Rescue Therapies for Steroid-refractory Acute Severe Ulcerative Colitis: A Systematic Review and Network Meta-analysis

Background and Aims Approximately 40% of patients with steroid-refractory acute severe ulcerative colitis [SR ASUC] require colectomies. Advanced therapies may reduce the short-term colectomy rates in patients with SR ASUC. However, comparative clinical studies evaluating the effectiveness of these rescue therapies are lacking. Therefore, we conducted a network meta-analysis to study the effectiveness of rescue therapies for SR ASUC.Methods Six randomised, controlled trials and 15 cohort studies, including 2004 patients, were analysed. Rescue drugs included tofacitinib, infliximab with a 5 or 10 mg/kg induction dose at 0, 2, and 6 weeks [IFX and IFX10, respectively], IFX with an accelerated regimen of three 5-mg/kg induction doses timed according to clinical need [accelerated IFX], tacrolimus, ciclosporin [CyA], ustekinumab, and adalimumab. Treatments were compared with a placebo.Results Tofacitinib odds ratio [OR]: 0.09 (95% confidence interval [CI]: 0.02-0.52]), accelerated IFX (OR: 0.16 [95% CI: 0.03-0.94]), IFX (OR: 0.2 [95% CI: 0.07-0.58]), and tacrolimus (OR: 0.24 [95% CI: 0.06-0.96]) significantly reduced the short-term colectomy rates compared with placebo. IFX10 and CyA tended to prevent colectomies. However, ustekinumab and adalimumab did not significantly affect the colectomy rates.Conclusion This is the first network meta-analysis to investigate the efficacy of advanced therapies in reducing short-term colectomy rates in patients with SR ASUC. Tofacitinib, accelerated IFX, standard IFX, and tacrolimus significantly reduced the colectomy rates in SR ASUC patients compared with placebo. Thus, advanced therapies should be considered for rescue therapies in patients with SR ASUC. Graphical Abstract