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

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

Han Hee Lee  1 , Virginia Solitano  2 , Sujay Singh  3 , Ashwin N Ananthakrishnan  4 , Vipul Jairath  5 , Gaurav Syal  6 , Brigid S Boland  6 , Pradipta Ghosh  7 , John T Chang  8 , Siddharth Singh  9
Affiliations
Review

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

Han Hee Lee et al. Clin Gastroenterol Hepatol. .

Abstract

Background and aims: We sought to ascertain how prior exposure to tumor necrosis factor (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 randomized controlled trials 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 interleukin-23 antagonists) and Janus kinase inhibitors.

Results: Lymphocyte trafficking inhibitors were more efficacious in TNF antagonist-naïve vs exposed patients (5 trials; odds ratio [OR], 1.88; 95% confidence interval [CI], 1.02-3.49), whereas JAK inhibitors were less efficacious in TNF antagonist-naïve vs exposed patients (6 trials; ratio of OR, 0.47; 95% CI, 0.22-1.01). No significant difference was observed in efficacy of selective interleukin-23 antagonists vs placebo in TNF antagonist-naïve vs exposed patients (6 trials; ratio of OR, 1.07; 95% CI, 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.

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Conflict of interest statement

Conflicts of Interest:

  1. Han Hee Lee: None to report

  2. Virginia Solitano: None to report

  3. Sujay Singh: None to report

  4. Ashwin N. Ananthakrishnan: None to report

  5. Vipul Jairath: has received has received consulting/advisory board fees from AbbVie, Alimentiv Inc, Arena pharmaceuticals, Asahi Kasei Pharma, Asieris, Astra Zeneca, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring, Flagship Pioneering, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genentech, Gilead, Janssen, Merck, Mylan, Pandion, Pendopharm, Pfizer, Protagonist, Prometheus, Reistone Biopharma, Roche, Sandoz, Second Genome,Takeda, Teva, Topivert, Ventyx, Vividion; speaker’s fees from, Abbvie, Ferring, Galapagos, Janssen Pfizer Shire, Takeda, Fresenius Kabi

  6. Gaurav Syal: Research grants from Pfizer

  7. Brigid S. Boland: Research grants from Prometheus Biosciences/Merck, Gilead, Mirador and consulting fees from Bristol Myers Squibb, Merck and Pfizer

  8. Pradipta Ghosh: None to report

  9. John T. Chang: Consulting fees from AbbVie, Merck

  10. Siddharth Singh: Research grants from Pfizer

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