Network Meta-Analysis: Efficacy of Biological Therapies and Small Molecules as Maintenance Therapy in Ulcerative Colitis.

Background: Numerous biologics and small molecules are licensed as maintenance therapy for ulcerative colitis (UC). Differences in the design of randomised controlled trials (RCTs) have not been considered when comparing efficacy between them.

Objective: To examine the relative efficacy of biologics and small molecules by network meta-analysis according to trial design.

Methods: We searched the literature to 27 February 2025 for RCTs. We judged efficacy using clinical remission, endoscopic improvement, endoscopic remission, or corticosteroid-free remission and according to previous exposure or non-exposure to advanced therapies. Random effects model with data reported as pooled relative risks (RR) with 95% confidence intervals (CI); drugs ranked by p-score.

Results: We identified 28 RCTs, 16 re-randomising 6568 patients and 12 treating through 3771 patients. In re-randomised studies, upadacitinib 30 mg o.d. ranked first for clinical remission (RR of failure to achieve clinical remission = 0.52; 95% CI 0.44-0.61, p-score 0.99) and endoscopic improvement (RR = 0.43; 95% CI 0.35-0.52, p-score 0.99). Vedolizumab 300 mg 4-weekly ranked first for endoscopic remission (RR = 0.73; 95% CI 0.64-0.84, p-score 0.92) and guselkumab 200 mg 4-weekly first for corticosteroid-free remission (RR = 0.40; 95% CI 0.28-0.55, p-score 0.95). In treat-through studies, etrasimod 2 mg o.d. ranked first for clinical remission (RR = 0.73; 95% CI 0.64-0.83, p-score 0.88) and infliximab 10 mg/kg 8-weekly first for endoscopic improvement (RR = 0.64; 95% CI 0.56-0.74, p-score 0.94).

Conclusions: In network meta-analysis, upadacitinib and etrasimod were consistently efficacious as maintenance therapy in UC.