Immunomodulators and Advanced Therapies for Induction of Remission in Crohn's Disease: A Systematic Review and Network Meta-Analysis.
Level 1 - systematic review of randomized trials
Systematic review and network meta-analysis of randomized controlled trials
PubMed 40973970 · doi:10.1093/ibd/izaf191
What was done
A systematic review and network meta-analysis was conducted of databases searched through June 2025 to compare immunomodulators and advanced therapies for induction of remission in Crohn's disease. The analysis included randomized controlled trials with treatment durations ranging from 2 to 30 weeks. Outcomes assessed were clinical remission and response, endoscopic remission, and safety. Effect sizes were estimated as risk ratios (RR) and risk differences (RD) with 95% confidence intervals, and certainty was evaluated using GRADE.
What was found
A total of 79 RCTs comprising 20,724 participants were included. For clinical remission versus placebo, moderate GRADE certainty was found for adalimumab plus thiopurines (RR 2.87, 95% CI 1.99–4.14; RD 35.3%; NNT 3), guselkumab (RR 2.50, 95% CI 1.95–3.21; RD 28.4%; NNT 4), adalimumab monotherapy (RR 2.46, 95% CI 1.84–3.29; RD 27.6%; NNT 4), infliximab plus thiopurines (RR 2.43, 95% CI 1.71–3.44; RD 27.0%; NNT 4), and ustekinumab (RR 2.04, 95% CI 1.69–2.46; RD 19.6%; NNT 5). For endoscopic remission, risankizumab had moderate GRADE certainty versus placebo (RR 3.48, 95% CI 2.18–5.58; RD 17.4%). Certainty regarding safety varied, though agents appeared generally safe short-term.
Why it matters
This study provides an updated comparative synthesis of both combination regimens and newer targeted agents, confirming that anti-TNF plus immunomodulator combinations retain strong efficacy for induction alongside newer biologic classes.
Limits
Follow-up was restricted to induction periods of 2 to 30 weeks, preventing evaluation of long-term maintenance or delayed adverse events. Certainty of evidence did not exceed moderate, and estimates for newer therapies were limited by greater statistical imprecision.