Comparative Efficacy of Biologics and Small Molecule in Ulcerative Colitis: A Systematic Review and Network Meta-analysis

BACKGROUND & AIMS: Treatment options for moderate to severe ulcerative colitis (UC) are increasing rapidly, but the lack of comparative efficacy trials makes treatment choices a clinical challenge. This network- meta-analysis aimed to compare the relative efficacy of biologics and small molecules in achieving remission in patients with moderate to severe UC. METHODS: The literature was searched up to May 2024. Phase 3 placebo or active comparator randomized controlled trials were included. The primary outcome was induction and maintenance of endoscopic improvement (Mayo Endoscopic Score [MES] <= 1). Secondary outcomes were the induction and maintenance of clinical remission, endoscopic (MES [ 0) and histological remission. A sub-analysis was performed based on the randomized controlled trial design and previous exposure to biologic therapy. RESULTS: We identified 36 studies that met our inclusion criteria, with 14,270 patients with UC. Upadacitinib ranked highest in inducing clinical remission (99.6%), and endoscopic improvement (99.2%), followed by risankizumab (91.4%) and (82.3%), respectively. In maintenance of endoscopic improvement, upadacitinib ranked fi rst (98.6%) followed by fi lgotinib 200 mg (79.2%). Risankizumab ranked fi rst in the induction of histological remission (89.4%), followed by guselkumab (88.3%). Upadacitinib ranked fi rst (93.1%) in maintaining histological remission, followed by guselkumab (89.5%). CONCLUSION: Upadacitinib appears to be superior to other therapies in achieving clinical remission, endoscopic improvement and remission, and histological remission. Furthermore, novel biologics such as risankizumab and guselkumab ranked high in achieving these outcomes. This study highlights the efficacy of small molecule drugs and novel selective interleukin-23s as alternatives to other biologics.