Comparative Efficacy of Advanced Therapies for Management of Moderate-to-Severe Crohn's Disease: 2025 AGA Evidence Synthesis.

Abstract

Background & aims: We performed an updated systematic review and network meta-analysis to inform the 2025 American Gastroenterological Association Clinical Guidelines on the management of moderate-to-severe Crohn's disease (CD).

Methods: We searched multiple electronic databases from inception through August 14, 2024, to identify randomized controlled trials in adults with moderate-to-severe CD, comparing advanced therapies (eg, tumor necrosis factor antagonists, vedolizumab, interleukin 12/23, or interleukin 23p19 antagonists, and/or Janus kinase inhibitors) with placebo or another active comparator. Our primary outcomes were induction and maintenance of clinical remission; analyses were stratified by biologic therapy exposure status. We performed a network meta-analysis using a frequentist approach and applied the Grading of Recommendations, Assessment, Development and Evaluation to appraise certainty of evidence.

Results: We identified 28 trials of induction therapy and 22 trials of maintenance therapy of advanced therapies in patients with moderate-to-severe CD. In biologic-naïve patients, moderate-to-high certainty evidence supported the use of infliximab, adalimumab, vedolizumab, ustekinumab, risankizumab, mirikizumab, and guselkumab, and low certainty evidence supported the use of certolizumab pegol and upadacitinib over no treatment for inducing remission. Among active comparators, moderate-to-high certainty evidence supported the use of adalimumab and ustekinumab compared with certolizumab pegol and upadacitinib. Among patients with prior exposure to biologics, moderate-to-high certainty evidence supported the use of adalimumab, ustekinumab, risankizumab, guselkumab, and upadacitinib, and low certainty evidence supported the use of vedolizumab and mirikizumab, over no treatment, for inducing remission. Among active comparators, moderate certainty evidence supported the use of risankizumab and guselkumab compared with vedolizumab and ustekinumab.

Conclusions: Using Grading of Recommendations, Assessment, Development and Evaluation to appraise quality of evidence, this updated network meta-analysis can inform positioning of advanced therapies for the treatment of biologic-naïve and biologic-exposed patients with moderate-to-severe CD.