Trial Outcomes & Findings for A Open-Label Study Of CP-690,550 As Long-Term Therapy (48 Weeks) In Subjects With Crohn's Disease (NCT NCT01470599)

Last Updated: 2017-10-16

Results Overview

Pre-specified cardiovascular events were adjudicated by committees of external experts who were blinded to treatment assignment. Potential events of interest (pEoI) were identified by the investigator, sponsor, review of alerts from central electrocardiogram assessments, and by search of adverse events (AE)/serious adverse event (SAE) listings for events coded to death (coronary and non-coronary), myocardial infarction (non-fatal), all coronary revascularization, unstable angina, stroke (fatal and non-fatal), transient ischemic attack, congestive heart failure, peripheral arterial vascular disease, dyspnoea, and chest pain. The independent reviewers (IRs) determined if the pEoI met the criteria for EoI classification according to the definitions summarized from the Clinical Data Interchange Standards Consortium 'Standardized Definitions for End Point Events in Cardiovascular Trials' published October 2010.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

150 participants

Primary outcome timeframe

From baseline to Week 52

Results posted on

2017-10-16

Participant Flow

This study was conducted in participants who completed the 26-week maintenance treatment of Study A3921084 or who withdrew early due to A3921084 study treatment failure according to prespecified criteria.

Participants were assigned to either the 5 milligram (mg) twice daily (BID) or 10 mg BID treatment group according to clinical remission status as assessed by Crohn's Disease Activity Index (CDAI) score at the end of the A3921084 study treatment visit or early termination visit due to A3921084 study treatment failure.

Participant milestones

Participant milestones
Measure	Tofacitinib 5 mg BID Tofacitinib 5 mg tablet for oral administration at a dose of 5 mg BID for up to 48 weeks.	Tofacitinib 10 mg BID Tofacitinib 10 mg tablets (2 x 5 mg tablets) for oral administration at a dose of 10 mg BID for up to 48 weeks.
Overall Study STARTED	62	88
Overall Study COMPLETED	43	45
Overall Study NOT COMPLETED	19	43

Reasons for withdrawal

Reasons for withdrawal
Measure	Tofacitinib 5 mg BID Tofacitinib 5 mg tablet for oral administration at a dose of 5 mg BID for up to 48 weeks.	Tofacitinib 10 mg BID Tofacitinib 10 mg tablets (2 x 5 mg tablets) for oral administration at a dose of 10 mg BID for up to 48 weeks.
Overall Study Did not meet entrance criteria	1	0
Overall Study Lost to Follow-up	2	1
Overall Study Withdrawal by Subject	3	4
Overall Study Other	1	0
Overall Study Protocol Violation	3	1
Overall Study Adverse event related to study drug	2	5
Overall Study Insufficient clinical response	6	27
Overall Study Adverse event not related to study drug	1	5

Baseline Characteristics

A Open-Label Study Of CP-690,550 As Long-Term Therapy (48 Weeks) In Subjects With Crohn's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tofacitinib 5 mg BID n=62 Participants Tofacitinib 5 mg tablet for oral administration at a dose of 5 mg BID for up to 48 weeks.	Tofacitinib 10 mg BID n=88 Participants Tofacitinib 10 mg tablets (2 x 5 mg tablets) for oral administration at a dose of 10 mg BID for up to 48 weeks.	Total n=150 Participants Total of all reporting groups
Sex: Female, Male Female	30 Participants n=5 Participants	41 Participants n=7 Participants	71 Participants n=5 Participants
Sex: Female, Male Male	32 Participants n=5 Participants	47 Participants n=7 Participants	79 Participants n=5 Participants
Age, Continuous	41.0 Years STANDARD_DEVIATION 12.6 • n=5 Participants	38.2 Years STANDARD_DEVIATION 11.6 • n=7 Participants	39.4 Years STANDARD_DEVIATION 12.1 • n=5 Participants

PRIMARY outcome

Timeframe: From baseline to Week 52

Population: Participants in the SAS who had pEoI and were adjudicated by IRs

Outcome measures

Outcome measures
Measure	Tofacitinib 5 mg BID Tofacitinib 5 mg tablet for oral administration at a dose of 5 mg BID for up to 48 weeks.	Tofacitinib 10 mg BID n=2 Participants Tofacitinib 10 mg tablets (2 x 5 mg tablets) for oral administration at a dose of 10 mg BID for up to 48 weeks.
Adjudicated Potential Cardiovascular Events	—	0 Number of events meeting criteria

PRIMARY outcome

Timeframe: From baseline to Week 52

Population: Participants in the SAS who had pEoI and were adjudicated by IRs

Pre-specified malignancy events were adjudicated by committees of external experts who were blinded to treatment assignment. pEoI were identified by the investigator, sponsor, potential primary event notifications (i.e. malignancies excluding non-melanoma skin cancers) for a specific protocol, events submitted for histopathology review for potential malignancies which met the criteria for potential malignancies, and by search of AE/SAE listings for events coded to Malignant tumors Standard Medical Dictionary for Regulatory Activities (MedDRA) Queries (SMQ) (20000194). IRs determined if the pEoI met the criteria for EoI classification according to the International Classification of Diseases for Oncology, a ten-digit multi-axial classification of the site (4 characters), morphology (4 digits), behavior (1 digit), and grading (1 digit) of neoplasms.

Outcome measures

Outcome measures
Measure	Tofacitinib 5 mg BID n=1 Participants Tofacitinib 5 mg tablet for oral administration at a dose of 5 mg BID for up to 48 weeks.	Tofacitinib 10 mg BID n=1 Participants Tofacitinib 10 mg tablets (2 x 5 mg tablets) for oral administration at a dose of 10 mg BID for up to 48 weeks.
Adjudicated Malignancy Events	0 Number of events meeting criteria	1 Number of events meeting criteria

PRIMARY outcome

Timeframe: From baseline to Week 52

Population: Participants in the SAS who had pEoI and were adjudicated by IRs

Pre-specified liver injury events were adjudicated by blinded committees of external experts. pEoI were identified by investigator, sponsor \& search of clinical, safety \& laboratory databases (potential Hy's law event, ALT/AST ≥5 x ULN, events meeting hepatic discontinuation criteria, SAEs coded to MedDRA hepatobiliary system organ class (SOC), AEs/SAEs coded to MedDRA liver infections or infectious biliary disorders SMQ, AEs coded to MedDRA drug-induced liver injury (DILI) preferred term or any death with ALT or AST ≥3xULN, bilirubin ≥2xULN or jaundice). IRs determined if the pEoI met the criteria for EoI classification by assessing DILI (definite, highly likely, probable, possible, unlikely, unrelated or undetermined), pattern (hepatocellular, mixed, cholestatic or undetermined), likely, competing or alternative cause(s), severity (mild, moderate, severe, fatal/transplantation or undetermined), Hy's law case, recovery \& liver failure (all yes, no or undetermined).

Outcome measures

Outcome measures
Measure	Tofacitinib 5 mg BID Tofacitinib 5 mg tablet for oral administration at a dose of 5 mg BID for up to 48 weeks.	Tofacitinib 10 mg BID n=1 Participants Tofacitinib 10 mg tablets (2 x 5 mg tablets) for oral administration at a dose of 10 mg BID for up to 48 weeks.
Adjudicated Hepatic Injury Events	—	0 Number of events meeting criteria

PRIMARY outcome

Timeframe: From baseline to Week 52

Population: Participants in the SAS who had pEoI and were adjudicated by IRs

Pre-specified opportunistic infection events were adjudicated by blinded committees of external experts. pEoI were identified by investigator, sponsor \& search of SAE listings for serious infections coded to MedDRA infections \& infestations SOC \&/or events meeting pre-specified criteria for IR pre-screening to determine if adjudication is required. IRs determined if the pEoI met the criteria for EoI classification according to definitions for opportunistic infections (invasive fungal infections per the European Organization for Research \& Treatment of Cancer/Invasive Fungal Infections Cooperative Group \& the National Institute of Allergy \& Infectious Diseases Mycoses Study Group \[EORTC/MSG\] Consensus Group definitions, endemic fungal infections per the EORTC/MSG Consensus Group definitions, other fungal infections, viral, bacterial \& parasitic infections \& vaccine dissemination) \& special interest infections (actinomycosis, Legionella \& mononucleosis-like toxoplasmosis).

Outcome measures

Outcome measures
Measure	Tofacitinib 5 mg BID n=4 Participants Tofacitinib 5 mg tablet for oral administration at a dose of 5 mg BID for up to 48 weeks.	Tofacitinib 10 mg BID n=4 Participants Tofacitinib 10 mg tablets (2 x 5 mg tablets) for oral administration at a dose of 10 mg BID for up to 48 weeks.
Adjudicated Opportunistic Infection Events	1 Number of events meeting criteria	1 Number of events meeting criteria

PRIMARY outcome

Timeframe: From baseline to Week 52

Population: Participants in the SAS who had pEoI and were adjudicated by IRs

Pre-specified GI perforation events were adjudicated by committees of external experts who were blinded to treatment assignment. The pEoI were identified via search of AE/SAE listings using the MedDRA GI Perforation SMQ. The IRs determined if the pEoI met the criteria for EoI classification based on whether a GI perforation occurred and if yes, the location within the GI tract, possible contributing medical conditions and/or concomitant medications.

Outcome measures

Outcome measures
Measure	Tofacitinib 5 mg BID Tofacitinib 5 mg tablet for oral administration at a dose of 5 mg BID for up to 48 weeks.	Tofacitinib 10 mg BID n=2 Participants Tofacitinib 10 mg tablets (2 x 5 mg tablets) for oral administration at a dose of 10 mg BID for up to 48 weeks.
Adjudicated Gastrointestinal (GI) Perforation Events	—	2 Number of events meeting criteria

PRIMARY outcome

Timeframe: From baseline to Week 52

Population: Participants in the SAS who had pEoI and were adjudicated by IRs

Pre-specified ILD events were adjudicated by committees of external experts who were blinded to treatment assignment. pEoI were identified by searches of the clinical, safety \& laboratory databases (AEs coded to the MedDRA ILD SMQ and events nominated by the study clinician or clinical lead). The IRs determined if the pEoI met the criteria for EoI classification by assessment of the ILD event (probably ILD, possible ILD, alternative diagnosis likely, other or insufficient information to classify).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Week 48

Population: Full analysis set (FAS) - consisted of all participants enrolled in this OL extension study.

CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid or very soft stools, intensity of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity. Clinical remission was defined as a CDAI score of less than (\<) 150. Sustained clinical remission was defined as being in clinical remission (CDAI score \<150) at both Week 24 and Week 48. 95 percent (%) Clopper-Pearson exact confidence interval reported for the proportions. n = number of participants with non-missing data.

Outcome measures

Outcome measures
Measure	Tofacitinib 5 mg BID n=62 Participants Tofacitinib 5 mg tablet for oral administration at a dose of 5 mg BID for up to 48 weeks.	Tofacitinib 10 mg BID n=88 Participants Tofacitinib 10 mg tablets (2 x 5 mg tablets) for oral administration at a dose of 10 mg BID for up to 48 weeks.
Percentage of Participants in Clinical Remission and Sustained Clinical Remission at Week 48 Clinical remission (n=33, 36)	87.88 Percent Interval 71.8 to 96.6	55.56 Percent Interval 38.1 to 72.06
Percentage of Participants in Clinical Remission and Sustained Clinical Remission at Week 48 Sustained clinical remission (n=32, 35)	75.00 Percent Interval 56.6 to 88.54	34.29 Percent Interval 19.13 to 52.21

SECONDARY outcome

Timeframe: Baseline and Weeks 8, 16, 24, 36, 48 and 52/follow-up

Population: Participants in the FAS who met clinical remission criteria at baseline of this study

CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid or very soft stools, intensity of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity. Clinical remission was defined as a CDAI score of \<150. Sustained clinical remission was defined as being in clinical remission (CDAI score \<150) at both Week 24 and Week 48. 95% Clopper-Pearson exact confidence interval reported for the proportions. n = number of participants with non-missing data.

Outcome measures

Outcome measures
Measure	Tofacitinib 5 mg BID n=61 Participants Tofacitinib 5 mg tablet for oral administration at a dose of 5 mg BID for up to 48 weeks.	Tofacitinib 10 mg BID n=4 Participants Tofacitinib 10 mg tablets (2 x 5 mg tablets) for oral administration at a dose of 10 mg BID for up to 48 weeks.
Percentage of Participants in Clinical Remission and Sustained Clinical Remission Among Participants in Clinical Remission at Baseline of This Study Clinical remission: Baseline (n=61, 4)	100.00 Percentage of participants Interval 94.13 to 100.0	100.00 Percentage of participants Interval 39.76 to 100.0
Percentage of Participants in Clinical Remission and Sustained Clinical Remission Among Participants in Clinical Remission at Baseline of This Study Clinical remission: Week 8 (n=53, 4)	75.47 Percentage of participants Interval 61.72 to 86.24	50.00 Percentage of participants Interval 6.76 to 93.24
Percentage of Participants in Clinical Remission and Sustained Clinical Remission Among Participants in Clinical Remission at Baseline of This Study Clinical remission: Week 16 (n=52, 4)	84.62 Percentage of participants Interval 71.92 to 93.12	75.00 Percentage of participants Interval 19.41 to 99.37
Percentage of Participants in Clinical Remission and Sustained Clinical Remission Among Participants in Clinical Remission at Baseline of This Study Clinical remission: Week 24 (n=48, 4)	85.42 Percentage of participants Interval 72.24 to 93.93	25.00 Percentage of participants Interval 0.63 to 80.59
Percentage of Participants in Clinical Remission and Sustained Clinical Remission Among Participants in Clinical Remission at Baseline of This Study Clinical remission: Week 36 (n=40, 3)	92.50 Percentage of participants Interval 79.61 to 98.43	33.33 Percentage of participants Interval 0.84 to 90.57
Percentage of Participants in Clinical Remission and Sustained Clinical Remission Among Participants in Clinical Remission at Baseline of This Study Clinical remission: Week 48 (n=32, 3)	87.50 Percentage of participants Interval 71.01 to 96.49	100.00 Percentage of participants Interval 29.24 to 100.0
Percentage of Participants in Clinical Remission and Sustained Clinical Remission Among Participants in Clinical Remission at Baseline of This Study Clinical remission: Week 52/follow-up (n=37, 3)	64.86 Percentage of participants Interval 47.46 to 79.79	33.33 Percentage of participants Interval 0.84 to 90.57
Percentage of Participants in Clinical Remission and Sustained Clinical Remission Among Participants in Clinical Remission at Baseline of This Study Sustained clinical remission (n=31, 3)	77.42 Percentage of participants Interval 58.9 to 90.41	33.33 Percentage of participants Interval 0.84 to 90.57

SECONDARY outcome

Timeframe: Baseline and Weeks 8, 16, 24, 36, 48 and 52/follow-up

Population: Participants in the FAS who met clinical response or clinical remission criteria at baseline of this study

CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid or very soft stools, intensity of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity. Clinical remission was defined as a CDAI score of \<150. Sustained clinical remission was defined as being in clinical remission (CDAI score \<150) at both Week 24 and Week 48. Clinical response was defined as a CDAI score reduction of at least 100 points from the A3921083 study baseline value. 95% Clopper-Pearson exact confidence interval reported for the proportions. n = number of participants with non-missing data.

Outcome measures

Outcome measures
Measure	Tofacitinib 5 mg BID n=62 Participants Tofacitinib 5 mg tablet for oral administration at a dose of 5 mg BID for up to 48 weeks.	Tofacitinib 10 mg BID n=23 Participants Tofacitinib 10 mg tablets (2 x 5 mg tablets) for oral administration at a dose of 10 mg BID for up to 48 weeks.
Percentage of Participants in Clinical Remission and Sustained Clinical Remission Among Participants in Clinical Response (CDAI-100 Response) or Clinical Remission at Baseline of This Study Clinical remission: Baseline (n=62, 23)	98.39 Percentage of participants Interval 91.34 to 99.96	17.39 Percentage of participants Interval 4.95 to 38.78
Percentage of Participants in Clinical Remission and Sustained Clinical Remission Among Participants in Clinical Response (CDAI-100 Response) or Clinical Remission at Baseline of This Study Clinical remission: Week 8 (n=54, 20)	75.93 Percentage of participants Interval 62.36 to 86.51	35.00 Percentage of participants Interval 15.39 to 59.22
Percentage of Participants in Clinical Remission and Sustained Clinical Remission Among Participants in Clinical Response (CDAI-100 Response) or Clinical Remission at Baseline of This Study Clinical remission: Week 16 (n=53, 19)	84.91 Percentage of participants Interval 72.41 to 93.25	36.84 Percentage of participants Interval 16.29 to 61.64
Percentage of Participants in Clinical Remission and Sustained Clinical Remission Among Participants in Clinical Response (CDAI-100 Response) or Clinical Remission at Baseline of This Study Clinical remission: Week 24 (n=49, 16)	83.67 Percentage of participants Interval 70.34 to 92.68	43.75 Percentage of participants Interval 19.75 to 70.12
Percentage of Participants in Clinical Remission and Sustained Clinical Remission Among Participants in Clinical Response (CDAI-100 Response) or Clinical Remission at Baseline of This Study Clinical remission: Week 36 (n=41, 13)	90.24 Percentage of participants Interval 76.87 to 97.28	38.46 Percentage of participants Interval 13.86 to 68.42
Percentage of Participants in Clinical Remission and Sustained Clinical Remission Among Participants in Clinical Response (CDAI-100 Response) or Clinical Remission at Baseline of This Study Clinical remission: Week 48 (n=33, 10)	87.88 Percentage of participants Interval 71.8 to 96.6	50.00 Percentage of participants Interval 18.71 to 81.29
Percentage of Participants in Clinical Remission and Sustained Clinical Remission Among Participants in Clinical Response (CDAI-100 Response) or Clinical Remission at Baseline of This Study Clinical remission: Week 52/follow-up (n=38, 12)	65.79 Percentage of participants Interval 48.65 to 80.37	41.67 Percentage of participants Interval 15.17 to 72.33
Percentage of Participants in Clinical Remission and Sustained Clinical Remission Among Participants in Clinical Response (CDAI-100 Response) or Clinical Remission at Baseline of This Study Sustained clinical remission (n=32, 10)	75.00 Percentage of participants Interval 56.6 to 88.54	30.00 Percentage of participants Interval 6.67 to 62.25

SECONDARY outcome

Timeframe: From baseline to Week 52

Population: Participants in the FAS who met clinical remission criteria at baseline of this study

Relapse was defined as an increase in CDAI of more than (\>) 100 points from the baseline and an absolute CDAI score of \>220 points. CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid or very soft stools, intensity of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity. Data presented are rates estimated from Kaplan-Meier curves. n = number of participants remaining at risk.

Outcome measures

Outcome measures
Measure	Tofacitinib 5 mg BID n=61 Participants Tofacitinib 5 mg tablet for oral administration at a dose of 5 mg BID for up to 48 weeks.	Tofacitinib 10 mg BID n=4 Participants Tofacitinib 10 mg tablets (2 x 5 mg tablets) for oral administration at a dose of 10 mg BID for up to 48 weeks.
Time to Relapse Among Participants in Clinical Remission at Baseline Week 8 (n=55, 4)	6.78 Percentage of participants Interval 3.38 to 11.78	NA Percentage of participants No participants had a relapse event by Week 8.
Time to Relapse Among Participants in Clinical Remission at Baseline Week 16 (n=51, 3)	11.86 Percentage of participants Interval 7.15 to 17.87	25.00 Percentage of participants Interval 4.56 to 53.66
Time to Relapse Among Participants in Clinical Remission at Baseline Week 24 (n=46, 3)	15.46 Percentage of participants Interval 9.98 to 22.05	25.00 Percentage of participants Interval 4.56 to 53.66
Time to Relapse Among Participants in Clinical Remission at Baseline Week 36 (n=38, 3)	21.42 Percentage of participants Interval 14.82 to 28.83	25.00 Percentage of participants Interval 4.56 to 53.66
Time to Relapse Among Participants in Clinical Remission at Baseline Week 48 (n=7, 0)	24.69 Percentage of participants Interval 17.21 to 32.89	NA Percentage of participants No participants remained at risk of a relapse event by Week 48.

SECONDARY outcome

Timeframe: Baseline and Weeks 8, 16, 24, 36, 48 and 52/follow-up

Population: FAS

Outcome measures

Outcome measures
Measure	Tofacitinib 5 mg BID n=62 Participants Tofacitinib 5 mg tablet for oral administration at a dose of 5 mg BID for up to 48 weeks.	Tofacitinib 10 mg BID n=88 Participants Tofacitinib 10 mg tablets (2 x 5 mg tablets) for oral administration at a dose of 10 mg BID for up to 48 weeks.
Observed CDAI Score by Week Baseline (n=62, 88)	77.13 Score on a scale Standard Deviation 43.22	291.19 Score on a scale Standard Deviation 95.78
Observed CDAI Score by Week Week 8 (n=54, 75)	105.39 Score on a scale Standard Deviation 75.82	176.96 Score on a scale Standard Deviation 82.39
Observed CDAI Score by Week Week 16 (n=53, 66)	86.58 Score on a scale Standard Deviation 65.23	178.94 Score on a scale Standard Deviation 72.25
Observed CDAI Score by Week Week 24 (n=49, 59)	85.12 Score on a scale Standard Deviation 56.67	163.66 Score on a scale Standard Deviation 79.73
Observed CDAI Score by Week Week 36 (n=41, 48)	73.34 Score on a scale Standard Deviation 59.52	158.67 Score on a scale Standard Deviation 89.15
Observed CDAI Score by Week Week 48 (n=33, 36)	73.91 Score on a scale Standard Deviation 70.23	154.11 Score on a scale Standard Deviation 71.47
Observed CDAI Score by Week Week 52/Follow-up (n=38, 43)	129.32 Score on a scale Standard Deviation 114.82	180.65 Score on a scale Standard Deviation 98.80

SECONDARY outcome

Timeframe: Weeks 8, 16, 24, 36, 48 and 52/follow-up

Population: FAS

Outcome measures

Outcome measures
Measure	Tofacitinib 5 mg BID n=62 Participants Tofacitinib 5 mg tablet for oral administration at a dose of 5 mg BID for up to 48 weeks.	Tofacitinib 10 mg BID n=88 Participants Tofacitinib 10 mg tablets (2 x 5 mg tablets) for oral administration at a dose of 10 mg BID for up to 48 weeks.
Change From Baseline Observed CDAI Score by Week Week 8 (n=54, 75)	26.96 Score on a scale Standard Deviation 62.68	-114.31 Score on a scale Standard Deviation 112.44
Change From Baseline Observed CDAI Score by Week Week 16 (n=53, 66)	11.72 Score on a scale Standard Deviation 52.25	-112.02 Score on a scale Standard Deviation 111.09
Change From Baseline Observed CDAI Score by Week Week 24 (n=49, 59)	6.33 Score on a scale Standard Deviation 44.48	-122.69 Score on a scale Standard Deviation 117.65
Change From Baseline Observed CDAI Score by Week Week 36 (n=41, 48)	-10.78 Score on a scale Standard Deviation 40.35	-139.81 Score on a scale Standard Deviation 126.18
Change From Baseline Observed CDAI Score by Week Week 48 (n=33, 36)	-4.79 Score on a scale Standard Deviation 60.09	-121.94 Score on a scale Standard Deviation 129.21
Change From Baseline Observed CDAI Score by Week Week 52/Follow-up (n=38, 43)	47.66 Score on a scale Standard Deviation 109.73	-107.42 Score on a scale Standard Deviation 119.05

SECONDARY outcome

Timeframe: Week 48

Population: Participants in FAS who were on steroids at baseline of this study

Steroid-free clinical remission at Week 48 was a CDAI \<150 points in participants who were steroid-free at Week 48. CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid or very soft stools, intensity of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity.

Outcome measures

Outcome measures
Measure	Tofacitinib 5 mg BID n=2 Participants Tofacitinib 5 mg tablet for oral administration at a dose of 5 mg BID for up to 48 weeks.	Tofacitinib 10 mg BID n=11 Participants Tofacitinib 10 mg tablets (2 x 5 mg tablets) for oral administration at a dose of 10 mg BID for up to 48 weeks.
Percentage of Participants Achieving a Steroid-Free Clinical Remission at Week 48 - Among Subjects on Steroids at A3921086 Baseline	50.00 Percentage of participants Interval 1.26 to 98.74	9.09 Percentage of participants Interval 0.23 to 41.28

SECONDARY outcome

Timeframe: Weeks 8, 16, 24, 36 and 48

Population: SAS

Use of corticosteroids (yes or no) was recorded at baseline and throughout the study. Percentage of participants taking corticosteriod at each visit was reported.

Outcome measures

Outcome measures
Measure	Tofacitinib 5 mg BID n=62 Participants Tofacitinib 5 mg tablet for oral administration at a dose of 5 mg BID for up to 48 weeks.	Tofacitinib 10 mg BID n=88 Participants Tofacitinib 10 mg tablets (2 x 5 mg tablets) for oral administration at a dose of 10 mg BID for up to 48 weeks.
Corticosteroid Use Over Time Week 16	4.84 Percentage of participants	13.64 Percentage of participants
Corticosteroid Use Over Time Baseline	1.61 Percentage of participants	20.45 Percentage of participants
Corticosteroid Use Over Time Week 8	4.84 Percentage of participants	21.59 Percentage of participants
Corticosteroid Use Over Time Week 24	4.84 Percentage of participants	12.50 Percentage of participants
Corticosteroid Use Over Time Week 36	3.23 Percentage of participants	10.23 Percentage of participants
Corticosteroid Use Over Time Week 48	1.61 Percentage of participants	7.95 Percentage of participants

SECONDARY outcome

Timeframe: From baseline to Week 48

Population: FAS

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 open label treatment and for the remaining treatment period of 40 weeks. Percentage of participants whose study treatment were switched from 5 mg BID to 10 mg BID or 10 mg BID to 5 mg BID after initial assignment was reported.

Outcome measures

Outcome measures
Measure	Tofacitinib 5 mg BID n=62 Participants Tofacitinib 5 mg tablet for oral administration at a dose of 5 mg BID for up to 48 weeks.	Tofacitinib 10 mg BID n=88 Participants Tofacitinib 10 mg tablets (2 x 5 mg tablets) for oral administration at a dose of 10 mg BID for up to 48 weeks.
Percentage of Participants Switching From 5 mg BID to 10 mg BID or 10 mg BID to 5 mg BID After Initial Assignment by Visit Baseline	0 Percentage of participants Interval 0.0 to 5.78	0 Percentage of participants Interval 0.0 to 4.11
Percentage of Participants Switching From 5 mg BID to 10 mg BID or 10 mg BID to 5 mg BID After Initial Assignment by Visit Week 8	25.81 Percentage of participants Interval 15.53 to 38.5	0 Percentage of participants Interval 0.0 to 4.11
Percentage of Participants Switching From 5 mg BID to 10 mg BID or 10 mg BID to 5 mg BID After Initial Assignment by Visit Week 16	6.45 Percentage of participants Interval 1.79 to 15.7	0 Percentage of participants Interval 0.0 to 4.11
Percentage of Participants Switching From 5 mg BID to 10 mg BID or 10 mg BID to 5 mg BID After Initial Assignment by Visit Week 24	3.23 Percentage of participants Interval 0.39 to 11.71	2.27 Percentage of participants Interval 0.28 to 7.97
Percentage of Participants Switching From 5 mg BID to 10 mg BID or 10 mg BID to 5 mg BID After Initial Assignment by Visit Week 36	0 Percentage of participants Interval 0.0 to 5.78	1.14 Percentage of participants Interval 0.03 to 6.17
Percentage of Participants Switching From 5 mg BID to 10 mg BID or 10 mg BID to 5 mg BID After Initial Assignment by Visit Week 48	0 Percentage of participants Interval 0.0 to 5.78	0 Percentage of participants Interval 0.0 to 4.11

SECONDARY outcome

Timeframe: Baseline and Weeks 8, 16, 24, 36, 48 and 52/follow-up

Population: FAS

Fecal calprotectin is an inflammatory marker for the gastrointestinal tract and considered as a measurement of neutrophil migration to the gastrointestinal tract. Higher values indicate more serious inflammation. n = number of participants with non-missing data.

Outcome measures

Outcome measures
Measure	Tofacitinib 5 mg BID n=62 Participants Tofacitinib 5 mg tablet for oral administration at a dose of 5 mg BID for up to 48 weeks.	Tofacitinib 10 mg BID n=88 Participants Tofacitinib 10 mg tablets (2 x 5 mg tablets) for oral administration at a dose of 10 mg BID for up to 48 weeks.
Observed Change From Baseline in Fecal Calprotectin by Week Week 52/Follow-up (n=48, 57)	-51.33 mg per kilogram (mg/kg) Standard Deviation 453.73	-109.23 mg per kilogram (mg/kg) Standard Deviation 389.54
Observed Change From Baseline in Fecal Calprotectin by Week Week 8 (n=53, 71)	-105.51 mg per kilogram (mg/kg) Standard Deviation 436.41	-102.82 mg per kilogram (mg/kg) Standard Deviation 310.10
Observed Change From Baseline in Fecal Calprotectin by Week Week 16 (n=54, 64)	-144.65 mg per kilogram (mg/kg) Standard Deviation 423.20	-35.28 mg per kilogram (mg/kg) Standard Deviation 718.82
Observed Change From Baseline in Fecal Calprotectin by Week Week 24 (n=49, 55)	-120.49 mg per kilogram (mg/kg) Standard Deviation 511.49	-130.68 mg per kilogram (mg/kg) Standard Deviation 337.23
Observed Change From Baseline in Fecal Calprotectin by Week Week 36 (n=41, 42)	-169.92 mg per kilogram (mg/kg) Standard Deviation 354.30	-133.82 mg per kilogram (mg/kg) Standard Deviation 364.51
Observed Change From Baseline in Fecal Calprotectin by Week Week 48 (n=37, 38)	-189.61 mg per kilogram (mg/kg) Standard Deviation 462.61	-123.87 mg per kilogram (mg/kg) Standard Deviation 376.70

SECONDARY outcome

Timeframe: Baseline and Weeks 8, 16, 24, 36, 48 and 52/follow-up

Population: FAS

The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement. n = number of participants with non-missing data.

Outcome measures

Outcome measures
Measure	Tofacitinib 5 mg BID n=62 Participants Tofacitinib 5 mg tablet for oral administration at a dose of 5 mg BID for up to 48 weeks.	Tofacitinib 10 mg BID n=88 Participants Tofacitinib 10 mg tablets (2 x 5 mg tablets) for oral administration at a dose of 10 mg BID for up to 48 weeks.
Observed Change From Baseline in High Sensitivity C-reactive Protein (CRP) by Week Week 8 (n=61, 82)	-0.44 mg per liter (mg/L) Standard Deviation 14.78	-4.81 mg per liter (mg/L) Standard Deviation 26.76
Observed Change From Baseline in High Sensitivity C-reactive Protein (CRP) by Week Week 16 (n=58, 72)	-2.46 mg per liter (mg/L) Standard Deviation 14.54	-7.96 mg per liter (mg/L) Standard Deviation 25.11
Observed Change From Baseline in High Sensitivity C-reactive Protein (CRP) by Week Week 24 (n=54, 61)	-2.76 mg per liter (mg/L) Standard Deviation 17.59	-9.26 mg per liter (mg/L) Standard Deviation 30.20
Observed Change From Baseline in High Sensitivity C-reactive Protein (CRP) by Week Week 36 (n=46, 51)	-4.42 mg per liter (mg/L) Standard Deviation 22.29	-12.09 mg per liter (mg/L) Standard Deviation 30.61
Observed Change From Baseline in High Sensitivity C-reactive Protein (CRP) by Week Week 48 (n=43, 44)	-4.55 mg per liter (mg/L) Standard Deviation 17.81	-11.45 mg per liter (mg/L) Standard Deviation 31.30
Observed Change From Baseline in High Sensitivity C-reactive Protein (CRP) by Week Week 52/Follow-up (n=54, 71)	3.86 mg per liter (mg/L) Standard Deviation 21.57	-4.72 mg per liter (mg/L) Standard Deviation 31.34

SECONDARY outcome

Timeframe: Baseline and Week 48/early termination (ET)

Population: FAS

The IBDQ is a psychometrically validated patient reported outcome (PRO) instrument for measuring disease-specific quality of life (QoL) in participants with inflammatory bowel disease (IBD). IBDQ consists of 32 items, each item score ranged from 1 (worst possible response) to 7 (best possible response). The 32 items are grouped into 4 domains: bowel function, emotional status, systemic symptoms and social function. The 4 domains are scored as follows: bowel symptoms 10 to 70; systemic symptoms 5 to 35; emotional function 12 to 84; social function 5 to 35. For each domain, a higher score indicates better QoL. Total score is the sum of each item score, and ranged from 32 to 224 with a higher score indicating a better QoL. Positive change in total score indicated improvement in QoL. n = number of participants with non-missing data.

Outcome measures

Outcome measures
Measure	Tofacitinib 5 mg BID n=62 Participants Tofacitinib 5 mg tablet for oral administration at a dose of 5 mg BID for up to 48 weeks.	Tofacitinib 10 mg BID n=88 Participants Tofacitinib 10 mg tablets (2 x 5 mg tablets) for oral administration at a dose of 10 mg BID for up to 48 weeks.
Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score and Domain Scores (Bowel Function, Emotional Status, Systemic Symptoms, and Social Function) at Baseline and Week 48/ET Visit IBDQ Total Score, Baseline (n=62, 87)	187.23 Score on a scale Standard Deviation 20.38	127.32 Score on a scale Standard Deviation 34.17
Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score and Domain Scores (Bowel Function, Emotional Status, Systemic Symptoms, and Social Function) at Baseline and Week 48/ET Visit IBDQ Total Score, Week 48/ET (n=57, 83)	179.26 Score on a scale Standard Deviation 29.89	144.42 Score on a scale Standard Deviation 42.16
Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score and Domain Scores (Bowel Function, Emotional Status, Systemic Symptoms, and Social Function) at Baseline and Week 48/ET Visit Bowel Function Score, Baseline (n=62, 87)	58.56 Score on a scale Standard Deviation 6.86	40.71 Score on a scale Standard Deviation 9.90
Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score and Domain Scores (Bowel Function, Emotional Status, Systemic Symptoms, and Social Function) at Baseline and Week 48/ET Visit Bowel Function Score, Week 48/ET (n=57, 83)	55.70 Score on a scale Standard Deviation 9.82	46.70 Score on a scale Standard Deviation 12.38
Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score and Domain Scores (Bowel Function, Emotional Status, Systemic Symptoms, and Social Function) at Baseline and Week 48/ET Visit Emotional Status Score, Baseline (n=62, 87)	69.68 Score on a scale Standard Deviation 8.58	48.61 Score on a scale Standard Deviation 14.42
Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score and Domain Scores (Bowel Function, Emotional Status, Systemic Symptoms, and Social Function) at Baseline and Week 48/ET Visit Emotional Status Score, Week 48/ET (n=57, 83)	66.98 Score on a scale Standard Deviation 12.27	53.19 Score on a scale Standard Deviation 17.32
Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score and Domain Scores (Bowel Function, Emotional Status, Systemic Symptoms, and Social Function) at Baseline and Week 48/ET Visit Systemic Symptoms Score, Baseline (n=62, 87)	26.95 Score on a scale Standard Deviation 5.36	17.20 Score on a scale Standard Deviation 5.55
Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score and Domain Scores (Bowel Function, Emotional Status, Systemic Symptoms, and Social Function) at Baseline and Week 48/ET Visit Systemic Symptoms Score, Week 48/ET (n=57, 83)	25.82 Score on a scale Standard Deviation 6.28	20.35 Score on a scale Standard Deviation 7.07
Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score and Domain Scores (Bowel Function, Emotional Status, Systemic Symptoms, and Social Function) at Baseline and Week 48/ET Visit Social Function Score, Baseline (n=62, 87)	32.03 Score on a scale Standard Deviation 3.59	20.80 Score on a scale Standard Deviation 8.96
Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score and Domain Scores (Bowel Function, Emotional Status, Systemic Symptoms, and Social Function) at Baseline and Week 48/ET Visit Social Function Score, Week 48/ET (n=57, 83)	30.75 Score on a scale Standard Deviation 5.17	24.18 Score on a scale Standard Deviation 8.98

SECONDARY outcome

Timeframe: Baseline and Week 48/ET

Population: Participants in the FAS who had non-missing data at Week 48/ET visit

The IBDQ is a psychometrically validated PRO instrument for measuring disease-specific QoL in participants with IBD. IBDQ consists of 32 items, each item score ranged from 1 (worst possible response) to 7 (best possible response). The 32 items are grouped into 4 domains: bowel function, emotional status, systemic symptoms and social function. The 4 domains are scored as follows: bowel symptoms 10 to 70; systemic symptoms 5 to 35; emotional function 12 to 84; social function 5 to 35. For each domain, a higher score indicates better QoL. Total score is the sum of each item score, and ranged from 32 to 224 with a higher score indicating a better QoL. Positive change in total score indicated improvement in QoL.

Outcome measures

Outcome measures
Measure	Tofacitinib 5 mg BID n=57 Participants Tofacitinib 5 mg tablet for oral administration at a dose of 5 mg BID for up to 48 weeks.	Tofacitinib 10 mg BID n=83 Participants Tofacitinib 10 mg tablets (2 x 5 mg tablets) for oral administration at a dose of 10 mg BID for up to 48 weeks.
Change From Baseline IBDQ Total Score and Domain Scores (Bowel Function, Emotional Status, Systemic Symptoms, and Social Function) at Week 48/ET Visit IBDQ Total Score, Week 48/ET	-7.98 Score on a scale Standard Deviation 24.93	18.84 Score on a scale Standard Deviation 40.45
Change From Baseline IBDQ Total Score and Domain Scores (Bowel Function, Emotional Status, Systemic Symptoms, and Social Function) at Week 48/ET Visit Bowel Function Score, Week 48/ET	-2.72 Score on a scale Standard Deviation 8.30	6.37 Score on a scale Standard Deviation 12.41
Change From Baseline IBDQ Total Score and Domain Scores (Bowel Function, Emotional Status, Systemic Symptoms, and Social Function) at Week 48/ET Visit Emotional Status Score, Week 48/ET	-3.07 Score on a scale Standard Deviation 10.48	5.36 Score on a scale Standard Deviation 15.00
Change From Baseline IBDQ Total Score and Domain Scores (Bowel Function, Emotional Status, Systemic Symptoms, and Social Function) at Week 48/ET Visit Systemic Symptoms Score, Week 48/ET	-1.00 Score on a scale Standard Deviation 4.83	3.45 Score on a scale Standard Deviation 7.43
Change From Baseline IBDQ Total Score and Domain Scores (Bowel Function, Emotional Status, Systemic Symptoms, and Social Function) at Week 48/ET Visit Social Function Score, Week 48/ET	-1.19 Score on a scale Standard Deviation 4.24	3.66 Score on a scale Standard Deviation 8.89

SECONDARY outcome

Timeframe: Week 48/ET

Population: Participants in the FAS who had non-missing data at Week 48/ET visit

The IBDQ is a psychometrically validated PRO instrument for measuring disease-specific QoL in participants with IBD. IBDQ consists of 32 items, each item score ranged from 1 (worst possible response) to 7 (best possible response). Total score is the sum of each item score, and ranged from 32 to 224 with a higher score indicating a better QoL. A score ≥170 corresponds to clinical remission. 95% Clopper-Pearson exact confidence interval reported for the proportions.

Outcome measures

Outcome measures
Measure	Tofacitinib 5 mg BID n=57 Participants Tofacitinib 5 mg tablet for oral administration at a dose of 5 mg BID for up to 48 weeks.	Tofacitinib 10 mg BID n=83 Participants Tofacitinib 10 mg tablets (2 x 5 mg tablets) for oral administration at a dose of 10 mg BID for up to 48 weeks.
Percentage of Participants With an IBDQ Total Score of Greater Than or Equal to (≥) 170 at Week 48/ET Visit	70.18 Percentage of participants Interval 56.6 to 81.57	31.33 Percentage of participants Interval 21.59 to 42.44

SECONDARY outcome

Timeframe: Week 48/ET visit

Population: Participants in the FAS who had a response to PRTI assessment at Week 48/ET visit

The IBD PRTI modified questionnaire comprises 3 individual questions administered to the participant: participant satisfaction with study treatment; participant preference for study drug over prior treatment (this question on participant preference for study drug is prefaced by a simple question of previous treatment/s for IBD received in order to place the preference question into context) and participant willingness to reuse the study treatment again. Each of these questions (except the question on previous treatment, which is informational only) is scored on a 5 point Likert scale. PSA = Patient Satisfaction Assessment; PPTA = Patient Previous Treatment Assessment; PPA = Patient Preference Assessment; PWA = Patient Willingness Assessment.

Outcome measures

Outcome measures
Measure	Tofacitinib 5 mg BID n=42 Participants Tofacitinib 5 mg tablet for oral administration at a dose of 5 mg BID for up to 48 weeks.	Tofacitinib 10 mg BID n=46 Participants Tofacitinib 10 mg tablets (2 x 5 mg tablets) for oral administration at a dose of 10 mg BID for up to 48 weeks.
Percentage of Participants With a Response to the Patient-Reported Treatment Impact (PRTI) Assessment at Week 48/ET Visit by Category PPTA: Injectable prescription medicines	40.5 Percentage of participants	32.6 Percentage of participants
Percentage of Participants With a Response to the Patient-Reported Treatment Impact (PRTI) Assessment at Week 48/ET Visit by Category PPTA: Prescription medicines taken by mouth	45.2 Percentage of participants	43.5 Percentage of participants
Percentage of Participants With a Response to the Patient-Reported Treatment Impact (PRTI) Assessment at Week 48/ET Visit by Category PSA: Extremely dissatisfied	0 Percentage of participants	0 Percentage of participants
Percentage of Participants With a Response to the Patient-Reported Treatment Impact (PRTI) Assessment at Week 48/ET Visit by Category PSA: Dissatisfied	0 Percentage of participants	8.7 Percentage of participants
Percentage of Participants With a Response to the Patient-Reported Treatment Impact (PRTI) Assessment at Week 48/ET Visit by Category PSA: Neither satisfied nor dissatisfied	0 Percentage of participants	17.4 Percentage of participants
Percentage of Participants With a Response to the Patient-Reported Treatment Impact (PRTI) Assessment at Week 48/ET Visit by Category PSA: Satisfied	33.3 Percentage of participants	41.3 Percentage of participants
Percentage of Participants With a Response to the Patient-Reported Treatment Impact (PRTI) Assessment at Week 48/ET Visit by Category PSA: Extremely satisfied	66.7 Percentage of participants	32.6 Percentage of participants
Percentage of Participants With a Response to the Patient-Reported Treatment Impact (PRTI) Assessment at Week 48/ET Visit by Category PPTA: Surgery	2.4 Percentage of participants	0 Percentage of participants
Percentage of Participants With a Response to the Patient-Reported Treatment Impact (PRTI) Assessment at Week 48/ET Visit by Category PPTA: Prescription medicines & surgery	7.1 Percentage of participants	13.0 Percentage of participants
Percentage of Participants With a Response to the Patient-Reported Treatment Impact (PRTI) Assessment at Week 48/ET Visit by Category PPTA: No treatment	4.8 Percentage of participants	10.9 Percentage of participants
Percentage of Participants With a Response to the Patient-Reported Treatment Impact (PRTI) Assessment at Week 48/ET Visit by Category PPA: Definitely prefer the drug I am receiving now	88.1 Percentage of participants	56.5 Percentage of participants
Percentage of Participants With a Response to the Patient-Reported Treatment Impact (PRTI) Assessment at Week 48/ET Visit by Category PPA: Slight preference for drug I'm receiving now	4.8 Percentage of participants	21.7 Percentage of participants
Percentage of Participants With a Response to the Patient-Reported Treatment Impact (PRTI) Assessment at Week 48/ET Visit by Category PPA: I have no preference either way	7.1 Percentage of participants	17.4 Percentage of participants
Percentage of Participants With a Response to the Patient-Reported Treatment Impact (PRTI) Assessment at Week 48/ET Visit by Category PPA: Slight preference for previous treatment	0 Percentage of participants	4.3 Percentage of participants
Percentage of Participants With a Response to the Patient-Reported Treatment Impact (PRTI) Assessment at Week 48/ET Visit by Category PPA: No, I definitely prefer my previous treatment	0 Percentage of participants	0 Percentage of participants
Percentage of Participants With a Response to the Patient-Reported Treatment Impact (PRTI) Assessment at Week 48/ET Visit by Category PWA: Would definitely want to use same drug again	83.3 Percentage of participants	60.9 Percentage of participants
Percentage of Participants With a Response to the Patient-Reported Treatment Impact (PRTI) Assessment at Week 48/ET Visit by Category PWA: Might want to use the same drug again	14.3 Percentage of participants	23.9 Percentage of participants
Percentage of Participants With a Response to the Patient-Reported Treatment Impact (PRTI) Assessment at Week 48/ET Visit by Category PWA: I am not sure	2.4 Percentage of participants	10.9 Percentage of participants
Percentage of Participants With a Response to the Patient-Reported Treatment Impact (PRTI) Assessment at Week 48/ET Visit by Category PWA: Might not want to use same drug again	0 Percentage of participants	0 Percentage of participants
Percentage of Participants With a Response to the Patient-Reported Treatment Impact (PRTI) Assessment at Week 48/ET Visit by Category PWA: Definitely not want to use same drug again	0 Percentage of participants	4.3 Percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 48/ET visit

Population: FAS

The component and domain scores were scored using the United States (US) 1998 general population norms. The resulting norm-based T scores for both the SF36 version 2 and SF36 health domain scales and component summary measures have means of 50 and standard deviations of 10. Higher scores indicate better health-related QoL. n = number of participants with non-missing data.

Outcome measures

Outcome measures
Measure	Tofacitinib 5 mg BID n=62 Participants Tofacitinib 5 mg tablet for oral administration at a dose of 5 mg BID for up to 48 weeks.	Tofacitinib 10 mg BID n=88 Participants Tofacitinib 10 mg tablets (2 x 5 mg tablets) for oral administration at a dose of 10 mg BID for up to 48 weeks.
Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 48/ET Visit Physical component score, Baseline (n=62, 86)	50.15 Score on a scale Standard Deviation 6.73	37.80 Score on a scale Standard Deviation 9.53
Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 48/ET Visit Physical component score, Week 48/ET (n=57, 83)	48.43 Score on a scale Standard Deviation 8.22	41.87 Score on a scale Standard Deviation 10.06
Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 48/ET Visit Mental Component Score, Baseline (n=62, 86)	50.25 Score on a scale Standard Deviation 9.11	37.17 Score on a scale Standard Deviation 11.94
Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 48/ET Visit Mental Component Score, Week 48/ET (n=57, 83)	48.79 Score on a scale Standard Deviation 10.64	39.60 Score on a scale Standard Deviation 12.87
Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 48/ET Visit Physical Functioning Domain, Baseline (n=62, 86)	53.35 Score on a scale Standard Deviation 5.50	43.50 Score on a scale Standard Deviation 10.37
Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 48/ET Visit Physical Functioning Domain, Week 48/ET (n=57, 83)	51.40 Score on a scale Standard Deviation 8.59	46.81 Score on a scale Standard Deviation 10.22
Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 48/ET Visit Role Physical Domain, Baseline (n=62, 86)	50.97 Score on a scale Standard Deviation 8.22	35.93 Score on a scale Standard Deviation 11.30
Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 48/ET Visit Role Physical Domain, Week 48/ET (n=57, 83)	49.38 Score on a scale Standard Deviation 8.78	40.04 Score on a scale Standard Deviation 12.99
Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 48/ET Visit Bodily Pain Domain, Baseline (n=62, 87)	51.32 Score on a scale Standard Deviation 8.55	35.31 Score on a scale Standard Deviation 9.14
Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 48/ET Visit Bodily Pain Domain, Week 48/ET (n=57, 83)	49.57 Score on a scale Standard Deviation 10.30	41.04 Score on a scale Standard Deviation 12.69
Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 48/ET Visit General Health Domain, Baseline (n=62, 87)	41.60 Score on a scale Standard Deviation 9.51	31.74 Score on a scale Standard Deviation 8.41
Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 48/ET Visit General Health Domain, Week 48/ET (n=57, 83)	40.39 Score on a scale Standard Deviation 10.08	33.45 Score on a scale Standard Deviation 10.16
Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 48/ET Visit Vitality Domain, Baseline (n=62, 87)	52.78 Score on a scale Standard Deviation 10.68	36.92 Score on a scale Standard Deviation 9.88
Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 48/ET Visit Vitality Domain, Week 48/ET (n=57, 83)	51.06 Score on a scale Standard Deviation 11.38	41.03 Score on a scale Standard Deviation 12.38
Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 48/ET Visit Social Functioning Domain, Baseline (n=62, 87)	51.81 Score on a scale Standard Deviation 7.21	36.38 Score on a scale Standard Deviation 12.29
Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 48/ET Visit Social Functioning Domain, Week 48/ET (n=57, 83)	49.42 Score on a scale Standard Deviation 9.64	39.82 Score on a scale Standard Deviation 13.39
Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 48/ET Visit Role Emotional Domain, Baseline (n=62, 86)	50.12 Score on a scale Standard Deviation 8.85	38.55 Score on a scale Standard Deviation 12.73
Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 48/ET Visit Role Emotional Domain, Week 48/ET (n=57, 83)	47.97 Score on a scale Standard Deviation 10.78	41.13 Score on a scale Standard Deviation 13.15
Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 48/ET Visit Mental Health Domain, Baseline (n=62, 87)	49.89 Score on a scale Standard Deviation 9.84	37.61 Score on a scale Standard Deviation 11.98
Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 48/ET Visit Mental Health Domain, Week 48/ET (n=57, 83)	49.24 Score on a scale Standard Deviation 10.27	40.13 Score on a scale Standard Deviation 12.52

SECONDARY outcome

Timeframe: Baseline and Week 48/ET visit

Population: FAS

The component and domain scores were scored using the US 1998 general population norms. The resulting norm-based T scores for both the SF36 version 2 and SF36 health domain scales and component summary measures have means of 50 and standard deviations of 10. Higher scores indicate better health-related QoL. n = number of participants with non-missing data.

Outcome measures

Outcome measures
Measure	Tofacitinib 5 mg BID n=62 Participants Tofacitinib 5 mg tablet for oral administration at a dose of 5 mg BID for up to 48 weeks.	Tofacitinib 10 mg BID n=88 Participants Tofacitinib 10 mg tablets (2 x 5 mg tablets) for oral administration at a dose of 10 mg BID for up to 48 weeks.
Change From Baseline SF-36 Component and Domain Scores at Week 48/ET Visit Bodily Pain Domain, Week 48/ET (n=57, 83)	-1.60 Score on a scale Standard Deviation 7.90	6.15 Score on a scale Standard Deviation 12.92
Change From Baseline SF-36 Component and Domain Scores at Week 48/ET Visit Physical component score, Week 48/ET (n=57, 83)	-1.47 Score on a scale Standard Deviation 7.17	4.47 Score on a scale Standard Deviation 11.06
Change From Baseline SF-36 Component and Domain Scores at Week 48/ET Visit Mental Component Score, Week 48/ET (n=57, 83)	-1.88 Score on a scale Standard Deviation 9.05	3.07 Score on a scale Standard Deviation 11.53
Change From Baseline SF-36 Component and Domain Scores at Week 48/ET Visit Physical Functioning Domain, Week 48/ET (n=57, 83)	-1.80 Score on a scale Standard Deviation 7.50	3.49 Score on a scale Standard Deviation 10.74
Change From Baseline SF-36 Component and Domain Scores at Week 48/ET Visit Role Physical Domain, Week 48/ET (n=57, 83)	-1.38 Score on a scale Standard Deviation 7.87	4.60 Score on a scale Standard Deviation 12.62
Change From Baseline SF-36 Component and Domain Scores at Week 48/ET Visit General Health Domain, Week 48/ET (n=57, 83)	-1.42 Score on a scale Standard Deviation 10.00	2.25 Score on a scale Standard Deviation 7.99
Change From Baseline SF-36 Component and Domain Scores at Week 48/ET Visit Vitality Domain, Week 48/ET (n=57, 83)	-1.63 Score on a scale Standard Deviation 10.39	4.47 Score on a scale Standard Deviation 12.16
Change From Baseline SF-36 Component and Domain Scores at Week 48/ET Visit Social Functioning Domain, Week 48/ET (n=57, 83)	-2.92 Score on a scale Standard Deviation 9.09	3.69 Score on a scale Standard Deviation 13.46
Change From Baseline SF-36 Component and Domain Scores at Week 48/ET Visit Role Emotional Domain, Week 48/ET (n=57, 82)	-2.26 Score on a scale Standard Deviation 10.29	3.28 Score on a scale Standard Deviation 11.38
Change From Baseline SF-36 Component and Domain Scores at Week 48/ET Visit Mental Health Domain, Week 48/ET (n=57, 83)	-1.02 Score on a scale Standard Deviation 8.63	2.87 Score on a scale Standard Deviation 11.72

SECONDARY outcome

Timeframe: Baseline and Week 48/ET visit

Population: FAS

EQ5D is a participant rated questionnaire to assess health-related QoL in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, selfcare, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state ("confined to bed"). Scoring formula developed by EuroQol Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range from 0.594 to 1.000; a higher score indicates a better health state. n = number of participants with non-missing data.

Outcome measures

Outcome measures
Measure	Tofacitinib 5 mg BID n=62 Participants Tofacitinib 5 mg tablet for oral administration at a dose of 5 mg BID for up to 48 weeks.	Tofacitinib 10 mg BID n=88 Participants Tofacitinib 10 mg tablets (2 x 5 mg tablets) for oral administration at a dose of 10 mg BID for up to 48 weeks.
EuroQoL 5 Dimensions Questionnaire (EQ-5D) Utility Scores at Baseline and Week 48/ET Visit Utility Score, Baseline (n=62, 85)	0.85 Score on a scale Standard Deviation 0.21	0.57 Score on a scale Standard Deviation 0.28
EuroQoL 5 Dimensions Questionnaire (EQ-5D) Utility Scores at Baseline and Week 48/ET Visit Utility Score, Week 48/ET (n=57, 83)	0.84 Score on a scale Standard Deviation 0.16	0.66 Score on a scale Standard Deviation 0.31

SECONDARY outcome

Timeframe: Baseline and Week 48/ET visit

Population: Participants in the FAS who had non-missing data at Week 48/ET visit

Outcome measures

Outcome measures
Measure	Tofacitinib 5 mg BID n=57 Participants Tofacitinib 5 mg tablet for oral administration at a dose of 5 mg BID for up to 48 weeks.	Tofacitinib 10 mg BID n=83 Participants Tofacitinib 10 mg tablets (2 x 5 mg tablets) for oral administration at a dose of 10 mg BID for up to 48 weeks.
Change From Baseline EQ-5D Utility Scores at Week 48/ET Visit	-0.02 Score on a scale Standard Deviation 0.21	0.10 Score on a scale Standard Deviation 0.36

SECONDARY outcome

Timeframe: Baseline and Week 48/ET visit

Population: FAS

EQ5D is a participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 millimeters (mm) (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. n = number of participants with non-missing data.

Outcome measures

Outcome measures
Measure	Tofacitinib 5 mg BID n=62 Participants Tofacitinib 5 mg tablet for oral administration at a dose of 5 mg BID for up to 48 weeks.	Tofacitinib 10 mg BID n=88 Participants Tofacitinib 10 mg tablets (2 x 5 mg tablets) for oral administration at a dose of 10 mg BID for up to 48 weeks.
EQ-5D Visual Analogue Scale (VAS) Scores at Baseline and Week 8/ET Visit VAS Score, Baseline (n=62, 86)	77.98 mm Standard Deviation 16.18	48.60 mm Standard Deviation 19.21
EQ-5D Visual Analogue Scale (VAS) Scores at Baseline and Week 8/ET Visit VAS Score, Week 48/ET (n=57, 83)	73.40 mm Standard Deviation 18.54	57.60 mm Standard Deviation 24.60

SECONDARY outcome

Timeframe: Baseline and Week 48/ET visit

Population: Participants in the FAS who had non-missing data at Week 48/ET visit

EQ5D is a participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 mm (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state.

Outcome measures

Outcome measures
Measure	Tofacitinib 5 mg BID n=57 Participants Tofacitinib 5 mg tablet for oral administration at a dose of 5 mg BID for up to 48 weeks.	Tofacitinib 10 mg BID n=83 Participants Tofacitinib 10 mg tablets (2 x 5 mg tablets) for oral administration at a dose of 10 mg BID for up to 48 weeks.
Change From Baseline EQ-5D VAS Scores at Week 8/ET Visit	-3.79 mm Standard Deviation 20.56	10.16 mm Standard Deviation 26.57

SECONDARY outcome

Timeframe: From baseline to Week 52/follow-up

Population: SAS

The number of participants hospitalized due to Crohn's disease were recorded at every study visit.

Outcome measures

Outcome measures
Measure	Tofacitinib 5 mg BID n=62 Participants Tofacitinib 5 mg tablet for oral administration at a dose of 5 mg BID for up to 48 weeks.	Tofacitinib 10 mg BID n=88 Participants Tofacitinib 10 mg tablets (2 x 5 mg tablets) for oral administration at a dose of 10 mg BID for up to 48 weeks.
Percentage of Participants Hospitalized Due to Crohn's Disease	11.3 Percentage of participants	15.9 Percentage of participants

SECONDARY outcome

Timeframe: From baseline to Week 52/follow-up

Population: SAS

The length of hospitalizations due to Crohn's disease were recorded at every study visit.

Outcome measures

Outcome measures
Measure	Tofacitinib 5 mg BID n=62 Participants Tofacitinib 5 mg tablet for oral administration at a dose of 5 mg BID for up to 48 weeks.	Tofacitinib 10 mg BID n=88 Participants Tofacitinib 10 mg tablets (2 x 5 mg tablets) for oral administration at a dose of 10 mg BID for up to 48 weeks.
Length of Hospitalizations Due to Crohn's Disease <3 days	1.6 Percentage of participnats	2.3 Percentage of participnats
Length of Hospitalizations Due to Crohn's Disease 3 to 6 days	6.5 Percentage of participnats	10.2 Percentage of participnats
Length of Hospitalizations Due to Crohn's Disease 7 to 10 days	0 Percentage of participnats	3.4 Percentage of participnats
Length of Hospitalizations Due to Crohn's Disease > 10 days	0 Percentage of participnats	3.4 Percentage of participnats

Adverse Events

Tofacitinib 5 mg BID

Serious events: 5 serious events

Other events: 42 other events

Deaths: 0 deaths

Tofacitinib 10 mg BID

Serious events: 14 serious events

Other events: 58 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Pfizer ClinicalTrials.gov Call Center

Pfizer, Inc.

Phone: 1-800-718-1021

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Tofacitinib 5 mg BID n=62 participants at risk Tofacitinib 5 mg tablet for oral administration at a dose of 5 mg BID for up to 48 weeks.	Tofacitinib 10 mg BID n=88 participants at risk Tofacitinib 10 mg tablets (2 x 5 mg tablets) for oral administration at a dose of 10 mg BID for up to 48 weeks.
Gastrointestinal disorders Colon dysplasia	1.6% 1/62 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment. Non-SAEs were recorded from time of first dose of study treatment through last participant visit. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/88 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment. Non-SAEs were recorded from time of first dose of study treatment through last participant visit. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Crohn's disease	4.8% 3/62 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment. Non-SAEs were recorded from time of first dose of study treatment through last participant visit. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	8.0% 7/88 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment. Non-SAEs were recorded from time of first dose of study treatment through last participant visit. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/62 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment. Non-SAEs were recorded from time of first dose of study treatment through last participant visit. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	2.3% 2/88 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment. Non-SAEs were recorded from time of first dose of study treatment through last participant visit. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
General disorders Chest pain	1.6% 1/62 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment. Non-SAEs were recorded from time of first dose of study treatment through last participant visit. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/88 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment. Non-SAEs were recorded from time of first dose of study treatment through last participant visit. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
General disorders Influenza like illness	1.6% 1/62 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment. Non-SAEs were recorded from time of first dose of study treatment through last participant visit. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/88 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment. Non-SAEs were recorded from time of first dose of study treatment through last participant visit. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
General disorders Pyrexia	0.00% 0/62 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment. Non-SAEs were recorded from time of first dose of study treatment through last participant visit. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	1.1% 1/88 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment. Non-SAEs were recorded from time of first dose of study treatment through last participant visit. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Hepatobiliary disorders Biliary colic	0.00% 0/62 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment. Non-SAEs were recorded from time of first dose of study treatment through last participant visit. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	1.1% 1/88 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment. Non-SAEs were recorded from time of first dose of study treatment through last participant visit. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Immune system disorders Hypersensitivity	0.00% 0/62 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment. Non-SAEs were recorded from time of first dose of study treatment through last participant visit. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	1.1% 1/88 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment. Non-SAEs were recorded from time of first dose of study treatment through last participant visit. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Anal abscess	0.00% 0/62 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment. Non-SAEs were recorded from time of first dose of study treatment through last participant visit. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	1.1% 1/88 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment. Non-SAEs were recorded from time of first dose of study treatment through last participant visit. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Diarrhoea infectious	1.6% 1/62 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment. Non-SAEs were recorded from time of first dose of study treatment through last participant visit. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/88 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment. Non-SAEs were recorded from time of first dose of study treatment through last participant visit. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Pyelonephritis	1.6% 1/62 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment. Non-SAEs were recorded from time of first dose of study treatment through last participant visit. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/88 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment. Non-SAEs were recorded from time of first dose of study treatment through last participant visit. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Infections and infestations Vulval abscess	0.00% 0/62 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment. Non-SAEs were recorded from time of first dose of study treatment through last participant visit. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	1.1% 1/88 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment. Non-SAEs were recorded from time of first dose of study treatment through last participant visit. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Injury, poisoning and procedural complications Incisional hernia	0.00% 0/62 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment. Non-SAEs were recorded from time of first dose of study treatment through last participant visit. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	1.1% 1/88 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment. Non-SAEs were recorded from time of first dose of study treatment through last participant visit. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Renal and urinary disorders Acute kidney injury	1.6% 1/62 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment. Non-SAEs were recorded from time of first dose of study treatment through last participant visit. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/88 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment. Non-SAEs were recorded from time of first dose of study treatment through last participant visit. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Reproductive system and breast disorders Perineal fistula	0.00% 0/62 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment. Non-SAEs were recorded from time of first dose of study treatment through last participant visit. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	1.1% 1/88 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment. Non-SAEs were recorded from time of first dose of study treatment through last participant visit. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.6% 1/62 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment. Non-SAEs were recorded from time of first dose of study treatment through last participant visit. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/88 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment. Non-SAEs were recorded from time of first dose of study treatment through last participant visit. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Skin and subcutaneous tissue disorders Hyperhidrosis	1.6% 1/62 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment. Non-SAEs were recorded from time of first dose of study treatment through last participant visit. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	0.00% 0/88 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment. Non-SAEs were recorded from time of first dose of study treatment through last participant visit. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.
Investigations C-reactive protein increased	0.00% 0/62 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment. Non-SAEs were recorded from time of first dose of study treatment through last participant visit. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.	1.1% 1/88 • SAEs were assessed from informed consent through and including 28 calendar days after last administration of study treatment. Non-SAEs were recorded from time of first dose of study treatment through last participant visit. The same event may appear as both an AE and an SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant and as nonserious in another participant, or 1 participant may have experienced both a serious and nonserious event during the study.