Comparative efficacy of immunomodulators, biologics, and advanced therapies for steroid-refractory acute severe ulcerative colitis: A network meta-analysis and time-to-event analysis

Background: Acute severe ulcerative colitis (ASUC) is a life-threatening condition. Corticosteroids are the first-line treatment, however, about 30 % of patients may not respond. This network meta-analysis evaluated the efficacy of advanced therapies and immunomodulators as rescue treatments for steroid-refractory ASUC. Methods: On March 1, 2025, a systematic search was conducted using four online databases. We included studies that evaluated the use of advanced therapies and other immunomodulators in steroid-refractory ASUC. The primary outcome was the colectomy rate at 1, 3, and 12 months. Odds ratios (ORs) with 95 % confidence intervals (CI) were calculated. For colectomy-free survival, the hazard ratio (HR) was estimated using a stratified Cox model. Results: Eighteen studies, including 2057 patients, were included. Treatment with standard infliximab was associated with improved colectomy-free survival compared to cyclosporine (cyclosporine (Cyclosporine capsules) capsules) therapy (HR: 0.54, 95 % CI: 0.42–0.72, p < 0.001). No differences were observed between standard and either accelerated or intensified infliximab. At 1 month, no differences in colectomy rates were observed across treatments. At 3 months, tofacitinib (OR, 0.14; 95 % CI, 0.02–0.89) and standard infliximab (OR, 0.55; 95 % CI, 0.33–0.89) were associated with lower colectomy rates compared to cyclosporine (cyclosporine (Cyclosporine capsules) capsules). At 12 months, intensified (OR, 0.23; 95 % CI, 0.07–0.75), standard (OR, 0.40; 95 % CI, 0.25–0.64), and accelerated infliximab (OR, 0.44; 95 % CI, 0.20–0.97) were superior to cyclosporine (cyclosporine (Cyclosporine capsules) capsules). Conclusions: Colectomy rates were similar across treatments at 1 month. At 3 months, standard infliximab and tofacitinib were associated with lower colectomy rates than cyclosporine (cyclosporine (Cyclosporine capsules) capsules). By 12 months, standard, intensified, and accelerated infliximab showed lower rates than cyclosporine (cyclosporine (Cyclosporine capsules) capsules).