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Center for Global Research Data

Vedolizumab vs. Adalimumab in Ulcerative Colitis: Validation of Indirect Comparisons

Lead Investigator: Neeraj Narula, Hamilton Health Sciences
Title of Proposal Research: Vedolizumab vs. Adalimumab in Ulcerative Colitis: Validation of Indirect Comparisons
Vivli Data Request: 7542
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) affects over 120,000 Canadians and is an inflammatory bowel disease that affects the large intestine and is characterized by diarrhea, rectal bleeding, abdominal pain, urgency, and tenesmus. Patients with severe UC and/or disease that cannot be adequately controlled with corticosteroids are candidates for biologic monoclonal antibody treatments such as vedolizumab and adalimumab.

Vedolizumab and adalimumab are two biologic therapies that have demonstrated efficacy in achieving and maintaining remission through several pivotal placebo-controlled trials, including ULTRA 1 (NCT00385736), ULTRA 2 (NCT00408629), and GEMINI 1 (NCT00783718). Recently, the VARSITY trial (NCT02497469) demonstrated the superiority of vedolizumab to adalimumab among patients with moderate to severe UC. While studies comparing provide robust evidence to inform positioning of therapies, trials are costly and time-consuming. Therefore, there is increasing interest in performing indirect comparisons of biologics using patient-level data from different placebo-controlled clinical trials. However, the reliability of these comparisons relative to trials comparing active therapies remains unclear.

The Mayo Score is a tool that is used to determine UC disease activity and is comprised of four patient-reported and endoscopic assessments: stool frequency, rectal bleeding, endoscopic findings, and physician’s global assessment. Each parameter is scored from 0 to 3, with higher scores indicating greater disease severity. The total Mayo Score ranges from 0 to 12, while the partial Mayo Score excludes the endoscopic subscore and thus ranges from 0 to 9. While the Mayo Score has been widely used in clinical trials for UC as primary endpoints, mucosal healing (determined by endoscopy) remains an important target of treatment as well.

The primary objective of this study is to compare the efficacy of vedolizumab and adalimumab to achieve post-induction (week 6/8) mucosal healing as determined by the Mayo Score. The secondary objectives of this study include clinical remission at one-year and mucosal healing at one-year. Additionally, clinical response, reduction in markers of disease activity (e.g. fecal calprotectin, C-reactive protein), and reduction in histologic measures of disease activity at post-induction (week 6/8) and one-year will be analyzed.

Data from GEMINI 1 and VARSITY, which is being requested from Vivli, will be pooled to obtain a cohort of biologic-naïve UC patients treated with adalimumab. Biologic-naïve patients treated with adalimumab in ULTRA 1 and ULTRA 2, which is also being requested from Vivli, will be pooled to comprise the adalimumab cohort.

Requested Studies:

A Multicenter, Randomized, Double-blind Placebo-controlled Study of the Human Anti-TNF Monoclonal Antibody Adalimumab for the Induction of Clinical Remission in Subjects With Moderately to Severely Active Ulcerative Colitis
Data Contributor: AbbVie
Study ID: NCT00385736
Sponsor ID: M06-826

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 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 Randomized, Double-Blind, Double-Dummy, Multicenter, Active-Controlled Study to Evaluate the Efficacy and Safety of Vedolizumab IV Compared to Adalimumab SC in Subjects With Ulcerative Colitis
Data Contributor: Takeda
Study ID: NCT02497469
Sponsor ID: MLN0002-3026