Outcomes from Induction Using Ustekinumab or Vedolizumab Among Patients Who Have Prior Biologic Intolerance vs Biologic Failure in Ulcerative colitis and Crohn’s disease

Lead Investigator: Neeraj Narula, Hamilton Health Sciences
Title of Proposal Research: Outcomes from Induction Using Ustekinumab or Vedolizumab Among Patients Who Have Prior Biologic Intolerance vs Biologic Failure in Ulcerative colitis and Crohn’s disease
Vivli Data Request: 9332
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) both fall under the category of inflammatory bowel diseases (IBD). UC primarily targets the large intestine and manifests through symptoms such as diarrhea, rectal bleeding, abdominal pain, a constant urge for bowel movements, and tenesmus (a sensation of needing to defecate even when the bowels are empty). CD, on the other hand, can impact any part of the gastrointestinal tract, although it often affects the ileum and colon. CD patients typically experience symptoms like abdominal pain, weight loss, and diarrhea. In cases where the disease proves severe or unresponsive to conventional therapies, such as corticosteroids, healthcare professionals may explore the potential benefits of employing biologic agents and small molecule treatments as alternative therapeutic strategies.
Biologic agents, also known as biologic therapies, are a category of treatments, typically proteins or antibodies, designed to target specific components of the immune system involved in the inflammatory process of IBD. They are used to modulate the immune response and reduce inflammation in the gut. Two notable biologic therapies, ustekinumab and vedolizumab, have gained approval for the treatment of both UC and CD. Their efficacy and ability to maintain a positive response have been substantiated through various placebo-controlled trials, including GEMINI 1 (NCT00783718), UNITI 1 (NCT01369329), UNITI 2 (NCT01369342), and UNIFI (NCT02407236).
Clinical remission is a critical outcome measure in assessing the effectiveness of treatments. It refers to a state in which the patient experiences a significant reduction or complete absence of symptoms related to the disease. In the case of IBD, it means the patient is no longer experiencing symptoms like abdominal pain, diarrhea, rectal bleeding, or the constant urge for bowel movements. It has been observed within these trials that patients who have previously used biologics have lower rates of clinical and endoscopic response compared to biologic-na├»ve patients. This ‘previous use’ includes those patients who did not have symptomatic improvement but also encompasses those who may have had adverse events to prior therapy. This is what we refer to as biologic intolerance.
The primary objective of this study is to assess whether IBD patients with prior biologic intolerance have similar achievement of clinical remission and response to ustekinumab and vedolizumab as those who have had a prior failure of one biologic treatment.
Patient-level data from GEMINI 1 and UNIFI is being requested from Vivli, while patient-level data from UNITI 1 and UNITI 2 is being requested from the YODA Project. This research will provide valuable insights into the potential of these biologic agents to induce clinical remission, even in patients with a history of biologic intolerance.

Requested Studies:

A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Protocol to Evaluate the Safety and Efficacy of Ustekinumab Induction and Maintenance Therapy in Subjects With Moderately to Severely Active Ulcerative Colitis
Data Contributor: Johnson & Johnson
Study ID: NCT02407236
Sponsor ID: CR106920

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, 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

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