Trial Outcomes & Findings for A Study To Investigate Safety And Efficacy Of CP-690,550 For Induction Therapy In Subjects With Moderate To Severe Crohn's Disease (NCT NCT01393626)

Last Updated: 2017-04-28

Results Overview

Clinical remission was a CDAI \< 150 points. CDAI is a composite index consisting of a weighted scoring of 8 disease variables: number of liquid or very soft stools, extent of abdominal pain, general well-being, occurrence of extra-intestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI score was based partly on entries (7 days before evaluation) from participant's diary kept while on study. CDAI scores range from 0 to approximately 600, higher score indicates higher disease activity. The 15 mg BID treatment group was closed to further enrolment early on in the study by Protocol Amendment 5 after only 16 participants were enrolled into this group. Therefore, the efficacy analysis was not performed for this group because the results may be difficult to interpret due to the small sample size.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

280 participants

Primary outcome timeframe

Week 8

Results posted on

2017-04-28

Participant Flow

280 participants were randomized to treatment but only 279 participants received treated.

Participant milestones

Participant milestones
Measure	Placebo Placebo tablets to match tofacitinib 5 milligrams (mg) for oral administration twice daily (BID) for 8 weeks.	Tofacitinib 5 mg BID Tofacitinib tablets for oral administration at a dose of 5 mg BID for 8 weeks.	Tofacitinib 10 mg BID Tofacitinib tablets for oral administration at a dose of 10 mg BID for 8 weeks.	Tofacitinib 15 mg BID Tofacitinib tablets for oral administration at a dose of 15 mg BID for 8 weeks.
Overall Study STARTED	91	86	86	16
Overall Study COMPLETED	73	74	74	15
Overall Study NOT COMPLETED	18	12	12	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo tablets to match tofacitinib 5 milligrams (mg) for oral administration twice daily (BID) for 8 weeks.	Tofacitinib 5 mg BID Tofacitinib tablets for oral administration at a dose of 5 mg BID for 8 weeks.	Tofacitinib 10 mg BID Tofacitinib tablets for oral administration at a dose of 10 mg BID for 8 weeks.	Tofacitinib 15 mg BID Tofacitinib tablets for oral administration at a dose of 15 mg BID for 8 weeks.
Overall Study Adverse Event	2	1	5	0
Overall Study Did not meet entrance criteria	1	0	0	0
Overall Study Lack of Efficacy	6	6	4	1
Overall Study Lost to Follow-up	1	1	1	0
Overall Study Withdrawal by Subject	6	4	0	0
Overall Study Other	1	0	0	0
Overall Study Protocol Violation	1	0	2	0

Baseline Characteristics

A Study To Investigate Safety And Efficacy Of CP-690,550 For Induction Therapy In Subjects With Moderate To Severe Crohn's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=91 Participants Placebo tablets to match tofacitinib 5 mg for oral administration BID for 8 weeks.	Tofacitinib 5 mg BID n=86 Participants Tofacitinib tablets for oral administration at a dose of 5 mg BID for 8 weeks.	Tofacitinib 10 mg BID n=86 Participants Tofacitinib tablets for oral administration at a dose of 10 mg BID for 8 weeks.	Tofacitinib 15 mg BID n=16 Participants Tofacitinib tablets for oral administration at a dose of 15 mg BID for 8 weeks.	Total n=279 Participants Total of all reporting groups
Age, Continuous	37.2 Years STANDARD_DEVIATION 11.7 • n=5 Participants	40.2 Years STANDARD_DEVIATION 11.5 • n=7 Participants	39.3 Years STANDARD_DEVIATION 13.7 • n=5 Participants	41.3 Years STANDARD_DEVIATION 14.3 • n=4 Participants	39.0 Years STANDARD_DEVIATION 12.4 • n=21 Participants
Sex: Female, Male Female	60 Participants n=5 Participants	32 Participants n=7 Participants	47 Participants n=5 Participants	7 Participants n=4 Participants	146 Participants n=21 Participants
Sex: Female, Male Male	31 Participants n=5 Participants	54 Participants n=7 Participants	39 Participants n=5 Participants	9 Participants n=4 Participants	133 Participants n=21 Participants

PRIMARY outcome

Timeframe: Week 8

Population: Full analysis set (FAS) - included all randomized participants who received at least 1 dose of investigational product and who had a qualified CDAI score calculated using the hematocrit value measured at baseline visit (Day 1). Participants with missing values were treated as non-responders.

Outcome measures

Outcome measures
Measure	Placebo n=90 Participants Placebo tablets to match tofacitinib 5 mg for oral administration BID for 8 weeks.	Tofacitinib 5 mg BID n=85 Participants Tofacitinib tablets for oral administration at a dose of 5 mg BID for 8 weeks.	Tofacitinib 10 mg BID n=86 Participants Tofacitinib tablets for oral administration at a dose of 10 mg BID for 8 weeks.	Tofacitinib 15 mg BID Tofacitinib tablets for oral administration at a dose of 15 mg BID for 8 weeks.
Percentage of Participants in Clinical Remission (as Defined by a Crohn's Disease Activity Index [CDAI] Score of Less Than [<] 150 Points) at Week 8	36.67 Percentage of Participants Interval 26.75 to 47.49	43.53 Percentage of Participants Interval 32.8 to 54.72	43.02 Percentage of Participants Interval 32.39 to 54.15	—

SECONDARY outcome

Timeframe: Weeks 2 and 4

Population: FAS, participants with missing values were treated as non-responders.

Clinical remission was a CDAI \<150 points. CDAI is a composite index consisting of a weighted scoring of 8 disease variables: number of liquid or very soft stools, extent of abdominal pain, general well-being, occurrence of extra-intestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI score was based partly on entries (7 days before evaluation) from participant's diary kept while on study. CDAI scores range from 0 to approximately 600, higher score indicates higher disease activity. The 15 mg BID treatment group was closed to further enrolment early on in the study by Protocol Amendment 5 after only 16 participants were enrolled into this group. Therefore, the efficacy analysis was not performed for this group because the results may be difficult to interpret due to the small sample size.

Outcome measures

Outcome measures
Measure	Placebo n=90 Participants Placebo tablets to match tofacitinib 5 mg for oral administration BID for 8 weeks.	Tofacitinib 5 mg BID n=85 Participants Tofacitinib tablets for oral administration at a dose of 5 mg BID for 8 weeks.	Tofacitinib 10 mg BID n=86 Participants Tofacitinib tablets for oral administration at a dose of 10 mg BID for 8 weeks.	Tofacitinib 15 mg BID Tofacitinib tablets for oral administration at a dose of 15 mg BID for 8 weeks.
Percentage of Participants in Clinical Remission (CDAI <150) at Weeks 2 and 4 Week 2	10.00 Percentage of Participants Interval 4.68 to 18.14	9.41 Percentage of Participants Interval 4.15 to 17.71	9.30 Percentage of Participants Interval 4.1 to 17.51	—
Percentage of Participants in Clinical Remission (CDAI <150) at Weeks 2 and 4 Week 4	21.11 Percentage of Participants Interval 13.21 to 30.99	24.71 Percentage of Participants Interval 15.99 to 35.25	22.09 Percentage of Participants Interval 13.86 to 32.33	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, and 8

Population: FAS, participants with missing values were treated as non-responders.

Clinical response-70 was defined as a reduction in CDAI score from baseline of at least 70 points. CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid or very soft stools, extent of abdominal pain, general well-being, occurrence of extra-intestinal 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. The 15 mg BID treatment group was closed to further enrolment early on in the study by Protocol Amendment 5 after only 16 participants were enrolled into this group. Therefore, the efficacy analysis was not performed for this group because the results may be difficult to interpret due to the small sample size.

Outcome measures

Outcome measures
Measure	Placebo n=90 Participants Placebo tablets to match tofacitinib 5 mg for oral administration BID for 8 weeks.	Tofacitinib 5 mg BID n=85 Participants Tofacitinib tablets for oral administration at a dose of 5 mg BID for 8 weeks.	Tofacitinib 10 mg BID n=86 Participants Tofacitinib tablets for oral administration at a dose of 10 mg BID for 8 weeks.	Tofacitinib 15 mg BID Tofacitinib tablets for oral administration at a dose of 15 mg BID for 8 weeks.
Percentage of Participants Achieving Clinical Response-70 (as Defined by a Decrease in CDAI Score of at Least 70 Points From Baseline) at Weeks 2, 4, and 8 Week 2	37.78 Percentage of Participants Interval 27.77 to 48.62	47.06 Percentage of Participants Interval 36.13 to 58.19	44.19 Percentage of Participants Interval 33.48 to 55.3	—
Percentage of Participants Achieving Clinical Response-70 (as Defined by a Decrease in CDAI Score of at Least 70 Points From Baseline) at Weeks 2, 4, and 8 Week 4	50.00 Percentage of Participants Interval 39.27 to 60.73	57.65 Percentage of Participants Interval 46.45 to 68.3	56.98 Percentage of Participants Interval 45.85 to 67.61	—
Percentage of Participants Achieving Clinical Response-70 (as Defined by a Decrease in CDAI Score of at Least 70 Points From Baseline) at Weeks 2, 4, and 8 Week 8	62.22 Percentage of Participants Interval 51.38 to 72.23	76.47 Percentage of Participants Interval 66.03 to 85.0	74.42 Percentage of Participants Interval 63.87 to 83.22	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, and 8

Population: FAS, participants with missing values were treated as non-responders.

Clinical response-100 was defined as a reduction in CDAI score from baseline of at least 100 points. CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid or very soft stools, extent of abdominal pain, general well-being, occurrence of extra-intestinal 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. The 15 mg BID treatment group was closed to further enrolment early on in the study by Protocol Amendment 5 after only 16 participants were enrolled into this group. Therefore, the efficacy analysis was not performed for this group because the results may be difficult to interpret due to the small sample size.

Outcome measures

Outcome measures
Measure	Placebo n=90 Participants Placebo tablets to match tofacitinib 5 mg for oral administration BID for 8 weeks.	Tofacitinib 5 mg BID n=85 Participants Tofacitinib tablets for oral administration at a dose of 5 mg BID for 8 weeks.	Tofacitinib 10 mg BID n=86 Participants Tofacitinib tablets for oral administration at a dose of 10 mg BID for 8 weeks.	Tofacitinib 15 mg BID Tofacitinib tablets for oral administration at a dose of 15 mg BID for 8 weeks.
Percentage of Participants Achieving Clinical Response-100 (as Defined by a Decrease in CDAI Score of at Least 100 Points From Baseline) at Weeks 2, 4, and 8 Week 4	37.78 Percentage of Participants Interval 27.77 to 48.62	48.24 Percentage of Participants Interval 37.26 to 59.34	45.35 Percentage of Participants Interval 34.58 to 56.45	—
Percentage of Participants Achieving Clinical Response-100 (as Defined by a Decrease in CDAI Score of at Least 100 Points From Baseline) at Weeks 2, 4, and 8 Week 8	54.44 Percentage of Participants Interval 43.6 to 64.98	70.59 Percentage of Participants Interval 59.71 to 79.98	68.60 Percentage of Participants Interval 57.7 to 78.19	—
Percentage of Participants Achieving Clinical Response-100 (as Defined by a Decrease in CDAI Score of at Least 100 Points From Baseline) at Weeks 2, 4, and 8 Week 2	23.33 Percentage of Participants Interval 15.06 to 33.43	34.12 Percentage of Participants Interval 24.18 to 45.2	32.56 Percentage of Participants Interval 22.84 to 43.52	—

SECONDARY outcome

Timeframe: Baseline, Weeks 2, 4, and 8

Population: FAS, participants with missing values were treated as non-responders.

Clinical response-100 was defined as a reduction in CDAI score from baseline of at least 100 points. Clinical remission was a CDAI \< 150 points. CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid or very soft stools, extent of abdominal pain, general well-being, occurrence of extra-intestinal 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. The 15 mg BID treatment group was closed to further enrolment early on in the study by Protocol Amendment 5 after only 16 participants were enrolled into this group. Therefore, the efficacy analysis was not performed for this group because the results may be difficult to interpret due to the small sample size.

Outcome measures

Outcome measures
Measure	Placebo n=90 Participants Placebo tablets to match tofacitinib 5 mg for oral administration BID for 8 weeks.	Tofacitinib 5 mg BID n=85 Participants Tofacitinib tablets for oral administration at a dose of 5 mg BID for 8 weeks.	Tofacitinib 10 mg BID n=86 Participants Tofacitinib tablets for oral administration at a dose of 10 mg BID for 8 weeks.	Tofacitinib 15 mg BID Tofacitinib tablets for oral administration at a dose of 15 mg BID for 8 weeks.
Percentage of Participants Achieving Either Clinical Response-100 or Clinical Remission (CDAI<150) at Weeks 2, 4, and 8 Week 2	24.44 Percentage of Participants Interval 16.0 to 34.64	34.12 Percentage of Participants Interval 24.18 to 45.2	32.56 Percentage of Participants Interval 22.84 to 43.52	—
Percentage of Participants Achieving Either Clinical Response-100 or Clinical Remission (CDAI<150) at Weeks 2, 4, and 8 Week 4	38.89 Percentage of Participants Interval 28.79 to 49.74	49.41 Percentage of Participants Interval 38.39 to 60.48	46.51 Percentage of Participants Interval 35.68 to 57.59	—
Percentage of Participants Achieving Either Clinical Response-100 or Clinical Remission (CDAI<150) at Weeks 2, 4, and 8 Week 8	55.56 Percentage of Participants Interval 44.7 to 66.04	71.76 Percentage of Participants Interval 60.96 to 81.0	69.77 Percentage of Participants Interval 58.92 to 79.21	—

SECONDARY outcome

Timeframe: Weeks 2, 4, and 8

Population: FAS. Number of Participants Analyzed is the number of participants in the analysis set, n is the number of participants with non-missing data.

CDAI is a composite index consisting of weighted scoring of 8 disease variables: number of liquid or very soft stools, extent of abdominal pain, general well-being, occurrence of extra-intestinal 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	Placebo n=90 Participants Placebo tablets to match tofacitinib 5 mg for oral administration BID for 8 weeks.	Tofacitinib 5 mg BID n=85 Participants Tofacitinib tablets for oral administration at a dose of 5 mg BID for 8 weeks.	Tofacitinib 10 mg BID n=86 Participants Tofacitinib tablets for oral administration at a dose of 10 mg BID for 8 weeks.	Tofacitinib 15 mg BID n=16 Participants Tofacitinib tablets for oral administration at a dose of 15 mg BID for 8 weeks.
CDAI Scores at Weeks 2, 4, and 8 Week 8 (n=80, 77, 75, 15)	194.90 Score on a scale Standard Deviation 111.88	162.77 Score on a scale Standard Deviation 87.67	159.08 Score on a scale Standard Deviation 81.30	172.47 Score on a scale Standard Deviation 119.28
CDAI Scores at Weeks 2, 4, and 8 Week 2 (n=85, 78, 77, 16)	258.04 Score on a scale Standard Deviation 89.79	237.60 Score on a scale Standard Deviation 67.87	241.21 Score on a scale Standard Deviation 75.27	270.31 Score on a scale Standard Deviation 90.78
CDAI Scores at Weeks 2, 4, and 8 Week 4 (n=81, 78, 71, 15)	228.65 Score on a scale Standard Deviation 102.01	213.38 Score on a scale Standard Deviation 86.04	203.58 Score on a scale Standard Deviation 86.69	228.27 Score on a scale Standard Deviation 103.01

SECONDARY outcome

Timeframe: Weeks 2, 4, and 8

Population: FAS. Number of Participants Analyzed is the number of participants in the analysis set, n is the number of participants with non-missing data.

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.

Outcome measures

Outcome measures
Measure	Placebo n=90 Participants Placebo tablets to match tofacitinib 5 mg for oral administration BID for 8 weeks.	Tofacitinib 5 mg BID n=85 Participants Tofacitinib tablets for oral administration at a dose of 5 mg BID for 8 weeks.	Tofacitinib 10 mg BID n=86 Participants Tofacitinib tablets for oral administration at a dose of 10 mg BID for 8 weeks.	Tofacitinib 15 mg BID n=16 Participants Tofacitinib tablets for oral administration at a dose of 15 mg BID for 8 weeks.
C-Reactive Protein (CRP) Serum Concentrations at Weeks 2, 4, and 8 Week 2 (n=89, 84, 81, 16)	17.28 Milligrams per liter (mg/L) Standard Deviation 23.07	8.26 Milligrams per liter (mg/L) Standard Deviation 11.40	8.56 Milligrams per liter (mg/L) Standard Deviation 14.03	7.89 Milligrams per liter (mg/L) Standard Deviation 9.42
C-Reactive Protein (CRP) Serum Concentrations at Weeks 2, 4, and 8 Week 4 (n=83, 82, 78, 16)	18.94 Milligrams per liter (mg/L) Standard Deviation 31.26	8.17 Milligrams per liter (mg/L) Standard Deviation 10.60	9.48 Milligrams per liter (mg/L) Standard Deviation 21.35	10.33 Milligrams per liter (mg/L) Standard Deviation 16.80
C-Reactive Protein (CRP) Serum Concentrations at Weeks 2, 4, and 8 Week 8 (n=80, 77, 74, 15)	18.12 Milligrams per liter (mg/L) Standard Deviation 26.42	9.49 Milligrams per liter (mg/L) Standard Deviation 15.33	6.55 Milligrams per liter (mg/L) Standard Deviation 11.00	5.77 Milligrams per liter (mg/L) Standard Deviation 7.74

SECONDARY outcome

Timeframe: Weeks 2, 4, and 8

Population: FAS. Number of Participants Analyzed is the number of participants in the analysis set, n is the number of participants with non-missing data.

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.

Outcome measures

Outcome measures
Measure	Placebo n=90 Participants Placebo tablets to match tofacitinib 5 mg for oral administration BID for 8 weeks.	Tofacitinib 5 mg BID n=85 Participants Tofacitinib tablets for oral administration at a dose of 5 mg BID for 8 weeks.	Tofacitinib 10 mg BID n=86 Participants Tofacitinib tablets for oral administration at a dose of 10 mg BID for 8 weeks.	Tofacitinib 15 mg BID n=16 Participants Tofacitinib tablets for oral administration at a dose of 15 mg BID for 8 weeks.
Calprotectin Fecal Concentrations at Weeks 2, 4, and 8 Week 2 (n=81, 76, 73, 16)	492.95 mg per kilogram (mg/kg) Standard Deviation 664.51	384.81 mg per kilogram (mg/kg) Standard Deviation 342.90	403.35 mg per kilogram (mg/kg) Standard Deviation 352.57	455.10 mg per kilogram (mg/kg) Standard Deviation 461.87
Calprotectin Fecal Concentrations at Weeks 2, 4, and 8 Week 4 (n=81, 82, 71, 16)	493.26 mg per kilogram (mg/kg) Standard Deviation 682.81	467.09 mg per kilogram (mg/kg) Standard Deviation 377.65	359.30 mg per kilogram (mg/kg) Standard Deviation 306.88	338.11 mg per kilogram (mg/kg) Standard Deviation 391.65
Calprotectin Fecal Concentrations at Weeks 2, 4, and 8 Week 8 (n=75, 66, 72, 14)	428.45 mg per kilogram (mg/kg) Standard Deviation 479.36	417.70 mg per kilogram (mg/kg) Standard Deviation 336.75	385.66 mg per kilogram (mg/kg) Standard Deviation 316.71	349.61 mg per kilogram (mg/kg) Standard Deviation 365.37

SECONDARY outcome

Timeframe: Pre-dose, 20 minutes, 40 minutes, 1 hour, and 2 to 3 hours post-dose on Day 1 and Week 8/ET visit

Population: Pharmacokinetic analysis set - included all participants who received at least one dose of study medication and had at least one measurable plasma concentration. n is the number of observations (i.e. non-missing concentrations) at each timepoint.

Plasma samples were collected from participants for the determination of tofacitinib concentrations. Only samples from tofacitinib-treated participants were subsequently analyzed. Plasma concentration data are summarized by nominal sample collection times specified in the protocol, and actual sample collection times may be different.

Outcome measures

Outcome measures
Measure	Placebo n=85 Participants Placebo tablets to match tofacitinib 5 mg for oral administration BID for 8 weeks.	Tofacitinib 5 mg BID n=86 Participants Tofacitinib tablets for oral administration at a dose of 5 mg BID for 8 weeks.	Tofacitinib 10 mg BID n=16 Participants Tofacitinib tablets for oral administration at a dose of 10 mg BID for 8 weeks.	Tofacitinib 15 mg BID Tofacitinib tablets for oral administration at a dose of 15 mg BID for 8 weeks.
Tofacitinib Plasma Concentrations From 0 to 2 Hours Post Dose on Day 1 and at Week 8/Early Termination (ET) Visit Day 1, 0 hours (n=83, 83, 16)	0.006687 nanograms per milliliter Standard Deviation 0.049144	1.193 nanograms per milliliter Standard Deviation 9.0312	NA nanograms per milliliter Standard Deviation NA Number of observations above the lower limit of quantification equals (=) 0.	—
Tofacitinib Plasma Concentrations From 0 to 2 Hours Post Dose on Day 1 and at Week 8/Early Termination (ET) Visit Day 1, 20 minutes (n=82, 83, 16)	27.44 nanograms per milliliter Standard Deviation 27.335	62.28 nanograms per milliliter Standard Deviation 60.795	65.83 nanograms per milliliter Standard Deviation 63.232	—
Tofacitinib Plasma Concentrations From 0 to 2 Hours Post Dose on Day 1 and at Week 8/Early Termination (ET) Visit Day 1, 40 minutes (n=82, 81, 16)	41.03 nanograms per milliliter Standard Deviation 24.210	84.61 nanograms per milliliter Standard Deviation 47.470	151.4 nanograms per milliliter Standard Deviation 61.288	—
Tofacitinib Plasma Concentrations From 0 to 2 Hours Post Dose on Day 1 and at Week 8/Early Termination (ET) Visit Day 1, 1 hour (n=83, 83, 16)	41.22 nanograms per milliliter Standard Deviation 18.432	82.48 nanograms per milliliter Standard Deviation 40.782	149.9 nanograms per milliliter Standard Deviation 42.220	—
Tofacitinib Plasma Concentrations From 0 to 2 Hours Post Dose on Day 1 and at Week 8/Early Termination (ET) Visit Day 1, 2 hours (n=83, 82, 16)	31.85 nanograms per milliliter Standard Deviation 12.442	70.01 nanograms per milliliter Standard Deviation 24.838	106.1 nanograms per milliliter Standard Deviation 26.661	—
Tofacitinib Plasma Concentrations From 0 to 2 Hours Post Dose on Day 1 and at Week 8/Early Termination (ET) Visit Week 8/ET, 0 hours (n=78, 72, 13)	4.216 nanograms per milliliter Standard Deviation 7.1089	11.57 nanograms per milliliter Standard Deviation 21.453	23.89 nanograms per milliliter Standard Deviation 45.837	—
Tofacitinib Plasma Concentrations From 0 to 2 Hours Post Dose on Day 1 and at Week 8/Early Termination (ET) Visit Week 8/ET, 20 minutes (n=70, 70, 12)	25.89 nanograms per milliliter Standard Deviation 21.485	71.14 nanograms per milliliter Standard Deviation 54.969	127.6 nanograms per milliliter Standard Deviation 89.861	—
Tofacitinib Plasma Concentrations From 0 to 2 Hours Post Dose on Day 1 and at Week 8/Early Termination (ET) Visit Week 8/ET, 40 minutes (n=70, 69, 12)	37.75 nanograms per milliliter Standard Deviation 23.891	93.09 nanograms per milliliter Standard Deviation 46.471	148.7 nanograms per milliliter Standard Deviation 58.948	—
Tofacitinib Plasma Concentrations From 0 to 2 Hours Post Dose on Day 1 and at Week 8/Early Termination (ET) Visit Week 8/ET, 1 hour (n=70, 69, 12)	37.47 nanograms per milliliter Standard Deviation 21.384	83.14 nanograms per milliliter Standard Deviation 35.100	144.7 nanograms per milliliter Standard Deviation 48.137	—
Tofacitinib Plasma Concentrations From 0 to 2 Hours Post Dose on Day 1 and at Week 8/Early Termination (ET) Visit Week 8/ET, 2 hours (n=72, 70, 13)	27.61 nanograms per milliliter Standard Deviation 15.742	62.38 nanograms per milliliter Standard Deviation 27.505	92.03 nanograms per milliliter Standard Deviation 27.806	—

SECONDARY outcome

Timeframe: Baseline, Week 8/ET visit

Population: FAS. N is the number of subjects in the analysis set, Number of Participants Analyzed is the number of subjects with non-missing data.

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.

Outcome measures

Outcome measures
Measure	Placebo n=88 Participants Placebo tablets to match tofacitinib 5 mg for oral administration BID for 8 weeks.	Tofacitinib 5 mg BID n=84 Participants Tofacitinib tablets for oral administration at a dose of 5 mg BID for 8 weeks.	Tofacitinib 10 mg BID n=81 Participants Tofacitinib tablets for oral administration at a dose of 10 mg BID for 8 weeks.	Tofacitinib 15 mg BID n=16 Participants Tofacitinib tablets for oral administration at a dose of 15 mg BID for 8 weeks.
Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score and Domain Scores (Bowel Function, Emotional Status, Systemic Symptoms, and Social Function) at Baseline and Week 8/ET Visit Bowel Function Score, Week 8/ET	45.76 Score on a scale Standard Deviation 12.19	50.94 Score on a scale Standard Deviation 11.02	50.69 Score on a scale Standard Deviation 11.02	52.50 Score on a scale Standard Deviation 13.81
Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score and Domain Scores (Bowel Function, Emotional Status, Systemic Symptoms, and Social Function) at Baseline and Week 8/ET Visit Social Function Score, Baseline	19.62 Score on a scale Standard Deviation 7.28	19.48 Score on a scale Standard Deviation 6.62	18.23 Score on a scale Standard Deviation 7.09	23.00 Score on a scale Standard Deviation 6.29
Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score and Domain Scores (Bowel Function, Emotional Status, Systemic Symptoms, and Social Function) at Baseline and Week 8/ET Visit Social Function Score, Week 8/ET	23.23 Score on a scale Standard Deviation 8.47	26.43 Score on a scale Standard Deviation 7.57	25.83 Score on a scale Standard Deviation 7.80	26.38 Score on a scale Standard Deviation 9.58
Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score and Domain Scores (Bowel Function, Emotional Status, Systemic Symptoms, and Social Function) at Baseline and Week 8/ET Visit IBDQ Total Score, Baseline	118.50 Score on a scale Standard Deviation 28.48	117.89 Score on a scale Standard Deviation 27.98	113.67 Score on a scale Standard Deviation 28.45	124.19 Score on a scale Standard Deviation 26.97
Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score and Domain Scores (Bowel Function, Emotional Status, Systemic Symptoms, and Social Function) at Baseline and Week 8/ET Visit IBDQ Total Score, Week 8/ET	144.99 Score on a scale Standard Deviation 37.97	159.14 Score on a scale Standard Deviation 35.39	156.64 Score on a scale Standard Deviation 36.66	159.00 Score on a scale Standard Deviation 47.98
Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score and Domain Scores (Bowel Function, Emotional Status, Systemic Symptoms, and Social Function) at Baseline and Week 8/ET Visit Bowel Function Score, Baseline	37.78 Score on a scale Standard Deviation 8.17	37.39 Score on a scale Standard Deviation 9.37	36.29 Score on a scale Standard Deviation 7.72	37.50 Score on a scale Standard Deviation 9.78
Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score and Domain Scores (Bowel Function, Emotional Status, Systemic Symptoms, and Social Function) at Baseline and Week 8/ET Visit Emotional Status Score, Baseline	45.88 Score on a scale Standard Deviation 13.04	45.34 Score on a scale Standard Deviation 13.27	44.55 Score on a scale Standard Deviation 13.27	47.25 Score on a scale Standard Deviation 10.41
Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score and Domain Scores (Bowel Function, Emotional Status, Systemic Symptoms, and Social Function) at Baseline and Week 8/ET Visit Emotional Status Score, Week 8/ET	56.31 Score on a scale Standard Deviation 14.39	59.54 Score on a scale Standard Deviation 13.78	58.32 Score on a scale Standard Deviation 14.71	57.25 Score on a scale Standard Deviation 20.07
Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score and Domain Scores (Bowel Function, Emotional Status, Systemic Symptoms, and Social Function) at Baseline and Week 8/ET Visit Systemic Symptoms Score, Baseline	15.22 Score on a scale Standard Deviation 5.24	15.58 Score on a scale Standard Deviation 4.36	14.60 Score on a scale Standard Deviation 4.78	16.44 Score on a scale Standard Deviation 5.35
Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score and Domain Scores (Bowel Function, Emotional Status, Systemic Symptoms, and Social Function) at Baseline and Week 8/ET Visit Systemic Symptoms Score, Week 8/ET	19.70 Score on a scale Standard Deviation 6.51	22.24 Score on a scale Standard Deviation 6.30	21.80 Score on a scale Standard Deviation 6.27	22.88 Score on a scale Standard Deviation 7.05

SECONDARY outcome

Timeframe: Baseline, Week 8/ET visit

Population: FAS. N is the number of subjects in the analysis set, Number of Participants Analyzed is the maximum number of subjects with non-missing data.

IBDQ is a validated PRO instrument for measuring QOL in IBD consisting of 32 items scored from 1 (worst response) to 7 (best response). 32 items are grouped into 4 domains scored as follows: bowel symptoms 10 - 70; systemic symptoms 5 - 35; emotional function 12 - 84; social function 5 - 35. For each domain, higher score indicates better QOL. Total score is the sum of each item score, \& ranged from 32 to 224 with a higher score indicating better QOL. Positive change in total score indicated improvement in QOL. Adjusted means were derived from an ANCOVA model with baseline value as covariate, treatment group \& prior use of anti-tumor necrosis factor (TNF) alpha (α) treatments as factors. The 15 mg BID treatment group was closed to further enrolment early in the study by Protocol Amendment 5 after only 16 participants were enrolled in this group. Therefore, the efficacy analysis was not performed for this group as the results may be difficult to interpret due to the small sample size.

Outcome measures

Outcome measures
Measure	Placebo n=88 Participants Placebo tablets to match tofacitinib 5 mg for oral administration BID for 8 weeks.	Tofacitinib 5 mg BID n=84 Participants Tofacitinib tablets for oral administration at a dose of 5 mg BID for 8 weeks.	Tofacitinib 10 mg BID n=81 Participants Tofacitinib tablets for oral administration at a dose of 10 mg BID for 8 weeks.	Tofacitinib 15 mg BID Tofacitinib tablets for oral administration at a dose of 15 mg BID for 8 weeks.
Change From Baseline IBDQ Total Score and Domain Scores (Bowel Function, Emotional Status, Systemic Symptoms, and Social Function) at Week 8/ET Visit Using Analysis of Covariance (ANCOVA) IBDQ Total Score	26.58 Score on a scale Standard Error 3.76	41.20 Score on a scale Standard Error 3.90	40.05 Score on a scale Standard Error 3.90	—
Change From Baseline IBDQ Total Score and Domain Scores (Bowel Function, Emotional Status, Systemic Symptoms, and Social Function) at Week 8/ET Visit Using Analysis of Covariance (ANCOVA) Bowel Function Score	8.36 Score on a scale Standard Error 1.23	13.76 Score on a scale Standard Error 1.28	13.88 Score on a scale Standard Error 1.28	—
Change From Baseline IBDQ Total Score and Domain Scores (Bowel Function, Emotional Status, Systemic Symptoms, and Social Function) at Week 8/ET Visit Using Analysis of Covariance (ANCOVA) Emotional Status Score	10.33 Score on a scale Standard Error 1.37	13.87 Score on a scale Standard Error 1.42	12.54 Score on a scale Standard Error 1.43	—
Change From Baseline IBDQ Total Score and Domain Scores (Bowel Function, Emotional Status, Systemic Symptoms, and Social Function) at Week 8/ET Visit Using Analysis of Covariance (ANCOVA) Systemic Symptoms Score	4.41 Score on a scale Standard Error 0.66	6.70 Score on a scale Standard Error 0.69	6.68 Score on a scale Standard Error 0.69	—
Change From Baseline IBDQ Total Score and Domain Scores (Bowel Function, Emotional Status, Systemic Symptoms, and Social Function) at Week 8/ET Visit Using Analysis of Covariance (ANCOVA) Social Function Score	3.68 Score on a scale Standard Error 0.79	7.03 Score on a scale Standard Error 0.82	6.95 Score on a scale Standard Error 0.82	—

SECONDARY outcome

Timeframe: Week 8/ET visit

Population: FAS

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. Positive change in total score indicated improvement in QOL.

Outcome measures

Outcome measures
Measure	Placebo n=88 Participants Placebo tablets to match tofacitinib 5 mg for oral administration BID for 8 weeks.	Tofacitinib 5 mg BID n=84 Participants Tofacitinib tablets for oral administration at a dose of 5 mg BID for 8 weeks.	Tofacitinib 10 mg BID n=81 Participants Tofacitinib tablets for oral administration at a dose of 10 mg BID for 8 weeks.	Tofacitinib 15 mg BID n=16 Participants Tofacitinib tablets for oral administration at a dose of 15 mg BID for 8 weeks.
Percentage of Participants With an IBDQ Total Score of Greater Than or Equal to (≥) 170 at Week 8/ET Visit	26.1 Percentage of Participants	45.2 Percentage of Participants	43.2 Percentage of Participants	43.8 Percentage of Participants

SECONDARY outcome

Timeframe: Week 8/ET visit

Population: FAS. Number of Participants Analyzed is the number of participants in the analysis set.

Outcome measures

Outcome measures
Measure	Placebo n=90 Participants Placebo tablets to match tofacitinib 5 mg for oral administration BID for 8 weeks.	Tofacitinib 5 mg BID n=85 Participants Tofacitinib tablets for oral administration at a dose of 5 mg BID for 8 weeks.	Tofacitinib 10 mg BID n=86 Participants Tofacitinib tablets for oral administration at a dose of 10 mg BID for 8 weeks.	Tofacitinib 15 mg BID n=16 Participants Tofacitinib tablets for oral administration at a dose of 15 mg BID for 8 weeks.
Percentage of Participants With ≥16 Point Increase From Baseline in IBDQ Total Score at Week 8/ET Visit	61.4 Percentage of Participants	75.0 Percentage of Participants	76.5 Percentage of Participants	75.0 Percentage of Participants

SECONDARY outcome

Timeframe: Week 8/ET visit

Population: FAS. Number of Participants Analyzed is the number of participants in the analysis set.

The IBD Patient Reported Treatment Impact Modified (PRTI) 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 re-use 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	Placebo n=90 Participants Placebo tablets to match tofacitinib 5 mg for oral administration BID for 8 weeks.	Tofacitinib 5 mg BID n=85 Participants Tofacitinib tablets for oral administration at a dose of 5 mg BID for 8 weeks.	Tofacitinib 10 mg BID n=86 Participants Tofacitinib tablets for oral administration at a dose of 10 mg BID for 8 weeks.	Tofacitinib 15 mg BID n=16 Participants Tofacitinib tablets for oral administration at a dose of 15 mg BID for 8 weeks.
Percentage of Participants With a Response to the Patient-Reported Treatment Impact Assessment (PRTI) at Week 8/ET Visit by Category PPA: Definitely prefer the drug I am receiving now	33.0 Percentage of Participants	42.2 Percentage of Participants	48.1 Percentage of Participants	56.3 Percentage of Participants
Percentage of Participants With a Response to the Patient-Reported Treatment Impact Assessment (PRTI) at Week 8/ET Visit by Category PSA: Extremely dissatisfied	17.0 Percentage of Participants	6.0 Percentage of Participants	7.4 Percentage of Participants	6.3 Percentage of Participants
Percentage of Participants With a Response to the Patient-Reported Treatment Impact Assessment (PRTI) at Week 8/ET Visit by Category PSA: Dissatisfied	10.2 Percentage of Participants	9.6 Percentage of Participants	6.2 Percentage of Participants	0 Percentage of Participants
Percentage of Participants With a Response to the Patient-Reported Treatment Impact Assessment (PRTI) at Week 8/ET Visit by Category PSA: Neither satisfied nor dissatisfied	25.0 Percentage of Participants	19.3 Percentage of Participants	16.0 Percentage of Participants	25.0 Percentage of Participants
Percentage of Participants With a Response to the Patient-Reported Treatment Impact Assessment (PRTI) at Week 8/ET Visit by Category PSA: Satisfied	40.9 Percentage of Participants	45.8 Percentage of Participants	43.2 Percentage of Participants	25.0 Percentage of Participants
Percentage of Participants With a Response to the Patient-Reported Treatment Impact Assessment (PRTI) at Week 8/ET Visit by Category PSA: Extremely satisfied	6.8 Percentage of Participants	19.3 Percentage of Participants	27.2 Percentage of Participants	43.8 Percentage of Participants
Percentage of Participants With a Response to the Patient-Reported Treatment Impact Assessment (PRTI) at Week 8/ET Visit by Category PPTA: Injectable prescription medicines	42.0 Percentage of Participants	39.5 Percentage of Participants	22.2 Percentage of Participants	37.5 Percentage of Participants
Percentage of Participants With a Response to the Patient-Reported Treatment Impact Assessment (PRTI) at Week 8/ET Visit by Category PPTA: Prescription medicines taken by mouth	37.5 Percentage of Participants	44.4 Percentage of Participants	56.8 Percentage of Participants	43.8 Percentage of Participants
Percentage of Participants With a Response to the Patient-Reported Treatment Impact Assessment (PRTI) at Week 8/ET Visit by Category PPTA: Surgery	2.3 Percentage of Participants	2.5 Percentage of Participants	0 Percentage of Participants	0 Percentage of Participants
Percentage of Participants With a Response to the Patient-Reported Treatment Impact Assessment (PRTI) at Week 8/ET Visit by Category PPTA:Prescription medicines and surgery	5.7 Percentage of Participants	7.4 Percentage of Participants	8.6 Percentage of Participants	6.3 Percentage of Participants
Percentage of Participants With a Response to the Patient-Reported Treatment Impact Assessment (PRTI) at Week 8/ET Visit by Category PPTA: No treatment	12.5 Percentage of Participants	6.2 Percentage of Participants	12.3 Percentage of Participants	12.5 Percentage of Participants
Percentage of Participants With a Response to the Patient-Reported Treatment Impact Assessment (PRTI) at Week 8/ET Visit by Category PPA: Slight preference for drug I'm receiving now	19.3 Percentage of Participants	27.7 Percentage of Participants	22.2 Percentage of Participants	25.0 Percentage of Participants
Percentage of Participants With a Response to the Patient-Reported Treatment Impact Assessment (PRTI) at Week 8/ET Visit by Category PPA: I have no preference either way	28.4 Percentage of Participants	19.3 Percentage of Participants	13.6 Percentage of Participants	18.8 Percentage of Participants
Percentage of Participants With a Response to the Patient-Reported Treatment Impact Assessment (PRTI) at Week 8/ET Visit by Category PPA: Slight preference for previous treatment	9.1 Percentage of Participants	2.4 Percentage of Participants	7.4 Percentage of Participants	0 Percentage of Participants
Percentage of Participants With a Response to the Patient-Reported Treatment Impact Assessment (PRTI) at Week 8/ET Visit by Category PPA: No, I definitely prefer my previous treatment	10.2 Percentage of Participants	8.4 Percentage of Participants	8.6 Percentage of Participants	0 Percentage of Participants
Percentage of Participants With a Response to the Patient-Reported Treatment Impact Assessment (PRTI) at Week 8/ET Visit by Category PWA: Would definitely want to use same drug again	44.3 Percentage of Participants	53.0 Percentage of Participants	61.7 Percentage of Participants	50.0 Percentage of Participants
Percentage of Participants With a Response to the Patient-Reported Treatment Impact Assessment (PRTI) at Week 8/ET Visit by Category PWA: Might want to use the same drug again	11.4 Percentage of Participants	24.1 Percentage of Participants	17.3 Percentage of Participants	37.5 Percentage of Participants
Percentage of Participants With a Response to the Patient-Reported Treatment Impact Assessment (PRTI) at Week 8/ET Visit by Category PWA: I am not sure	20.5 Percentage of Participants	10.8 Percentage of Participants	8.6 Percentage of Participants	6.3 Percentage of Participants
Percentage of Participants With a Response to the Patient-Reported Treatment Impact Assessment (PRTI) at Week 8/ET Visit by Category PWA: Might not want to use same drug again	6.8 Percentage of Participants	2.4 Percentage of Participants	4.9 Percentage of Participants	0 Percentage of Participants
Percentage of Participants With a Response to the Patient-Reported Treatment Impact Assessment (PRTI) at Week 8/ET Visit by Category PWA: Definitely not want to use same drug again	17.0 Percentage of Participants	9.6 Percentage of Participants	7.4 Percentage of Participants	6.3 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline, Week 8/ET visit

Population: FAS. N is the number of subjects in the analysis set, Number of Participants Analyzed is the maximum number of subjects with non-missing data.

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 SF-36 version 2 and SF-36 health domain scales and component summary measures have means of 50 and standard deviations of 10. Higher scores indicate better health-related QOL.

Outcome measures

Outcome measures
Measure	Placebo n=87 Participants Placebo tablets to match tofacitinib 5 mg for oral administration BID for 8 weeks.	Tofacitinib 5 mg BID n=84 Participants Tofacitinib tablets for oral administration at a dose of 5 mg BID for 8 weeks.	Tofacitinib 10 mg BID n=81 Participants Tofacitinib tablets for oral administration at a dose of 10 mg BID for 8 weeks.	Tofacitinib 15 mg BID n=16 Participants Tofacitinib tablets for oral administration at a dose of 15 mg BID for 8 weeks.
Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 8/ET Visit Mental Component Score, Baseline	36.50 Score on a Scale Standard Deviation 12.26	34.85 Score on a Scale Standard Deviation 11.68	35.84 Score on a Scale Standard Deviation 10.68	39.26 Score on a Scale Standard Deviation 11.85
Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 8/ET Visit Role Emotional Domain, Week 8/ET	43.06 Score on a Scale Standard Deviation 12.43	44.77 Score on a Scale Standard Deviation 12.46	43.76 Score on a Scale Standard Deviation 11.94	42.90 Score on a Scale Standard Deviation 16.58
Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 8/ET Visit Physical component score, Baseline	37.12 Score on a Scale Standard Deviation 7.66	38.49 Score on a Scale Standard Deviation 6.78	35.28 Score on a Scale Standard Deviation 8.49	37.09 Score on a Scale Standard Deviation 9.14
Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 8/ET Visit Physical component score, Week 8/ET	40.84 Score on a Scale Standard Deviation 9.23	45.23 Score on a Scale Standard Deviation 8.85	44.29 Score on a Scale Standard Deviation 9.41	47.01 Score on a Scale Standard Deviation 7.97
Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 8/ET Visit Mental Component Score, Week 8/ET	42.46 Score on a Scale Standard Deviation 11.21	43.69 Score on a Scale Standard Deviation 12.15	43.65 Score on a Scale Standard Deviation 11.87	42.73 Score on a Scale Standard Deviation 16.37
Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 8/ET Visit Physical Functioning Domain, Baseline	43.73 Score on a Scale Standard Deviation 8.93	43.56 Score on a Scale Standard Deviation 8.81	41.36 Score on a Scale Standard Deviation 10.03	42.66 Score on a Scale Standard Deviation 9.04
Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 8/ET Visit Physical Functioning Domain, Week 8/ET	46.55 Score on a Scale Standard Deviation 8.93	49.68 Score on a Scale Standard Deviation 8.43	48.37 Score on a Scale Standard Deviation 8.78	49.57 Score on a Scale Standard Deviation 8.99
Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 8/ET Visit Role Physical Domain, Baseline	35.34 Score on a Scale Standard Deviation 9.94	36.36 Score on a Scale Standard Deviation 9.71	32.57 Score on a Scale Standard Deviation 10.92	37.68 Score on a Scale Standard Deviation 12.43
Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 8/ET Visit Role Physical Domain, Week 8/ET	39.92 Score on a Scale Standard Deviation 10.64	44.49 Score on a Scale Standard Deviation 11.52	42.84 Score on a Scale Standard Deviation 11.59	44.39 Score on a Scale Standard Deviation 13.18
Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 8/ET Visit Bodily Pain Domain, Baseline	34.69 Score on a Scale Standard Deviation 8.79	35.22 Score on a Scale Standard Deviation 8.44	33.32 Score on a Scale Standard Deviation 8.25	34.98 Score on a Scale Standard Deviation 8.23
Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 8/ET Visit Bodily Pain Domain, Week 8/ET	40.81 Score on a Scale Standard Deviation 10.43	44.68 Score on a Scale Standard Deviation 11.29	45.10 Score on a Scale Standard Deviation 10.41	47.61 Score on a Scale Standard Deviation 11.21
Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 8/ET Visit General Health Domain, Baseline	30.58 Score on a Scale Standard Deviation 7.21	31.37 Score on a Scale Standard Deviation 7.15	29.56 Score on a Scale Standard Deviation 7.52	32.08 Score on a Scale Standard Deviation 12.42
Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 8/ET Visit General Health Domain, Week 8/ET	34.36 Score on a Scale Standard Deviation 8.50	36.79 Score on a Scale Standard Deviation 8.53	37.19 Score on a Scale Standard Deviation 10.75	37.98 Score on a Scale Standard Deviation 13.51
Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 8/ET Visit Vitality Domain, Baseline	35.06 Score on a Scale Standard Deviation 9.70	34.66 Score on a Scale Standard Deviation 7.86	35.80 Score on a Scale Standard Deviation 9.05	37.55 Score on a Scale Standard Deviation 11.88
Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 8/ET Visit Vitality Domain, Week 8/ET	41.20 Score on a Scale Standard Deviation 11.45	45.22 Score on a Scale Standard Deviation 11.94	44.60 Score on a Scale Standard Deviation 12.53	48.77 Score on a Scale Standard Deviation 13.41
Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 8/ET Visit Social Functioning Domain, Baseline	34.71 Score on a Scale Standard Deviation 11.83	35.53 Score on a Scale Standard Deviation 11.69	33.83 Score on a Scale Standard Deviation 11.36	35.90 Score on a Scale Standard Deviation 10.61
Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 8/ET Visit Social Functioning Domain, Week 8/ET	40.02 Score on a Scale Standard Deviation 12.33	45.01 Score on a Scale Standard Deviation 11.79	43.46 Score on a Scale Standard Deviation 11.43	43.63 Score on a Scale Standard Deviation 14.94
Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 8/ET Visit Role Emotional Domain, Baseline	38.45 Score on a Scale Standard Deviation 13.98	37.20 Score on a Scale Standard Deviation 12.96	35.34 Score on a Scale Standard Deviation 13.23	39.12 Score on a Scale Standard Deviation 14.02
Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 8/ET Visit Mental Health Domain, Baseline	37.60 Score on a Scale Standard Deviation 12.30	35.95 Score on a Scale Standard Deviation 11.38	36.98 Score on a Scale Standard Deviation 11.09	41.27 Score on a Scale Standard Deviation 10.27
Short Form 36 Health Survey (SF-36) Component and Domain Scores at Baseline and Week 8/ET Visit Mental Health Domain, Week 8/ET	43.75 Score on a Scale Standard Deviation 11.02	43.58 Score on a Scale Standard Deviation 11.67	44.76 Score on a Scale Standard Deviation 11.64	43.00 Score on a Scale Standard Deviation 15.96

SECONDARY outcome

Timeframe: Baseline, Week 8/ET visit

Population: FAS. N is the number of subjects in the analysis set, Number of Participants Analyzed is the maximum number of subjects with non-missing data.

The component and domain scores were scored using the US 1998 general population norms. The resulting norm-based T scores for both the SF-36 version 2 and SF-36 health domain scales and component summary measures have means of 50 and standard deviations of 10. Higher scores indicate better health-related QOL. Adjusted means were derived from the ANCOVA model with baseline value as a covariate, treatment group and prior use of anti-TNF alpha treatments as factors. The 15 mg BID treatment group was closed to further enrolment early on in the study by Protocol Amendment 5 after only 16 participants were enrolled into this group. Therefore, the efficacy analysis was not performed for this group because the results may be difficult to interpret due to the small sample size.

Outcome measures

Outcome measures
Measure	Placebo n=87 Participants Placebo tablets to match tofacitinib 5 mg for oral administration BID for 8 weeks.	Tofacitinib 5 mg BID n=84 Participants Tofacitinib tablets for oral administration at a dose of 5 mg BID for 8 weeks.	Tofacitinib 10 mg BID n=81 Participants Tofacitinib tablets for oral administration at a dose of 10 mg BID for 8 weeks.	Tofacitinib 15 mg BID Tofacitinib tablets for oral administration at a dose of 15 mg BID for 8 weeks.
Change From Baseline SF-36 Component and Domain Scores at Week 8/ET Visit Using ANCOVA Bodily Pain Domain	6.41 Score on a Scale Standard Error 1.132	9.94 Score on a Scale Standard Error 1.174	11.10 Score on a Scale Standard Error 1.171	—
Change From Baseline SF-36 Component and Domain Scores at Week 8/ET Visit Using ANCOVA Physical component score	3.72 Score on a Scale Standard Error 0.927	7.28 Score on a Scale Standard Error 0.967	8.07 Score on a Scale Standard Error 0.956	—
Change From Baseline SF-36 Component and Domain Scores at Week 8/ET Visit Using ANCOVA Mental Component Score	6.47 Score on a Scale Standard Error 1.143	7.88 Score on a Scale Standard Error 1.178	7.13 Score on a Scale Standard Error 1.180	—
Change From Baseline SF-36 Component and Domain Scores at Week 8/ET Visit Using ANCOVA Physical Functioning Domain	3.01 Score on a Scale Standard Error 0.850	6.14 Score on a Scale Standard Error 0.876	5.59 Score on a Scale Standard Error 0.876	—
Change From Baseline SF-36 Component and Domain Scores at Week 8/ET Visit Using ANCOVA Role Physical Domain	5.02 Score on a Scale Standard Error 1.152	8.76 Score on a Scale Standard Error 1.191	8.95 Score on a Scale Standard Error 1.183	—
Change From Baseline SF-36 Component and Domain Scores at Week 8/ET Visit Using ANCOVA General Health Domain	3.62 Score on a Scale Standard Error 0.897	5.55 Score on a Scale Standard Error 0.937	7.03 Score on a Scale Standard Error 0.933	—
Change From Baseline SF-36 Component and Domain Scores at Week 8/ET Visit Using ANCOVA Vitality Domain	5.55 Score on a Scale Standard Error 1.190	9.84 Score on a Scale Standard Error 1.225	8.05 Score on a Scale Standard Error 1.233	—
Change From Baseline SF-36 Component and Domain Scores at Week 8/ET Visit Using ANCOVA Social Functioning Domain	5.25 Score on a Scale Standard Error 1.163	9.72 Score on a Scale Standard Error 1.206	8.66 Score on a Scale Standard Error 1.204	—
Change From Baseline SF-36 Component and Domain Scores at Week 8/ET Visit Using ANCOVA Role Emotional Domain	5.59 Score on a Scale Standard Error 1.222	7.28 Score on a Scale Standard Error 1.257	7.14 Score on a Scale Standard Error 1.260	—
Change From Baseline SF-36 Component and Domain Scores at Week 8/ET Visit Using ANCOVA Mental Health Domain	6.46 Score on a Scale Standard Error 1.100	7.05 Score on a Scale Standard Error 1.136	7.41 Score on a Scale Standard Error 1.134	—

SECONDARY outcome

Timeframe: Baseline, Week 8/ET visit

Population: FAS. N is the number of subjects in the analysis set, Number of Participants Analyzed is the maximum number of subjects with non-missing data.

EQ-5D 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, self-care, 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.

Outcome measures

Outcome measures
Measure	Placebo n=90 Participants Placebo tablets to match tofacitinib 5 mg for oral administration BID for 8 weeks.	Tofacitinib 5 mg BID n=85 Participants Tofacitinib tablets for oral administration at a dose of 5 mg BID for 8 weeks.	Tofacitinib 10 mg BID n=86 Participants Tofacitinib tablets for oral administration at a dose of 10 mg BID for 8 weeks.	Tofacitinib 15 mg BID n=16 Participants Tofacitinib tablets for oral administration at a dose of 15 mg BID for 8 weeks.
EuroQoL 5 Dimensions Questionnaire (EQ-5D) Utility Scores at Baseline and Week 8/ET Visit Utility Score, Baseline	0.56 Score on a Scale Standard Deviation 0.29	0.58 Score on a Scale Standard Deviation 0.26	0.49 Score on a Scale Standard Deviation 0.31	0.61 Score on a Scale Standard Deviation 0.24
EuroQoL 5 Dimensions Questionnaire (EQ-5D) Utility Scores at Baseline and Week 8/ET Visit Utility Score, Week 8/ET	0.64 Score on a Scale Standard Deviation 0.27	0.71 Score on a Scale Standard Deviation 0.28	0.71 Score on a Scale Standard Deviation 0.27	0.77 Score on a Scale Standard Deviation 0.30

SECONDARY outcome

Timeframe: Baseline, Week 8/ET visit

Population: FAS. N is the number of subjects in the analysis set, Number of Participants Analyzed is the number of subjects with non-missing data.

EQ-5D is a participant rated questionnaire to assess health-related QoL via a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self-care, usual activities, pain \& discomfort, anxiety \& depression; 1 = better health state (no problems); 3 = worst health state ("confined to bed"). Scoring formula developed by EuroQol Group assigns a utility value for each domain. Score is transformed to a total score ranging from -0.594 to 1.000; higher score indicates better health state. Adjusted means were derived from the ANCOVA model with baseline value as a covariate, treatment group \& prior use of anti-TNFα treatments as factors. The 15 mg BID treatment group was closed to further enrolment early on in the study by Protocol Amendment 5 after only 16 participants were enrolled into this group. Therefore, the efficacy analysis was not performed for this group because the results may be difficult to interpret due to the small sample size.

Outcome measures

Outcome measures
Measure	Placebo n=84 Participants Placebo tablets to match tofacitinib 5 mg for oral administration BID for 8 weeks.	Tofacitinib 5 mg BID n=84 Participants Tofacitinib tablets for oral administration at a dose of 5 mg BID for 8 weeks.	Tofacitinib 10 mg BID n=80 Participants Tofacitinib tablets for oral administration at a dose of 10 mg BID for 8 weeks.	Tofacitinib 15 mg BID Tofacitinib tablets for oral administration at a dose of 15 mg BID for 8 weeks.
Change From Baseline EQ-5D Utility Scores at Week 8/ET Visit Using ANCOVA	0.08 Score on a Scale Standard Error 0.029	0.14 Score on a Scale Standard Error 0.030	0.16 Score on a Scale Standard Error 0.030	—

SECONDARY outcome

Timeframe: Baseline, Week 8/ET visit

Population: FAS. N is the number of subjects in the analysis set, Number of Participants Analyzed is the maximum number of subjects with non-missing data.

Outcome measures

Outcome measures
Measure	Placebo n=90 Participants Placebo tablets to match tofacitinib 5 mg for oral administration BID for 8 weeks.	Tofacitinib 5 mg BID n=85 Participants Tofacitinib tablets for oral administration at a dose of 5 mg BID for 8 weeks.	Tofacitinib 10 mg BID n=86 Participants Tofacitinib tablets for oral administration at a dose of 10 mg BID for 8 weeks.	Tofacitinib 15 mg BID n=16 Participants Tofacitinib tablets for oral administration at a dose of 15 mg BID for 8 weeks.
EQ-5D Visual Analogue Scale (VAS) Scores at Baseline and Week 8/ET Visit VAS Score, Week 8/ET	58.32 mm Standard Deviation 21.31	67.07 mm Standard Deviation 19.39	65.77 mm Standard Deviation 19.71	69.81 mm Standard Deviation 21.11
EQ-5D Visual Analogue Scale (VAS) Scores at Baseline and Week 8/ET Visit VAS Score, Baseline	46.83 mm Standard Deviation 18.63	49.51 mm Standard Deviation 18.03	42.74 mm Standard Deviation 18.04	52.06 mm Standard Deviation 24.11

SECONDARY outcome

Timeframe: Baseline, Week 8/ET visit

Population: FAS. N is the number of subjects in the analysis set, Number of Participants Analyzed is the maximum number of subjects with non-missing data.

EQ-5D 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. Adjusted means were derived from the ANCOVA model with baseline value as a covariate, treatment group \& prior use of anti-TNF alpha treatments as factors. The 15 mg BID treatment group was closed to further enrolment early on in the study by Protocol Amendment 5 after only 16 participants were enrolled into this group. Therefore, the efficacy analysis was not performed for this group because the results may be difficult to interpret due to the small sample size.

Outcome measures

Outcome measures
Measure	Placebo n=90 Participants Placebo tablets to match tofacitinib 5 mg for oral administration BID for 8 weeks.	Tofacitinib 5 mg BID n=85 Participants Tofacitinib tablets for oral administration at a dose of 5 mg BID for 8 weeks.	Tofacitinib 10 mg BID n=86 Participants Tofacitinib tablets for oral administration at a dose of 10 mg BID for 8 weeks.	Tofacitinib 15 mg BID Tofacitinib tablets for oral administration at a dose of 15 mg BID for 8 weeks.
Change From Baseline EQ-5D VAS Scores at Week 8/ET Visit Using ANCOVA	11.97 mm Standard Error 2.166	19.56 mm Standard Error 2.252	20.62 mm Standard Error 2.222	—

Adverse Events

Placebo

Serious events: 3 serious events

Other events: 43 other events

Deaths: 0 deaths

Tofacitinib 5 mg BID

Serious events: 3 serious events

Other events: 37 other events

Deaths: 0 deaths

Tofacitinib 10 mg BID

Serious events: 10 serious events

Other events: 42 other events

Deaths: 0 deaths

Tofacitinib 15 mg BID

Serious events: 0 serious events

Other events: 9 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 The sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days from the time submitted to the sponsor for review. The PI must remove any previously undisclosed Confidential Information (other than the Study results themselves) before public release.
Publication restrictions are in place

Restriction type: OTHER