Center for Global Research Data

Predictors of Placebo Response and Remission in Ulcerative Colitis and Crohn’s Disease

Lead Investigator: Neeraj Narula, Hamilton Health Sciences
Title of Proposal Research: Predictors of Placebo Response and Remission in Ulcerative Colitis and Crohn’s Disease
Vivli Data Request: 7591, 7392
Funding Source: None
Potential Conflicts of Interest: Neeraj Narula holds a McMaster University Department of Medicine Internal Career Award. Neeraj Narula has received honoraria from Janssen, Abbvie, Takeda, Pfizer, Merck, Lupin and Ferring. None of the listed conflicts of interest are aware of or are involved in this research

Summary of the Proposed Research:

Ulcerative colitis (UC) and Crohn’s disease (CD) are types of inflammatory bowel disease. UC affects the large intestine and is characterized by diarrhea, rectal bleeding, abdominal pain, urgency, and tenesmus (feeling the need for a bowel movement despite an empty bowel). CD can affect any area along the gastrointestinal tract, although many patients present with disease in the ileum and colon and experience symptoms including abdominal pain, weight loss, and diarrhea. Treatments for UC and CD must demonstrate efficacy and safety to obtain regulatory approval. Clinical trials for UC and CD are designed to assess the effect of a treatment and are often placebo-controlled when assessing novel biologic drugs. Placebo treatments do not contain any ingredients of therapeutic value and are often considered ‘sugar pills’. Despite receiving placebo, patients may still experience an improvement in their condition. Although high placebo response rates in clinical trials have been previously reported, it is unclear what factors may influence the response rate. Previous meta-analyses for UC have suggested factors such as disease duration, endoscopic disease severity, rectal bleeding score at baseline, and class of treatment may play a role in placebo response and remission rates. The primary objective of this study is to evaluate predictors of clinical response among patients who received placebo treatment. Data from GEMINI 1, ACT 1, ACT 2, PURSUIT, ULTRA, and OCTAVE will be pooled to obtain a cohort of UC patients who were treated with placebo for the entire duration of the trial. Data from UNITI-1, UNITI-2, IM-UNITI, GEMINI-2, GEMINI-3, and CLASSIC-1 will be assessed for CD.

Requested Studies:

A Phase II Study of the Human Anti-TNF Antibody Adalimumab for the Induction of Clinical Remission in Subjects With Crohn’s Disease
Study ID: NCT00055523
Sponsor ID: M02-403
Data Contributor: AbbVie

A Phase 3, Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction and Maintenance of Clinical Response and Remission by MLN0002 in Patients With Moderate to Severe Ulcerative Colitis
Data Contributor: Takeda
Study ID: NCT00783718
Sponsor ID: C13006

A Phase 3, Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction and Maintenance of Clinical Response and Remission by Vedolizumab (MLN0002) in Patients With Moderate to Severe Crohn’s Disease
Data Contributor: Takeda
Study ID: NCT00783692
Sponsor ID: C13007

A Randomized, Placebo-controlled, Double-blind Trial to Evaluate the Safety and Efficacy of Infliximab in Patients With Active Ulcerative Colitis
Data Contributor: Johnson & Johnson
Study ID: NCT00036439
Sponsor ID: CR004777

A Randomized, Placebo-controlled, Double-blind Trial to Evaluate the Safety and Efficacy of Infliximab in Patients With Active Ulcerative Colitis
Data Contributor: Johnson & Johnson
Study ID: NCT00096655
Sponsor ID: CR004783

A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Safety and Efficacy of Ustekinumab Induction Therapy in Subjects With Moderately to Severely Active Crohn’s Disease (UNITI-2)
Data Contributor: Johnson & Johnson
Study ID: NCT01369342
Sponsor ID: CR018418

A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Safety and Efficacy of Ustekinumab Maintenance Therapy in Subjects With Moderately to Severely Active Crohn’s Disease
Data Contributor: Johnson & Johnson
Study ID: NCT01369355
Sponsor ID: CR018421

A Phase 3, Randomized, Placebo-Controlled, Blinded, Multicenter Study of the Induction of Clinical Response and Remission by Vedolizumab in Patients With Moderate to Severe Crohn’s Disease
Data Contributor: Takeda
Study ID: NCT01224171
Sponsor ID: C13011

A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Safety and Efficacy of Ustekinumab Induction Therapy in Subjects With Moderately to Severely Active Crohn’s Disease Who Have Failed or Are Intolerant to TNF Antagonist Therapy (UNITI-1)
Data Contributor: Johnson & Johnson
Study ID: NCT01369329
Sponsor ID: CR018415

(Note: Additional studies added as part of Data Request 7591)

A Phase 3 Multicenter, Randomized, Placebo-controlled, Double-blind Study to Evaluate the Safety and Efficacy of Golimumab Maintenance Therapy, Administered Subcutaneously, in Subjects With Moderately to Severely Active Ulcerative Colitis
Data Contributor: Johnson & Johnson
Study ID: NCT00488631
Sponsor ID: CR014179

A Multicenter, Randomized, Double-blind, Placebo-controlled Study of the Human Anti-TNF Monoclonal Antibody Adalimumab for the Induction and Maintenance of Clinical Remission in Subjects With Moderately to Severely Active Ulcerative Colitis
Data Contributor: AbbVie
Study ID: NCT00408629
Sponsor ID: M06-827

A Multicentre, Randomized, Double-blind, Placebo-controlled, Parallel-group Study Of Oral Cp-690,550 As An Induction Therapy In Subjects With Moderate To Severe Ulcerative Colitis
Data Contributor: Pfizer Inc.
Study ID: NCT01465763
Sponsor ID: A3921094

A Multicentre, Randomized, Double-blind, Placebo-controlled, Parallel-group Study Of Oral Cp-690,550 As An Induction Therapy In Subjects With Moderate To Severe Ulcerative Colitis
Data Contributor: Pfizer Inc.
Study ID: NCT01458951
Sponsor ID: A3921095

A Multicentre, Randomized, Double-blind, Placebo-controlled, Parallel-group Study Of Oral Cp-690,550 As A Maintenance Therapy In Subjects With Ulcerative Colitis
Data Contributor: Pfizer Inc.
Study ID: NCT01458574
Sponsor ID: A3921096

Public Disclosures:

Wong ECL, Dulai PS, Marshall JK, Jairath V, Reinisch W, Narula N. Predictors of Placebo Induction Response and Remission in Ulcerative Colitis. Clin Gastroenterol Hepatol. 2022 Aug 24:S1542-3565(22)00811-4. doi: 10.1016/j.cgh.2022.08.015