Week 16
Tofacitinib 5 mg BID
62
53
86.58
65.23
77.00
-10
278
53
11.72
52.25
5.00
-98
172
Tofacitinib 10 mg BID
8866
178.9472.25
181.007367
66-112.02 111.09 -100.50
-477
114
Total
150
119
137.8182.92
132.00-10367
119-56.91 108.70-23.00-477
172
Week 24
Tofacitinib 5 mg BID
62
49
85.12
56.67
75.00
-10
192
49
6.33
44.48
1.00
-91
92
Tofacitinib 10 mg BID
8859
163.6679.73
160.00-10407
59-122.69 117.65 -103.00
-494
140
Total
150
108
128.0380.18
124.00-10407
108-64.16 112.05-32.00-494
140
Week 36
Tofacitinib 5 mg BID
62
41
73.34
59.52
58.00
-2
230
41
-10.7840.35-15.00-72
105
Tofacitinib 10 mg BID
88
48
158.6789.15
150.00-10376
48-139.81 126.18 -116.00
-494
19
Total
150
89
119.3687.66
100.00-10376
89-80.37 115.87-42.00-494
105
Week 48
Tofacitinib 5 mg BID
62
33
73.91
70.23
67.00
-10
332
33
-4.79
60.09
-13.00-125
201
Tofacitinib 10 mg BID
88
36154.11
71.47
147.5049334
36-121.94 129.21-84.50
-460
114
Total
150
69
115.7581.11
108.00-10334
69-65.91 117.33-36.00-460
201
Follow-up
Tofacitinib 5 mg BID
62
38
129.32114.82102.00
-10
467
38
47.66
109.73
15.00
-80
413
Tofacitinib 10 mg BID
88
43180.6598.80
162.0017429
43-107.42 119.05 -106.00
-392
87
Total
150
81
156.57109.03141.00-10467
81-34.67 138.11-22.00-392
413
Subjects were analyzed as per their initial dose assignment.
Abbreviations: BID = twice daily; CDAI = Crohn’s Disease Activity Index; FAS = Full Analysis Set; Max = maximum; Min = minimum; N = number of subjects
in the analysis set; n = number of subjects with non-missing data; SD = standard deviation.

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Protocol A3921086 – 14 July 2017 – Final

Steroid-Free Clinical Remission
Among subjects on steroids at baseline, 1 of 2 subjects (50.0%, 95% CI: 1.26%, 98.74%) in
the tofacitinib 5 mg BID group and 1/11 subjects (9.1%, 95% CI: 0.23%, 41.28%) in thetofacitinib 10 mg BID achieved steroid-free clinical remission at Week 48 (Table 10).
Table 10. Proportion of Subjects Achieving a Steroid-Free Clinical Remission at
Week 48 (FAS) - Among Subjects on Steroids at A3921086 Baseline
Observed
NnRate (%)
95%a CI
Tofacitinib 5 mg BID
2
1
50.00
1.26, 98.74
Tofacitinib 10 mg BID
11
1
9.09
0.23, 41.28
Total
13
2
15.38
1.92, 45.45
Subjects were analyzed as per their initial dose assignment.
Clinical remission was defined as CDAI <150.
Abbreviations: BID = twice daily; CDAI = Crohn’s Disease Activity Index; CI = confidence interval;
FAS = Full Analysis Set; N = number of subjects with non-missing data; n = number of subjects meeting thebinary endpoint criteria.
a. 95% Clopper-Pearson exact CI reported for the proportions.

090177e18c5cd567\Approved\Approved On: 19-Jul-2017 09:47 (GMT)

Corticosteroid Use Over Time
Corticosteroid use over time is shown in Table 11. Notably for subjects in the tofacitinib
5 mg BID group, steroid use at baseline given that subjects were already in clinical remission
was expectedly very low. For subjects in the tofacitinib 10 mg BID group, corticosteroid use
generally decreased over time.
Table 11. Corticosteroid Use Over Time
Tofacitinib 5 mg BID
Tofacitinib 10 mg BID
Total
N=62
N=88
N=150
n (%)
n (%)
n (%)
Baseline
1 (1.61)
18 (20.45)
19 (12.67)
Week 83 (4.84)
19 (21.59)
22 (14.67)
Week 16
3 (4.84)
12 (13.64)
15 (10.00)
Week 24
3 (4.84)
11 (12.50)
14 (9.33)
Week 36
2 (3.23)
9 (10.23)
11 (7.33)
Week 48
1 (1.61)
7 (7.95)
8 (5.33)
Subjects were analyzed as per their initial dose assignment.
Summary statistics of dose reported in mg.
Abbreviations: BID = twice daily; n = number of subjects taking corticosteroid at visit; N = number of subjects
with non-missing data.

Study Treatment Dose Adjustment
Per the protocol, a single study treatment dose adjustment was allowed, at the discretion of
the Investigator, from 5 mg BID to 10 mg BID or from 10 mg BID to 5 mg BID, after the
initial 8 weeks of fixed OL treatment (Table 12).

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Protocol A3921086 – 14 July 2017 – Final

Table 12. Proportion of Subjects Switching from 5 mg to 10 mg or 10 mg to 5 mg
After Initial Assignment by Visit (FAS)
Tofacitinib 5 mg BID
N=62
n (%)

Tofacitinib 10 mg BID
Total
N=88
N=150
n (%)
n (%)
Baseline000Week 816 (25.81)
0
16 (10.67)
Week 164 (6.45)04 (2.67)
Week 24
2 (3.23)
2 (2.27)
4 (2.67)
Week 360
1 (1.14)1 (0.67)
Week 48000Subjects were analyzed as per their initial dose assignment.
Abbreviations: BID = twice daily; FAS = Full Analysis Set; n=number of subjects switching dose; N = numberof subjects with non-missing data.

The majority of dose adjustments occurred for subjects in the tofacitinib 5 mg BID group(subjects who were in clinical remission at baseline) up to 10 mg BID at Week 8;
4 additional subjects switched by Week 16 and 2 additional subjects switched by Week 24.

090177e18c5cd567\Approved\Approved On: 19-Jul-2017 09:47 (GMT)PRO Results:
Mean (SD) IBDQ total scores at baseline were 187.23 (20.38) in the tofacitinib 5 mg BID
group and 127.32 (34.17) in the tofacitinib 10 mg BID group. The IBDQ mean total scoreremained high (≥170) at Week 48/ET for subjects in the tofacitinib 5 mg BID group and did
not decrease greatly from baseline. For subjects remaining in the study in the tofacitinib
10 mg BID group, the overall mean (SD) IBDQ total score was 144.42 (42.16) at
Week 48/ET, corresponding to a mean (SD) change from the baseline score of 18.84 (40.45),
although no statistical testing was performed (Table 13).

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Public Disclosure Synopsis
Protocol A3921086 – 14 July 2017 – Final

Table 13. Descriptive Statistics of Observed and Change From Baseline of Total IBDQ and Domain Scores, at Week 48/ET(FAS)

090177e18c5cd567\Approved\Approved On: 19-Jul-2017 09:47 (GMT)N
IBDQ Total Score
Baseline
Tofacitinib 5 mg BID
62
Tofacitinib 10 mg BID
88
Total
150
Week 48/ET
Tofacitinib 5 mg BID
62
Tofacitinib 10 mg BID
88
Total
150
Bowel Function Score
Baseline
Tofacitinib 5 mg BID
62
Tofacitinib 10 mg BID
88
Total
150
Week 48/ET
Tofacitinib 5 mg BID
62
Tofacitinib 10 mg BID
88
Total
150
Emotional Status Score
Baseline
Tofacitinib 5 mg BID
62
Tofacitinib 10 mg BID
88
Total
150
Week 48/ET
Tofacitinib 5 mg BID
62
Tofacitinib 10 mg BID
88
Total
150
Systemic Symptoms Score Baseline
Baseline
Tofacitinib 5 mg BID
62
Tofacitinib 10 mg BID
88
Total
150

Observed Data
SDMedian

n

Mean

Min

Max

62
87
149

187.23
127.32152.25

20.38
34.17
41.56

188.00125.00160.00

144
61
61

224
193
224

57
83
140

179.26144.42158.61

29.89
42.16
41.28

180.00148.00165.00

91
44
44

224
217
224

62
87
149

58.56
40.71
48.14

6.86
9.90
12.42

59.00
41.00
49.00

40
18
18

70
60
70

57
83
140

55.70
46.70
50.36

9.82
12.38
12.21

56.00
49.00
52.00

30
18
18

70
66
70

62
87
149

69.68
48.61
57.38

8.58
14.42
16.12

72.00
47.00
60.00

48
20
20

84
80
84

57
83
140

66.98
53.19
58.81

12.27
17.32
16.85

69.00
54.00
61.50

32
13
13

84
83
84

62
87
149

26.95
17.20
21.26

5.36
5.55
7.28

27.00
17.00
22.00

12
6
6

35
29
35

Page 25

Change from Baseline
SD
Median
Min

n

Mean

Max

57
83
140

-7.98
18.84
7.92

24.93
40.45
37.29

-1.00
11.00
3.50

-81
-70
-81

43
140
140

57
83
140

-2.72
6.37
2.67

8.30
12.41
11.78

0.00
5.00
3.00

-26
-27
-27

8
37
37

57
83
140

-3.07
5.36
1.93

10.48
15.00
13.94

-1.00
3.00
1.00

-30
-24
-30

29
48
48

Public Disclosure Synopsis
Protocol A3921086 – 14 July 2017 – Final

Table 13. Descriptive Statistics of Observed and Change From Baseline of Total IBDQ and Domain Scores, at Week 48/ET(FAS)

090177e18c5cd567\Approved\Approved On: 19-Jul-2017 09:47 (GMT)

N

n

Mean

Observed Data
SDMedian

Min

n

Mean

Change from Baseline
SD
MedianMin

Max
Week 48/ET
Tofacitinib 5 mg BID
62
57
25.82
6.28
26.00
10
35
57
-1.00
4.83
0.00
-15
8
Tofacitinib 10 mg BID
88
83
20.35
7.07
21.00
6
34
83
3.45
7.43
2.00
-10
27
Total
150
140
22.58
7.26
23.00
6
35
140
1.64
6.84
1.00
-15
27
Social Function Score
Baseline
Tofacitinib 5 mg BID
62
62
32.03
3.59
33.00
16
35
Tofacitinib 10 mg BID
88
87
20.80
8.96
21.00
5
35
Total
150
149
25.48
9.10
29.00
5
35
Week 48/ET
Tofacitinib 5 mg BID
62
57
30.75
5.17
31.00
10
35
57
-1.19
4.24
0.00
-15
9
Tofacitinib 10 mg BID
88
83
24.18
8.98
27.00
5
35
83
3.66
8.89
1.00
-21
30
Total
150
140
26.86
8.30
30.00
5
35
140
1.69
7.72
0.00
-21
30
Subjects were analyzed as per their initial dose assignment.
Baseline assessments were performed at Week 26 of Study A3921084.
Abbreviations: BID = twice daily; ET = Early Termination; IBDQ = Inflammatory Bowel Disease Questionnaire; FAS = Full Analysis Set; Max = maximum;
Min = minimum; N = number of subjects in the analysis set; n = number of subjects with non-missing data; SD = standard deviation.

Page 26

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Public Disclosure Synopsis
Protocol A3921086 – 14 July 2017 – Final

The proportion of subjects with an IBDQ total score ≥170 at baseline was 79.0% in thetofacitinib 5 mg BID group and 11.5% of subjects in the tofacitinib 10 mg BID group, with a
gradual increase in the proportion of subjects with an IBDQ total score ≥170 observed for
those in the tofacitinib 10 mg BID group at Week 48 (Table 14).
Table 14. Proportion of Subjects With IBDQ Total Score ≥170 at Week 48/ET (FAS)
Observed
NnRate (%)

95%a CI

090177e18c5cd567\Approved\Approved On: 19-Jul-2017 09:47 (GMT)

Baseline
Tofacitinib 5 mg BID
62
49
79.03
66.82, 88.34
Tofacitinib 10 mg BID
87
10
11.49
5.65, 20.12
Total
149
59
39.60
31.69, 47.93
Week 48/ET
Tofacitinib 5 mg BID
57
40
70.18
56.60, 81.57
Tofacitinib 10 mg BID
83
26
31.33
21.59, 42.44
Total
140
66
47.14
38.66, 55.75
Subjects were analyzed as per their initial dose assignment.
Abbreviations: BID = twice daily; CI = confidence interval; ET = Early Termination; IBDQ = Inflammatory
Bowel Disease Questionnaire; FAS = Full Analysis Set; N = number of subjects at baseline in the analysis set;n = number of subjects meeting the binary endpoint criteria of IBDQ total score ≥170.
a. 95% Clopper-Pearson exact CI reported for the proportions.

Most subjects in both treatment groups reported positive outcomes of “extremely satisfied”
or “satisfied” for the endpoint of patient satisfaction assessment, with 66.7% and 33.3% ofsubjects, respectively in the tofacitinib 5 mg BID group and 32.6% and 41.3% of subjects,
respectively in the tofacitinib 10 mg BID group. The majority of subjects (ie, >50%) in both
treatment groups also reported positive outcomes for the endpoints of patient preference
assessment (‘yes, I definitely prefer the drug that I am receiving now’; 88.1% and 56.5% ofsubjects in the tofacitinib 5 mg BID and 10 mg BID group, respectively) and patient
willingness assessment (‘yes, I would definitely want to use the same drug again’; 83.3% and60.9% of subjects in the tofacitinib 5 mg BID and 10 mg BID group, respectively), withslightly higher proportions of subjects in the tofacitinib 5 mg BID group compared tosubjects in the tofacitinib 10 mg BID group, respectively (Table 15).

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Protocol A3921086 – 14 July 2017 – Final

Table 15. Summary of PRTI Data (FAS)

090177e18c5cd567\Approved\Approved On: 19-Jul-2017 09:47 (GMT)

Tofacitinib
5 mg BID
N=62

Tofacitinib
10 mg BID
N=88

Total

N=150
Patient Satisfaction Assessment, number (%)
of subjects
n
42
46
88
Extremely dissatisfied
000
Dissatisfied
0
4 (8.7)4 (4.5)Neither satisfied nor dissatisfied0
8 (17.4)
8 (9.1)
Satisfied
14 (33.3)
19 (41.3)
33 (37.5)
Extremely satisfied
28 (66.7)
15 (32.6)
43 (48.9)
Patient Previous Treatment Assessment,
number (%) of subjects
n
42
46
88
Injectable prescription medicines
17 (40.5)
15 (32.6)
32 (36.4)
Prescription medicines taken by mouth
19 (45.2)
20 (43.5)
39 (44.3)
Surgery
1 (2.4)0
1 (1.1)
Prescription medicines and surgery
3 (7.1)6 (13.0)
9 (10.2)
No treatment
2 (4.8)5 (10.9)7 (8.0)Patient Preference Assessment, number (%) of
subjects
n
42
46
88
Yes, I definitely prefer the drug that I am
37 (88.1)
26 (56.5)
63 (71.6)
receiving now
I have a slight preference for the drug that I am
2 (4.8)10 (21.7)
12 (13.6)
receiving now
I have no preference either way
3 (7.1)8 (17.4)
11 (12.5)
I have a slight preference for my previous
0
2 (4.3)2 (2.3)treatment
No, I definitely prefer my previous treatment
000Patient Willingness Assessment, number (%) of
subjects
n
42
46
88
Yes, I would definitely want to use the same
35 (83.3)
28 (60.9)
63 (71.6)
drug again
I might want to use the same drug again
6 (14.3)
11 (23.9)
17 (19.3)
I am not sure
1 (2.4)5 (10.9)
6 (6.8)
I might not want to use the same drug again000No, I definitely would not want to use the same0
2 (4.3)2 (2.3)drug again
Subjects were analyzed as per their initial dose assignment.
Percent based on number of subjects with non-missing values within the analysis set.
Previous treatment refers to treatments prior to the A3921086 study.
Abbreviations: BID = twice daily; FAS = Full Analysis Set; N = number of subjects in the analysis set;n = number of responders; PRTI = Patient-Reported Treatment Impact.

SF-36 component values and change from baselines scores are shown in Table 16. In
general, for subjects remaining in the study, component scores decreased from baseline in thetofacitinib 5 mg BID group and increased from baseline in the tofacitinib 10 mg BID groupat Week 48. However, mean changes from baseline were generally small across all domains
for both tofacitinib groups.

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Public Disclosure Synopsis
Protocol A3921086 – 14 July 2017 – Final

Table 16. Descriptive Statistics of Observed and Change From Baseline Mean in SF-36 Domain and Component Scores, at
Week 48/ET (FAS)

090177e18c5cd567\Approved\Approved On: 19-Jul-2017 09:47 (GMT)N
Physical Component Score
Baseline
Tofacitinib 5 mg BID
62
Tofacitinib 10 mg BID
88
Total
150
Week 48/ET
Tofacitinib 5 mg BID
62
Tofacitinib 10 mg BID
88
Total
150
Mental Component Score
Baseline
Tofacitinib 5 mg BID
62
Tofacitinib 10 mg BID
88
Total
150
Week 48/ET
Tofacitinib 5 mg BID
62
Tofacitinib 10 mg BID
88
Total
150
Physical Functioning Domain
Baseline
Tofacitinib 5 mg BID
62
Tofacitinib 10 mg BID
88
Total
150
Week 48/ET
Tofacitinib 5 mg BID
62
Tofacitinib 10 mg BID
88
Total
150
Role Physical Domain
Baseline
Tofacitinib 5 mg BID
62
Tofacitinib 10 mg BID
88
Total
150

Observed Data
SDMedian

n

Mean

Min

Max

62
86
148

50.15
37.80
42.97

6.73
9.53
10.43

50.72
39.21
44.25

26.9
12.8
12.8

61.1
54.3
61.1

57
83
140

48.43
41.87
44.54

8.22
10.06
9.87

51.27
43.58
46.08

23.5
20.1
20.1

59.6
58.9
59.6

62
86
148

50.25
37.17
42.65

9.11
11.94
12.60

51.78
36.59
45.51

20.3
7.3
7.3

62.0
58.2
62.0

57
83
140

48.79
39.60
43.34

10.64
12.87
12.80

50.88
41.27
47.03

20.1
12.7
12.7

64.4
59.9
64.4

62
86
148

53.35
43.50
47.63

5.50
10.37
9.93

55.07
45.86
50.97

32.6
18.2
18.2

57.1
57.1
57.1

57
83
140

51.40
46.81
48.68

8.59
10.22
9.83

55.07
50.97
53.02

18.2
22.3
18.2

57.1
57.1
57.1

62
86
148

50.97
35.93
42.23

8.22
11.30
12.54

54.24
35.15
44.69

23.2
18.4
18.4

56.6
56.6
56.6

Page 29

Change from Baseline
SD
Median
Min

n

Mean

Max

57
82
139

-1.47
4.47
2.03

7.17
11.06
10.06

-0.84
2.80
0.68

-24.4
-19.2
-24.4

12.3
43.8
43.8

57
82
139

-1.88
3.07
1.04

9.05
11.53
10.83

-1.60
2.51
-0.10

-33.6
-26.7
-33.6

20.4
28.4
28.4

57
82
139

-1.80
3.49
1.33

7.50
10.74
9.87

0.00
0.00
0.00

-36.8
-28.7
-36.8

14.3
38.9
38.9

Public Disclosure Synopsis
Protocol A3921086 – 14 July 2017 – Final

090177e18c5cd567\Approved\Approved On: 19-Jul-2017 09:47 (GMT)

Table 16. Descriptive Statistics of Observed and Change From Baseline Mean in SF-36 Domain and Component Scores, at
Week 48/ET (FAS)

Week 48/ET
Tofacitinib 5 mg BID
Tofacitinib 10 mg BID
Total
Bodily Pain Domain
Baseline
Tofacitinib 5 mg BID
Tofacitinib 10 mg BID
Total
Week 48/ET
Tofacitinib 5 mg BID
Tofacitinib 10 mg BID
Total
General Health Domain
Baseline
Tofacitinib 5 mg BID
Tofacitinib 10 mg BID
Total
Week 48/ET
Tofacitinib 5 mg BID
Tofacitinib 10 mg BID
Total
Vitality Domain
Baseline
Tofacitinib 5 mg BID
Tofacitinib 10 mg BID
Total
Week 48/ET
Tofacitinib 5 mg BID
Tofacitinib 10 mg BID
Total

Observed Data
SDMedian

N

n

Mean

62
88
150

57
83
140

49.38
40.04
43.84

8.78
12.99
12.32

62
88
150

62
87
149

51.32
35.31
41.98

62
88
150

57
83
140

62
88
150

Change from Baseline
SD
Median
Min

Min

Max

n

Mean

54.24
42.31
47.08

28.0
18.4
18.4

56.6
56.6
56.6

57
82
139

-1.38
4.60
2.15

7.87
12.62
11.28

0.00
2.39
0.00

-21.5
-38.2
-38.2

19.1
38.2
38.2

8.55
9.14
11.89

50.05
32.56
40.47

28.4
19.2
19.2

60.9
60.9
60.9

49.57
41.04
44.51

10.30
12.69
12.47

52.55
40.47
45.06

23.4
19.2
19.2

60.9
60.9
60.9

57
83
140

-1.60
6.15
2.99

7.90
12.92
11.75

0.00
4.17
0.00

-21.7
-30.0
-30.0

12.5
41.7
41.7

62
87
149

41.60
31.74
35.84

9.51
8.41
10.11

41.18
30.84
35.54

23.8
16.8
16.8

63.7
57.6
63.7

62
88
150

57
83
140

40.39
33.45
36.27

10.08
10.16
10.66

38.83
30.84
34.84

19.1
16.8
16.8

63.7
63.7
63.7

57
83
140

-1.42
2.25
0.75

10.00
7.99
9.01

-2.35
0.00
0.00

-30.5
-14.1
-30.5

21.1
24.4
24.4

62
88
150

62
87
149

52.78
36.92
43.52

10.68
9.88
12.85

54.95
36.99
42.97

22.0
22.0
22.0

69.9
57.9
69.9

62
88
150

57
83
140

51.06
41.03
45.11

11.38
12.38
12.93

51.95
39.98
45.97

22.0
22.0
22.0

69.9
66.9
69.9

57
83
140

-1.63
4.47
1.99

10.39
12.16
11.82

-2.99
2.99
0.00

-35.9
-15.0
-35.9

23.9
44.9
44.9

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MaxPublic Disclosure Synopsis
Protocol A3921086 – 14 July 2017 – Final

Table 16. Descriptive Statistics of Observed and Change From Baseline Mean in SF-36 Domain and Component Scores, at
Week 48/ET (FAS)

090177e18c5cd567\Approved\Approved On: 19-Jul-2017 09:47 (GMT)

N

n

Mean

Observed Data
SDMedian

Min

n

Mean

Change from Baseline
SD
MedianMinMax
Social Functioning Domain
Baseline
Tofacitinib 5 mg BID
62
62
51.81
7.21
56.40
24.1
56.4
Tofacitinib 10 mg BID
88
87
36.38
12.29
34.89
13.4
56.4
Total
150
149
42.80
12.94
45.65
13.4
56.4
Week 48/ET
Tofacitinib 5 mg BID
62
57
49.42
9.64
56.40
18.8
56.4
57
-2.92
9.09
0.00
-37.6
32.3
Tofacitinib 10 mg BID
88
83
39.82
13.39
40.27
13.4
56.4
83
3.69
13.46
5.38
-43.0
37.6
Total
150
140
43.73
12.87
45.65
13.4
56.4
140
1.00
12.28
0.00
-43.0
37.6
Role Emotional Domain
Baseline
Tofacitinib 5 mg BID
62
62
50.12
8.85
55.68
10.2
55.7
Tofacitinib 10 mg BID
88
86
38.55
12.73
40.54
10.2
55.7
Total
150
148
43.40
12.61
44.32
10.2
55.7
Week 48/ET
Tofacitinib 5 mg BID
62
57
47.97
10.78
55.68
21.6
55.7
57
-2.26
10.29
0.00
-30.3
30.3
Tofacitinib 10 mg BID
88
83
41.13
13.15
44.32
10.2
55.7
82
3.28
11.38
0.00
-26.5
30.3
Total
150
140
43.92
12.66
48.11
10.2
55.7
139
1.01
11.24
0.00
-30.3
30.3
Mental Health Domain
Baseline
Tofacitinib 5 mg BID
62
62
49.89
9.84
52.35
21.9
63.4
Tofacitinib 10 mg BID
88
87
37.61
11.98
38.50
8.0
60.7
Total
150
149
42.72
12.66
44.04
8.0
63.4
Week 48/ET
Tofacitinib 5 mg BID
62
57
49.24
10.27
52.35
21.9
63.4
57
-1.02
8.63
0.00
-24.9
30.5
Tofacitinib 10 mg BID
88
83
40.13
12.52
41.27
10.8
63.4
83
2.87
11.72
2.77
-24.9
30.5
Total
150
140
43.84
12.46
46.81
10.8
63.4
140
1.29
10.71
0.00
-24.9
30.5
Subjects were analyzed as per their initial dose assignment.
Abbreviations: BID = twice daily; ET = Early Termination; FAS = Full Analysis Set; Max = maximum; Min = minimum; N = number of subjects in the analysis
set; n = number of subjects with non-missing data; SD = standard deviation; SF-36 = 36-Item Short Form Health Survey.

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Protocol A3921086 – 14 July 2017 – Final

090177e18c5cd567\Approved\Approved On: 19-Jul-2017 09:47 (GMT)

Mean baseline EQ-5D Utility and VAS scores were 0.85 and 77.98, respectively for subjects
in the tofacitinib 5 mg BID group and 0.57 and 48.60, respectively for subjects in thetofacitinib 10 mg BID group. No notable changes from baseline in EQ-5D utility were noted
for either treatment group. A notable increase from baseline in VAS scores was observed for
subjects remaining in the tofacitinib 10 mg group at Week 48, with a mean (SD) change frombaseline of 10.16 (26.57) observed at Week 48/ET (Table 17).

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Public Disclosure Synopsis
Protocol A3921086 – 14 July 2017 – Final

Table 17. Descriptive Statistics of Observed and Change From Baseline Mean in EQ-5D Utility and VAS Score, by Visit(FAS)

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N

n

Mean

Observed Data
SDMedian

Min

n

Mean

Change from Baseline
SD
MedianMin

Max
Utility Score
Baseline
Tofacitinib 5 mg BID
62
62
0.85
0.21
1.00
0.05
1.00
Tofacitinib 10 mg BID
88
85
0.57
0.28
0.69
-0.32
1.00
Total
150
147
0.69
0.29
0.73
-0.32
1.00
Week 48/ET
Tofacitinib 5 mg BID
62
57
0.84
0.16
0.85
0.19
1.00
57
-0.02
0.21
0.00
-0.53
0.74
Tofacitinib 10 mg BID
88
83
0.66
0.31
0.73
-0.24
1.00
81
0.10
0.36
0.07
-0.76
1.32
Total
150
140
0.73
0.27
0.76
-0.24
1.00
138
0.05
0.31
0.00
-0.76
1.32
VAS Score
Baseline
Tofacitinib 5 mg BID
62
62
77.98
16.18
80.00
20.00
100.00Tofacitinib 10 mg BID
88
86
48.60
19.21
50.00
8.00
80.00
Total
150
148
60.91
23.10
65.00
8.00
100.00Week 48/ET
Tofacitinib 5 mg BID
62
57
73.40
18.54
75.00
30.00
100.00
57
-3.79
20.56
-1.00
-60.0047.00
Tofacitinib 10 mg BID
88
83
57.60
24.60
61.00
9.00
100.00
82
10.16
26.57
10.00
-40.00
92.00
Total
150
140
64.04
23.59
70.00
9.00
100.00
139
4.44
25.16
0.00
-60.0092.00
Subjects were analyzed as per their initial dose assignment.
Abbreviations: BID = twice daily; ET = Early Termination; EQ-5D = EuroQOL 5 Dimensions questionnaire; FAS = Full Analysis Set; Max = maximum;
Min = minimum; N = number of subjects in the analysis set; n = number of subjects with non-missing data; SD = standard deviation; VAS = visual analog scale.

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Protocol A3921086 – 14 July 2017 – Final

Overall, 7 subjects (11.3%) and 14 subjects (15.9%) in the tofacitinib 5 mg BID and 10 mg
BID groups, respectively were hospitalized due to CD during the study. The mean length of
hospitalization related to CD was 3.8 days for subjects in the tofacitinib 5 mg BID group and7.1 days for subjects in the tofacitinib 10 mg BID group (Table 18).
Table 18. Number and Length of Hospitalizations due to Crohn’s Disease

Number of Subjects Hospitalized,
n(%)

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Length of Hospitalization (days, %)
<3
3-6
7-10
>10

Tofacitinib 5 mg
BID (N=62)
7 (11.3)

Tofacitinib 10 mg
BID (N=88)
14 (15.9)

Total(N=150)21 (14.0)

1 (1.6)4 (6.5)00

2 (2.3)9 (10.2)
3 (3.4)3 (3.4)3 (2.0)13 (8.7)
3 (2.0)3 (2.0)Mean (SD)3.80 (1.64)
7.06 (5.15)
6.32 (4.76)
Median
4.00
5.00
4.50
Range
1-5
2-20
1-20
Subjects were analyzed as per their initial dose assignment.
Subjects were only counted once in the row "Number of Subjects Hospitalized".
Abbreviations: BID = twice daily; N = number of subjects in the analysis set; n = number of subjects with
non-missing data; SD = standard deviation.

Pharmacodynamic (Biomarker) Results:
The changes from baseline in serum CRP values by week are presented in Table 19. Mean
(SD) baseline hsCRP values were 10.28 (18.58) mg/L for subjects in the tofacitinib 5 mg
BID group and 20.72 (30.51) mg/L for subjects in the tofacitinib 10 mg BID group.
A decrease from baseline values in CRP was observed at each time point in both treatmentgroups with the greatest decrease from baseline at Week 48 (mean [SD] changeof -4.55 [17.81] mg/L) for subjects remaining in the tofacitinib 5 mg BID group and at
Week 36 (mean [SD] change of -12.09 [30.61] mg/L) for subjects remaining in the tofacitinib
10 mg BID group.

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Table 19. Change From Baseline in CRP (mg/L), by Week (FAS)
n
Mean
SD
MedianMin
Max
Baseline
Tofacitinib 5 mg BID
62
10.28
18.58
3.62
0.1
98.4
Tofacitinib 10 mg
85
20.72
30.51
8.82
0.1
166.2
BID
Total
147
16.32
26.58
6.12
0.1
166.2
Week 8
Tofacitinib 5 mg BID
61
-0.44
14.78
-0.12
-45.9
59.2
Tofacitinib 10 mg
82
-4.81
26.76
-1.37
-122.7
102.1
BID
Total
143
-2.95
22.48
-0.32
-122.7102.1
Week 16
Tofacitinib 5 mg BID
58
-2.46
14.54
-0.07
-90.4
21.7
Tofacitinib 10 mg
72
-7.96
25.11
-1.18
-144.9
43.9
BID
Total
130
-5.51
21.17
-0.58
-144.943.9
Week 24
Tofacitinib 5 mg BID
54
-2.76
17.59
-0.58
-92.2
29.8
Tofacitinib 10 mg
61
-9.26
30.20
-1.68
-159.9
59.1
BID
Total
115
-6.21
25.19
-0.96
-159.959.1
Week 36
Tofacitinib 5 mg BID
46
-4.42
22.29
-0.27
-88.8
80.7
Tofacitinib 10 mg
51-12.0930.61-1.70-157.7
36.5
BID
Total
97
-8.45
27.13
-0.91
-157.7
80.7
Week 48
Tofacitinib 5 mg BID
43
-4.55
17.81
-0.64
-91.1
22.6
Tofacitinib 10 mg
44-11.4531.30-1.54-155.3
51.1
BID
Total
87
-8.04
25.63
-0.83
-155.3
51.1
Follow-up
Tofacitinib 5 mg BID
54
3.86
21.57
0.34
-84.3
72.7
Tofacitinib 10 mg
71
-4.72
31.34
0.26
-154.4
44.4
BID
Total
125
-1.01
27.78
0.34
-154.4
72.7
Subjects were analyzed as per their initial dose assignment.
Abbreviations: BID = twice daily; CRP = C-reactive protein; FAS = Full Analysis Set; Max = maximum; Min =minimum; n = number of subjects with non-missing data; SD = standard deviation.

The changes from baseline in FEC values by week are presented in Table 20. Mean (SD)baseline FEC values were 431.52 (483.37) mg/kg for subjects in the tofacitinib 5 mg BID
group and 486.06 (309.75) mg/kg for subjects in the tofacitinib 10 mg BID group.
Mean concentrations of FEC decreased at each time point in both treatment groups. The
greatest mean change from baseline in FEC was observed at Week 48 (mean [SD] changeof -189.61 [462.61] mg/kg) for subjects remaining in the tofacitinib 5 mg BID group and at
Week 36 (mean [SD] change of -133.82 [364.51] mg/kg) for subjects remaining in thetofacitinib 10 mg BID group.

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Table 20. Change From Baseline in Fecal Calprotectin (mg/kg), by Week (FAS)
n
Mean
SD
MedianMin
Max
Baseline
Tofacitinib 5 mg BID
61
431.52483.37274.0025.2
3128.0Tofacitinib 10 mg
80486.06309.75528.0025.2
1065.0
BID
Total
141
462.46393.71442.0025.2
3128.0Week 8
Tofacitinib 5 mg BID
53-105.51436.41-13.00-2291
654.0
Tofacitinib 10 mg
71-102.82
310.10-47.00-959.0
528.0
BID
Total
124
-103.97367.76-32.50-2291
654.0
Week 16
Tofacitinib 5 mg BID
54-144.65423.20-44.90-2393
633.0
Tofacitinib 10 mg
64-35.28718.82-82.50-979.04999.0
BID
Total
118
-85.33601.95-63.50-2393
4999.0Week 24
Tofacitinib 5 mg BID
49-120.49511.49-54.00-2923
827.0
Tofacitinib 10 mg
55-130.68
337.23-65.00
-1027
703.0
BID
Total
104
-125.88426.11-59.00-2923
827.0
Week 36
Tofacitinib 5 mg BID
41-169.92354.30-56.00-1654
528.8
Tofacitinib 10 mg
42-133.82364.51-52.00-985.0
592.0
BID
Total
83
-151.65357.77-56.00-1654
592.0
Week 48
Tofacitinib 5 mg BID
37-189.61462.61-98.80-2123
745.8
Tofacitinib 10 mg
38-123.87376.70-102.00-977.0
910.0
BID
Total
75
-156.30
419.71-98.80-2123
910.0
Follow-up
Tofacitinib 5 mg BID
48-51.33453.73
0.00
-2219
777.8
Tofacitinib 10 mg
57-109.23389.54-59.00
-1019
791.0
BID
Total
105
-82.76419.03-15.00-2219
791.0
Subjects were analyzed as per their initial dose assignment.
Abbreviations: BID = twice daily; FAS = Full Analysis Set; Max = maximum; Min = minimum; n = number ofsubjects with non-missing data; SD = standard deviation.

Safety Results:
A summary of SAEs is provided in Table 21. SAEs were reported in 8.1% of subjects in thetofacitinib 5 mg BID group and 15.9% of subjects in the tofacitinib 10 mg BID group. The
most frequently reported SAE in both treatment groups was CD, which occurred in a higher
proportion of subjects in the tofacitinib 10 mg BID group (7 subjects, 8.0%) who entered thestudy with active disease not in remission compared to the tofacitinib 5 mg BID group, which
comprised subjects who entered the study in remission (3 subjects, 4.8%).

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Table 21. Treatment-Emergent Serious Adverse Events by System Organ Class andPreferred Term (All Causalities)
System Organ Class
Preferred Term

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Number (%) of Subjects:
Evaluable for adverse events
With adverse events

Tofacitinib
5 mg BID
n(%)
n1
n2

Tofacitinib
10 mg BID
n(%)
n1

62
5 (8.06)88
14(15.91)

Total
n2

n(%)

n1

n2

150
19
(12.67)

Gastrointestinal disorders
4 (6.45)40
9 (10.23)
91
13 (8.67)
13
1
Colon dysplasia
1 (1.61)10000
1 (0.67)
1
0
Crohn’s disease
3 (4.84)
30
7 (7.95)
71
10 (6.67)
10
1
Small intestinal obstruction000
2 (2.27)20
2 (1.33)
2
0General disorders and2 (3.23)20
1 (1.14)10
3 (2.00)
30
administration site conditions
Chest pain
1 (1.61)10000
1 (0.67)
10Influenza like illness
1 (1.61)10000
1 (0.67)
10
Pyrexia000
1 (1.14)10
1 (0.67)
1
0
Hepatobiliary disorders000
1 (1.14)10
1 (0.67)
10Biliary colic000
1 (1.14)10
1 (0.67)1
0
Immune system disorders000
1 (1.14)1
1
1 (0.67)1
1Hypersensitivity
000
1 (1.14)1
1
1 (0.67)
1
1
Infections and infestations
2 (3.23)21
2 (2.27)20
4 (2.67)
4
1
Anal abscess000
1 (1.14)10
1 (0.67)
1
0
Diarrhoea infectious
1 (1.61)10000
1 (0.67)
1
0
Pyelonephritis
1 (1.61)1
1
0
00
1 (0.67)
1
1
Vulval abscess000
1 (2.44)10
1 (1.41)10Injury, poisoning and procedural
000
1 (1.14)10
1 (0.67)
10complications
Incisional hernia
000
1 (1.14)10
1 (0.67)
10Investigations
00
0
1 (1.14)20
1 (0.67)
20
C-reactive protein increased
000
1 (1.14)20
1 (0.67)
20
Renal and urinary disorders
1 (1.61)10000
1 (0.67)
1
0
Acute kidney injury
1 (1.61)10000
1 (0.67)
10
Reproductive system and breast000
1 (1.14)10
1 (0.67)10disorders
Perineal fistula000
1 (1.14)10
1 (0.67)
10
Respiratory, thoracic and1 (1.61)10000
1 (0.67)
1
0
mediastinal disorders
Dyspnoea
1 (1.61)10000
1 (0.67)10Skin and subcutaneous tissue
1 (1.61)10000
1 (0.67)10disorders
Hyperhidrosis
1 (1.61)10000
1 (0.67)
10Subjects were analyzed as per their initial dose assignment.
Except for ’n1’ and ’n2’ subjects were only counted once per treatment for each row.
MedDRA (version 19.0) coding dictionary applied.
Includes data up to 999 days after last dose of study drug.
Percentage cutoff based upon frequency in any treatment group.
Abbreviations: BID = twice daily; MedDRA = Medical Dictionary for Regulatory Activities; n = number ofsubjects in this reporting group affected by any occurrence of this adverse event, All Causalities; n1: the numberof occurrences of treatment-emergent all causalities adverse events; n2: the number of occurrences oftreatment-emergent causally related to treatment adverse events.

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There were no deaths during the study.
A summary of treatment-emergent non-serious AEs in >2% of subjects is provided inTable 22. The most frequently reported non-serious AE in both treatment groups was CDwith 19 (30.7%) subjects in the tofacitinib 5 mg BID group and 11 (12.5%) subjects in thetofacitinib 10 mg BID group.
Table 22. Treatment-Emergent Non-Serious Adverse Events by System Organ Classand Preferred Term in >2% of Subjects
System Organ Class
Preferred Term

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Number (%) of Subjects:
Evaluable for adverse events
With adverse events

Tofacitinib
5 mg BID
n(%)
n1

n2

62
42 (67.74)

Tofacitinib
10 mg BID
n(%)
n1 n2
88
58
(65.91)

Total
n(%)

n1

n2

150
100 (66.67)

Blood and lymphatic systemdisordersAnemia
Ear and labyrinth disorders
VertigoGastrointestinal disorders

3 (4.84)

53

4 (4.55)

42

7 (4.67)

9

5

3 (4.84)0030 (48.39)

5
0
0
50

3
0
0
5

4
2
2
64

2
0
0
18

7 (4.67)
2 (1.33)
2 (1.33)
64 (42.67)

9
2
2
114

5
0
0
23

Abdominal distension
Abdominal pain
Abdominal pain upper
Anal fissure
Aphthous ulcer
Constipation
Crohn’s disease

2 (3.23)
7 (11.29)
1 (1.61)
1 (1.61)
1 (1.61)
2 (3.23)
19 (30.65)

2
7
1
1
1
2
22

0
1
0
0
0
0
4

3
8
2
2
3
1
13

0
1
2
0
0
1
3

5 (3.33)
14 (9.33)
3 (2.00)
3 (2.00)
4 (2.67)
3 (2.00)
30 (20.00)

5
15
3
3
4
3
35

0
2
2
0
0
1
7

Diarrhoea
Dyspepsia
Flatulence
Food poisoning
Haematochezia
Haemorrhoids
NauseaProctalgia
Toothache
Vomiting
General disorders andadministration site conditions
Chest pain
Cyst
FatiguePyrexia
Infections and infestations

3 (4.84)00
2 (3.23)
1 (1.61)02 (3.23)
1 (1.61)
3 (4.84)
1 (1.61)
6 (9.68)

3
0
0
2
1
0
2
1
3
2
6

0
0
0
0
0
0
0
0
0
0
2

1
6
2
0
2
4
9
2
0
6
13

0
4
0
0
0
0
3
0
0
4
4

4 (2.67)
3 (2.00)
2 (1.33)
2 (1.33)
3 (2.00)
4 (2.67)
11 (7.33)
3 (2.00)
3 (2.00)
7 (4.67)
18 (12.00)

4
6
2
2
3
4
11
3
3
8
19

0
4
0
0
0
0
3
0
0
4
6

2 (3.23)
2 (3.23)
1 (1.61)
1 (1.61)
25 (40.32)

2
2
1
1
48

1
0
0
1
24

2
0
4
7
39

1
0
0
3
16

4 (2.67)
2 (1.33)
5 (3.33)
7 (4.67)
54 (36.00)

4
2
5
8
87

2
0
0
4
40

Bartholin’s abscess
Bartholinitis
Cystitis00
2 (3.23)

0
0
2

0
0
1

4 (4.55)
2 (2.27)
2 (2.27)34(38.64)3 (3.41)
7 (7.95)
2 (2.27)
2 (2.27)
3 (3.41)
1 (1.14)11(12.50)1 (1.14)
3 (3.41)
2 (2.27)02 (2.27)
4 (4.55)
9 (10.23)
2 (2.27)0
6 (6.82)12(13.64)2 (2.27)04 (4.55)
6 (6.82)29(32.95)
1 (2.44)
2 (4.88)
0

1
2
0

0
0
0

1 (1.41)
2 (2.82)
2 (1.33)

1
2
2

0
0
1

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Table 22. Treatment-Emergent Non-Serious Adverse Events by System Organ Classand Preferred Term in >2% of Subjects

090177e18c5cd567\Approved\Approved On: 19-Jul-2017 09:47 (GMT)

System Organ Class
Preferred Term
Folliculitis
Gastroenteritis
Herpes zoster
Influenza
Nasopharyngitis
Oral herpes
Pharyngitis
Upper respiratory tract infection
Urinary tract infection
Vaginal infection
Vaginitis bacterial
Vulvovaginal candidiasis
Vulvovaginal mycotic infection
Investigations
Blood alkaline phosphataseincreased
Blood creatine phosphokinase
increased
C-reactive protein increased
Gamma-glutamyltransferase
increased
Lymphocyte count decreased
Smear cervix abnormal
Weight decreased
Metabolism and nutrition
disorders
Dehydration
Hypercholesterolaemia
Vitamin B12 deficiency
Musculoskeletal andconnective tissue disorders
Arthralgia
Back pain
Muscle spasms
Neoplasms, benign, malignant
and unspecified (incl. cysts andpolyps)Acrochordon
Nervous system disorders
Headache
Psychiatric disorders
Anxiety
Insomnia
Reproductive system andbreast disorders
Amenorrhoea
Balanoposthitis
Erectile dysfunction
Oligomenorrhoea

Tofacitinib
5 mg BID
n(%)
n1
0
0
7 (11.29)
7
1 (1.61)
1
5 (8.06)5
8 (12.90)
11
3 (4.84)
32 (3.23)
22 (3.23)2
8 (12.90)
14
1 (3.33)
1
0
0
0
0
0
0
7 (11.29)
14
2 (3.23)
2

n2
0
1
1
1
6
2
1
1
9
1
0
0
0
10
2

Tofacitinib
10 mg BID
n(%)
n1 n2
2 (2.27)22
2 (2.27)22
2 (2.27)
2
1
8 (9.09)94
7 (7.95)
7
3
0
0
0
0
0
0
2 (2.27)20
7 (7.95)84000
1 (2.44)10
1 (2.44)10
2 (4.88)20
8 (9.09)
14 11
0
0
0

3 (4.84)n(%)
2 (1.33)
9 (6.00)
3 (2.00)
13 (8.67)
15 (10.00)
3 (2.00)
2 (1.33)
4 (2.67)
15 (10.00)
1 (1.41)
1 (1.41)
1 (1.41)
2 (2.82)
15 (10.00)
2 (1.33)

n1
2
9
3
14
18
3
2
4
22
1
1
1
2
28
2

n2
2
3
2
5
9
2
1
1
13
1
0
0
0
21
2

4

3

5 (5.68)

53

8 (5.33)

96

2 (3.23)
2 (3.23)

2
2

0
2

0
0

0
0

0
0

2 (1.33)
2 (1.33)2
20
2

1 (1.61)
1 (3.33)
2 (3.23)
0

1
1
2
0

1
1
1
0

2 (2.27)0
1 (1.14)5 (5.68)

8
0
1
7

8
0
0
0

3 (2.00)
1 (1.41)
3 (2.00)
5 (3.33)

9
1
3
7

9
1
1
0

0
0
0
7 (11.29)

0
0
0
9

0
0
0
0

3
2
2
14

0
0
0
3

2 (1.33)
2 (1.33)
2 (1.33)
20 (13.33)

3
2
2
23

0
0
0
3

5 (8.06)
1 (1.61)
2 (3.23)
0

6
1
2
0

0
0
0
0

2 (2.27)
2 (2.27)
2 (2.27)13(14.77)8 (9.09)
4 (4.55)
2 (2.27)
2 (2.27)

8
4
2
2

3
0
0
0

13 (8.67)
5 (3.33)
4 (2.67)
2 (1.33)

14
5
4
2

3
0
0
0

0
1 (1.61)
1 (1.61)
2 (3.23)02 (3.23)
2 (6.25)

0
2
2
2
0
2
2

0
1
1
1
0
1
0

2 (2.27)
2 (2.27)
2 (2.27)
3 (3.41)
3 (3.41)04 (4.55)

2
2
2
3
3
0
14

0
2
2
0
0
0
1

2 (1.33)
3 (2.00)
3 (2.00)
5 (3.33)
3 (2.00)
2 (1.33)
6 (4.00)

2
4
4
5
3
2
6

0
3
3
1
0
1
1

0
1 (3.13)
1 (3.13)
0

0
1
1
0

0
0
0
0

1 (2.44)00
1 (2.44)

1
0
0
1

1
0
0
0

1 (1.41)
1 (1.27)
1 (1.27)
1 (1.41)

1
1
1
1

1
0
0
0

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Total

Public Disclosure Synopsis
Protocol A3921086 – 14 July 2017 – Final

Table 22. Treatment-Emergent Non-Serious Adverse Events by System Organ Classand Preferred Term in >2% of Subjects

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System Organ Class
Preferred Term

Tofacitinib
5 mg BID
n(%)
n1
0
0
0
0
1 (1.61)1

Tofacitinib
10 mg BID
n(%)
n1 n2
1 (2.13)10
1 (2.44)10
2 (2.27)
2
1

Total

n2
n(%)
n1
n2
Testicular swelling0
1 (1.27)
10
Vulvovaginal pruritus0
1 (1.41)
10
Respiratory, thoracic, and1
3 (2.00)
3
2
mediastinal disordersCough
1 (1.61)1
1
2 (2.27)
21
3 (2.00)
3
2
Skin and subcutaneous tissue
1 (1.61)1
0
4 (4.55)
42
5 (3.33)52
disorders
Dermatitis
000
2 (2.27)2
1
2 (1.33)
2
1Rash
1 (1.61)10
2 (2.27)
21
3 (2.00)
3
1
Subjects were analyzed as per their initial dose assignment.
Except for ’n1’ and ’n2’ subjects were only counted once per treatment for each row.
MedDRA (version 19.0) coding dictionary applied.
Includes data up to 999 days after last dose of study drug.
Percentage cutoff based upon frequency in any treatment group.
Abbreviations: BID = twice daily; MedDRA = Medical Dictionary for Regulatory Activities; n = number ofsubjects in this reporting group affected by any occurrence of this adverse event, All Causalities; n1: the numberof occurrences of treatment-emergent all causalities adverse events; n2: the number of occurrences oftreatment-emergent causally related to treatment adverse events.

Clinical Laboratory Evaluations
In general, a greater mean percent increase from baseline was observed for each lipid
parameter across all timepoints for subjects remaining in the tofacitinib 10 mg BID group,compared to those remaining in the tofacitinib 5 mg BID group, with the exception of
triglycerides in the tofacitinib 5 mg BID group, although these changes were not consideredclinically meaningful and were similar to what has been observed with tofacitinib treatment
in other studies of other indications.
The most common hematological abnormalities were observed for absolute neutrophil counts
and absolute lymphocytes. However, AEs of neutrophil count decreased and lymphocyte
count decreased were uncommon among subjects in both treatment groups (neutrophil countdecreased reported in 1 subject in the tofacitinib 10 mg BID group only and lymphocyte
count decreased reported in 1 and 2 subjects in the tofacitinib 5 mg BID and tofacitinib
10 mg BID groups, respectively).
Clinical chemistry abnormalities were few, with the most commonly reported abnormality
observed for creatine kinase with 11 subjects in the tofacitinib 5 mg BID group and
14 subjects in the tofacitinib 10 mg BID group. AEs of blood creatine phosphokinase
increased were reported in 3 subjects in the tofacitinib 5 mg BID group and 5 subjects intofacitinib 10 mg BID group. No AEs relating to rhabdomyolysis or myositis were reported
during the study.
Adjudicated AEs
There were no cases of confirmed adjudicated cardiovascular events or ILD events.
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Public Disclosure Synopsis
Protocol A3921086 – 14 July 2017 – Final

One subject in the tofacitinib 5 mg BID group had an event of Herpes zoster that met thecriteria for opportunistic infection (reported as multidermatomal, nonadjacent or >2 adjacentdermatomes), and 1 subject in the tofacitinib 10 mg BID group had an event of Varicella that
met the criteria for opportunistic infection, reported as systemic, disseminated andmultidermatomal.
One hepatic event of Biliary colic in the tofacitinib 10 mg BID group was adjudicated anddid not meet the criteria for a hepatic injury but was considered as possible Gilbert syndrome.
Two subjects in the tofacitinib 10 mg BID group had events that met adjudication criteria for
GI perforation (Perineal fistula and Anal abscess). The event of Perineal fistula was
attributed by the adjudication committee to concomitant medication and concurrent medical
condition, and Anal abscess was attributed to concurrent medical condition.
Two subjects, 1 in each treatment group, had an event that was adjudicated for malignancy.
Of those, 1 subject in the tofacitinib 10 mg BID group (11091001) had an event of Basal cell
carcinoma that met adjudication criteria for malignancy events. The other event (Colon
dysplasia) was also adjudicated but was determined not to meet the criteria for malignancy.

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CONCLUSION(S):•

Tofacitinib appeared to be well tolerated as a long-term maintenance therapy in subjects
with CD. There were no deaths during this study. A greater proportion of subjects in thetofacitinib 10 mg BID group experienced severe and serious AEs, and AEs that led to
discontinuation compared to subjects in the tofacitinib 5 mg BID group with insufficient
clinical response accounting for the majority of the discontinuations. Rates of serious
infection and adjudicated events were low and similar between the tofacitinib dosegroups.

•There were no clinically meaningful differences in mean lipid levels between thetreatment groups at any time point with mean levels generally remaining stable over timewith modest elevations from baseline values.

•

At Week 48, the proportions of subjects in the tofacitinib 5 mg BID group in clinicalremission and sustained clinical remission based on observed data were 87.9%(29/33 subjects remaining in the study) and 75.0% (24/32 subjects), respectively.

•

At Week 48, the proportions of subjects in the tofacitinib 10 mg BID group in clinicalremission and sustained clinical remission based on observed data were 55.6%(20/36 subjects remaining in the study) and 34.3% (12/35 subjects), respectively.

•

Efficacy and safety were analyzed by initial dose assignment. Within and between dosegroup analyses are confounded by dose switching between treatment groups that was
permitted after 8 weeks of treatment. Notably, the large majority of subjects who
switched doses were those who switched from 5 mg BID to 10 mg BID.

•

The IBDQ mean total score remained high (≥170) at each time point for subjects
remaining in the study in the tofacitinib 5 mg BID group and did not decrease greatly

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Public Disclosure Synopsis
Protocol A3921086 – 14 July 2017 – Finalfrom baseline. For subjects remaining in the study in the tofacitinib 10 mg BID group
there was a numerical increase in mean change from baseline in the total IBDQ score.
Decreases in hsCRP and FEC from baseline were observed at each time point in both
treatment groups, with the magnitude of the decrease in hsCRP from baseline being
numerically greater at each time point for subjects in the tofacitinib 10 mg group than for
those in the tofacitinib 5 mg BID group.

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