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Study to Evaluate the Safety and Efficacy of Two Adalimumab Dosing Regimens in Subjects With Moderate to Severe Ulcerative Colitis

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ClinicalTrials.gov Identifier: NCT02065622
Recruitment Status : Completed
First Posted : February 19, 2014
Results First Posted : October 8, 2020
Last Update Posted : November 23, 2020
Sponsor:
Information provided by (Responsible Party):
AbbVie

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Ulcerative Colitis (UC)
Interventions Drug: Adalimumab
Other: Placebo
Enrollment 952
Recruitment Details

This study included a Main Study (120 sites in 19 countries) and a Japan Sub-Study (22 sites in Japan).

After a 3-week screening period, participants were randomized 3:2 to an 8-week double-blind (DB) Induction Period with 2 adalimumab dosing regimens (Induction Standard Dose [I-SD] or Induction Higher Dose [I-HD]).

Pre-assignment Details At Week 8, participants in Main Study were re-randomized (2:2:1) into 44-week DB Maintenance Period with 3 adalimumab dosing regimens (M-SD, M-HD, or an exploratory Therapeutic Drug Monitoring [TDM] Regimen). Participants in Japan Sub-study were re-randomized (1:1) into 44-week DB Maintenance Period with 2 adalimumab dosing regimens (M-SD, M-HD).
Arm/Group Title Induction (Main Study + Japan Sub-study): I-SD Induction (Main Study + Japan Sub-study): I-HD Maintenance (Main Study + Japan Sub-study): M-SD Maintenance (Main Study + Japan Sub-study): M-HD Maintenance (Main Study): TDM Regimen
Hide Arm/Group Description Induction Standard Dose (I-SD): Double-blind adalimumab regimen of 160 mg at Week 0 followed by 80 mg at Week 2, 40 mg at Week 4, and 40 mg at Week 6. Induction Higher Dose (I-HD): Double-blind adalimumab regimen of 160 mg at Weeks 0, 1, 2, and 3 followed by 40 mg at Week 4 and 40 mg at Week 6. Maintenance Standard Dose (M-SD): Double-blind adalimumab 40 mg every other week (eow), for 44 weeks. Maintenance Higher Dose (M-HD): Double-blind adalimumab 40 mg every week (ew) for 44 weeks. Exploratory Therapeutic Drug Monitoring (TDM) Regimen: Double-blind adalimumab 40 mg eow at Week 8 and Week 10, with possible dose adjustments at Weeks 12, 24, and 37 based on criteria assessing blinded adalimumab serum concentration and rectal bleeding subscore assessments.
Period Title: Induction Study
Started 379 573 0 0 0
Enrolled in Main Study 340 512 0 0 0
Enrolled in Japan Sub-Study 39 61 0 0 0
Completed 332 514 0 0 0
Not Completed 47 59 0 0 0
Reason Not Completed
Adverse Event             13             19             0             0             0
Withdrawal by Subject             3             5             0             0             0
Lost to Follow-up             1             0             0             0             0
Lack of Efficacy             22             27             0             0             0
Requires Alternative/Prohibited Therapy             4             5             0             0             0
Subject Noncompliance             1             1             0             0             0
Other, Not Specified             3             2             0             0             0
Period Title: Maintenance Study
Started 0 0 345 350 151
Completed 0 0 221 246 105
Not Completed 0 0 124 104 46
Reason Not Completed
Adverse Event             0             0             25             22             11
Withdrawal by Subject             0             0             11             5             7
Lost to Follow-up             0             0             4             1             1
Lack of Efficacy             0             0             70             55             19
Requires Alternative/Prohibited Therapy             0             0             7             3             4
Subject Non-Compliance             0             0             1             3             2
Other, Not Specified             0             0             6             14             2
Unknown Reason             0             0             0             1             0
Arm/Group Title Induction (Main Study + Japan Sub-study): I-SD Induction (Main Study + Japan Sub-study): I-HD Total
Hide Arm/Group Description Induction Standard Dose: Double-blind adalimumab regimen of 160 mg at Week 0 followed by 80 mg at Week 2, 40 mg at Week 4, and 40 mg at Week 6. Induction Higher Dose: Double-blind adalimumab regimen of 160 mg at Weeks 0, 1, 2, and 3 followed by 40 mg at Week 4 and 40 mg at Week 6. Total of all reporting groups
Overall Number of Baseline Participants 379 573 952
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 379 participants 573 participants 952 participants
40.2  (13.14) 40.5  (12.89) 40.4  (12.98)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 379 participants 573 participants 952 participants
Female
166
  43.8%
239
  41.7%
405
  42.5%
Male
213
  56.2%
334
  58.3%
547
  57.5%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
White Number Analyzed 379 participants 573 participants 952 participants
326
  86.0%
484
  84.5%
810
  85.1%
Black or African American Number Analyzed 379 participants 573 participants 952 participants
8
   2.1%
16
   2.8%
24
   2.5%
Asian Number Analyzed 379 participants 573 participants 952 participants
44
  11.6%
70
  12.2%
114
  12.0%
Native Hawaiian/Other Pacific Islander Number Analyzed 379 participants 573 participants 952 participants
0
   0.0%
1
   0.2%
1
   0.1%
Multiracial Number Analyzed 379 participants 573 participants 952 participants
1
   0.3%
1
   0.2%
2
   0.2%
Missing Number Analyzed 379 participants 573 participants 952 participants
0
   0.0%
1
   0.2%
1
   0.1%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Hispanic or Latino Number Analyzed 379 participants 573 participants 952 participants
19
   5.0%
28
   4.9%
47
   4.9%
Japanese Number Analyzed 379 participants 573 participants 952 participants
39
  10.3%
61
  10.6%
100
  10.5%
Other, Not Specified Number Analyzed 379 participants 573 participants 952 participants
321
  84.7%
484
  84.5%
805
  84.6%
Region  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 379 participants 573 participants 952 participants
65
  17.2%
113
  19.7%
178
  18.7%
Non-United States Number Analyzed 379 participants 573 participants 952 participants
314
  82.8%
460
  80.3%
774
  81.3%
Full Mayo Score (FMS)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 379 participants 570 participants 949 participants
8.69  (1.509) 8.87  (1.571) 8.80  (1.548)
[1]
Measure Description: The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy, and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease).
[2]
Measure Analysis Population Description: participants with an assessment
FMS: Rectal Bleeding Subscore   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 379 participants 570 participants 949 participants
1.68  (0.955) 1.75  (0.967) 1.72  (0.962)
[1]
Measure Description: The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy, and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease).
[2]
Measure Analysis Population Description: participants with an assessment
1.Primary Outcome
Title Induction Period Primary Endpoint: Percentage of Participants With Clinical Remission Per Full Mayo Score (FMS) at Week 8
Hide Description The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy [confirmed by a central reader], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Clinical remission per FMS is defined as Mayo Score ≤ 2 and no individual subscore > 1.
Time Frame Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
Induction Study Intent-to-Treat (ITT) set: all participants who were randomized at Baseline. Non-responder imputation.
Arm/Group Title Induction (Main Study): I-SD Induction (Main Study): I-HD Induction (Main Study + Japan Sub-study): I-SD Induction (Main Study + Japan Sub-study): I-HD
Hide Arm/Group Description:
Induction Standard Dose: Double-blind adalimumab regimen of 160 mg at Week 0 followed by 80 mg at Week 2, 40 mg at Week 4, and 40 mg at Week 6.
Induction Higher Dose: Double-blind adalimumab regimen of 160 mg at Weeks 0, 1, 2, and 3 followed by 40 mg at Week 4 and 40 mg at Week 6.
Induction Standard Dose: Double-blind adalimumab regimen of 160 mg at Week 0 followed by 80 mg at Week 2, 40 mg at Week 4, and 40 mg at Week 6.
Induction Higher Dose: Double-blind adalimumab regimen of 160 mg at Weeks 0, 1, 2, and 3 followed by 40 mg at Week 4 and 40 mg at Week 6.
Overall Number of Participants Analyzed 340 512 379 573
Measure Type: Number
Unit of Measure: percentage of participants
10.9 13.3 11.6 13.8
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Induction (Main Study): I-SD, Induction (Main Study): I-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel test adjusted for previous infliximab use and baseline corticosteroid use.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.269
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 2.5
Confidence Interval (2-Sided) 95%
-2.0 to 7.0
Estimation Comments Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Induction (Main Study): I-SD, Induction (Main Study): I-HD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.447
Comments [Not Specified]
Method Breslow-Day test
Comments Breslow-Day test of homogeneity across strata.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Induction (Main Study + Japan Sub-study): I-SD, Induction (Main Study + Japan Sub-study): I-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel test adjusted for previous infliximab use and baseline corticosteroid use.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.301
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 2.3
Confidence Interval (2-Sided) 95%
-2.0 to 6.6
Estimation Comments Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Induction (Main Study + Japan Sub-study): I-SD, Induction (Main Study + Japan Sub-study): I-HD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.502
Comments [Not Specified]
Method Breslow-Day test
Comments Breslow-Day test of homogeneity across strata.
2.Primary Outcome
Title Maintenance Period Primary Endpoint: Percentage of Week 8 Responders (Per FMS) With Clinical Remission (Per FMS) at Week 52
Hide Description The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy [confirmed by a central reader], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 responders (per FMS) are defined as participants with a decrease in Full Mayo score of ≥ 3 points and ≥ 30% from Baseline plus a decrease from baseline in the rectal bleeding subscore (RBS) ≥ 1 or an absolute RBS ≤ 1. Clinical remission per FMS is defined as Mayo Score ≤ 2 and no individual subscore > 1.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-Responder population (I-ITT-RP): all participants in the Induction ITT population who achieve Week 8 response based on the FMS utilizing the endoscopy subscore provided by the central reader. Non-responder imputation. Per protocol, the TDM Regimen arm was used to analyze exploratory outcome measures only (and therefore is not included).
Arm/Group Title Maintenance (Main Study): M-SD Maintenance (Main Study): M-HD Maintenance (Main Study + Japan Sub-study): M-SD Maintenance (Main Study + Japan Sub-study): M-HD
Hide Arm/Group Description:
Maintenance Standard Dose: Double-blind adalimumab 40 mg every other week (eow), for 44 weeks.
Maintenance Higher Dose: Double-blind adalimumab 40 mg every week (ew) for 44 weeks.
Maintenance Standard Dose: Double-blind adalimumab 40 mg every other week (eow), for 44 weeks.
Maintenance Higher Dose: Double-blind adalimumab 40 mg every week (ew) for 44 weeks.
Overall Number of Participants Analyzed 145 152 163 175
Measure Type: Number
Unit of Measure: percentage of participants
29.0 39.5 30.1 41.1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maintenance (Main Study): M-SD, Maintenance (Main Study): M-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.069
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 9.9
Confidence Interval (2-Sided) 95%
-0.8 to 20.6
Estimation Comments Risk difference = Adalimumab 40mg EW - Adalimumab 40mg EOW.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maintenance (Main Study): M-SD, Maintenance (Main Study): M-HD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.085
Comments [Not Specified]
Method Breslow-Day test
Comments Breslow-Day test of homogeneity across strata.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Maintenance (Main Study + Japan Sub-study): M-SD, Maintenance (Main Study + Japan Sub-study): M-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.045
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 10.3
Confidence Interval (2-Sided) 95%
0.2 to 20.4
Estimation Comments Risk difference = Adalimumab 40mg EW - Adalimumab 40mg EOW.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Maintenance (Main Study + Japan Sub-study): M-SD, Maintenance (Main Study + Japan Sub-study): M-HD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.106
Comments [Not Specified]
Method Breslow-Day test
Comments Breslow-Day test of homogeneity across strata.
3.Secondary Outcome
Title Induction Period Ranked Secondary Endpoint 1: Percentage of Participants With Endoscopic Improvement at Week 8
Hide Description The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy [confirmed by a central reader], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Endoscopic improvement is defined as an endoscopy subscore of 0 or 1.
Time Frame Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
Induction Study Intent-to-Treat (ITT) set: all participants who were randomized at Baseline. Non-responder imputation.
Arm/Group Title Induction (Main Study): I-SD Induction (Main Study): I-HD Induction (Main Study + Japan Sub-study): I-SD Induction (Main Study + Japan Sub-study): I-HD
Hide Arm/Group Description:
Induction Standard Dose: Double-blind adalimumab regimen of 160 mg at Week 0 followed by 80 mg at Week 2, 40 mg at Week 4, and 40 mg at Week 6.
Induction Higher Dose: Double-blind adalimumab regimen of 160 mg at Weeks 0, 1, 2, and 3 followed by 40 mg at Week 4 and 40 mg at Week 6.
Induction Standard Dose: Double-blind adalimumab regimen of 160 mg at Week 0 followed by 80 mg at Week 2, 40 mg at Week 4, and 40 mg at Week 6.
Induction Higher Dose: Double-blind adalimumab regimen of 160 mg at Weeks 0, 1, 2, and 3 followed by 40 mg at Week 4 and 40 mg at Week 6.
Overall Number of Participants Analyzed 340 512 379 573
Measure Type: Number
Unit of Measure: percentage of participants
27.1 31.1 26.9 30.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Induction (Main Study): I-SD, Induction (Main Study): I-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel test adjusted for previous infliximab use and baseline corticosteroid use.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.181
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 4.2
Confidence Interval (2-Sided) 95%
-2.0 to 10.5
Estimation Comments Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Induction (Main Study + Japan Sub-study): I-SD, Induction (Main Study + Japan Sub-study): I-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel test adjusted for previous infliximab use and baseline corticosteroid use.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.200
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 3.8
Confidence Interval (2-Sided) 95%
-2.0 to 9.7
Estimation Comments Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).
4.Secondary Outcome
Title Induction Period Ranked Secondary Endpoint 2: Percentage of Participants With Fecal Calprotectin < 150 mg/kg at Week 8
Hide Description [Not Specified]
Time Frame Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
Induction Study Intent-to-Treat (ITT) set: all participants who were randomized at Baseline. Non-responder imputation.
Arm/Group Title Induction (Main Study): I-SD Induction (Main Study): I-HD Induction (Main Study + Japan Sub-study): I-SD Induction (Main Study + Japan Sub-study): I-HD
Hide Arm/Group Description:
Induction Standard Dose: Double-blind adalimumab regimen of 160 mg at Week 0 followed by 80 mg at Week 2, 40 mg at Week 4, and 40 mg at Week 6.
Induction Higher Dose: Double-blind adalimumab regimen of 160 mg at Weeks 0, 1, 2, and 3 followed by 40 mg at Week 4 and 40 mg at Week 6.
Induction Standard Dose: Double-blind adalimumab regimen of 160 mg at Week 0 followed by 80 mg at Week 2, 40 mg at Week 4, and 40 mg at Week 6.
Induction Higher Dose: Double-blind adalimumab regimen of 160 mg at Weeks 0, 1, 2, and 3 followed by 40 mg at Week 4 and 40 mg at Week 6.
Overall Number of Participants Analyzed 340 512 379 573
Measure Type: Number
Unit of Measure: percentage of participants
27.1 31.1 26.9 30.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Induction (Main Study): I-SD, Induction (Main Study): I-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel test adjusted for previous infliximab use and baseline corticosteroid use.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.300
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 3.0
Confidence Interval (2-Sided) 95%
-2.6 to 8.6
Estimation Comments Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Induction (Main Study + Japan Sub-study): I-SD, Induction (Main Study + Japan Sub-study): I-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel test adjusted for previous infliximab use and baseline corticosteroid use.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.254
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 3.1
Confidence Interval (2-Sided) 95%
-2.2 to 8.4
Estimation Comments Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).
5.Secondary Outcome
Title Induction Period Ranked Secondary Endpoint 3: Percentage of Participants With Inflammatory Bowel Disease Questionnaire (IBDQ) Response (Increase of IBDQ ≥ 16 From Baseline) at Week 8
Hide Description The IBDQ is a self-administered 32-item questionnaire to evaluate quality of life across 4 dimensional scores: bowel, systemic, social and emotional. Responses to each question range from 1 (severe problem) to 7 (normal health). Total IBDQ score is the sum of the responses to the individual IBDQ questions, and ranges from 32 to 224 with higher scores indicating a better quality of life.
Time Frame Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
Induction Study Intent-to-Treat (ITT) set: all participants who were randomized at Baseline. Non-responder imputation.
Arm/Group Title Induction (Main Study): I-SD Induction (Main Study): I-HD Induction (Main Study + Japan Sub-study): I-SD Induction (Main Study + Japan Sub-study): I-HD
Hide Arm/Group Description:
Induction Standard Dose: Double-blind adalimumab regimen of 160 mg at Week 0 followed by 80 mg at Week 2, 40 mg at Week 4, and 40 mg at Week 6.
Induction Higher Dose: Double-blind adalimumab regimen of 160 mg at Weeks 0, 1, 2, and 3 followed by 40 mg at Week 4 and 40 mg at Week 6.
Induction Standard Dose: Double-blind adalimumab regimen of 160 mg at Week 0 followed by 80 mg at Week 2, 40 mg at Week 4, and 40 mg at Week 6.
Induction Higher Dose: Double-blind adalimumab regimen of 160 mg at Weeks 0, 1, 2, and 3 followed by 40 mg at Week 4 and 40 mg at Week 6.
Overall Number of Participants Analyzed 340 512 379 573
Measure Type: Number
Unit of Measure: percentage of participants
60.9 67.2 60.7 65.3
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Induction (Main Study): I-SD, Induction (Main Study): I-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel test adjusted for previous infliximab use and baseline corticosteroid use.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.050
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 6.5
Confidence Interval (2-Sided) 95%
-0.0 to 13.1
Estimation Comments Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Induction (Main Study + Japan Sub-study): I-SD, Induction (Main Study + Japan Sub-study): I-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel test adjusted for previous infliximab use and baseline corticosteroid use.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.131
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 4.8
Confidence Interval (2-Sided) 95%
-1.4 to 11.0
Estimation Comments Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).
6.Secondary Outcome
Title Induction Period Ranked Secondary Endpoint 4: Percentage of Participants With Clinical Response Per FMS at Week 8
Hide Description The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy [confirmed by a central reader], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Clinical response is defined as a decrease in FMS of ≥ 3 points and ≥ 30% from baseline, plus a decrease in the rectal bleeding subscore (RBS) ≥ 1 or an absolute RBS ≤ 1.
Time Frame Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
Induction Study Intent-to-Treat (ITT) set: all participants who were randomized at Baseline. Non-responder imputation.
Arm/Group Title Induction (Main Study): I-SD Induction (Main Study): I-HD Induction (Main Study + Japan Sub-study): I-SD Induction (Main Study + Japan Sub-study): I-HD
Hide Arm/Group Description:
Induction Standard Dose: Double-blind adalimumab regimen of 160 mg at Week 0 followed by 80 mg at Week 2, 40 mg at Week 4, and 40 mg at Week 6.
Induction Higher Dose: Double-blind adalimumab regimen of 160 mg at Weeks 0, 1, 2, and 3 followed by 40 mg at Week 4 and 40 mg at Week 6.
Induction Standard Dose: Double-blind adalimumab regimen of 160 mg at Week 0 followed by 80 mg at Week 2, 40 mg at Week 4, and 40 mg at Week 6.
Induction Higher Dose: Double-blind adalimumab regimen of 160 mg at Weeks 0, 1, 2, and 3 followed by 40 mg at Week 4 and 40 mg at Week 6.
Overall Number of Participants Analyzed 340 512 379 573
Measure Type: Number
Unit of Measure: percentage of participants
40.0 47.1 38.8 47.3
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Induction (Main Study): I-SD, Induction (Main Study): I-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel test adjusted for previous infliximab use and baseline corticosteroid use.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.035
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 7.3
Confidence Interval (2-Sided) 95%
0.5 to 14.1
Estimation Comments Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Induction (Main Study + Japan Sub-study): I-SD, Induction (Main Study + Japan Sub-study): I-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel test adjusted for previous infliximab use and baseline corticosteroid use.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 8.7
Confidence Interval (2-Sided) 95%
2.3 to 15.1
Estimation Comments Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).
7.Secondary Outcome
Title Induction Period Ranked Secondary Endpoint 5: Percentage of Participants With Endoscopic Remission at Week 8
Hide Description The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy [confirmed by a central reader], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Endoscopic remission is defined as an endoscopy subscore of 0.
Time Frame Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
Induction Study Intent-to-Treat (ITT) set: all participants who were randomized at Baseline. Non-responder imputation.
Arm/Group Title Induction (Main Study): I-SD Induction (Main Study): I-HD Induction (Main Study + Japan Sub-study): I-SD Induction (Main Study + Japan Sub-study): I-HD
Hide Arm/Group Description:
Induction Standard Dose: Double-blind adalimumab regimen of 160 mg at Week 0 followed by 80 mg at Week 2, 40 mg at Week 4, and 40 mg at Week 6.
Induction Higher Dose: Double-blind adalimumab regimen of 160 mg at Weeks 0, 1, 2, and 3 followed by 40 mg at Week 4 and 40 mg at Week 6.
Induction Standard Dose: Double-blind adalimumab regimen of 160 mg at Week 0 followed by 80 mg at Week 2, 40 mg at Week 4, and 40 mg at Week 6.
Induction Higher Dose: Double-blind adalimumab regimen of 160 mg at Weeks 0, 1, 2, and 3 followed by 40 mg at Week 4 and 40 mg at Week 6.
Overall Number of Participants Analyzed 340 512 379 573
Measure Type: Number
Unit of Measure: percentage of participants
10.0 13.1 10.0 12.9
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Induction (Main Study): I-SD, Induction (Main Study): I-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel test adjusted for previous infliximab use and baseline corticosteroid use.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.160
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 3.2
Confidence Interval (2-Sided) 95%
-1.3 to 7.6
Estimation Comments Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Induction (Main Study + Japan Sub-study): I-SD, Induction (Main Study + Japan Sub-study): I-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel test adjusted for previous infliximab use and baseline corticosteroid use.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.166
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 2.9
Confidence Interval (2-Sided) 95%
-1.2 to 7.1
Estimation Comments Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).
8.Secondary Outcome
Title Induction Period Ranked Secondary Endpoint 6: Percentage of Participants Achieving Response in IBDQ Bowel Symptom Domain at Week 8
Hide Description The IBDQ is a self-administered 32-item questionnaire to evaluate quality of life across 4 dimensional scores: bowel, systemic, social and emotional. Responses to each question range from 1 (severe problem) to 7 (normal health). The range for Bowel Symptom domain score is 10 (severe problem) to 70 (normal health). Response in IBDQ Bowel Symptom domain is defined as an increase of IBDQ Bowel Symptom domain score ≥ 6.
Time Frame Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
Induction Study Intent-to-Treat (ITT) set: all participants who were randomized at Baseline. Non-responder imputation.
Arm/Group Title Induction (Main Study): I-SD Induction (Main Study): I-HD Induction (Main Study + Japan Sub-study): I-SD Induction (Main Study + Japan Sub-study): I-HD
Hide Arm/Group Description:
Induction Standard Dose: Double-blind adalimumab regimen of 160 mg at Week 0 followed by 80 mg at Week 2, 40 mg at Week 4, and 40 mg at Week 6.
Induction Higher Dose: Double-blind adalimumab regimen of 160 mg at Weeks 0, 1, 2, and 3 followed by 40 mg at Week 4 and 40 mg at Week 6.
Induction Standard Dose: Double-blind adalimumab regimen of 160 mg at Week 0 followed by 80 mg at Week 2, 40 mg at Week 4, and 40 mg at Week 6.
Induction Higher Dose: Double-blind adalimumab regimen of 160 mg at Weeks 0, 1, 2, and 3 followed by 40 mg at Week 4 and 40 mg at Week 6.
Overall Number of Participants Analyzed 340 512 379 573
Measure Type: Number
Unit of Measure: percentage of participants
63.2 71.3 63.1 69.8
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Induction (Main Study): I-SD, Induction (Main Study): I-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel test adjusted for previous infliximab use and baseline corticosteroid use.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.011
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 8.3
Confidence Interval (2-Sided) 95%
1.9 to 14.7
Estimation Comments Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Induction (Main Study + Japan Sub-study): I-SD, Induction (Main Study + Japan Sub-study): I-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel test adjusted for previous infliximab use and baseline corticosteroid use.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.025
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 7.0
Confidence Interval (2-Sided) 95%
0.9 to 13.0
Estimation Comments Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).
9.Secondary Outcome
Title Induction Period Ranked Secondary Endpoint 7: Percentage of Participants Achieving Response in IBDQ Fatigue Item at Week 8
Hide Description The IBDQ is a self-administered 32-item questionnaire to evaluate quality of life across 4 dimensional scores: bowel, systemic, social and emotional. Responses to each question range from 1 (severe problem) to 7 (normal health). The IBDQ Fatigue item score range is from 1 (severe problem) to 7 (normal health). Response is defined as an increase of IBDQ Fatigue item score ≥ 1.
Time Frame Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
Induction Study Intent-to-Treat (ITT) set: all participants who were randomized at Baseline. Non-responder imputation.
Arm/Group Title Induction (Main Study): I-SD Induction (Main Study): I-HD Induction (Main Study + Japan Sub-study): I-SD Induction (Main Study + Japan Sub-study): I-HD
Hide Arm/Group Description:
Induction Standard Dose: Double-blind adalimumab regimen of 160 mg at Week 0 followed by 80 mg at Week 2, 40 mg at Week 4, and 40 mg at Week 6.
Induction Higher Dose: Double-blind adalimumab regimen of 160 mg at Weeks 0, 1, 2, and 3 followed by 40 mg at Week 4 and 40 mg at Week 6.
Induction Standard Dose: Double-blind adalimumab regimen of 160 mg at Week 0 followed by 80 mg at Week 2, 40 mg at Week 4, and 40 mg at Week 6.
Induction Higher Dose: Double-blind adalimumab regimen of 160 mg at Weeks 0, 1, 2, and 3 followed by 40 mg at Week 4 and 40 mg at Week 6.
Overall Number of Participants Analyzed 340 512 379 573
Measure Type: Number
Unit of Measure: percentage of participants
57.1 61.1 57.5 59.9
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Induction (Main Study): I-SD, Induction (Main Study): I-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel test adjusted for previous infliximab use and baseline corticosteroid use.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.218
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 4.2
Confidence Interval (2-Sided) 95%
-2.5 to 10.9
Estimation Comments Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Induction (Main Study + Japan Sub-study): I-SD, Induction (Main Study + Japan Sub-study): I-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel test adjusted for previous infliximab use and baseline corticosteroid use.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.456
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 2.4
Confidence Interval (2-Sided) 95%
-4.0 to 8.8
Estimation Comments Risk difference = (adalimumab higher induction dose - adalimumab standard induction dose).
10.Secondary Outcome
Title Maintenance Period Ranked Secondary Endpoint 1: Percentage of Week 8 Responders (Per FMS) With Endoscopic Improvement at Week 52
Hide Description The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy [confirmed by a central reader], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 responders are defined as participants with a decrease in FMS of ≥ 3 points and ≥ 30% from Baseline plus a decrease in the rectal bleeding subscore (RBS) ≥ 1 or an absolute RBS ≤ 1. Endoscopic improvement is defined as an endoscopy subscore of 0 or 1.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-Responder population (I-ITT-RP): all participants in the Induction ITT population who achieve Week 8 response based on the FMS utilizing the endoscopy subscore provided by the central reader. Non-responder imputation. Per protocol, the TDM Regimen arm was used to analyze exploratory outcome measures only (and therefore is not included).
Arm/Group Title Maintenance (Main Study): M-SD Maintenance (Main Study): M-HD Maintenance (Main Study + Japan Sub-study): M-SD Maintenance (Main Study + Japan Sub-study): M-HD
Hide Arm/Group Description:
Maintenance Standard Dose: Double-blind adalimumab 40 mg every other week (eow), for 44 weeks.
Maintenance Higher Dose: Double-blind adalimumab 40 mg every week (ew) for 44 weeks.
Maintenance Standard Dose: Double-blind adalimumab 40 mg every other week (eow), for 44 weeks.
Maintenance Higher Dose: Double-blind adalimumab 40 mg every week (ew) for 44 weeks.
Overall Number of Participants Analyzed 145 152 163 175
Measure Type: Number
Unit of Measure: percentage of participants
41.4 51.3 41.7 52.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maintenance (Main Study): M-SD, Maintenance (Main Study): M-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.098
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 9.5
Confidence Interval (2-Sided) 95%
-1.7 to 20.8
Estimation Comments Risk difference = Adalimumab 40mg EW - Adalimumab 40mg EOW.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maintenance (Main Study + Japan Sub-study): M-SD, Maintenance (Main Study + Japan Sub-study): M-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.066
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 9.9
Confidence Interval (2-Sided) 95%
-0.7 to 20.5
Estimation Comments Risk difference = Adalimumab 40mg EW - Adalimumab 40mg EOW.
11.Secondary Outcome
Title Maintenance Period Ranked Secondary Endpoint 2: Percentage of Week 8 Responders With Steroid Usage at Baseline and Steroid Free at Least 90 Days at Week 52
Hide Description The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy [confirmed by a central reader], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 responders, per FMS, are defined as participants with a decrease in FMS of ≥ 3 points and ≥ 30% from Baseline plus a decrease in the rectal bleeding subscore (RBS) ≥ 1 or an absolute RBS ≤ 1.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
I-ITT-RP: participants in the Induction ITT population who achieve Week 8 response based on the FMS utilizing the endoscopy subscore provided by the central reader. Participants with steroid use at Baseline. Non-responder imputation. Per protocol, TDM Regimen arm was used to analyze exploratory outcome measures only (and therefore is not included).
Arm/Group Title Maintenance (Main Study): M-SD Maintenance (Main Study): M-HD Maintenance (Main Study + Japan Sub-study): M-SD Maintenance (Main Study + Japan Sub-study): M-HD
Hide Arm/Group Description:
Maintenance Standard Dose: Double-blind adalimumab 40 mg every other week (eow), for 44 weeks.
Maintenance Higher Dose: Double-blind adalimumab 40 mg every week (ew) for 44 weeks.
Maintenance Standard Dose: Double-blind adalimumab 40 mg every other week (eow), for 44 weeks.
Maintenance Higher Dose: Double-blind adalimumab 40 mg every week (ew) for 44 weeks.
Overall Number of Participants Analyzed 92 95 103 108
Measure Type: Number
Unit of Measure: percentage of participants
53.3 74.7 54.4 74.1
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maintenance (Main Study): M-SD, Maintenance (Main Study): M-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments Risk difference = Adalimumab 40mg EW - Adalimumab 40mg EOW.
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 21.5
Confidence Interval (2-Sided) 95%
7.6 to 35.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maintenance (Main Study + Japan Sub-study): M-SD, Maintenance (Main Study + Japan Sub-study): M-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 19.7
Confidence Interval (2-Sided) 95%
6.6 to 32.7
Estimation Comments Risk difference = Adalimumab 40mg EW - Adalimumab 40mg EOW.
12.Secondary Outcome
Title Maintenance Period Ranked Secondary Endpoint 3: Percentage of Week 8 Responders With Steroid Usage at Baseline and Steroid Free at Least 90 Days and With Clinical Remission at Week 52
Hide Description The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy [confirmed by a central reader], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 responders, per FMS, are defined as participants with a decrease in FMS of ≥ 3 points and ≥ 30% from Baseline plus a decrease in the rectal bleeding subscore (RBS) ≥ 1 or an absolute RBS ≤ 1. Clinical remission is defined as FMS ≤ 2 with no subscore > 1.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
I-ITT-RP: participants in the Induction ITT population who achieve Week 8 response based on the FMS utilizing the endoscopy subscore provided by the central reader. Participants with steroid use at Baseline. Non-responder imputation. Per protocol, TDM Regimen arm was used to analyze exploratory outcome measures only (and therefore is not included).
Arm/Group Title Maintenance (Main Study): M-SD Maintenance (Main Study): M-HD Maintenance (Main Study + Japan Sub-study): M-SD Maintenance (Main Study + Japan Sub-study): M-HD
Hide Arm/Group Description:
Maintenance Standard Dose: Double-blind adalimumab 40 mg every other week (eow), for 44 weeks.
Maintenance Higher Dose: Double-blind adalimumab 40 mg every week (ew) for 44 weeks.
Maintenance Standard Dose: Double-blind adalimumab 40 mg every other week (eow), for 44 weeks.
Maintenance Higher Dose: Double-blind adalimumab 40 mg every week (ew) for 44 weeks.
Overall Number of Participants Analyzed 92 95 103 108
Measure Type: Number
Unit of Measure: percentage of participants
27.2 38.9 28.2 39.8
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maintenance (Main Study): M-SD, Maintenance (Main Study): M-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.093
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 11.5
Confidence Interval (2-Sided) 95%
-1.9 to 25.0
Estimation Comments Risk difference = Adalimumab 40mg EW - Adalimumab 40mg EOW.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maintenance (Main Study + Japan Sub-study): M-SD, Maintenance (Main Study + Japan Sub-study): M-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.088
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 11.1
Confidence Interval (2-Sided) 95%
-1.7 to 23.8
Estimation Comments Risk difference = Adalimumab 40mg EW - Adalimumab 40mg EOW.
13.Secondary Outcome
Title Maintenance Period Ranked Secondary Endpoint 4: Percentage of Week 8 Remitters (Per FMS) With Clinical Remission (Per FMS) at Week 52
Hide Description The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy [confirmed by a central reader], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 remitters are defined as participants with clinical remission (per FMS) at Week 8. Clinical remission is defined as a FMS ≤ 2 with no subscore > 1. Endoscopy subscore provided by the central reader.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-Remitter (ITT-RM) Population included all participants in the ITT population who achieved Week 8 remission based on the FMS utilizing the endoscopy subscore provided by the central reader. Non-responder imputation. Per protocol, TDM Regimen arm was used to analyze exploratory outcome measures only (and therefore is not included).
Arm/Group Title Maintenance (Main Study): M-SD Maintenance (Main Study): M-HD Maintenance (Main Study + Japan Sub-study): M-SD Maintenance (Main Study + Japan Sub-study): M-HD
Hide Arm/Group Description:
Maintenance Standard Dose: Double-blind adalimumab 40 mg every other week (eow), for 44 weeks.
Maintenance Higher Dose: Double-blind adalimumab 40 mg every week (ew) for 44 weeks.
Maintenance Standard Dose: Double-blind adalimumab 40 mg every other week (eow), for 44 weeks.
Maintenance Higher Dose: Double-blind adalimumab 40 mg every week (ew) for 44 weeks.
Overall Number of Participants Analyzed 37 42 45 52
Measure Type: Number
Unit of Measure: percentage of participants
40.5 57.1 44.4 55.8
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maintenance (Main Study): M-SD, Maintenance (Main Study): M-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.161
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 15.9
Confidence Interval (2-Sided) 95%
-6.3 to 38.2
Estimation Comments Risk difference = Adalimumab 40mg EW - Adalimumab 40mg EOW.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maintenance (Main Study + Japan Sub-study): M-SD, Maintenance (Main Study + Japan Sub-study): M-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.312
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 10.4
Confidence Interval (2-Sided) 95%
-9.8 to 30.6
Estimation Comments Risk difference = Adalimumab 40mg EW - Adalimumab 40mg EOW.
14.Secondary Outcome
Title Maintenance Period Ranked Secondary Endpoint 5: Percentage of Week 8 Remitters (Per FMS) With Endoscopic Improvement at Week 52
Hide Description The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy [confirmed by a central reader], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 remitters are defined as participants with clinical remission (per FMS) at Week 8. Clinical remission is defined as a FMS ≤ 2 with no subscore > 1. Endoscopic improvement is defined as an endoscopy subscore of 0 or 1. Endoscopy subscore provided by the central reader.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-Remitter (ITT-RM) Population included all participants in the ITT population who achieved Week 8 remission based on the FMS utilizing the endoscopy subscore provided by the central reader. Non-responder imputation. Per protocol, TDM Regimen arm was used to analyze exploratory outcome measures only (and therefore is not included).
Arm/Group Title Maintenance (Main Study): M-SD Maintenance (Main Study): M-HD Maintenance (Main Study + Japan Sub-study): M-SD Maintenance (Main Study + Japan Sub-study): M-HD
Hide Arm/Group Description:
Maintenance Standard Dose: Double-blind adalimumab 40 mg every other week (eow), for 44 weeks.
Maintenance Higher Dose: Double-blind adalimumab 40 mg every week (ew) for 44 weeks.
Maintenance Standard Dose: Double-blind adalimumab 40 mg every other week (eow), for 44 weeks.
Maintenance Higher Dose: Double-blind adalimumab 40 mg every week (ew) for 44 weeks.
Overall Number of Participants Analyzed 37 42 45 52
Measure Type: Number
Unit of Measure: percentage of participants
51.4 64.3 55.6 61.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maintenance (Main Study): M-SD, Maintenance (Main Study): M-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.272
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 12.3
Confidence Interval (2-Sided) 95%
-9.7 to 34.4
Estimation Comments Risk difference = Adalimumab 40mg EW - Adalimumab 40mg EOW.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maintenance (Main Study + Japan Sub-study): M-SD, Maintenance (Main Study + Japan Sub-study): M-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.600
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 5.3
Confidence Interval (2-Sided) 95%
-14.6 to 25.2
Estimation Comments Risk difference = Adalimumab 40mg EW - Adalimumab 40mg EOW.
15.Secondary Outcome
Title Maintenance Period Ranked Secondary Endpoint 6: Percentage of Week 8 Remitters (Per FMS) With Steroid Usage at Baseline and Steroid Free at Least 90 Days at Week 52
Hide Description The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy [confirmed by a central reader], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 remitters are defined as participants with clinical remission (per FMS) at Week 8. Clinical remission is defined as a FMS ≤ 2 with no subscore > 1.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-RM Population: participants in ITT population who achieved Week 8 remission based on the FMS utilizing the endoscopy subscore provided by the central reader. Participants with steroid use at Baseline. Non-responder imputation. Per protocol, TDM Regimen arm was used to analyze exploratory outcome measures only (and therefore is not included).
Arm/Group Title Maintenance (Main Study): M-SD Maintenance (Main Study): M-HD Maintenance (Main Study + Japan Sub-study): M-SD Maintenance (Main Study + Japan Sub-study): M-HD
Hide Arm/Group Description:
Maintenance Standard Dose: Double-blind adalimumab 40 mg every other week (eow), for 44 weeks.
Maintenance Higher Dose: Double-blind adalimumab 40 mg every week (ew) for 44 weeks.
Maintenance Standard Dose: Double-blind adalimumab 40 mg every other week (eow), for 44 weeks.
Maintenance Higher Dose: Double-blind adalimumab 40 mg every week (ew) for 44 weeks.
Overall Number of Participants Analyzed 26 27 32 35
Measure Type: Number
Unit of Measure: percentage of participants
53.8 77.8 56.3 71.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maintenance (Main Study): M-SD, Maintenance (Main Study): M-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.074
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 23.8
Confidence Interval (2-Sided) 95%
-2.3 to 49.9
Estimation Comments Risk difference = Adalimumab 40mg EW - Adalimumab 40mg EOW.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maintenance (Main Study + Japan Sub-study): M-SD, Maintenance (Main Study + Japan Sub-study): M-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.210
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 15.0
Confidence Interval (2-Sided) 95%
-8.5 to 38.4
Estimation Comments Risk difference = Adalimumab 40mg EW - Adalimumab 40mg EOW.
16.Secondary Outcome
Title Maintenance Period Ranked Secondary Endpoint 7: Percentage of Week 8 Remitters (Per FMS) With Steroid Usage at Baseline and Steroid Free at Least 90 Days and With Clinical Remission (Per FMS) at Week 52
Hide Description The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy [confirmed by a central reader], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 remitters are defined as participants with clinical remission (per FMS) at Week 8. Clinical remission is defined as a FMS ≤ 2 with no subscore > 1.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-RM Population: all participants in the ITT population who achieved Week 8 remission based on the FMS utilizing the endoscopy subscore provided by the central reader. Participants with steroid usage. Non-responder imputation. Per protocol, the TDM Regimen arm was used to analyze exploratory outcome measures only (and therefore is not included).
Arm/Group Title Maintenance (Main Study): M-SD Maintenance (Main Study): M-HD Maintenance (Main Study + Japan Sub-study): M-SD Maintenance (Main Study + Japan Sub-study): M-HD
Hide Arm/Group Description:
Maintenance Standard Dose: Double-blind adalimumab 40 mg every other week (eow), for 44 weeks.
Maintenance Higher Dose: Double-blind adalimumab 40 mg every week (ew) for 44 weeks.
Maintenance Standard Dose: Double-blind adalimumab 40 mg every other week (eow), for 44 weeks.
Maintenance Higher Dose: Double-blind adalimumab 40 mg every week (ew) for 44 weeks.
Overall Number of Participants Analyzed 26 27 32 35
Measure Type: Number
Unit of Measure: percentage of participants
34.6 55.6 37.5 51.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maintenance (Main Study): M-SD, Maintenance (Main Study): M-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.151
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 20.0
Confidence Interval (2-Sided) 95%
-7.3 to 47.3
Estimation Comments Risk difference = Adalimumab 40mg EW - Adalimumab 40mg EOW.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maintenance (Main Study + Japan Sub-study): M-SD, Maintenance (Main Study + Japan Sub-study): M-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.299
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 12.8
Confidence Interval (2-Sided) 95%
-11.3 to 36.8
Estimation Comments Risk difference = Adalimumab 40mg EW - Adalimumab 40mg EOW.
17.Secondary Outcome
Title Maintenance Period Ranked Secondary Endpoint 8: Percentage of Week 8 Responders (Per FMS) With IBDQ Response (Increase of IBDQ ≥ 16 From Baseline) at Week 52
Hide Description The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy [confirmed by a central reader], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 responders are defined as participants with a decrease in FMS of ≥ 3 points and ≥ 30% from Baseline plus a decrease in the rectal bleeding subscore (RBS) ≥ 1 or an absolute RBS ≤ 1. The IBDQ is a self-administered 32-item questionnaire to evaluate quality of life across 4 dimensional scores: bowel, systemic, social and emotional. Responses to each question range from 1 (severe problem) to 7 (normal health). Total IBDQ score is the sum of responses to the individual IBDQ questions, and ranges from 32 to 224 with higher scores indicating a better quality of life.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-Responder population (ITT-RP): all participants in the Induction ITT population who achieve Week 8 response based on the FMS utilizing the endoscopy subscore provided by the central reader. Non-responder imputation. Per protocol, the TDM Regimen arm was used to analyze exploratory outcome measures only (and therefore is not included).
Arm/Group Title Maintenance (Main Study): M-SD Maintenance (Main Study): M-HD Maintenance (Main Study + Japan Sub-study): M-SD Maintenance (Main Study + Japan Sub-study): M-HD
Hide Arm/Group Description:
Maintenance Standard Dose: Double-blind adalimumab 40 mg every other week (eow), for 44 weeks.
Maintenance Higher Dose: Double-blind adalimumab 40 mg every week (ew) for 44 weeks.
Maintenance Standard Dose: Double-blind adalimumab 40 mg every other week (eow), for 44 weeks.
Maintenance Higher Dose: Double-blind adalimumab 40 mg every week (ew) for 44 weeks.
Overall Number of Participants Analyzed 145 152 163 175
Measure Type: Number
Unit of Measure: percentage of participants
62.1 66.4 62.6 65.7
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maintenance (Main Study): M-SD, Maintenance (Main Study): M-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.422
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 4.5
Confidence Interval (2-Sided) 95%
-6.4 to 15.3
Estimation Comments Risk difference = Adalimumab 40mg EW - Adalimumab 40mg EOW.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maintenance (Main Study + Japan Sub-study): M-SD, Maintenance (Main Study + Japan Sub-study): M-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.513
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 3.4
Confidence Interval (2-Sided) 95%
-6.8 to 13.6
Estimation Comments Risk difference = Adalimumab 40mg EW - Adalimumab 40mg EOW.
18.Secondary Outcome
Title Maintenance Period Ranked Secondary Endpoint 9: Percentage of Week 8 Non-Responders With Clinical Remission (Per FMS) at Week 52
Hide Description The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy [confirmed by a central reader], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 non-responders are defined as participants not meeting the criteria of response (defined as a decrease in FMS of ≥ 3 points and ≥ 30% from baseline, plus a decrease in the rectal bleeding subscore [RBS] ≥ 1 or an absolute RBS ≤ 1) at Week 8. Clinical remission is defined as a FMS ≤ 2 with no subscore > 1.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-Non-Responder (ITT-NRP) Population: all participants in ITT who did not achieve Week 8 response based on the Full Mayo Score utilizing the endoscopy subscore provided by the central reader. Non-responder imputation. Per protocol, TDM Regimen arm was used to analyze exploratory outcome measures only (and therefore is not included).
Arm/Group Title Maintenance (Main Study): M-SD Maintenance (Main Study): M-HD Maintenance (Main Study + Japan Sub-study): M-SD Maintenance (Main Study + Japan Sub-study): M-HD
Hide Arm/Group Description:
Maintenance Standard Dose: Double-blind adalimumab 40 mg every other week (eow), for 44 weeks.
Maintenance Higher Dose: Double-blind adalimumab 40 mg every week (ew) for 44 weeks.
Maintenance Standard Dose: Double-blind adalimumab 40 mg every other week (eow), for 44 weeks.
Maintenance Higher Dose: Double-blind adalimumab 40 mg every week (ew) for 44 weeks.
Overall Number of Participants Analyzed 157 152 182 175
Measure Type: Number
Unit of Measure: percentage of participants
12.1 15.8 12.1 16.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maintenance (Main Study): M-SD, Maintenance (Main Study): M-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.351
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 3.7
Confidence Interval (2-Sided) 95%
-4.1 to 11.4
Estimation Comments Risk difference = Adalimumab 40mg EW - Adalimumab 40mg EOW.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maintenance (Main Study + Japan Sub-study): M-SD, Maintenance (Main Study + Japan Sub-study): M-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.292
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 3.9
Confidence Interval (2-Sided) 95%
-3.3 to 11.1
Estimation Comments Risk difference = Adalimumab 40mg EW - Adalimumab 40mg EOW.
19.Secondary Outcome
Title Maintenance Period Ranked Secondary Endpoint 10: Percentage of Week 8 Non-Remitters With Clinical Remission (Per FMS) at Week 52
Hide Description The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy [confirmed by a central reader], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 non-remitters are defined as participants not meeting the criteria of clinical remission at Week 8. Clinical remission is defined as a FMS ≤ 2 with no subscore > 1.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-Non-Remitter (ITT-NRM) Population: all participants in ITT who did not achieve Week 8 remission based on the FMS utilizing the endoscopy subscore provided by the central reader. Non-responder imputation. Per protocol, TDM Regimen arm was used to analyze exploratory outcome measures only (and therefore is not included).
Arm/Group Title Maintenance (Main Study): M-SD Maintenance (Main Study): M-HD Maintenance (Main Study + Japan Sub-study): M-SD Maintenance (Main Study + Japan Sub-study): M-HD
Hide Arm/Group Description:
Maintenance Standard Dose: Double-blind adalimumab 40 mg every other week (eow), for 44 weeks.
Maintenance Higher Dose: Double-blind adalimumab 40 mg every week (ew) for 44 weeks.
Maintenance Standard Dose: Double-blind adalimumab 40 mg every other week (eow), for 44 weeks.
Maintenance Higher Dose: Double-blind adalimumab 40 mg every week (ew) for 44 weeks.
Overall Number of Participants Analyzed 265 262 300 298
Measure Type: Number
Unit of Measure: percentage of participants
17.4 22.9 17.0 23.8
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maintenance (Main Study): M-SD, Maintenance (Main Study): M-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.121
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 5.4
Confidence Interval (2-Sided) 95%
-1.4 to 12.1
Estimation Comments Risk difference = Adalimumab 40mg EW - Adalimumab 40mg EOW.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maintenance (Main Study + Japan Sub-study): M-SD, Maintenance (Main Study + Japan Sub-study): M-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.046
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 6.5
Confidence Interval (2-Sided) 95%
0.1 to 12.8
Estimation Comments Risk difference = Adalimumab 40mg EW - Adalimumab 40mg EOW.
20.Secondary Outcome
Title Maintenance Period Ranked Secondary Endpoint 11: Percentage of Week 8 Responders (Per FMS) With Endoscopic Subscore of 0 at Week 52
Hide Description The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy [confirmed by a central reader], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 responders (per Full Mayo score) are defined as participants with a decrease in Full Mayo score of ≥ 3 points and ≥ 30% from Baseline plus a decrease in the rectal bleeding subscore (RBS) ≥ 1 or an absolute RBS ≤ 1. Endoscopic remission is defined as an endoscopy subscore of 0.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-RP: participants in the Induction ITT population who achieve Week 8 response based on the FMS utilizing the endoscopy subscore provided by the central reader. Participants who were remitters at Week 8. Non-responder imputation. Per protocol, TDM Regimen arm was used to analyze exploratory outcome measures only (and therefore is not included).
Arm/Group Title Maintenance (Main Study): M-SD Maintenance (Main Study): M-HD Maintenance (Main Study + Japan Sub-study): M-SD Maintenance (Main Study + Japan Sub-study): M-HD
Hide Arm/Group Description:
Maintenance Standard Dose: Double-blind adalimumab 40 mg every other week (eow), for 44 weeks.
Maintenance Higher Dose: Double-blind adalimumab 40 mg every week (ew) for 44 weeks.
Maintenance Standard Dose: Double-blind adalimumab 40 mg every other week (eow), for 44 weeks.
Maintenance Higher Dose: Double-blind adalimumab 40 mg every week (ew) for 44 weeks.
Overall Number of Participants Analyzed 145 152 163 175
Measure Type: Number
Unit of Measure: percentage of participants
27.6 35.5 27.0 35.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maintenance (Main Study): M-SD, Maintenance (Main Study): M-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.159
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 7.5
Confidence Interval (2-Sided) 95%
-2.9 to 17.9
Estimation Comments Risk difference = Adalimumab 40mg EW - Adalimumab 40mg EOW.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maintenance (Main Study + Japan Sub-study): M-SD, Maintenance (Main Study + Japan Sub-study): M-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.109
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 8.0
Confidence Interval (2-Sided) 95%
-1.8 to 17.9
Estimation Comments Risk difference = Adalimumab 40mg EW - Adalimumab 40mg EOW.
21.Secondary Outcome
Title Maintenance Period Ranked Secondary Endpoint 12: Percentage of Week 8 Remitters (Per FMS) With Endoscopic Subscore of 0 at Week 52
Hide Description The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy [confirmed by a central reader], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 remitters are defined as participants with clinical remission (per FMS) at Week 8. Clinical remission is defined as a FMS ≤ 2 with no subscore > 1. Endoscopic remission is defined as an endoscopy subscore of 0.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-Remitter (ITT-RM) Population: all participants in ITT who achieved Week 8 remission based on the Full Mayo Score utilizing the endoscopy subscore provided by the central reader. Non-responder imputation. Per protocol, TDM Regimen arm was used to analyze exploratory outcome measures only (and therefore is not included).
Arm/Group Title Maintenance (Main Study): M-SD Maintenance (Main Study): M-HD Maintenance (Main Study + Japan Sub-study): M-SD Maintenance (Main Study + Japan Sub-study): M-HD
Hide Arm/Group Description:
Maintenance Standard Dose: Double-blind adalimumab 40 mg every other week (eow), for 44 weeks.
Maintenance Higher Dose: Double-blind adalimumab 40 mg every week (ew) for 44 weeks.
Maintenance Standard Dose: Double-blind adalimumab 40 mg every other week (eow), for 44 weeks.
Maintenance Higher Dose: Double-blind adalimumab 40 mg every week (ew) for 44 weeks.
Overall Number of Participants Analyzed 37 42 45 52
Measure Type: Number
Unit of Measure: percentage of participants
45.9 47.6 42.2 44.2
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maintenance (Main Study): M-SD, Maintenance (Main Study): M-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.903
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 1.4
Confidence Interval (2-Sided) 95%
-21.0 to 23.8
Estimation Comments Risk difference = Adalimumab 40mg EW - Adalimumab 40mg EOW.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maintenance (Main Study + Japan Sub-study): M-SD, Maintenance (Main Study + Japan Sub-study): M-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.901
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 1.3
Confidence Interval (2-Sided) 95%
-18.8 to 21.3
Estimation Comments Risk difference = Adalimumab 40mg EW - Adalimumab 40mg EOW.
22.Secondary Outcome
Title Maintenance Period Ranked Secondary Endpoint 13: Percentage of Week 8 Responders (Per FMS) With Response in IBDQ Bowel Symptom Domain at Week 52
Hide Description The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy [confirmed by a central reader], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 responders are defined as participants with a decrease in FMS of ≥ 3 points and ≥ 30% from Baseline plus a decrease in the rectal bleeding subscore [RBS] ≥ 1 or an absolute RBS ≤ 1. The IBDQ is a self-administered 32-item questionnaire to evaluate quality of life across 4 dimensional scores: bowel, systemic, social and emotional. Responses to each question range from 1 (severe problem) to 7 (normal health). Bowel Symptom domain score range is 10 (severe problem) to 70 (normal health). Response is defined as increase of Bowel Symptom domain score ≥ 6 from baseline.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-Responder population (ITT-RP): all participants in the Induction ITT population who achieve Week 8 response based on the FMS utilizing the endoscopy subscore provided by the central reader. Non-responder imputation. Per protocol, TDM Regimen arm was used to analyze exploratory outcome measures only (and therefore is not included).
Arm/Group Title Maintenance (Main Study): M-SD Maintenance (Main Study): M-HD Maintenance (Main Study + Japan Sub-study): M-SD Maintenance (Main Study + Japan Sub-study): M-HD
Hide Arm/Group Description:
Maintenance Standard Dose: Double-blind adalimumab 40 mg every other week (eow), for 44 weeks.
Maintenance Higher Dose: Double-blind adalimumab 40 mg every week (ew) for 44 weeks.
Maintenance Standard Dose: Double-blind adalimumab 40 mg every other week (eow), for 44 weeks.
Maintenance Higher Dose: Double-blind adalimumab 40 mg every week (ew) for 44 weeks.
Overall Number of Participants Analyzed 145 152 163 175
Measure Type: Number
Unit of Measure: percentage of participants
62.1 69.7 62.6 71.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maintenance (Main Study): M-SD, Maintenance (Main Study): M-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.160
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 7.7
Confidence Interval (2-Sided) 95%
-3.0 to 18.4
Estimation Comments Risk difference = Adalimumab 40mg EW - Adalimumab 40mg EOW.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maintenance (Main Study + Japan Sub-study): M-SD, Maintenance (Main Study + Japan Sub-study): M-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.076
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 9.1
Confidence Interval (2-Sided) 95%
-0.9 to 19.1
Estimation Comments Risk difference = Adalimumab 40mg EW - Adalimumab 40mg EOW.
23.Secondary Outcome
Title Maintenance Period Ranked Secondary Endpoint 14: Percentage of Week 8 Responders (Per FMS) With Response in IBDQ Fatigue Item at Week 52
Hide Description The Mayo score is a tool designed to measure disease activity for ulcerative colitis. The FMS ranges from 0 (normal or inactive disease) to 12 (severe disease) and is calculated as the sum of 4 subscores (stool frequency, rectal bleeding, endoscopy [confirmed by a central reader], and physician's global assessment), each of which ranges from 0 (normal) to 3 (severe disease). Negative changes indicate improvement. Week 8 responders are defined as participants with a decrease in FMS of ≥ 3 points and ≥ 30% from Baseline plus a decrease in the rectal bleeding subscore (RBS) ≥ 1 or an absolute RBS ≤ 1. The IBDQ is a self-administered 32-item questionnaire to evaluate quality of life across 4 dimensional scores: bowel, systemic, social and emotional. Responses to each question range from 1 (severe problem) to 7 (normal health). Response in IBDQ fatigue item (range 1 [severe problem] to 7 [normal health]) is defined as increase of IBDQ fatigue item ≥ 1 from baseline.
Time Frame Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT-Responder population (ITT-RP): all participants in the Induction ITT population who achieve Week 8 response based on the FMS utilizing the endoscopy subscore provided by the central reader. Non-responder imputation. Per protocol, TDM Regimen arm was used to analyze exploratory outcome measures only (and therefore is not included).
Arm/Group Title Maintenance (Main Study): M-SD Maintenance (Main Study): M-HD Maintenance (Main Study + Japan Sub-study): M-SD Maintenance (Main Study + Japan Sub-study): M-HD
Hide Arm/Group Description:
Maintenance Standard Dose: Double-blind adalimumab 40 mg every other week (eow), for 44 weeks.
Maintenance Higher Dose: Double-blind adalimumab 40 mg every week (ew) for 44 weeks.
Maintenance Standard Dose: Double-blind adalimumab 40 mg every other week (eow), for 44 weeks.
Maintenance Higher Dose: Double-blind adalimumab 40 mg every week (ew) for 44 weeks.
Overall Number of Participants Analyzed 145 152 163 175
Measure Type: Number
Unit of Measure: percentage of participants
53.8 61.2 55.2 59.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Maintenance (Main Study): M-SD, Maintenance (Main Study): M-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.207
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 7.3
Confidence Interval (2-Sided) 95%
-4.0 to 18.6
Estimation Comments Risk difference = Adalimumab 40mg EW - Adalimumab 40mg EOW.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Maintenance (Main Study + Japan Sub-study): M-SD, Maintenance (Main Study + Japan Sub-study): M-HD
Comments Adjusted risk difference, 95% confidence interval for the difference in the proportions between the treatment groups and P-value were calculated using Cochran-Mantel-Haenszel (CMH) test adjusted for induction treatment regimen and week 8 remission status.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.440
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted risk difference
Estimated Value 4.2
Confidence Interval (2-Sided) 95%
-6.4 to 14.8
Estimation Comments Risk difference = Adalimumab 40mg EW - Adalimumab 40mg EOW.
Time Frame See time frame specifics detailed for each reporting group in their respective descriptions below. Participants were contacted 70 days following study drug discontinuation for an assessment of any new or ongoing adverse events, except those participants who continued on adalimumab therapy after the end of study participation.
Adverse Event Reporting Description Treatment-emergent adverse events (TEAEs) are presented.
 
Arm/Group Title Induction (Main Study + Japan Sub-study): I-SD Induction (Main Study + Japan Sub-study): I-HD Maintenance (Main Study + Japan Sub-study): M-SD Maintenance (Main Study + Japan Sub-study): M-HD Maintenance (Main Study): TDM Regimen
Hide Arm/Group Description

Induction Standard Dose: Double-blind adalimumab regimen of 160 mg at Week 0 followed by 80 mg at Week 2, 40 mg at Week 4, and 40 mg at Week 6.

TEAEs during induction period: events with an onset date on or after first dose date of study drug in induction period and up to 70 days after last dose date of the study drug in induction period and prior to first dose date of study drug in maintenance period. Mean duration of treatment was 57.5 days.

Induction Higher Dose: Double-blind adalimumab regimen of 160 mg at Weeks 0, 1, 2, and 3 followed by 40 mg at Week 4 and 40 mg at Week 6.

TEAEs during induction period: events with an onset date on or after first dose date of study drug in induction period and up to 70 days after last dose date of the study drug in induction period and prior to first dose date of study drug in maintenance period. Mean duration of treatment was 55.0 days.

Maintenance Standard Dose: Double-blind adalimumab 40 mg every other week (eow), for 44 weeks.

TEAEs during maintenance period: events with an onset date on or after first dose date of study drug in maintenance period and up to 70 days after the last dose date of the study drug in maintenance period. Mean duration of treatment was 251.5 days.

Maintenance Higher Dose: Double-blind adalimumab 40 mg every week (ew) for 44 weeks.

TEAEs during maintenance period: events with an onset date on or after first dose date of study drug in maintenance period and up to 70 days after the last dose date of the study drug in maintenance period. Mean duration of treatment was 263.1 days.

Double-blind adalimumab 40 mg eow at Week 8 and Week 10, with possible dose adjustments at Weeks 12, 24, and 37 based on criteria assessing blinded adalimumab serum concentration and rectal bleeding subscore (RBS) assessments.

TEAEs during maintenance period: events with an onset date on or after first dose date of study drug in maintenance period and up to 70 days after the last dose date of the study drug in maintenance period. Mean duration of treatment was 255.9 days.

All-Cause Mortality
Induction (Main Study + Japan Sub-study): I-SD Induction (Main Study + Japan Sub-study): I-HD Maintenance (Main Study + Japan Sub-study): M-SD Maintenance (Main Study + Japan Sub-study): M-HD Maintenance (Main Study): TDM Regimen
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/379 (0.53%)      4/573 (0.70%)      2/345 (0.58%)      2/350 (0.57%)      0/151 (0.00%)    
Hide Serious Adverse Events
Induction (Main Study + Japan Sub-study): I-SD Induction (Main Study + Japan Sub-study): I-HD Maintenance (Main Study + Japan Sub-study): M-SD Maintenance (Main Study + Japan Sub-study): M-HD Maintenance (Main Study): TDM Regimen
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   19/379 (5.01%)      22/573 (3.84%)      44/345 (12.75%)      44/350 (12.57%)      15/151 (9.93%)    
Blood and lymphatic system disorders           
ANAEMIA  1  3/379 (0.79%)  3 2/573 (0.35%)  2 1/345 (0.29%)  2 3/350 (0.86%)  4 0/151 (0.00%)  0
IRON DEFICIENCY ANAEMIA  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 1/350 (0.29%)  1 0/151 (0.00%)  0
LYMPHADENOPATHY  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 1/350 (0.29%)  1 0/151 (0.00%)  0
THROMBOCYTOSIS  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 1/350 (0.29%)  1 0/151 (0.00%)  0
Cardiac disorders           
ACUTE MYOCARDIAL INFARCTION  1  0/379 (0.00%)  0 0/573 (0.00%)  0 1/345 (0.29%)  1 0/350 (0.00%)  0 0/151 (0.00%)  0
CARDIAC ARREST  1  0/379 (0.00%)  0 1/573 (0.17%)  1 0/345 (0.00%)  0 0/350 (0.00%)  0 0/151 (0.00%)  0
CARDIAC FAILURE CONGESTIVE  1  0/379 (0.00%)  0 0/573 (0.00%)  0 1/345 (0.29%)  1 0/350 (0.00%)  0 0/151 (0.00%)  0
CORONARY ARTERY DISEASE  1  0/379 (0.00%)  0 0/573 (0.00%)  0 1/345 (0.29%)  1 0/350 (0.00%)  0 0/151 (0.00%)  0
MYOCARDIAL ISCHAEMIA  1  0/379 (0.00%)  0 0/573 (0.00%)  0 1/345 (0.29%)  1 0/350 (0.00%)  0 0/151 (0.00%)  0
Eye disorders           
EYELID PTOSIS  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 1/350 (0.29%)  1 0/151 (0.00%)  0
OPTIC ATROPHY  1  0/379 (0.00%)  0 0/573 (0.00%)  0 1/345 (0.29%)  1 0/350 (0.00%)  0 0/151 (0.00%)  0
Gastrointestinal disorders           
ABDOMINAL PAIN  1  1/379 (0.26%)  1 1/573 (0.17%)  1 1/345 (0.29%)  1 0/350 (0.00%)  0 0/151 (0.00%)  0
ABDOMINAL PAIN UPPER  1  0/379 (0.00%)  0 0/573 (0.00%)  0 1/345 (0.29%)  1 0/350 (0.00%)  0 0/151 (0.00%)  0
ANOGENITAL DYSPLASIA  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 1/350 (0.29%)  1 0/151 (0.00%)  0
COLITIS  1  0/379 (0.00%)  0 1/573 (0.17%)  1 2/345 (0.58%)  2 0/350 (0.00%)  0 0/151 (0.00%)  0
COLITIS ULCERATIVE  1  12/379 (3.17%)  17 13/573 (2.27%)  13 16/345 (4.64%)  16 18/350 (5.14%)  21 6/151 (3.97%)  6
DIARRHOEA  1  1/379 (0.26%)  1 0/573 (0.00%)  0 0/345 (0.00%)  0 0/350 (0.00%)  0 0/151 (0.00%)  0
DUODENAL ULCER PERFORATION  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 1/350 (0.29%)  1 0/151 (0.00%)  0
HAEMORRHOIDS  1  0/379 (0.00%)  0 1/573 (0.17%)  1 0/345 (0.00%)  0 0/350 (0.00%)  0 0/151 (0.00%)  0
LARGE INTESTINAL STENOSIS  1  0/379 (0.00%)  0 1/573 (0.17%)  1 0/345 (0.00%)  0 0/350 (0.00%)  0 0/151 (0.00%)  0
MALLORY-WEISS SYNDROME  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 0/350 (0.00%)  0 1/151 (0.66%)  1
NAUSEA  1  0/379 (0.00%)  0 0/573 (0.00%)  0 1/345 (0.29%)  1 0/350 (0.00%)  0 0/151 (0.00%)  0
PANCREATITIS ACUTE  1  0/379 (0.00%)  0 1/573 (0.17%)  1 1/345 (0.29%)  1 0/350 (0.00%)  0 0/151 (0.00%)  0
RECTAL HAEMORRHAGE  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 1/350 (0.29%)  1 0/151 (0.00%)  0
SMALL INTESTINAL OBSTRUCTION  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 0/350 (0.00%)  0 1/151 (0.66%)  1
UPPER GASTROINTESTINAL HAEMORRHAGE  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 0/350 (0.00%)  0 1/151 (0.66%)  1
VOMITING  1  0/379 (0.00%)  0 0/573 (0.00%)  0 1/345 (0.29%)  1 0/350 (0.00%)  0 0/151 (0.00%)  0
General disorders           
GAIT DISTURBANCE  1  0/379 (0.00%)  0 0/573 (0.00%)  0 1/345 (0.29%)  1 0/350 (0.00%)  0 0/151 (0.00%)  0
PYREXIA  1  0/379 (0.00%)  0 1/573 (0.17%)  1 1/345 (0.29%)  1 0/350 (0.00%)  0 0/151 (0.00%)  0
Hepatobiliary disorders           
BILE DUCT STONE  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 0/350 (0.00%)  0 1/151 (0.66%)  1
HEPATITIS  1  0/379 (0.00%)  0 1/573 (0.17%)  1 0/345 (0.00%)  0 0/350 (0.00%)  0 0/151 (0.00%)  0
PORTOSPLENOMESENTERIC VENOUS THROMBOSIS  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 0/350 (0.00%)  0 1/151 (0.66%)  1
Infections and infestations           
APPENDICITIS  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 1/350 (0.29%)  1 0/151 (0.00%)  0
BRONCHITIS  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 0/350 (0.00%)  0 1/151 (0.66%)  1
CLOSTRIDIUM DIFFICILE INFECTION  1  0/379 (0.00%)  0 1/573 (0.17%)  1 3/345 (0.87%)  3 0/350 (0.00%)  0 0/151 (0.00%)  0
CYTOMEGALOVIRUS COLITIS  1  0/379 (0.00%)  0 1/573 (0.17%)  1 0/345 (0.00%)  0 0/350 (0.00%)  0 0/151 (0.00%)  0
ERYSIPELAS  1  1/379 (0.26%)  1 0/573 (0.00%)  0 0/345 (0.00%)  0 0/350 (0.00%)  0 0/151 (0.00%)  0
EXTERNAL EAR CELLULITIS  1  0/379 (0.00%)  0 0/573 (0.00%)  0 1/345 (0.29%)  1 0/350 (0.00%)  0 0/151 (0.00%)  0
GASTROENTERITIS  1  0/379 (0.00%)  0 0/573 (0.00%)  0 1/345 (0.29%)  1 0/350 (0.00%)  0 0/151 (0.00%)  0
GASTROINTESTINAL INFECTION  1  0/379 (0.00%)  0 0/573 (0.00%)  0 1/345 (0.29%)  1 0/350 (0.00%)  0 0/151 (0.00%)  0
HERPES ZOSTER  1  1/379 (0.26%)  1 0/573 (0.00%)  0 0/345 (0.00%)  0 0/350 (0.00%)  0 0/151 (0.00%)  0
INFECTION  1  0/379 (0.00%)  0 1/573 (0.17%)  1 0/345 (0.00%)  0 0/350 (0.00%)  0 0/151 (0.00%)  0
OTITIS EXTERNA  1  0/379 (0.00%)  0 0/573 (0.00%)  0 1/345 (0.29%)  1 0/350 (0.00%)  0 0/151 (0.00%)  0
PELVIC INFLAMMATORY DISEASE  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 1/350 (0.29%)  1 0/151 (0.00%)  0
PERINEAL ABSCESS  1  0/379 (0.00%)  0 0/573 (0.00%)  0 1/345 (0.29%)  1 0/350 (0.00%)  0 0/151 (0.00%)  0
PERITONSILLAR ABSCESS  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 1/350 (0.29%)  1 0/151 (0.00%)  0
PNEUMONIA  1  1/379 (0.26%)  1 0/573 (0.00%)  0 2/345 (0.58%)  2 4/350 (1.14%)  4 0/151 (0.00%)  0
SEPSIS  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 0/350 (0.00%)  0 1/151 (0.66%)  1
STERNITIS  1  0/379 (0.00%)  0 0/573 (0.00%)  0 1/345 (0.29%)  1 0/350 (0.00%)  0 0/151 (0.00%)  0
TUBERCULOSIS  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 1/350 (0.29%)  1 1/151 (0.66%)  1
TUBERCULOSIS OF INTRATHORACIC LYMPH NODES  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 1/350 (0.29%)  1 0/151 (0.00%)  0
VARICELLA  1  0/379 (0.00%)  0 1/573 (0.17%)  1 0/345 (0.00%)  0 0/350 (0.00%)  0 0/151 (0.00%)  0
VIRAL INFECTION  1  0/379 (0.00%)  0 0/573 (0.00%)  0 1/345 (0.29%)  1 0/350 (0.00%)  0 0/151 (0.00%)  0
Injury, poisoning and procedural complications           
HUMERUS FRACTURE  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 1/350 (0.29%)  2 0/151 (0.00%)  0
MENISCUS INJURY  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 1/350 (0.29%)  1 0/151 (0.00%)  0
PATELLA FRACTURE  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 1/350 (0.29%)  1 0/151 (0.00%)  0
POST PROCEDURAL HAEMORRHAGE  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 0/350 (0.00%)  0 1/151 (0.66%)  1
RADIUS FRACTURE  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 1/350 (0.29%)  1 0/151 (0.00%)  0
RIB FRACTURE  1  0/379 (0.00%)  0 0/573 (0.00%)  0 1/345 (0.29%)  1 0/350 (0.00%)  0 0/151 (0.00%)  0
UPPER LIMB FRACTURE  1  0/379 (0.00%)  0 0/573 (0.00%)  0 1/345 (0.29%)  1 0/350 (0.00%)  0 0/151 (0.00%)  0
Investigations           
ALANINE AMINOTRANSFERASE INCREASED  1  0/379 (0.00%)  0 0/573 (0.00%)  0 1/345 (0.29%)  1 0/350 (0.00%)  0 0/151 (0.00%)  0
ASPARTATE AMINOTRANSFERASE INCREASED  1  0/379 (0.00%)  0 0/573 (0.00%)  0 1/345 (0.29%)  1 0/350 (0.00%)  0 0/151 (0.00%)  0
NEUTROPHIL COUNT DECREASED  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 1/350 (0.29%)  1 0/151 (0.00%)  0
WEIGHT DECREASED  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 1/350 (0.29%)  1 0/151 (0.00%)  0
Metabolism and nutrition disorders           
DEHYDRATION  1  0/379 (0.00%)  0 0/573 (0.00%)  0 1/345 (0.29%)  1 1/350 (0.29%)  1 0/151 (0.00%)  0
DIABETES MELLITUS  1  0/379 (0.00%)  0 0/573 (0.00%)  0 1/345 (0.29%)  1 0/350 (0.00%)  0 0/151 (0.00%)  0
HYPONATRAEMIA  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 1/350 (0.29%)  1 0/151 (0.00%)  0
HYPOVOLAEMIA  1  0/379 (0.00%)  0 1/573 (0.17%)  1 0/345 (0.00%)  0 0/350 (0.00%)  0 0/151 (0.00%)  0
Musculoskeletal and connective tissue disorders           
ARTHRALGIA  1  0/379 (0.00%)  0 0/573 (0.00%)  0 1/345 (0.29%)  1 2/350 (0.57%)  2 0/151 (0.00%)  0
OSTEOARTHRITIS  1  0/379 (0.00%)  0 0/573 (0.00%)  0 1/345 (0.29%)  1 0/350 (0.00%)  0 0/151 (0.00%)  0
PAIN IN EXTREMITY  1  0/379 (0.00%)  0 1/573 (0.17%)  1 0/345 (0.00%)  0 0/350 (0.00%)  0 0/151 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
BLADDER CANCER  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 1/350 (0.29%)  1 0/151 (0.00%)  0
FIBROMATOSIS  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 1/350 (0.29%)  4 0/151 (0.00%)  0
MALIGNANT MELANOMA  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 1/350 (0.29%)  1 0/151 (0.00%)  0
MALIGNANT MELANOMA IN SITU  1  1/379 (0.26%)  1 0/573 (0.00%)  0 0/345 (0.00%)  0 0/350 (0.00%)  0 0/151 (0.00%)  0
NON-SMALL CELL LUNG CANCER  1  0/379 (0.00%)  0 0/573 (0.00%)  0 1/345 (0.29%)  1 0/350 (0.00%)  0 0/151 (0.00%)  0
OESOPHAGEAL ADENOCARCINOMA  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 1/350 (0.29%)  1 0/151 (0.00%)  0
SQUAMOUS CELL CARCINOMA OF THE CERVIX  1  1/379 (0.26%)  1 0/573 (0.00%)  0 0/345 (0.00%)  0 0/350 (0.00%)  0 0/151 (0.00%)  0
UTERINE LEIOMYOMA  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 1/350 (0.29%)  1 0/151 (0.00%)  0
Nervous system disorders           
ALTERED STATE OF CONSCIOUSNESS  1  0/379 (0.00%)  0 0/573 (0.00%)  0 1/345 (0.29%)  1 0/350 (0.00%)  0 0/151 (0.00%)  0
CHRONIC INFLAMMATORY DEMYELINATING POLYRADICULONEUROPATHY  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 0/350 (0.00%)  0 1/151 (0.66%)  1
HYPOAESTHESIA  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 1/350 (0.29%)  1 0/151 (0.00%)  0
ISCHAEMIC STROKE  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 0/350 (0.00%)  0 1/151 (0.66%)  1
MONONEUROPATHY  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 1/350 (0.29%)  1 0/151 (0.00%)  0
Psychiatric disorders           
BINGE DRINKING  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 0/350 (0.00%)  0 1/151 (0.66%)  1
BIPOLAR DISORDER  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 1/350 (0.29%)  1 0/151 (0.00%)  0
Renal and urinary disorders           
HAEMATURIA  1  0/379 (0.00%)  0 0/573 (0.00%)  0 1/345 (0.29%)  1 0/350 (0.00%)  0 0/151 (0.00%)  0
NEPHROTIC SYNDROME  1  0/379 (0.00%)  0 0/573 (0.00%)  0 1/345 (0.29%)  1 0/350 (0.00%)  0 0/151 (0.00%)  0
RENAL FAILURE  1  0/379 (0.00%)  0 1/573 (0.17%)  1 0/345 (0.00%)  0 0/350 (0.00%)  0 0/151 (0.00%)  0
URINARY RETENTION  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 0/350 (0.00%)  0 1/151 (0.66%)  1
Reproductive system and breast disorders           
PROSTATOMEGALY  1  0/379 (0.00%)  0 0/573 (0.00%)  0 1/345 (0.29%)  1 0/350 (0.00%)  0 0/151 (0.00%)  0
Respiratory, thoracic and mediastinal disorders           
EMPHYSEMA  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 1/350 (0.29%)  1 0/151 (0.00%)  0
NASAL POLYPS  1  0/379 (0.00%)  0 0/573 (0.00%)  0 1/345 (0.29%)  1 0/350 (0.00%)  0 0/151 (0.00%)  0
NASAL SEPTUM DEVIATION  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 1/350 (0.29%)  1 0/151 (0.00%)  0
PULMONARY EMBOLISM  1  0/379 (0.00%)  0 0/573 (0.00%)  0 1/345 (0.29%)  1 2/350 (0.57%)  2 0/151 (0.00%)  0
SINUS POLYP  1  0/379 (0.00%)  0 0/573 (0.00%)  0 1/345 (0.29%)  1 0/350 (0.00%)  0 0/151 (0.00%)  0
Skin and subcutaneous tissue disorders           
ERYTHEMA NODOSUM  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 0/350 (0.00%)  0 1/151 (0.66%)  1
EXCESSIVE SKIN  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 1/350 (0.29%)  1 0/151 (0.00%)  0
LINEAR IGA DISEASE  1  0/379 (0.00%)  0 0/573 (0.00%)  0 1/345 (0.29%)  1 0/350 (0.00%)  0 0/151 (0.00%)  0
NIGHT SWEATS  1  0/379 (0.00%)  0 0/573 (0.00%)  0 1/345 (0.29%)  1 0/350 (0.00%)  0 0/151 (0.00%)  0
PEMPHIGOID  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 0/350 (0.00%)  0 1/151 (0.66%)  1
SUBCORNEAL PUSTULAR DERMATOSIS  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 1/350 (0.29%)  1 0/151 (0.00%)  0
Surgical and medical procedures           
WOUND DRAINAGE  1  0/379 (0.00%)  0 1/573 (0.17%)  1 0/345 (0.00%)  0 0/350 (0.00%)  0 0/151 (0.00%)  0
Vascular disorders           
HYPERTENSION  1  0/379 (0.00%)  0 0/573 (0.00%)  0 1/345 (0.29%)  1 0/350 (0.00%)  0 0/151 (0.00%)  0
THROMBOPHLEBITIS  1  0/379 (0.00%)  0 0/573 (0.00%)  0 0/345 (0.00%)  0 1/350 (0.29%)  1 0/151 (0.00%)  0
1
Term from vocabulary, MedDRA 22.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Induction (Main Study + Japan Sub-study): I-SD Induction (Main Study + Japan Sub-study): I-HD Maintenance (Main Study + Japan Sub-study): M-SD Maintenance (Main Study + Japan Sub-study): M-HD Maintenance (Main Study): TDM Regimen
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   74/379 (19.53%)      112/573 (19.55%)      140/345 (40.58%)      141/350 (40.29%)      47/151 (31.13%)    
Gastrointestinal disorders           
COLITIS ULCERATIVE  1  20/379 (5.28%)  22 18/573 (3.14%)  18 60/345 (17.39%)  70 47/350 (13.43%)  58 23/151 (15.23%)  29
Infections and infestations           
NASOPHARYNGITIS  1  16/379 (4.22%)  18 29/573 (5.06%)  34 47/345 (13.62%)  61 46/350 (13.14%)  57 11/151 (7.28%)  20
UPPER RESPIRATORY TRACT INFECTION  1  3/379 (0.79%)  3 6/573 (1.05%)  6 22/345 (6.38%)  25 19/350 (5.43%)  20 9/151 (5.96%)  10
Musculoskeletal and connective tissue disorders           
ARTHRALGIA  1  11/379 (2.90%)  11 18/573 (3.14%)  19 23/345 (6.67%)  27 23/350 (6.57%)  27 5/151 (3.31%)  5
Nervous system disorders           
HEADACHE  1  23/379 (6.07%)  32 48/573 (8.38%)  62 17/345 (4.93%)  19 22/350 (6.29%)  36 8/151 (5.30%)  9
Skin and subcutaneous tissue disorders           
RASH  1  11/379 (2.90%)  11 10/573 (1.75%)  10 11/345 (3.19%)  13 20/350 (5.71%)  24 4/151 (2.65%)  6
1
Term from vocabulary, MedDRA 22.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Global Medical Services
Organization: AbbVie
Phone: 800-633-9110
EMail: abbvieclinicaltrials@abbvie.com
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Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT02065622    
Other Study ID Numbers: M14-033
2013-001682-16 ( EudraCT Number )
First Submitted: February 17, 2014
First Posted: February 19, 2014
Results First Submitted: August 19, 2020
Results First Posted: October 8, 2020
Last Update Posted: November 23, 2020