Immunomodulators and Advanced Therapies for Induction of Remission in Crohn’s Disease: A Systematic Review and Network Meta-Analysis

Abstract

Background Previous reviews for Crohn’s disease (CD) treatment have rarely considered advanced and immunomodulator medical therapies together. Our aim was to compare all therapies for efficacy and safety in induction of remission. Methods We searched databases up to June 2025. Our outcomes were clinical remission and response, endoscopic remission, and safety outcomes. We performed network meta-analyses and estimated risk ratios (RR) and 95% CIs. We used GRADE to assess certainty of results, and surface under the cumulative ranking curve for ranking treatments. Results A total of 79 RCTs with 20724 participants were included. Interventions ranged from 2 to 30weeks. There was moderate GRADE certainty of effectiveness over placebo for clinical remission for combination of adalimumab with thiopurines (RR, 2.87; 95% CI, 1.99-4.14; RD (Risk difference) =35.3%; NNT(Number needed to treat) =3, large magnitude), guselkumab (RR, 2.5; 95% CI, 1.95-3.21; RD=28.4%; NNT=4, moderate magnitude, adalimumab (RR, 2.46; 95% CI, 1.84-3.29; RD=27.6% NNT=4, moderate magnitude), combination of infliximab with thiopurines (RR, 2.43; 95% CI, 1.71-3.44; RD=27%; NNT=4, moderate magnitude), and ustekinumab (RR, 2.04; 95% CI, 1.69-2.46; RD=19.6% NNT=5, small magnitude). For endoscopic remission, there was moderate GRADE certainty of effectiveness for risankizumab (RR, 3.48; 95% CI, 2.18-5.58; RD=17.4%, moderate magnitude). The certainty on safety varied, but treatments appear generally safe in the short term. Conclusion Combination of anti-tumor necrosis factors (anti-TNFs) and immunomodulators followed by anti-TNF monotherapy had large effect size with moderate certainty for the induction of clinical remission. More novel therapies appear to have similar effect sizes but with increased imprecision of the estimates.