Abstract Background In the SEQUENCE trial, risankizumab demonstrated non-inferiority to ustekinumab in clinical remission and was superior in attaining endoscopic remission by week 48. However, concerns have been raised about potential bias due to the open-label design and higher withdrawal rates in the ustekinumab arm. A Bayesian reanalysis using as-observed data and informative priors from prior randomized trials may offer a more balanced and decision-relevant estimate of comparative efficacy. This study aims to evaluate and compare the clinical and endoscopic efficacy of risankizumab and ustekinumab in moderate-to-severe Crohn’s disease through a Bayesian framework that synthesizes SEQUENCE trial data with prior evidence from randomized controlled trials. Methods We performed a systematic review of randomized controlled trials reporting clinical or endoscopic remission with risankizumab or ustekinumab in moderate-to-severe Crohn’s disease. The PubMed search (August 31, 2025) followed PRISMA 2020 guidelines and was registered in PROSPERO. Data extracted from the eligible trials were used to construct empirically derived beta priors for each treatment. A Bayesian conjugate beta-binomial model was applied to the as-observed data from the SEQUENCE trial to generate posterior distributions for clinical remission (CDAI 150) and endoscopic remission (SES-CD ≤4 with no subscore 1) at week 48. Sensitivity analyses were conducted using alternative prior assumptions, including non-informative and conservative priors. Results Among 1,192 identified studies, 47 were clinical trials. After detailed screening, six were selected as prior sources: FORTIFY for risankizumab, and IM-UNITI, Rutgeerts et al. (2008), GALAXI-1, GALAXI 2/3, and VIVID-1 for ustekinumab. Posterior estimates for clinical remission were 61.7% for risankizumab (95% CrI: 56.7–66.5) and 49.2% for ustekinumab (95% CrI: 45.2–53.3), with a 99.9% probability of superiority. For endoscopic remission, rates were 36.7% (95% CrI: 31.8–41.6) and 23.8% (95% CrI: 21.0–26.6), also favoring risankizumab with 99.9% probability. Across all sensitivity analyses, posterior probabilities consistently exceeded 99%, and credible intervals excluded the null. Conclusion This Bayesian reanalysis reinforces the superiority of risankizumab over ustekinumab in both clinical and endoscopic remission, with posterior probabilities of superiority exceeding 99% in all models. By formally incorporating prior evidence and quantifying uncertainty, Bayesian methods enhance interpretability and support robust therapeutic decisions in Crohn’s disease. References: Ferrante M, Panaccione R, Baert F, Bossuyt P, Colombel JF, Danese S, et al. Risankizumab as maintenance therapy for moderately to severely active Crohn’s disease: results from the multicentre, randomised, double-blind, placebo-controlled, withdrawal phase 3 FORTIFY maintenance trial. Lancet. 2022 May 28;399(10343):2031–46. doi:10.1016/S0140-6736(22)00466-4. Peyrin-Biroulet L, Chapman JC, Colombel JF, Caprioli F, D’Haens G, Ferrante M, et al. Risankizumab versus Ustekinumab for Moderate-to-Severe Crohn’s Disease. N Engl J Med. 2024 Jul 18;391(3):213–23. doi:10.1056/NEJMoa2314585. Danese S, Panaccione R, Feagan BG, Afzali A, Rubin DT, Sands BE, et al. Efficacy and safety of 48 weeks of guselkumab for patients with Crohn’s disease: maintenance results from the phase 2, randomised, double-blind GALAXI-1 trial. Lancet Gastroenterol Hepatol. 2024 Feb;9(2):133–46. doi:10.1016/S2468-1253(23)00318-7. Feagan BG, Sandborn WJ, Gasink C, Jacobstein D, Lang Y, Friedman JR, et al. Ustekinumab as induction and maintenance therapy for Crohn’s disease. N Engl J Med. 2016 Nov 17;375(20):1946–60. doi:10.1056/NEJMoa1602773. Ferrante M, D’Haens G, Jairath V, Danese S, Chen M, Ghosh S, et al. Efficacy and safety of mirikizumab in patients with moderately-to-severely active Crohn’s disease: a phase 3, multicentre, randomised, double-blind, placebo-controlled and active-controlled, treat-through study. Lancet. 2024 Dec 14;404(10453):2423–36. doi:10.1016/S0140-6736(24)01762-8. Rutgeerts P, Gasink C, Chan D, Lang Y, Pollack P, Colombel JF, et al. Efficacy of ustekinumab for inducing endoscopic healing in patients with Crohn’s disease. Gastroenterology. 2018 Oct;155(4):1045–58. doi:10.1053/j.gastro.2018.06.035. Panaccione R, Feagan BG, Afzali A, Rubin DT, Reinisch W, Panés J, et al; GALAXI 2 406(10501):358–75. doi:10.1016/S0140-6736(25)00681-6. Heuts S, Kawczynski MJ, Velders BJJ, Brophy JM, Hickey GL, Kowalewski M. Statistical primer: an introduction into the principles of Bayesian statistical analyses in clinical trials. Eur J Cardiothorac Surg. 2025;67(4):ezaf139. doi:10.1093/ejcts/ezaf139. Taylor, C., Puxty, K., Quasim, T., & Shaw, M. (2025). Understanding Bayesian analysis of clinical trials: an overview for clinicians. Critical care science, 37, e20250267. https://doi.org/10.62675/2965-2774.20250267 Conflict of interest: Dr. da Silva, Bruno César: Bruno has served as Speaker for J & J and Takeda Santana, Genoile Oliveira: Honoraria - Abbvie, Johnson & Johnson, Ferring, Takeda. Research - Abivax, Takeda, Johnson & Johnson, Roche, Sanofi, Polpharma. Advisory board - Abbvie, Johnson & Johnson, MSD. da Costa, Lilia Carolina Carneiro: No conflict of interest Chebli, Julio: Speaker Janssen, Takeda, Abbott, Abbvie, Pfizer
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