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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

Brief Summary:
To evaluate safety and efficacy of two adalimumab dosing regimens for induction and maintenance (standard and higher dosing) in achieving clinical remission in subjects with moderately to severely active ulcerative colitis.

Condition or disease Intervention/treatment Phase
Ulcerative Colitis (UC) Drug: Adalimumab Other: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 952 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-Blind, Randomized, Multicenter Study of Higher Versus Standard Adalimumab Dosing Regimens for Induction and Maintenance Therapy in Subjects With Moderately to Severely Active Ulcerative Colitis
Actual Study Start Date : March 27, 2014
Actual Primary Completion Date : September 5, 2019
Actual Study Completion Date : November 11, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Adalimumab

Arm Intervention/treatment
Experimental: Induction (Main Study + Japan Sub-study): I-SD
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.
Drug: Adalimumab
Other Name: Humira

Other: Placebo
Experimental: Induction (Main Study + Japan Sub-study): I-HD
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.
Drug: Adalimumab
Other Name: Humira

Experimental: Maintenance (Main Study + Japan Sub-study): M-SD
Maintenance Standard Dose: Double-blind adalimumab 40 mg every other week (eow), for 44 weeks.
Drug: Adalimumab
Other Name: Humira

Other: Placebo
Experimental: Maintenance (Main Study + Japan Sub-study): M-HD
Maintenance Higher Dose: Double-blind adalimumab 40 mg every week (ew) for 44 weeks.
Drug: Adalimumab
Other Name: Humira

Experimental: Maintenance (Main Study): 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 (RBS) assessments.
Drug: Adalimumab
Other Name: Humira

Other: Placebo



Primary Outcome Measures :
  1. Induction Period Primary Endpoint: Percentage of Participants With Clinical Remission Per Full Mayo Score (FMS) at Week 8 [ Time Frame: Week 8 ]
    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.

  2. Maintenance Period Primary Endpoint: Percentage of Week 8 Responders (Per FMS) With Clinical Remission (Per FMS) at Week 52 [ Time Frame: Week 52 ]
    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.


Secondary Outcome Measures :
  1. Induction Period Ranked Secondary Endpoint 1: Percentage of Participants With Endoscopic Improvement at Week 8 [ Time Frame: Week 8 ]
    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.

  2. Induction Period Ranked Secondary Endpoint 2: Percentage of Participants With Fecal Calprotectin < 150 mg/kg at Week 8 [ Time Frame: Week 8 ]
  3. 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 [ Time Frame: Week 8 ]
    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.

  4. Induction Period Ranked Secondary Endpoint 4: Percentage of Participants With Clinical Response Per FMS at Week 8 [ Time Frame: Week 8 ]
    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.

  5. Induction Period Ranked Secondary Endpoint 5: Percentage of Participants With Endoscopic Remission at Week 8 [ Time Frame: Week 8 ]
    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.

  6. Induction Period Ranked Secondary Endpoint 6: Percentage of Participants Achieving Response in IBDQ Bowel Symptom Domain at Week 8 [ Time Frame: Week 8 ]
    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.

  7. Induction Period Ranked Secondary Endpoint 7: Percentage of Participants Achieving Response in IBDQ Fatigue Item at Week 8 [ Time Frame: Week 8 ]
    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.

  8. Maintenance Period Ranked Secondary Endpoint 1: Percentage of Week 8 Responders (Per FMS) With Endoscopic Improvement at Week 52 [ Time Frame: Week 52 ]
    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.

  9. 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 [ Time Frame: Week 52 ]
    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.

  10. 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 [ Time Frame: Week 52 ]
    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.

  11. Maintenance Period Ranked Secondary Endpoint 4: Percentage of Week 8 Remitters (Per FMS) With Clinical Remission (Per FMS) at Week 52 [ Time Frame: Week 52 ]
    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.

  12. Maintenance Period Ranked Secondary Endpoint 5: Percentage of Week 8 Remitters (Per FMS) With Endoscopic Improvement at Week 52 [ Time Frame: Week 52 ]
    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.

  13. 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 [ Time Frame: Week 52 ]
    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.

  14. 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 [ Time Frame: Week 52 ]
    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.

  15. 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 [ Time Frame: Week 52 ]
    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.

  16. Maintenance Period Ranked Secondary Endpoint 9: Percentage of Week 8 Non-Responders With Clinical Remission (Per FMS) at Week 52 [ Time Frame: Week 52 ]
    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.

  17. Maintenance Period Ranked Secondary Endpoint 10: Percentage of Week 8 Non-Remitters With Clinical Remission (Per FMS) at Week 52 [ Time Frame: Week 52 ]
    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.

  18. Maintenance Period Ranked Secondary Endpoint 11: Percentage of Week 8 Responders (Per FMS) With Endoscopic Subscore of 0 at Week 52 [ Time Frame: Week 52 ]
    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.

  19. Maintenance Period Ranked Secondary Endpoint 12: Percentage of Week 8 Remitters (Per FMS) With Endoscopic Subscore of 0 at Week 52 [ Time Frame: Week 52 ]
    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.

  20. Maintenance Period Ranked Secondary Endpoint 13: Percentage of Week 8 Responders (Per FMS) With Response in IBDQ Bowel Symptom Domain at Week 52 [ Time Frame: Week 52 ]
    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.

  21. Maintenance Period Ranked Secondary Endpoint 14: Percentage of Week 8 Responders (Per FMS) With Response in IBDQ Fatigue Item at Week 52 [ Time Frame: Week 52 ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of Ulcerative Colitis (UC) for at least 90 days, confirmed by endoscopy during Screening period.
  • Active UC with Mayo Score of 6 to 12 points and endoscopy subscore of 2 to 3 despite concurrent or prior treatment with a full and adequate course, in the opinion of the Investigator, with oral corticosteroids or immunosuppressants or both. Mayo Score is confirmed by central reader.

Exclusion Criteria:

  • Subject with Crohn's disease (CD) or indeterminate colitis (IC).
  • Current diagnosis of fulminant colitis and/or toxic megacolon.
  • Subjects with disease limited to the rectum (ulcerative proctitis) during the screening endoscopy.
  • Chronic recurring infections or active tuberculosis (TB).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02065622


Locations
Show Show 173 study locations
Sponsors and Collaborators
AbbVie
Investigators
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Study Director: AbbVie Inc. AbbVie
  Study Documents (Full-Text)

Documents provided by AbbVie:
Statistical Analysis Plan  [PDF] September 13, 2019
Study Protocol  [PDF] June 16, 2016

Additional Information:
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Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT02065622    
Other Study ID Numbers: M14-033
2013-001682-16 ( EudraCT Number )
First Posted: February 19, 2014    Key Record Dates
Results First Posted: October 8, 2020
Last Update Posted: November 23, 2020
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
URL: https://www.abbvie.com/our-science/clinical-trials/clinical-trials-data-and-information-sharing/data-and-information-sharing-with-qualified-researchers.html

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by AbbVie:
Ulcerative Colitis
Additional relevant MeSH terms:
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Colitis
Colitis, Ulcerative
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases
Adalimumab
Anti-Inflammatory Agents
Antirheumatic Agents