Network Meta-Analysis: Comparative Efficacy of Biologics and Small Molecules in the Induction and Maintenance of Remission in Crohn's Disease

Background: Advances in medical management of Crohn's disease (CD) have transformed therapeutic goals. Clinical and endoscopic remission are important endpoints. Aim: To compare the efficacy of different advanced therapies in patients with CD. Methods: We performed a literature search up to January 2025. We included phase 3 randomised controlled trials (RCTs) against placebo or an active comparator. The primary endpoint was induction and maintenance of clinical remission (CD Activity Index [CDAI] < 150 points). Secondary endpoints included induction and maintenance of endoscopic remission (Simple Endoscopic Score for CD (SES-CD) of <= 4 or CD Endoscopic Index of Severity (CDEIS) of <= 4). We performed network meta-analysis (NMA) using the Frequentist method. Results: We included 39 studies. Induction of clinical remission analysis showed that infliximab combination with azathioprine ranked highest (93.2%), followed by guselkumab (88.6%) and adalimumab (76.9%). Guselkumab was superior to most interventions in inducing clinical remission. In maintenance of clinical remission, combination of infliximab and azathioprine ranked highest (75.7%) followed by mirikizumab (71.8%) and guselkumab (71.5%). There was no statistically significant difference between therapies in maintaining clinical remission. In induction of endoscopic remission, upadacitinib (88.5%) ranked highest, followed by risankizumab (73.7%) and guselkumab (73.4%). Guselkumab (74%) ranked highest in maintaining endoscopic remission, followed by adalimumab (67%) and mirikizumab (64%). Conclusion: Novel IL-23 inhibitors (such as mirikizumab, risankizumab and guselkumab) and anti-TNFs (such as infliximab and adalimumab) ranked high in the induction of clinical and endoscopic remission. This highlights the potential of novel advanced therapies for CD.