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Meta-Analysis
. 2025 Oct 1;120(10):2260-2267.
doi: 10.14309/ajg.0000000000003406. Epub 2025 Mar 12.

IL-23p19 Antagonists vs Ustekinumab for Treatment of Crohn's Disease: A Meta-Analysis of Randomized Controlled Trials

Claudia Dziegielewski  1 , Yuhong Yuan  2 , Christopher Ma  3   4 , Brigid S Boland  1 , John T Chang  1   5 , Gaurav Syal  6 , Sudheer Kumar Vuyyuru  2 , Laurent Peyrin-Biroulet  7   8   9 , Vipul Jairath  2   10 , Siddharth Singh  1   11
Affiliations
Meta-Analysis

IL-23p19 Antagonists vs Ustekinumab for Treatment of Crohn's Disease: A Meta-Analysis of Randomized Controlled Trials

Claudia Dziegielewski et al. Am J Gastroenterol. .

Abstract

Introduction: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing interleukin (IL)-23p19 antagonists with ustekinumab, stratified by prior biologic exposure, in patients with moderate-to-severe Crohn's disease (CD).

Methods: Through a systematic review through August 17, 2024, we identified phase 2 and 3 RCTs comparing IL-23p19 antagonists vs ustekinumab in adults with moderate-to-severe CD. The primary outcome was achieving clinical remission at ∼1 year, and secondary outcomes were achieving endoscopic remission and serious adverse events. We performed subgroup analyses based on prior exposure to biologic therapy, primarily tumor necrosis factor antagonists. Certainty of evidence was appraised using the Grading of Recommendations Assessment, Development, and Evaluation approach.

Results: We included 5 head-to-head RCTs with a treat-through design (n = 2,506), of which 1 was conducted exclusively in patients with prior tumor necrosis factor antagonist exposure. On meta-analysis, patients treated with IL-23p19 inhibitors may be more likely to achieve clinical remission (relative risk [RR], 1.18 95% confidence interval [CI] 1.02-1.36) (low certainty of evidence) and endoscopic remission (RR 1.53, 95% CI 1.07-2.20) compared with ustekinumab. On subgroup analysis, IL-23p19 antagonists are probably more efficacious than ustekinumab in patients with prior biologic exposure (clinical remission: RR 1.31, 95% CI 1.16-1.48; endoscopic remission: RR 1.61, 95% CI 1.27-2.05) (moderate to high certainty), but not in biologic-naive patients (clinical remission: RR 0.99, 95% CI 0.90-1.08; endoscopic remission: RR 1.16, 95% CI 0.82-1.65). IL-23p19 antagonists may be associated with a lower risk of serious adverse events as compared with ustekinumab (RR 0.79, 95% CI 0.61-1.02).

Discussion: IL-23p19 antagonists are probably more efficacious and safer than ustekinumab in patients with moderate-to-severe CD in patients with prior biologic exposure, but not in biologic-naive patients.

Keywords: comparative efficacy; guselkumab; head-to-head trials; inflammatory bowel disease; risankizumab.

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Conflict of interest statement

Conflicts of Interest:

CD: None to declare

YY: None to declare

CM: has received consulting fees from AbbVie, Alimentiv, Amgen, AVIR Pharma Inc, BioJAMP, Bristol Myers Squibb, Celltrion, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Takeda, Pendopharm, Pfizer, Roche, Sanofi; speakers’ fees from AbbVie, Amgen, AVIR Pharma Inc, Alimentiv, Bristol Myers Squibb, Ferring, Fresenius Kabi, Janssen, Takeda, Pendopharm, and Pfizer; royalties from Springer Publishing; research support from Ferring, Takeda, Pfizer.

BSB: has received research grants from Prometheus Biosciences/Merck, Gilead, Mirador and consulting fees from Bristol Myers Squibb, Merck and Pfizer

JTC: has received consulting fees from AbbVie, Merck

GS: has received research grant from Pfizer and advisory board fee from Janssen

SKV: has recieved consultation fee from Alimentiv Inc..

LP-B: has received consulting fee from Abbvie, Abivax, Adacyte, Alimentiv, Amgen, Applied Molecular Transport, Arena, Banook, Biogen, BMS, Celltrion, Connect Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, IAC Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Nordic Pharma, Novartis, Oncodesign Precision Medicine, ONO Pharma, OSE Immunotherapeuthics, Pandion Therapeuthics, Par’ Immune, Pfizer, Prometheus, Protagonist, Roche, Samsung, Sandoz, Sanofi, Satisfay, Takeda, Telavant, Theravance, Thermo Fischer, Tigenix, Tillots, Viatris, Vectivbio, Ventyx, Ysopia; grants from Celltrion, Fresenius Kabi, Medac, MSD, Takeda; and speakers’ fees from Abbvie, Amgen, Arena, Biogen, Celltrion, Ferring, Galapagos, Genentech, Gilead, Janssen, Lilly, Medac, MSD, Nordic Pharma, Pfizer, Sandoz, Takeda, Tillots, Viatris.

VJ: 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, Reistone Biopharma, Roche, Sandoz, Second Genome, Takeda, Teva, Topivert, Ventyx, and Vividion; and speaker’s fees from, Abbvie, Ferring, Galapagos, Janssen Pfizer Shire, Takeda, and Fresenius Kabi

SS: has received research grant from Pfizer

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