Crohn's Disease
Conditions
Keywords
tofacitinib, Xeljanz, CP-690,550, maintenance therapy
Brief summary
This study investigates safety and efficacy of CP-690,550 in adult patients with moderate to severe Crohn's disease who completed the double-blind induction treatment in Study A3921083 and achieved clinical response-100 and/or clinical remission (CDAI\<150) at Week 8.
Interventions
DRUGPlacebo
oral tablets twice daily
DRUGCP-690,550
oral tablets twice daily
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Subjects who met study entry criteria, and who completed Week 8 visit of Induction Study A3921083. * Subjects who achieve clinical response-100 (reduction in CDAI by 100 points) and/or clinical remission (CDAI\<150) in Study A3921083. * Women of childbearing potential must test negative for pregnancy prior to study enrolment.
Exclusion criteria
* Subjects who had major protocol violation (as determined by the Sponsor) in the A3921083 study. * Subjects likely to require any type of surgery during the study period. * Fecal culture/toxin assay indicating presence of pathogenic infection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Clinical Response-100 (as Defined by a Decrease in Crohn's Disease Activity Index [CDAI] Score of at Least 100 Points From Baseline) or Clinical Remission (CDAI Score Less Than [<]150) at Week 26 | Week 26 | Clinical response-100 was defined as a reduction in CDAI score of at least 100 points from baseline of the parent A3921083 study. Clinical remission was a CDAI score \<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 anti-diarrheal 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Clinical Response-100 at Weeks 4, 8, 12, 20 and 26 | Weeks 4, 8, 12, 20 and 26 | 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 extraintestinal symptoms, need for anti-diarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity. |
| Percentage of Participants in Clinical Remission at Weeks 4, 8, 12, 20 and 26 | Weeks 4, 8, 12, 20 and 26 | Clinical remission was a CDAI score \<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 extraintestinal symptoms, need for anti-diarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity. |
| Percentage of Participants in Clinical Remission at Week 4, 8, 12, 20 and 26 Among Participants in Remission at Baseline of Maintenance Study | Weeks 4, 8, 12, 20 and 26 | Clinical remission was a CDAI score \<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 extraintestinal symptoms, need for anti-diarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity. |
| Percentage of Participants in Sustained Clinical Remission (Defined as Being in Clinical Remission at Both Weeks 20 and 26) in the Maintenance Phase | Weeks 20 and 26 | Clinical remission was a CDAI score \<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 extraintestinal symptoms, need for anti-diarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity. |
| Percentage of Participants With Sustained Clinical Response-100 (Defined as Having at Least a Clinical Response-100 at Both Weeks 20 and 26 From the A3921083 Baseline) in the Maintenance Phase | Weeks 20 and 26 | 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. |
| CDAI Score by Week | Baseline and Weeks 4, 8, 12, 20 and 26 | 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 wellbeing, 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 |
| Change From Baseline in CDAI Score by Week | Weeks 4, 8, 12, 20 and 26 | 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 wellbeing, 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 |
| Percentage of Participants With Clinical Response-100 or Clinical Remission at Weeks 4, 8, 12 and 20 | Weeks 4, 8, 12 and 20 | Clinical response-100 was defined as a reduction in CDAI score of at least 100 points from baseline of the parent A3921083 study. Clinical remission was a CDAI score \<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 extraintestinal symptoms, need for anti-diarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity. |
| Percentage of Participants Achieving a Steroid-Free Clinical Remission at Week 26 of the Maintenance Phase - Among Participants on Steroids at A3921084 Baseline | Week 26 | 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 wellbeing, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body eight. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity. |
| C-Reactive Protein (CRP) by Week | Baseline and Weeks 4, 8, 12, 20 and 26 | 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. |
| Change From Baseline in CRP by Week | Weeks 4, 8, 12, 20 and 26 | 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. |
| Fecal Calprotectin by Week | Baseline and Weeks 8, 12 and 26 | 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. |
| Change From Baseline in Fecal Calprotectin by Week | Weeks 8, 12 and 26 | 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. |
| Tofacitinib Plasma Concentration by Nominal Post-Dose Sampling Time and Tofacitinib Dose | Pre-dose, 20 minutes, 40 minutes, 1 hour and 2 hours post-dose at Weeks 12 and 26/early termination visit | 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. |
| Kaplan-Meier Estimate of the Rate of Time to Relapse | Weeks 4, 8 12, 20 and 26 | Time to relapse was defined as increase in CDAI of more than (\>)100 points from the maintenance phase baseline and a CDAI score of \>220 points, or an increase to or above the baseline CDAI score in A3921083. 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 wellbeing, 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. |
Countries
Australia, Austria, Bulgaria, Canada, Czechia, France, Germany, Greece, Hungary, Israel, Japan, Netherlands, South Africa, South Korea, Spain, Ukraine, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo (two placebo tablets) to match tofacitinib for oral administration BID for 26 weeks. | 59 |
| Tofacitinib 5 mg BID Tofacitinib 5 mg (one placebo tablet and one tofacitinib tablet) for oral administration at a dose of 5 mg BID for 26 weeks. | 60 |
| Tofacitinib 10 mg BID Tofacitinib 10 mg (two tofacitinib tablets) for oral administration at a dose of 10 mg BID for 26 weeks. | 61 |
| Total | 180 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 5 | 3 |
| Overall Study | Does not meet entrance criteria | 1 | 0 | 1 |
| Overall Study | Lack of Efficacy | 26 | 21 | 16 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Other | 1 | 0 | 0 |
| Overall Study | Study terminated by sponsor | 1 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 2 | 1 |
Baseline characteristics
| Characteristic | Placebo | Total | Tofacitinib 10 mg BID | Tofacitinib 5 mg BID |
|---|---|---|---|---|
| Age, Customized Between 18 and 44 years | 34 Participants | 118 Participants | 40 Participants | 44 Participants |
| Age, Customized Between 45 and 64 years | 23 Participants | 58 Participants | 20 Participants | 15 Participants |
| Age, Customized Less than or equal to (<=)18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized More than or equal to (>=)65 years | 2 Participants | 4 Participants | 1 Participants | 1 Participants |
| Gender Female | 32 Participants | 86 Participants | 24 Participants | 30 Participants |
| Gender Male | 27 Participants | 94 Participants | 37 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 28 / 59 | 40 / 60 | 35 / 61 |
| serious Total, serious adverse events | 7 / 59 | 6 / 60 | 8 / 61 |
Outcome results
Primary
Percentage of Participants With Clinical Response-100 (as Defined by a Decrease in Crohn's Disease Activity Index [CDAI] Score of at Least 100 Points From Baseline) or Clinical Remission (CDAI Score Less Than [<]150) at Week 26
Clinical response-100 was defined as a reduction in CDAI score of at least 100 points from baseline of the parent A3921083 study. Clinical remission was a CDAI score \<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 anti-diarrheal 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.
Time frame: Week 26
Population: Modified full analysis set (mFAS), defined as all randomized participants who received at least 1 dose of investigational product (ie, active or placebo study medication) in this study and who were randomized into 1 of the tofacitinib (CP-690,550) dose groups in Study A3921083.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Clinical Response-100 (as Defined by a Decrease in Crohn's Disease Activity Index [CDAI] Score of at Least 100 Points From Baseline) or Clinical Remission (CDAI Score Less Than [<]150) at Week 26 | 38.10 Percentage of participants |
| Tofacitinib 5 mg BID | Percentage of Participants With Clinical Response-100 (as Defined by a Decrease in Crohn's Disease Activity Index [CDAI] Score of at Least 100 Points From Baseline) or Clinical Remission (CDAI Score Less Than [<]150) at Week 26 | 39.53 Percentage of participants |
| Tofacitinib 10 mg BID | Percentage of Participants With Clinical Response-100 (as Defined by a Decrease in Crohn's Disease Activity Index [CDAI] Score of at Least 100 Points From Baseline) or Clinical Remission (CDAI Score Less Than [<]150) at Week 26 | 55.81 Percentage of participants |
80% CI: [-12.11, 14.99]
80% CI: [4.07, 31.37]
Secondary
CDAI Score by Week
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 wellbeing, 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
Time frame: Baseline and Weeks 4, 8, 12, 20 and 26
Population: mFAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | CDAI Score by Week | Baseline | 135.05 Score on a scale | Standard Deviation 69.83 |
| Placebo | CDAI Score by Week | Week 4 | 168.24 Score on a scale | Standard Deviation 103.18 |
| Placebo | CDAI Score by Week | Week 8 | 171.87 Score on a scale | Standard Deviation 109.18 |
| Placebo | CDAI Score by Week | Week 12 | 181.38 Score on a scale | Standard Deviation 108.68 |
| Placebo | CDAI Score by Week | Week 20 | 161.76 Score on a scale | Standard Deviation 91.65 |
| Placebo | CDAI Score by Week | Week 26 | 137.05 Score on a scale | Standard Deviation 77.65 |
| Tofacitinib 5 mg BID | CDAI Score by Week | Week 26 | 134.77 Score on a scale | Standard Deviation 80.22 |
| Tofacitinib 5 mg BID | CDAI Score by Week | Baseline | 127.23 Score on a scale | Standard Deviation 60.46 |
| Tofacitinib 5 mg BID | CDAI Score by Week | Week 12 | 158.56 Score on a scale | Standard Deviation 119.41 |
| Tofacitinib 5 mg BID | CDAI Score by Week | Week 20 | 151.74 Score on a scale | Standard Deviation 106.09 |
| Tofacitinib 5 mg BID | CDAI Score by Week | Week 4 | 133.48 Score on a scale | Standard Deviation 89.94 |
| Tofacitinib 5 mg BID | CDAI Score by Week | Week 8 | 149.78 Score on a scale | Standard Deviation 99.56 |
| Tofacitinib 10 mg BID | CDAI Score by Week | Week 4 | 143.45 Score on a scale | Standard Deviation 84.26 |
| Tofacitinib 10 mg BID | CDAI Score by Week | Week 8 | 165.69 Score on a scale | Standard Deviation 95.46 |
| Tofacitinib 10 mg BID | CDAI Score by Week | Week 26 | 110.77 Score on a scale | Standard Deviation 76.3 |
| Tofacitinib 10 mg BID | CDAI Score by Week | Week 12 | 152.93 Score on a scale | Standard Deviation 82.77 |
| Tofacitinib 10 mg BID | CDAI Score by Week | Baseline | 133.98 Score on a scale | Standard Deviation 63.31 |
| Tofacitinib 10 mg BID | CDAI Score by Week | Week 20 | 112.32 Score on a scale | Standard Deviation 85.47 |
Secondary
Change From Baseline in CDAI Score by Week
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 wellbeing, 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
Time frame: Weeks 4, 8, 12, 20 and 26
Population: mFAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in CDAI Score by Week | Week 8 | 39.85 Score on a scale | Standard Deviation 83.68 |
| Placebo | Change From Baseline in CDAI Score by Week | Week 12 | 52.81 Score on a scale | Standard Deviation 113.91 |
| Placebo | Change From Baseline in CDAI Score by Week | Week 4 | 33.17 Score on a scale | Standard Deviation 76.41 |
| Placebo | Change From Baseline in CDAI Score by Week | Week 20 | 32.44 Score on a scale | Standard Deviation 96.18 |
| Placebo | Change From Baseline in CDAI Score by Week | Week 26 | 1.50 Score on a scale | Standard Deviation 93.91 |
| Tofacitinib 5 mg BID | Change From Baseline in CDAI Score by Week | Week 4 | 5.85 Score on a scale | Standard Deviation 69.52 |
| Tofacitinib 5 mg BID | Change From Baseline in CDAI Score by Week | Week 8 | 20.32 Score on a scale | Standard Deviation 69.59 |
| Tofacitinib 5 mg BID | Change From Baseline in CDAI Score by Week | Week 20 | 36.83 Score on a scale | Standard Deviation 90.92 |
| Tofacitinib 5 mg BID | Change From Baseline in CDAI Score by Week | Week 12 | 32.29 Score on a scale | Standard Deviation 88.35 |
| Tofacitinib 5 mg BID | Change From Baseline in CDAI Score by Week | Week 26 | 17.36 Score on a scale | Standard Deviation 79.81 |
| Tofacitinib 10 mg BID | Change From Baseline in CDAI Score by Week | Week 12 | 24.07 Score on a scale | Standard Deviation 84.46 |
| Tofacitinib 10 mg BID | Change From Baseline in CDAI Score by Week | Week 4 | 11.02 Score on a scale | Standard Deviation 72.22 |
| Tofacitinib 10 mg BID | Change From Baseline in CDAI Score by Week | Week 26 | -16.35 Score on a scale | Standard Deviation 75.65 |
| Tofacitinib 10 mg BID | Change From Baseline in CDAI Score by Week | Week 8 | 101.96 Score on a scale | Standard Deviation 101.96 |
| Tofacitinib 10 mg BID | Change From Baseline in CDAI Score by Week | Week 20 | -14.36 Score on a scale | Standard Deviation 78.58 |
Comparison: Week 4p-value: =0.063780% CI: [-51.1, -9.42]Linear mixed-effects model
Comparison: Week 8p-value: =0.305480% CI: [-47.43, 5.31]Linear mixed-effects model
Comparison: Week 12p-value: =0.131680% CI: [-78.57, -6.48]Linear mixed-effects model
Comparison: Week 20p-value: =0.570480% CI: [-59.01, 22.99]Linear mixed-effects model
Comparison: Week 26p-value: =0.838980% CI: [-44.22, 32.21]Linear mixed-effects model
Comparison: Week 4p-value: =0.145280% CI: [-44.27, -2.85]Linear mixed-effects model
Comparison: Week 8p-value: =0.639980% CI: [-36.03, 16.81]Linear mixed-effects model
Comparison: Week 12p-value: =0.194980% CI: [-73.57, -0.42]Linear mixed-effects model
Comparison: Week 20p-value: =0.135880% CI: [-88.62, -6.87]Linear mixed-effects model
Comparison: Week 26p-value: =0.08980% CI: [-88.03, -12.72]Linear mixed-effects model
Secondary
Change From Baseline in CRP by Week
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.
Time frame: Weeks 4, 8, 12, 20 and 26
Population: mFAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in CRP by Week | Week 20 | 11.48 milligram per liter (mg/L) | Standard Deviation 19.25 |
| Placebo | Change From Baseline in CRP by Week | Week 12 | 11.78 milligram per liter (mg/L) | Standard Deviation 17.85 |
| Placebo | Change From Baseline in CRP by Week | Week 4 | 10.66 milligram per liter (mg/L) | Standard Deviation 19.47 |
| Placebo | Change From Baseline in CRP by Week | Week 8 | 10.33 milligram per liter (mg/L) | Standard Deviation 24.33 |
| Placebo | Change From Baseline in CRP by Week | Week 26 | 24.07 milligram per liter (mg/L) | Standard Deviation 40.9 |
| Tofacitinib 5 mg BID | Change From Baseline in CRP by Week | Week 12 | 2.36 milligram per liter (mg/L) | Standard Deviation 12.15 |
| Tofacitinib 5 mg BID | Change From Baseline in CRP by Week | Week 4 | 0.84 milligram per liter (mg/L) | Standard Deviation 12.52 |
| Tofacitinib 5 mg BID | Change From Baseline in CRP by Week | Week 8 | 0.96 milligram per liter (mg/L) | Standard Deviation 9.8 |
| Tofacitinib 5 mg BID | Change From Baseline in CRP by Week | Week 20 | 2.92 milligram per liter (mg/L) | Standard Deviation 14.86 |
| Tofacitinib 5 mg BID | Change From Baseline in CRP by Week | Week 26 | 6.62 milligram per liter (mg/L) | Standard Deviation 13.07 |
| Tofacitinib 10 mg BID | Change From Baseline in CRP by Week | Week 26 | 0.59 milligram per liter (mg/L) | Standard Deviation 3.75 |
| Tofacitinib 10 mg BID | Change From Baseline in CRP by Week | Week 20 | 0.91 milligram per liter (mg/L) | Standard Deviation 6.75 |
| Tofacitinib 10 mg BID | Change From Baseline in CRP by Week | Week 4 | -0.97 milligram per liter (mg/L) | Standard Deviation 10.81 |
| Tofacitinib 10 mg BID | Change From Baseline in CRP by Week | Week 12 | 0.39 milligram per liter (mg/L) | Standard Deviation 3.66 |
| Tofacitinib 10 mg BID | Change From Baseline in CRP by Week | Week 8 | 1.29 milligram per liter (mg/L) | Standard Deviation 7.24 |
Comparison: Week 4p-value: <0.000195% CI: [-1.34, -0.53]Linear mixed-effects model
Comparison: Week 8p-value: =0.002495% CI: [-1.24, -0.28]Linear mixed-effects model
Comparison: Week 12p-value: =0.004495% CI: [-1.26, -0.24]Linear mixed-effects model
Comparison: Week 20p-value: =0.058295% CI: [-1.13, 0.02]Linear mixed-effects model
Comparison: Week 26p-value: =0.086595% CI: [-1.31, 0.09]Linear mixed-effects model
Comparison: Week 4p-value: <0.000195% CI: [-1.32, -0.52]Linear mixed-effects model
Comparison: Week 8p-value: =0.000295% CI: [-1.4, -0.45]Linear mixed-effects model
Comparison: Week 12p-value: <0.000195% CI: [-1.75, -0.71]Linear mixed-effects model
Comparison: Week 20p-value: <0.000195% CI: [-1.87, -0.74]Linear mixed-effects model
Comparison: Week 26p-value: <0.000195% CI: [-2.3, -0.95]Linear mixed-effects model
Secondary
Change From Baseline in Fecal Calprotectin by Week
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.
Time frame: Weeks 8, 12 and 26
Population: mFAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Fecal Calprotectin by Week | Week 12 | 103.55 milligrams per kilogram (mg/kg) | Standard Deviation 311.15 |
| Placebo | Change From Baseline in Fecal Calprotectin by Week | Week 8 | 69.22 milligrams per kilogram (mg/kg) | Standard Deviation 384.35 |
| Placebo | Change From Baseline in Fecal Calprotectin by Week | Week 26 | 579.10 milligrams per kilogram (mg/kg) | Standard Deviation 870.77 |
| Tofacitinib 5 mg BID | Change From Baseline in Fecal Calprotectin by Week | Week 12 | -1.81 milligrams per kilogram (mg/kg) | Standard Deviation 228.24 |
| Tofacitinib 5 mg BID | Change From Baseline in Fecal Calprotectin by Week | Week 8 | -59.73 milligrams per kilogram (mg/kg) | Standard Deviation 216.36 |
| Tofacitinib 5 mg BID | Change From Baseline in Fecal Calprotectin by Week | Week 26 | 154.17 milligrams per kilogram (mg/kg) | Standard Deviation 349.49 |
| Tofacitinib 10 mg BID | Change From Baseline in Fecal Calprotectin by Week | Week 8 | -123.95 milligrams per kilogram (mg/kg) | Standard Deviation 336.67 |
| Tofacitinib 10 mg BID | Change From Baseline in Fecal Calprotectin by Week | Week 26 | -33.75 milligrams per kilogram (mg/kg) | Standard Deviation 204.25 |
| Tofacitinib 10 mg BID | Change From Baseline in Fecal Calprotectin by Week | Week 12 | -107.04 milligrams per kilogram (mg/kg) | Standard Deviation 259.68 |
Comparison: Week 8p-value: =0.056695% CI: [-0.79, 0.01]Linear mixed-effects model
Comparison: Week 12p-value: =0.314495% CI: [-0.61, 0.2]Linear mixed-effects model
Comparison: Week 26p-value: =0.043495% CI: [-1.1, -0.02]Linear mixed-effects model
Comparison: Week 8p-value: =0.00595% CI: [-0.96, -0.18]Linear mixed-effects model
Comparison: Week 12p-value: =0.001795% CI: [-1.06, -0.25]Linear mixed-effects model
Comparison: Week 26p-value: <0.000195% CI: [-1.72, -0.67]Linear mixed-effects model
Secondary
C-Reactive Protein (CRP) by Week
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.
Time frame: Baseline and Weeks 4, 8, 12, 20 and 26
Population: mFAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | C-Reactive Protein (CRP) by Week | Baseline | 8.08 milligram per liter (mg/L) | Standard Deviation 13.88 |
| Placebo | C-Reactive Protein (CRP) by Week | Week 4 | 16.08 milligram per liter (mg/L) | Standard Deviation 24.62 |
| Placebo | C-Reactive Protein (CRP) by Week | Week 8 | 15.80 milligram per liter (mg/L) | Standard Deviation 28.98 |
| Placebo | C-Reactive Protein (CRP) by Week | Week 12 | 15.49 milligram per liter (mg/L) | Standard Deviation 17.8 |
| Placebo | C-Reactive Protein (CRP) by Week | Week 20 | 15.10 milligram per liter (mg/L) | Standard Deviation 20.37 |
| Placebo | C-Reactive Protein (CRP) by Week | Week 26 | 27.70 milligram per liter (mg/L) | Standard Deviation 41.76 |
| Tofacitinib 5 mg BID | C-Reactive Protein (CRP) by Week | Week 26 | 13.00 milligram per liter (mg/L) | Standard Deviation 13.65 |
| Tofacitinib 5 mg BID | C-Reactive Protein (CRP) by Week | Baseline | 7.08 milligram per liter (mg/L) | Standard Deviation 10.83 |
| Tofacitinib 5 mg BID | C-Reactive Protein (CRP) by Week | Week 12 | 8.19 milligram per liter (mg/L) | Standard Deviation 11.75 |
| Tofacitinib 5 mg BID | C-Reactive Protein (CRP) by Week | Week 20 | 10.07 milligram per liter (mg/L) | Standard Deviation 14.56 |
| Tofacitinib 5 mg BID | C-Reactive Protein (CRP) by Week | Week 4 | 8.04 milligram per liter (mg/L) | Standard Deviation 17.36 |
| Tofacitinib 5 mg BID | C-Reactive Protein (CRP) by Week | Week 8 | 8.03 milligram per liter (mg/L) | Standard Deviation 10.86 |
| Tofacitinib 10 mg BID | C-Reactive Protein (CRP) by Week | Week 4 | 7.62 milligram per liter (mg/L) | Standard Deviation 15.03 |
| Tofacitinib 10 mg BID | C-Reactive Protein (CRP) by Week | Week 8 | 7.24 milligram per liter (mg/L) | Standard Deviation 16.48 |
| Tofacitinib 10 mg BID | C-Reactive Protein (CRP) by Week | Week 26 | 3.57 milligram per liter (mg/L) | Standard Deviation 3.55 |
| Tofacitinib 10 mg BID | C-Reactive Protein (CRP) by Week | Week 12 | 5.57 milligram per liter (mg/L) | Standard Deviation 13.52 |
| Tofacitinib 10 mg BID | C-Reactive Protein (CRP) by Week | Baseline | 8.59 milligram per liter (mg/L) | Standard Deviation 16.43 |
| Tofacitinib 10 mg BID | C-Reactive Protein (CRP) by Week | Week 20 | 6.52 milligram per liter (mg/L) | Standard Deviation 18.26 |
Secondary
Fecal Calprotectin by Week
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.
Time frame: Baseline and Weeks 8, 12 and 26
Population: mFAS
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Fecal Calprotectin by Week | Week 12 | 441.40 milligrams per kilogram (mg/kg) | Standard Deviation 336.51 |
| Placebo | Fecal Calprotectin by Week | Week 26 | 939.11 milligrams per kilogram (mg/kg) | Standard Deviation 1037.39 |
| Placebo | Fecal Calprotectin by Week | Week 8 | 440.81 milligrams per kilogram (mg/kg) | Standard Deviation 350.71 |
| Placebo | Fecal Calprotectin by Week | Baseline | 380.43 milligrams per kilogram (mg/kg) | Standard Deviation 296.24 |
| Tofacitinib 5 mg BID | Fecal Calprotectin by Week | Baseline | 351.39 milligrams per kilogram (mg/kg) | Standard Deviation 290.67 |
| Tofacitinib 5 mg BID | Fecal Calprotectin by Week | Week 8 | 295.39 milligrams per kilogram (mg/kg) | Standard Deviation 272.25 |
| Tofacitinib 5 mg BID | Fecal Calprotectin by Week | Week 26 | 500.18 milligrams per kilogram (mg/kg) | Standard Deviation 337.83 |
| Tofacitinib 5 mg BID | Fecal Calprotectin by Week | Week 12 | 351.59 milligrams per kilogram (mg/kg) | Standard Deviation 303.08 |
| Tofacitinib 10 mg BID | Fecal Calprotectin by Week | Week 26 | 243.76 milligrams per kilogram (mg/kg) | Standard Deviation 219.04 |
| Tofacitinib 10 mg BID | Fecal Calprotectin by Week | Baseline | 399.33 milligrams per kilogram (mg/kg) | Standard Deviation 346.98 |
| Tofacitinib 10 mg BID | Fecal Calprotectin by Week | Week 8 | 283.76 milligrams per kilogram (mg/kg) | Standard Deviation 304.43 |
| Tofacitinib 10 mg BID | Fecal Calprotectin by Week | Week 12 | 194.00 milligrams per kilogram (mg/kg) | Standard Deviation 208.5 |
Secondary
Kaplan-Meier Estimate of the Rate of Time to Relapse
Time to relapse was defined as increase in CDAI of more than (\>)100 points from the maintenance phase baseline and a CDAI score of \>220 points, or an increase to or above the baseline CDAI score in A3921083. 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 wellbeing, 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.
Time frame: Weeks 4, 8 12, 20 and 26
Population: mFAS, n=number of participants remaining at risk
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Kaplan-Meier Estimate of the Rate of Time to Relapse | Week 20 (n=19,22,23) | 51.85 Percent Probability |
| Placebo | Kaplan-Meier Estimate of the Rate of Time to Relapse | Week 26 (n=1,1,2) | 69.59 Percent Probability |
| Placebo | Kaplan-Meier Estimate of the Rate of Time to Relapse | Week 4 (n=35,38,38) | 14.58 Percent Probability |
| Placebo | Kaplan-Meier Estimate of the Rate of Time to Relapse | Week 12 (n=24,30,27) | 39.18 Percent Probability |
| Placebo | Kaplan-Meier Estimate of the Rate of Time to Relapse | Week 8 (n=32,35,32) | 21.90 Percent Probability |
| Tofacitinib 5 mg BID | Kaplan-Meier Estimate of the Rate of Time to Relapse | Week 20 (n=19,22,23) | 39.11 Percent Probability |
| Tofacitinib 5 mg BID | Kaplan-Meier Estimate of the Rate of Time to Relapse | Week 8 (n=32,35,32) | 14.47 Percent Probability |
| Tofacitinib 5 mg BID | Kaplan-Meier Estimate of the Rate of Time to Relapse | Week 12 (n=24,30,27) | 26.69 Percent Probability |
| Tofacitinib 5 mg BID | Kaplan-Meier Estimate of the Rate of Time to Relapse | Week 26 (n=1,1,2) | 50.69 Percent Probability |
| Tofacitinib 5 mg BID | Kaplan-Meier Estimate of the Rate of Time to Relapse | Week 4 (n=35,38,38) | 7.14 Percent Probability |
| Tofacitinib 10 mg BID | Kaplan-Meier Estimate of the Rate of Time to Relapse | Week 26 (n=1,1,2) | 43.31 Percent Probability |
| Tofacitinib 10 mg BID | Kaplan-Meier Estimate of the Rate of Time to Relapse | Week 4 (n=35,38,38) | 11.63 Percent Probability |
| Tofacitinib 10 mg BID | Kaplan-Meier Estimate of the Rate of Time to Relapse | Week 12 (n=24,30,27) | 31.09 Percent Probability |
| Tofacitinib 10 mg BID | Kaplan-Meier Estimate of the Rate of Time to Relapse | Week 8 (n=32,35,32) | 23.51 Percent Probability |
| Tofacitinib 10 mg BID | Kaplan-Meier Estimate of the Rate of Time to Relapse | Week 20 (n=19,22,23) | 38.95 Percent Probability |
Comparison: Week 480% CI: [-16.14, 1.26]
Comparison: Week 880% CI: [-18.27, 3.41]
Comparison: Week 1280% CI: [-25.68, 0.72]
Comparison: Week 2080% CI: [-26.81, 1.34]
Comparison: Week 2680% CI: [-39.52, 1.72]
Comparison: Week 480% CI: [-12.39, 6.48]
Comparison: Week 880% CI: [-10.14, 13.36]
Comparison: Week 1280% CI: [-21.54, 5.36]
Comparison: Week 2080% CI: [-26.99, 1.19]
Comparison: Week 2680% CI: [-46.54, -6.02]
Secondary
Percentage of Participants Achieving a Steroid-Free Clinical Remission at Week 26 of the Maintenance Phase - Among Participants on Steroids at A3921084 Baseline
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 wellbeing, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body eight. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity.
Time frame: Week 26
Population: mFAS who were on steroids at A3921084 Baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Achieving a Steroid-Free Clinical Remission at Week 26 of the Maintenance Phase - Among Participants on Steroids at A3921084 Baseline | 16.67 Percentage of participants |
| Tofacitinib 5 mg BID | Percentage of Participants Achieving a Steroid-Free Clinical Remission at Week 26 of the Maintenance Phase - Among Participants on Steroids at A3921084 Baseline | 27.27 Percentage of participants |
| Tofacitinib 10 mg BID | Percentage of Participants Achieving a Steroid-Free Clinical Remission at Week 26 of the Maintenance Phase - Among Participants on Steroids at A3921084 Baseline | 33.33 Percentage of participants |
80% CI: [-11.44, 32.66]
80% CI: [-4.15, 37.49]
Secondary
Percentage of Participants Achieving Clinical Response-100 at Weeks 4, 8, 12, 20 and 26
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 extraintestinal symptoms, need for anti-diarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity.
Time frame: Weeks 4, 8, 12, 20 and 26
Population: mFAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants Achieving Clinical Response-100 at Weeks 4, 8, 12, 20 and 26 | Week 20 | 38.10 Percentage of participants |
| Placebo | Percentage of Participants Achieving Clinical Response-100 at Weeks 4, 8, 12, 20 and 26 | Week 12 | 50.00 Percentage of participants |
| Placebo | Percentage of Participants Achieving Clinical Response-100 at Weeks 4, 8, 12, 20 and 26 | Week 4 | 73.81 Percentage of participants |
| Placebo | Percentage of Participants Achieving Clinical Response-100 at Weeks 4, 8, 12, 20 and 26 | Week 8 | 66.67 Percentage of participants |
| Placebo | Percentage of Participants Achieving Clinical Response-100 at Weeks 4, 8, 12, 20 and 26 | Week 26 | 35.71 Percentage of participants |
| Tofacitinib 5 mg BID | Percentage of Participants Achieving Clinical Response-100 at Weeks 4, 8, 12, 20 and 26 | Week 12 | 55.81 Percentage of participants |
| Tofacitinib 5 mg BID | Percentage of Participants Achieving Clinical Response-100 at Weeks 4, 8, 12, 20 and 26 | Week 4 | 72.09 Percentage of participants |
| Tofacitinib 5 mg BID | Percentage of Participants Achieving Clinical Response-100 at Weeks 4, 8, 12, 20 and 26 | Week 8 | 62.79 Percentage of participants |
| Tofacitinib 5 mg BID | Percentage of Participants Achieving Clinical Response-100 at Weeks 4, 8, 12, 20 and 26 | Week 20 | 39.53 Percentage of participants |
| Tofacitinib 5 mg BID | Percentage of Participants Achieving Clinical Response-100 at Weeks 4, 8, 12, 20 and 26 | Week 26 | 37.21 Percentage of participants |
| Tofacitinib 10 mg BID | Percentage of Participants Achieving Clinical Response-100 at Weeks 4, 8, 12, 20 and 26 | Week 26 | 55.81 Percentage of participants |
| Tofacitinib 10 mg BID | Percentage of Participants Achieving Clinical Response-100 at Weeks 4, 8, 12, 20 and 26 | Week 20 | 51.16 Percentage of participants |
| Tofacitinib 10 mg BID | Percentage of Participants Achieving Clinical Response-100 at Weeks 4, 8, 12, 20 and 26 | Week 4 | 76.74 Percentage of participants |
| Tofacitinib 10 mg BID | Percentage of Participants Achieving Clinical Response-100 at Weeks 4, 8, 12, 20 and 26 | Week 12 | 51.16 Percentage of participants |
| Tofacitinib 10 mg BID | Percentage of Participants Achieving Clinical Response-100 at Weeks 4, 8, 12, 20 and 26 | Week 8 | 58.14 Percentage of participants |
Comparison: Week 480% CI: [-14.06, 10.63]
Comparison: Week 880% CI: [-17.15, 9.4]
Comparison: Week 1280% CI: [-8.04, 19.67]
Comparison: Week 2080% CI: [-12.11, 14.99]
Comparison: Week 2680% CI: [-11.88, 14.87]
Comparison: Week 480% CI: [-9.06, 14.92]
Comparison: Week 880% CI: [-21.94, 4.88]
Comparison: Week 1280% CI: [-12.74, 15.06]
Comparison: Week 2080% CI: [-0.63, 26.77]
Comparison: Week 2680% CI: [6.54, 33.66]
Secondary
Percentage of Participants in Clinical Remission at Week 4, 8, 12, 20 and 26 Among Participants in Remission at Baseline of Maintenance Study
Clinical remission was a CDAI score \<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 extraintestinal symptoms, need for anti-diarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity.
Time frame: Weeks 4, 8, 12, 20 and 26
Population: mFAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants in Clinical Remission at Week 4, 8, 12, 20 and 26 Among Participants in Remission at Baseline of Maintenance Study | Week 4 | 72.00 Percentage of participants |
| Placebo | Percentage of Participants in Clinical Remission at Week 4, 8, 12, 20 and 26 Among Participants in Remission at Baseline of Maintenance Study | Week 8 | 64.00 Percentage of participants |
| Placebo | Percentage of Participants in Clinical Remission at Week 4, 8, 12, 20 and 26 Among Participants in Remission at Baseline of Maintenance Study | Week 12 | 40.00 Percentage of participants |
| Placebo | Percentage of Participants in Clinical Remission at Week 4, 8, 12, 20 and 26 Among Participants in Remission at Baseline of Maintenance Study | Week 20 | 36.00 Percentage of participants |
| Placebo | Percentage of Participants in Clinical Remission at Week 4, 8, 12, 20 and 26 Among Participants in Remission at Baseline of Maintenance Study | Week 26 | 28.00 Percentage of participants |
| Tofacitinib 5 mg BID | Percentage of Participants in Clinical Remission at Week 4, 8, 12, 20 and 26 Among Participants in Remission at Baseline of Maintenance Study | Week 8 | 64.29 Percentage of participants |
| Tofacitinib 5 mg BID | Percentage of Participants in Clinical Remission at Week 4, 8, 12, 20 and 26 Among Participants in Remission at Baseline of Maintenance Study | Week 26 | 39.29 Percentage of participants |
| Tofacitinib 5 mg BID | Percentage of Participants in Clinical Remission at Week 4, 8, 12, 20 and 26 Among Participants in Remission at Baseline of Maintenance Study | Week 12 | 64.29 Percentage of participants |
| Tofacitinib 5 mg BID | Percentage of Participants in Clinical Remission at Week 4, 8, 12, 20 and 26 Among Participants in Remission at Baseline of Maintenance Study | Week 20 | 42.86 Percentage of participants |
| Tofacitinib 5 mg BID | Percentage of Participants in Clinical Remission at Week 4, 8, 12, 20 and 26 Among Participants in Remission at Baseline of Maintenance Study | Week 4 | 78.57 Percentage of participants |
| Tofacitinib 10 mg BID | Percentage of Participants in Clinical Remission at Week 4, 8, 12, 20 and 26 Among Participants in Remission at Baseline of Maintenance Study | Week 20 | 46.15 Percentage of participants |
| Tofacitinib 10 mg BID | Percentage of Participants in Clinical Remission at Week 4, 8, 12, 20 and 26 Among Participants in Remission at Baseline of Maintenance Study | Week 8 | 50.00 Percentage of participants |
| Tofacitinib 10 mg BID | Percentage of Participants in Clinical Remission at Week 4, 8, 12, 20 and 26 Among Participants in Remission at Baseline of Maintenance Study | Week 4 | 80.77 Percentage of participants |
| Tofacitinib 10 mg BID | Percentage of Participants in Clinical Remission at Week 4, 8, 12, 20 and 26 Among Participants in Remission at Baseline of Maintenance Study | Week 12 | 42.31 Percentage of participants |
| Tofacitinib 10 mg BID | Percentage of Participants in Clinical Remission at Week 4, 8, 12, 20 and 26 Among Participants in Remission at Baseline of Maintenance Study | Week 26 | 50.00 Percentage of participants |
Comparison: Week 480% CI: [-8.63, 21.78]
Comparison: Week 880% CI: [-16.63, 17.2]
Comparison: Week 1280% CI: [7.19, 41.38]
Comparison: Week 2080% CI: [-10.32, 24.03]
Comparison: Week 2680% CI: [-5.22, 27.79]
Comparison: Week 480% CI: [-6.41, 23.95]
Comparison: Week 880% CI: [-31.59, 3.59]
Comparison: Week 1280% CI: [-15.35, 19.97]
Comparison: Week 2080% CI: [-7.41, 27.71]
Comparison: Week 2680% CI: [4.96, 39.04]
Secondary
Percentage of Participants in Clinical Remission at Weeks 4, 8, 12, 20 and 26
Clinical remission was a CDAI score \<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 extraintestinal symptoms, need for anti-diarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity.
Time frame: Weeks 4, 8, 12, 20 and 26
Population: mFAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants in Clinical Remission at Weeks 4, 8, 12, 20 and 26 | Week 20 | 30.95 Percentage of participants |
| Placebo | Percentage of Participants in Clinical Remission at Weeks 4, 8, 12, 20 and 26 | Week 12 | 33.33 Percentage of participants |
| Placebo | Percentage of Participants in Clinical Remission at Weeks 4, 8, 12, 20 and 26 | Week 4 | 52.38 Percentage of participants |
| Placebo | Percentage of Participants in Clinical Remission at Weeks 4, 8, 12, 20 and 26 | Week 8 | 47.62 Percentage of participants |
| Placebo | Percentage of Participants in Clinical Remission at Weeks 4, 8, 12, 20 and 26 | Week 26 | 28.57 Percentage of participants |
| Tofacitinib 5 mg BID | Percentage of Participants in Clinical Remission at Weeks 4, 8, 12, 20 and 26 | Week 12 | 46.51 Percentage of participants |
| Tofacitinib 5 mg BID | Percentage of Participants in Clinical Remission at Weeks 4, 8, 12, 20 and 26 | Week 4 | 55.81 Percentage of participants |
| Tofacitinib 5 mg BID | Percentage of Participants in Clinical Remission at Weeks 4, 8, 12, 20 and 26 | Week 8 | 48.84 Percentage of participants |
| Tofacitinib 5 mg BID | Percentage of Participants in Clinical Remission at Weeks 4, 8, 12, 20 and 26 | Week 20 | 32.56 Percentage of participants |
| Tofacitinib 5 mg BID | Percentage of Participants in Clinical Remission at Weeks 4, 8, 12, 20 and 26 | Week 26 | 37.21 Percentage of participants |
| Tofacitinib 10 mg BID | Percentage of Participants in Clinical Remission at Weeks 4, 8, 12, 20 and 26 | Week 26 | 41.86 Percentage of participants |
| Tofacitinib 10 mg BID | Percentage of Participants in Clinical Remission at Weeks 4, 8, 12, 20 and 26 | Week 20 | 39.53 Percentage of participants |
| Tofacitinib 10 mg BID | Percentage of Participants in Clinical Remission at Weeks 4, 8, 12, 20 and 26 | Week 4 | 58.14 Percentage of participants |
| Tofacitinib 10 mg BID | Percentage of Participants in Clinical Remission at Weeks 4, 8, 12, 20 and 26 | Week 12 | 34.88 Percentage of participants |
| Tofacitinib 10 mg BID | Percentage of Participants in Clinical Remission at Weeks 4, 8, 12, 20 and 26 | Week 8 | 39.53 Percentage of participants |
Comparison: Week 480% CI: [-10.41, 17.28]
Comparison: Week 880% CI: [-12.67, 15.11]
Comparison: Week 1280% CI: [-0.31, 26.67]
Comparison: Week 2080% CI: [-11.33, 14.55]
Comparison: Week 2680% CI: [-4.36, 21.64]
Comparison: Week 480% CI: [-8.04, 19.56]
Comparison: Week 880% CI: [-21.83, 5.66]
Comparison: Week 1280% CI: [-11.63, 14.73]
Comparison: Week 2080% CI: [-4.64, 21.81]
Comparison: Week 2680% CI: [0.15, 26.43]
Secondary
Percentage of Participants in Sustained Clinical Remission (Defined as Being in Clinical Remission at Both Weeks 20 and 26) in the Maintenance Phase
Clinical remission was a CDAI score \<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 extraintestinal symptoms, need for anti-diarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity.
Time frame: Weeks 20 and 26
Population: mFAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants in Sustained Clinical Remission (Defined as Being in Clinical Remission at Both Weeks 20 and 26) in the Maintenance Phase | 21.43 Percentage of participants |
| Tofacitinib 5 mg BID | Percentage of Participants in Sustained Clinical Remission (Defined as Being in Clinical Remission at Both Weeks 20 and 26) in the Maintenance Phase | 23.26 Percentage of participants |
| Tofacitinib 10 mg BID | Percentage of Participants in Sustained Clinical Remission (Defined as Being in Clinical Remission at Both Weeks 20 and 26) in the Maintenance Phase | 39.53 Percentage of participants |
80% CI: [-9.75, 13.4]
80% CI: [5.57, 30.64]
Secondary
Percentage of Participants With Clinical Response-100 or Clinical Remission at Weeks 4, 8, 12 and 20
Clinical response-100 was defined as a reduction in CDAI score of at least 100 points from baseline of the parent A3921083 study. Clinical remission was a CDAI score \<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 extraintestinal symptoms, need for anti-diarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to approximately 600 points, higher score indicates higher disease activity.
Time frame: Weeks 4, 8, 12 and 20
Population: mFAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Clinical Response-100 or Clinical Remission at Weeks 4, 8, 12 and 20 | Week 4 | 73.81 Percentage of participants |
| Placebo | Percentage of Participants With Clinical Response-100 or Clinical Remission at Weeks 4, 8, 12 and 20 | Week 8 | 66.67 Percentage of participants |
| Placebo | Percentage of Participants With Clinical Response-100 or Clinical Remission at Weeks 4, 8, 12 and 20 | Week 20 | 40.48 Percentage of participants |
| Placebo | Percentage of Participants With Clinical Response-100 or Clinical Remission at Weeks 4, 8, 12 and 20 | Week 12 | 50.00 Percentage of participants |
| Tofacitinib 5 mg BID | Percentage of Participants With Clinical Response-100 or Clinical Remission at Weeks 4, 8, 12 and 20 | Week 8 | 67.44 Percentage of participants |
| Tofacitinib 5 mg BID | Percentage of Participants With Clinical Response-100 or Clinical Remission at Weeks 4, 8, 12 and 20 | Week 12 | 55.81 Percentage of participants |
| Tofacitinib 5 mg BID | Percentage of Participants With Clinical Response-100 or Clinical Remission at Weeks 4, 8, 12 and 20 | Week 4 | 74.42 Percentage of participants |
| Tofacitinib 5 mg BID | Percentage of Participants With Clinical Response-100 or Clinical Remission at Weeks 4, 8, 12 and 20 | Week 20 | 39.53 Percentage of participants |
| Tofacitinib 10 mg BID | Percentage of Participants With Clinical Response-100 or Clinical Remission at Weeks 4, 8, 12 and 20 | Week 20 | 51.16 Percentage of participants |
| Tofacitinib 10 mg BID | Percentage of Participants With Clinical Response-100 or Clinical Remission at Weeks 4, 8, 12 and 20 | Week 8 | 58.14 Percentage of participants |
| Tofacitinib 10 mg BID | Percentage of Participants With Clinical Response-100 or Clinical Remission at Weeks 4, 8, 12 and 20 | Week 4 | 79.07 Percentage of participants |
| Tofacitinib 10 mg BID | Percentage of Participants With Clinical Response-100 or Clinical Remission at Weeks 4, 8, 12 and 20 | Week 12 | 53.49 Percentage of participants |
Comparison: Week 480% CI: [-11.57, 12.79]
Comparison: Week 880% CI: [-12.29, 13.84]
Comparison: Week 1280% CI: [-8.04, 19.67]
Comparison: Week 2080% CI: [-14.56, 12.68]
Comparison: Week 480% CI: [-6.52, 17.04]
Comparison: Week 880% CI: [-21.94, 4.88]
Comparison: Week 1280% CI: [-10.4, 17.37]
Comparison: Week 2080% CI: [-3.08, 24.46]
Secondary
Percentage of Participants With Sustained Clinical Response-100 (Defined as Having at Least a Clinical Response-100 at Both Weeks 20 and 26 From the A3921083 Baseline) in the Maintenance Phase
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.
Time frame: Weeks 20 and 26
Population: mFAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Sustained Clinical Response-100 (Defined as Having at Least a Clinical Response-100 at Both Weeks 20 and 26 From the A3921083 Baseline) in the Maintenance Phase | 33.33 Percentage of participants |
| Tofacitinib 5 mg BID | Percentage of Participants With Sustained Clinical Response-100 (Defined as Having at Least a Clinical Response-100 at Both Weeks 20 and 26 From the A3921083 Baseline) in the Maintenance Phase | 25.58 Percentage of participants |
| Tofacitinib 10 mg BID | Percentage of Participants With Sustained Clinical Response-100 (Defined as Having at Least a Clinical Response-100 at Both Weeks 20 and 26 From the A3921083 Baseline) in the Maintenance Phase | 51.16 Percentage of participants |
80% CI: [-20.39, 4.88]
80% CI: [4.33, 31.33]
Secondary
Tofacitinib Plasma Concentration by Nominal Post-Dose Sampling Time and Tofacitinib Dose
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.
Time frame: Pre-dose, 20 minutes, 40 minutes, 1 hour and 2 hours post-dose at Weeks 12 and 26/early termination visit
Population: Pharmacokinetic analysis set - included all participants who received at least 1 dose of study medication and had at least 1 measurable plasma concentration. n=number of observations above lower limit of quantification.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Tofacitinib Plasma Concentration by Nominal Post-Dose Sampling Time and Tofacitinib Dose | Week 26/ET, 20 minutes (n=45, 48) | 40.98 nanograms per milliliter (ng/mL) | Standard Deviation 31.713 |
| Placebo | Tofacitinib Plasma Concentration by Nominal Post-Dose Sampling Time and Tofacitinib Dose | Week 12, 0 hours (n=43, 40) | 6.059 nanograms per milliliter (ng/mL) | Standard Deviation 7.4264 |
| Placebo | Tofacitinib Plasma Concentration by Nominal Post-Dose Sampling Time and Tofacitinib Dose | Week 12, 20 minutes (n=45, 40) | 31.56 nanograms per milliliter (ng/mL) | Standard Deviation 21.904 |
| Placebo | Tofacitinib Plasma Concentration by Nominal Post-Dose Sampling Time and Tofacitinib Dose | Week 12, 40 minutes (n=47, 41) | 47.05 nanograms per milliliter (ng/mL) | Standard Deviation 23.904 |
| Placebo | Tofacitinib Plasma Concentration by Nominal Post-Dose Sampling Time and Tofacitinib Dose | Week 12, 1 hour (n=46, 42) | 46.84 nanograms per milliliter (ng/mL) | Standard Deviation 20.365 |
| Placebo | Tofacitinib Plasma Concentration by Nominal Post-Dose Sampling Time and Tofacitinib Dose | Week 12, 2 hour (n=44, 42) | 36.52 nanograms per milliliter (ng/mL) | Standard Deviation 14.81 |
| Placebo | Tofacitinib Plasma Concentration by Nominal Post-Dose Sampling Time and Tofacitinib Dose | Week 26/ET, 0 hours (n=43, 46) | 6.183 nanograms per milliliter (ng/mL) | Standard Deviation 13.673 |
| Placebo | Tofacitinib Plasma Concentration by Nominal Post-Dose Sampling Time and Tofacitinib Dose | Week 26/ET, 40 minutes (n=46, 48) | 55.83 nanograms per milliliter (ng/mL) | Standard Deviation 44.421 |
| Placebo | Tofacitinib Plasma Concentration by Nominal Post-Dose Sampling Time and Tofacitinib Dose | Week 26/ET, 1 hour (n=45, 48) | 52.59 nanograms per milliliter (ng/mL) | Standard Deviation 42.291 |
| Placebo | Tofacitinib Plasma Concentration by Nominal Post-Dose Sampling Time and Tofacitinib Dose | Week 26/ET, 2 hours (n=44, 48) | 39.09 nanograms per milliliter (ng/mL) | Standard Deviation 22.606 |
| Tofacitinib 5 mg BID | Tofacitinib Plasma Concentration by Nominal Post-Dose Sampling Time and Tofacitinib Dose | Week 26/ET, 40 minutes (n=46, 48) | 85.66 nanograms per milliliter (ng/mL) | Standard Deviation 37.983 |
| Tofacitinib 5 mg BID | Tofacitinib Plasma Concentration by Nominal Post-Dose Sampling Time and Tofacitinib Dose | Week 26/ET, 20 minutes (n=45, 48) | 60.48 nanograms per milliliter (ng/mL) | Standard Deviation 51.084 |
| Tofacitinib 5 mg BID | Tofacitinib Plasma Concentration by Nominal Post-Dose Sampling Time and Tofacitinib Dose | Week 12, 2 hour (n=44, 42) | 69.79 nanograms per milliliter (ng/mL) | Standard Deviation 23.274 |
| Tofacitinib 5 mg BID | Tofacitinib Plasma Concentration by Nominal Post-Dose Sampling Time and Tofacitinib Dose | Week 12, 0 hours (n=43, 40) | 6.832 nanograms per milliliter (ng/mL) | Standard Deviation 5.7271 |
| Tofacitinib 5 mg BID | Tofacitinib Plasma Concentration by Nominal Post-Dose Sampling Time and Tofacitinib Dose | Week 26/ET, 2 hours (n=44, 48) | 64.15 nanograms per milliliter (ng/mL) | Standard Deviation 23.499 |
| Tofacitinib 5 mg BID | Tofacitinib Plasma Concentration by Nominal Post-Dose Sampling Time and Tofacitinib Dose | Week 12, 20 minutes (n=45, 40) | 58.53 nanograms per milliliter (ng/mL) | Standard Deviation 53.579 |
| Tofacitinib 5 mg BID | Tofacitinib Plasma Concentration by Nominal Post-Dose Sampling Time and Tofacitinib Dose | Week 26/ET, 0 hours (n=43, 46) | 9.510 nanograms per milliliter (ng/mL) | Standard Deviation 17.115 |
| Tofacitinib 5 mg BID | Tofacitinib Plasma Concentration by Nominal Post-Dose Sampling Time and Tofacitinib Dose | Week 12, 40 minutes (n=47, 41) | 85.23 nanograms per milliliter (ng/mL) | Standard Deviation 43.726 |
| Tofacitinib 5 mg BID | Tofacitinib Plasma Concentration by Nominal Post-Dose Sampling Time and Tofacitinib Dose | Week 26/ET, 1 hour (n=45, 48) | 86.25 nanograms per milliliter (ng/mL) | Standard Deviation 30.948 |
| Tofacitinib 5 mg BID | Tofacitinib Plasma Concentration by Nominal Post-Dose Sampling Time and Tofacitinib Dose | Week 12, 1 hour (n=46, 42) | 82.08 nanograms per milliliter (ng/mL) | Standard Deviation 33.779 |