Differential Efficacy of Advanced Therapies in Inducing Remission in Ulcerative Colitis Based on Prior Exposure to TNF Antagonists

Han Hee Lee; Virginia Solitano; Sujay Singh; Ashwin N Ananthakrishnan; Vipul Jairath; Gaurav Syal; Brigid S Boland; Pradipta Ghosh; John T Chang; Siddharth Singh

doi:10.1016/j.cgh.2024.12.007

Differential Efficacy of Advanced Therapies in Inducing Remission in Ulcerative Colitis Based on Prior Exposure to TNF Antagonists

Clin Gastroenterol Hepatol. 2024 Dec 26:S1542-3565(24)01132-7. doi: 10.1016/j.cgh.2024.12.007. Online ahead of print.

Authors

Affiliations

¹ Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, California, USA; Division of Gastroenterology, Department of Internal Medicine, Yeouido St. Mary's Hospital College of Medicine, The Catholic University of Korea, Seoul, South Korea.
² Department of Medicine, Division of Gastroenterology, Western University, London, ON, Canada; Division of Gastroenterology and Gastrointestinal Endoscopy, IRCCS Ospedale San Raffaele, Università Vita-Salute San Raffaele, Milan.
³ Michigan State University College of Human Medicine.
⁴ Division of Gastroenterology, Massachusetts General Hospital, Boston, MA; Harvard Medical School, Boston, MA.
⁵ Department of Medicine, Division of Gastroenterology, Western University, London, ON, Canada; Department of Epidemiology & Biostatistics, Western University, London, Ontario, Canada.
⁶ Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, California, USA.
⁷ Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, California, USA; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA.
⁸ Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, California, USA; Department of Medicine, Veterans Affairs San Diego Healthcare System, San Diego, CA.
⁹ Division of Gastroenterology, Department of Medicine, University of California San Diego, La Jolla, California, USA; Division of Biomedical Informatics, Department of Medicine, University of California San Diego, La Jolla, California, USA. Electronic address: sis040@ucsd.edu.

PMID: 39732355
DOI: 10.1016/j.cgh.2024.12.007

Abstract

Background and aims: We sought to ascertain how prior exposure to TNF antagonists impacts treatment response with various classes of advanced therapies in patients with ulcerative colitis (UC), through a systematic review and meta-analysis.

Methods: Through a systematic review of multiple databases through June 30, 2024, we identified 17 RCTs in 8871 adults with moderate-severe UC who were treated with different advanced therapies vs. placebo, and reported efficacy in induction of clinical remission, stratified by prior exposure to TNF antagonists. We calculated the ratio of odds ratio of achieving remission with active drug vs. placebo, in TNF antagonist-naïve vs. TNF antagonist-exposed patients. We grouped advanced therapies based on primary mechanism of action: lymphocyte trafficking inhibitors (anti-integrins and sphingosine-1 phosphate [S1P] receptor modulators), anti-interleukins (interleukin-12/23 antagonist and selective IL-23 antagonists) and Janus kinase inhibitors.

Results: Lymphocyte trafficking inhibitors were more efficacious in TNF antagonist-naïve vs. exposed patients (five trials; ratio of OR,1.88 [95% CI, 1.02-3.49]), whereas JAK inhibitors were less efficacious in TNF antagonist-naïve vs. exposed patients (six trials; ratio of OR,0.47 [0.22-1.01]). No significant difference was observed in efficacy of selective IL-23 antagonists vs. placebo in TNF antagonist-naïve vs. exposed patients (six trials; ratio of OR,1.07 [0.64-1.80]). There was minimal heterogeneity across analyses.

Conclusion: There is significant heterogeneity of treatment efficacy with different advanced therapies in inducing remission in patients with UC based on prior exposure to TNF antagonists, with plausible potentiation of JAK inhibitors and attenuation of lymphocyte trafficking inhibitors. Future studies on the mechanistic basis for these observations are warranted.

Keywords: Upadacitinib; biologics; inflammatory bowel diseases; infliximab; risankizumab.

Publication types

Review