Efficacy and safety profile of advanced therapies in Crohn's disease: a systematic review and network meta-analysis

Why clinicians should know about it

• Picked for Gastroenterology (paper of the day, 6 November 2026): Comparative efficacy and safety of Crohn's disease advanced therapies

Abstract

BACKGROUND: Crohn's disease (CD) is a chronic inflammatory bowel disorder characterized by a relapsing-remitting course and substantial heterogeneity in clinical presentation. This study aimed to assess the comparative efficacy and safety of approved biologic and small-molecule therapies for CD, with particular emphasis on guselkumab and mirikizumab. METHODS: A systematic review and frequentist network meta-analysis (NMA) was conducted in accordance with PRISMA-NMA, the Cochrane Handbook, and ISPOR guidelines. MEDLINE, EMBASE, and the Cochrane Library were searched from inception to June 2026. Phase 3 randomized controlled trials (RCTs) evaluating adalimumab, guselkumab, infliximab, mirikizumab, risankizumab, vedolizumab, upadacitinib, or ustekinumab in adults with CD were included. RESULTS: A total of 27 RCTs were included. During induction therapy, guselkumab 400 mg achieved the highest P-scores for both clinical response and remission and was associated with higher odds of these outcomes compared with placebo and several active comparators. Mirikizumab was also more effective than placebo but ranked in the middle of the treatment hierarchy. During maintenance therapy, guselkumab 200 mg and 100 mg achieved the highest rankings for clinical response and remission; however, differences between guselkumab and several active comparators were not statistically significant. These comparisons were predominantly informed by indirect evidence and should not be interpreted as establishing definitive clinical superiority. No consistent evidence of major safety differences was observed across interventions; however, heterogeneity and inconsistency in several safety networks limited the certainty of the comparisons. Although guselkumab achieved favourable rankings for serious adverse events and serious infections, few statistically significant differences were observed between active treatments. The results should be interpreted in the context of indirect comparisons and methodological heterogeneity among included studies. CONCLUSIONS: Within the limitations of an NMA based predominantly on indirect evidence, guselkumab achieved the highest rankings for several efficacy outcomes during both induction and maintenance therapy. Mirikizumab showed higher odds of response and remission than placebo, although its node was informed by a single eligible phase 3 study. Given differences in study populations and trial designs, particularly in maintenance studies, these findings should be interpreted cautiously and not as evidence of definitive clinical superiority.

Abstract as published, via PubMed.