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

Advances in medical management of Crohn's disease (CD) have transformed therapeutic goals. Clinical and endoscopic remission are important endpoints. To compare the efficacy of different advanced therapies in patients with CD. 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. 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%). 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.