Marla Dubinsky, MD: The Importance of Head-to-Head Trials in IBD

The rise of targeted therapies in inflammatory bowel disease (IBD) has prompted a growing need for comparative data between drugs to better inform treatment positioning amid an expanding armamentarium of therapeutic options.

Most randomized controlled trials for treatments in IBD have been performed only versus placebo rather than directly comparing treatments against one another, leaving clinicians with little guidance regarding what drug may be best suited for their patients. Recent head-to-head, comparative trials are providing further insight into treatment positioning with greater methodological quality to help clinicians make more informed prescribing decisions.¹

“Traditionally, in phase 3 or registration trials, often the comparator is placebo. In the clinic, we don't ever put a patient on nothing,” Marla Dubinsky, MD, chief of the division of pediatric gastroenterology at Mount Sinai Kravis Children’s Hospital, said in an interview with HCPLive. “It's not mimicking what we do in practice in terms of decision-making.”

Referencing the head-to-head SEQUENCE trial of risankizumab versus ustekinumab in Crohn disease (CD), Dubinsky described how these results help inform how clinicians treat specific patients based on the patient population in the study. Participants in SEQUENCE were required to demonstrate intolerance or inadequate response to ≥ 1 anti-TNF therapy, therefore informing clinicians’ approach to patients they may see who have CD and are refractory to anti-TNF.²

“The benefit is it helps me know tomorrow, after I've seen the results, if someone walks in the door that has moderate to severe Crohn's disease and is already failing at least one TNF, this is what I expect, and this is how I can counsel my patient,” she explained. “Data is really important, because if I'm just guessing and using my own personal experience, it doesn't always apply to that patient sitting in front of you.”

Though head-to-head trials in IBD are few and far between, other studies of note involving regulatory-approved advanced medical therapies include the VARSITY trial of vedolizumab versus adalimumab in UC and the SEAVUE trial of ustekinumab versus adalimumab in CD.³

“In the Crohn's era, I think we're pretty satisfied with where we are,” Dubinsky said, instead pointing to the need for more head-to-head data in ulcerative colitis due to the “explosion” of new oral and subcutaneous therapies in recent years.

Looking ahead, Dubinsky also predicted the rise of combination therapy, saying it is “going to be more where our discussion is next” after the current “revolution” of IL-23s progresses to an “evolution” of combination therapy building upon what she refers to as platform drugs.

“The paradigm shift will be using these therapies as a platform in TNF failures and making a decision as to whether you add or switch to a JAK inhibitor if you aren't achieving the remarkable results we see from SEQUENCE,” Dubinsky concluded.

References:

1. ^{Macaluso FS, Maida M, Grova M, et al. Head-to-head comparison of biological drugs for inflammatory bowel disease: from randomized controlled trials to real-world experience. Therap Adv Gastroenterol. 2021;14:17562848211010668. doi:10.1177/17562848211010668}
2. ^{Brooks, A. Marla Dubinsky, MD: Clinical Outcomes with Risankizumab Versus Ustekinumab in SEQUENCE. HCPLive. February 24, 2024. Accessed February 27, 2024. https://www.hcplive.com/view/marla-dubinsky-md-clinical-outcomes-risankizumab-ustekinumab-sequence}
3. ^{Dulai PS, Singh S, Jairath V, et al. Integrating Evidence to Guide Use of Biologics and Small Molecules for Inflammatory Bowel Diseases. Gastroenterology. https://doi.org/10.1053/j.gastro.2023.10.033}