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Meta-Analysis
. 2023 Sep;68(9):3702-3713.
doi: 10.1007/s10620-023-08014-z. Epub 2023 Jun 28.

Efficacy and Safety of IL-12/23 and IL-23 Inhibitors for Crohn's Disease: Systematic Review and Meta-Analysis

Sudheer Kumar Vuyyuru  1   2 , Virginia Solitano  1   2   3 , Malcolm Hogan  2 , John K MacDonald  2 , Alexa Zayadi  2 , Claire E Parker  2 , Bruce E Sands  4 , Remo Panaccione  5 , Neeraj Narula  6 , Brian G Feagan  1   2   7 , Siddharth Singh  8 , Vipul Jairath  1   2   7 , Christopher Ma  9   10   11   12
Affiliations
Meta-Analysis

Efficacy and Safety of IL-12/23 and IL-23 Inhibitors for Crohn's Disease: Systematic Review and Meta-Analysis

Sudheer Kumar Vuyyuru et al. Dig Dis Sci. 2023 Sep.

Abstract

Background: Targeting interleukin-23 (IL-23) is an important therapeutic strategy for Crohn's disease (CD).

Aims: This systematic review and meta-analysis assessed the efficacy and safety of selective IL-23p19 and IL-12/23p40 inhibitors in patients with moderate-to-severe CD.

Methods: MEDLINE, Embase, and the Cochrane library (CENTRAL) were searched from inception to May 24, 2023, for randomized, placebo- or active comparator-controlled induction and/or maintenance trials of selective IL-23p19 and IL-12/23p40 inhibitors in pediatric and adult patients with CD. The primary outcome was the proportion of patients in clinical remission. Secondary outcomes were clinical response, endoscopic remission, endoscopic response, and safety. Data were pooled using a random-effects model. Risk of bias and certainty of evidence were assessed using the Cochrane risk of bias tool and the GRADE criteria, respectively.

Results: Eighteen trials (n = 5561) were included. Most studies were rated as low risk of bias. Targeting IL-23 was significantly superior to placebo for inducing clinical (risk ratio [RR] = 1.87, 95% confidence interval [CI] 1.58-2.21) and endoscopic (RR = 3.20, 95%CI 2.17-4.70) remission and maintaining clinical remission (RR = 1.39, 95%CI 1.10-1.77) (GRADE high certainty evidence for all outcomes). Subgroup analysis showed that targeting IL-23 was superior to placebo for inducing clinical remission in biologic-naïve (RR = 2.20, 95%CI 1.46-3.32, I2 = 0%, p = 0.39) and biologic-experienced patients (RR = 1.82, 95%CI 1.27-2.60, I2 = 56.5%, p = 0.01). Targeting IL-23 was associated with a decreased risk of serious adverse events in induction (RR = 0.55, 95%CI 0.44-0.73) and maintenance (RR = 0.72, 95%CI 0.53-0.98) trials compared to placebo (high certainty evidence).

Conclusion: Targeting IL-23 is effective and safe for inducing and maintaining clinical and endoscopic remission in patients with moderate-to-severe CD.

Keywords: Biologic therapy; Crohn’s disease; Inflammatory bowel disease; Interleukin-23 inhibitors; Risankizumab; Ustekinumab.

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Conflict of interest statement

Declarations

Conflict of interest SKV and VS: None. MH, JKM, AZ, and CEP are employees of Alimentiv Inc. NN has received honoraria from Janssen, Abbvie, Takeda, Pfizer, Merck, Sandoz, Novartis, and Ferring. SS has received grant/research support from Pfizer and AbbVie and consulting fees from Pfizer. BES has received consulting and/or speaking from AbbVie; Abivax, Adiso Therapeutics, Alimentiv Inc., Amgen; Arena Pharmaceuticals, Artizan Biosciences, Artugen Therapeutics, AstraZeneca, Bacainn Therapeutics, Boehringer-Ingelheim, Boston Pharmaceuticals, Bristol Myers Squibb, Calibr, Celltrion Healthcare, ClostraBio, Cytoki Pharma, Connect Biopharma, Entera, Evommune, Fresenius Kabi, Galapagos, Genentech, Gilead Sciences, GlaxoSmith-Kline, Gossamer Bio, Imhotex, Immunic, Index Pharmaceuticals, Inotrem, Innovation Therapeutics, Ironwood Pharmaceuticals, Janssen, Kaleido, Kallyope, Lilly Pfizer, MiroBio, Morphic Therapeutics, MRM Health, OSE Immunotherapeutics, Progenity, Prometheus Biosciences, Protagonist Therapeutics, Q32 Bio, Redhill Biopharma, Sun Pharma, Surrozen, Synlogic, Takeda, Target RWE, Teva, Theravance Biopharma, TLL Pharmaceutical, USWM Enterprises, VielaBio, and VTA Labs; and consulting fees and stock options from Ventyx Biosciences. RP has received consulting fees from Abbott, AbbVie, Alimentiv Inc., Amgen, Arena Pharmaceuticals, AstraZeneca, Biogen, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Cosmos Pharmaceuticals, Eisai, Elan, Eli Lilly, Ferring, Galapagos, Fresenius Kabi, Genentech, Gilead Sciences, Glaxo-Smith Kline, JAMP Bio, Janssen, Merck, Mylan, Novartis, Oppilan Pharma, Organon, Pandion Pharma, Pendopharm, Pfizer, Progenity, Protagonist Therapeutics, Roche, Sandoz, Satisfai Health, Shire, Sublimity Therapeutics, Takeda Pharmaceuticals, Theravance Biopharma, Trellus, Viatris, and UCB. BGF has received grant/research support from Millennium Pharmaceuticals, Merck, Tillotts Pharma AG, AbbVie, Novartis Pharmaceuticals, Centocor Inc., Elan/Biogen, UCB Pharma, Bristol-Myers Squibb, Genentech, ActoGenix, and Wyeth Pharmaceuticals Inc.; consulting fees from Millennium Pharmaceuticals, Merck, Centocor Inc., Elan/Biogen, Janssen-Ortho, Teva Pharmaceuticals, Bristol Myers Squibb, Celgene, UCB Pharma, AbbVie, Astra Zeneca, Serono, Genentech, Tillotts Pharma AG, Unity Pharmaceuticals, Albireo Pharma, Given Imaging Inc., Salix Pharmaceuticals, Novonordisk, GSK, Actogenix, Prometheus Therapeutics and Diagnostics, Athersys, Axcan, Gilead, Pfizer, Shire, Wyeth, Zealand Pharma, Zyngenia, Gi-Care Pharma Inc., and Sigmoid Pharma; and speaker’s fees from UCB, AbbVie, and J&J/Janssen. 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. CM has received consulting fees from AbbVie, Alimentiv Inc., Amgen, AVIR Pharma Inc., Bio-JAMP, Bristol Myers Squibb, Celltrion, Ferring, Fresenius Kabi, Janssen, McKesson, Mylan, Takeda, Pendopharm, Pfizer, Roche; speaker’s fees from AbbVie, Amgen, AVIR Pharma Inc., Alimentiv Inc., Bristol Myers Squibb, Ferring, Fresenius Kabi, Janssen, Takeda, Pendopharm, and Pfizer; royalties from Springer Publishing; and research support from Ferring and Pfizer. Alimentiv Inc. is an academic gastrointestinal contract research organization, operating under the Alimentiv Health Trust. CM, BGF, and VJ are consultants to Alimentiv Inc. and have a primary academic appointment; they are not employees of Alimentiv and do not hold equity positions or shares in Alimentiv Inc.

Figures

Fig. 1
Fig. 1
PRISMA flow diagram
Fig. 2
Fig. 2
a Pooled efficacy of IL-12/23p40 and IL-23p19 antagonists for inducing clinical remission. b Pooled efficacy of IL-12/23p40 and IL-23p19 antagonists for inducing clinical response
Fig. 3
Fig. 3
a Pooled efficacy of IL-12/23p40 and IL-23p19 antagonists for inducing endoscopic remission. b Pooled efficacy of IL-12/23p40 and IL-23p19 antagonists for inducing endoscopic response
Fig. 4
Fig. 4
a Pooled efficacy of IL-12/23p40 and IL-23p19 antagonists for maintaining clinical remission. b Pooled efficacy of IL-12/23p40 and IL-23p19 antagonists for maintaining clinical response
See this image and copyright information in PMC

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