Network Meta‐Analysis: Histologic and Histo‐Endoscopic Improvement and Remission With Advanced Therapy in Ulcerative Colitis

ABSTRACT Background Histology has prognostic value in ulcerative colitis (UC). However, direct comparisons of histological endpoints are lacking. Aim To perform a network meta‐analysis (NMA) to compare histological endpoints with biologics and small molecules. Methods We searched four databases up until July 2024 for randomised controlled trials (RCTs) on advanced therapies for moderate‐to‐severe UC reporting histological endpoints. Outcomes included histological improvement or remission, and histo‐endoscopic improvement after induction or during maintenance. We used a random‐effects frequentist model and have reported outcomes as relative risk and 95% confidence interval. We estimated relative drug efficacy with the P ‐score. We conducted subgroup analysis by trial phase and evaluated risk of bias and evidence certainty. Results We included 24 RCTs (15 therapies, 8874 patients). Nineteen provided data on induction and 10 on maintenance; outcome definitions were similar. Etrasimod 2 mg/day ranked highest in achieving histologic improvement ( P ‐score 0.98) and remission ( P ‐score 0.90) following induction. Globally, guselkumab 200–400 mg ranked first for histo‐endoscopic improvement, while etrasimod 2 mg/day and upadacitinib 45 mg/day were superior in the subgroup analysis. During maintenance, upadacitinib 30 mg/day was superior in achieving histologic improvement and remission ( P ‐score 0.88 for both) and histo‐endoscopic improvement ( P ‐score 0.94). Etrasimod 2 mg/day ranked second for histologic remission ( P ‐score 0.70) and histo‐endoscopic improvement ( P ‐score 0.73), while mirikizumab 200 mg/month ranked second for histologic improvement. Conclusion These results support the ability of small molecules to achieve stringent endpoints in moderate‐to‐severe UC. Histological outcome data for biologics was sparser, particularly during maintenance. Head‐to‐head RCTs are imperative to better inform clinical practice.