Comparative outcomes of advanced medical rescue therapies in steroid-refractory acute severe ulcerative colitis: a systematic review and network meta-analysis

Background Steroid-refractory acute severe ulcerative colitis is a medical emergency associated with a substantial risk of colectomy. Although infliximab and calcineurin inhibitors are established rescue treatments, comparative evidence regarding alternative drugs, infliximab dosing strategies, and newer small-molecule therapies remains limited. We conducted a systematic review and network meta-analysis to compare the efficacy and safety of available medical rescue strategies. Methods PubMed/MEDLINE, Embase, Scopus, Web of Science, and Cochrane CENTRAL were searched from inception through June 30, 2026. Randomized controlled trials and comparative observational studies enrolling adults hospitalized with steroid-refractory acute severe ulcerative colitis were eligible. Separate frequentist random-effects network meta-analyses were conducted for colectomy at approximately 12–14 weeks, colectomy during hospitalization or within 30 days, colectomy at approximately 12 months, and serious adverse events. Effects were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). Risk of bias was assessed using RoB 2 and ROBINS-I. Results Of 5, 498 records identified, 18 studies involving 1, 529 participants met the eligibility criteria, including three randomized trials and 15 observational studies. At approximately 12–14 weeks, ciclosporin was associated with higher odds of colectomy than standard-dose infliximab (OR 2.19, 95% CI 1.17–4.12). Neither high-dose infliximab (OR 2.92, 95% CI 0.42–20.26) nor accelerated infliximab (OR 4.57, 95% CI 0.88–23.75) differed significantly from standard-dose infliximab. Ciclosporin was also associated with higher odds of early colectomy (OR 3.05, 95% CI 1.38–6.77) and 12-month colectomy (OR 3.65, 95% CI 1.98–6.72) than standard-dose infliximab. Tacrolimus and accelerated infliximab did not differ significantly from standard-dose infliximab at either time point. Serious adverse events were similar between ciclosporin and infliximab (OR 0.94, 95% CI 0.54–1.63). The networks contained no closed loops, and most observational studies were judged to have a serious risk of bias. Conclusions In the combined randomized and observational evidence, standard-dose infliximab was associated with lower colectomy odds than ciclosporin, without a detectable difference in serious adverse events. No consistent advantage was demonstrated for accelerated or high-dose infliximab. Because the apparent efficacy advantage of infliximab was driven predominantly by observational studies, whereas randomized trials showed comparable outcomes, the findings should be interpreted cautiously. Further adequately powered randomized comparisons incorporating contemporary biologic-exposed populations and newer small-molecule therapies are required. Systematic review registration https://www.crd.york.ac.uk/prospero/ , identifier CRD420261412884.