Comparative assessment of faecal microbiota transplantation and current therapies as induction treatment for active refractory ulcerative colitis: A systematic review and network meta-analysis

Abstract Background Emerging evidence suggests that faecal microbiota transplantation (FMT) can induce remission in patients with refractory to standard treatment ulcerative colitis (UC). Methods We performed a systematic review and network meta-analysis to assess the comparative efficacy and safety of FMT and current therapies as induction treatments in UC. We searched Medline, Embase, CENTRAL and grey literature sources up to October 2019. We included randomised controlled trials of patients with active UC that compared FMT, infliximab, adalimumab, golimumab, vedolizumab and tofacitinib to each other or placebo. Efficacy outcomes were clinical remission and response. Safety outcomes were incidence of any adverse event (AE), serious AEs and infections. We conducted random-effects network meta-analysis and ranked treatments based on the surface under the cumulative ranking (SUCRA) probabilities. Results Twenty trials (5177 patients) were included in the analysis. There was only one head to head RCT (vedolizumab vs. adalimumab). FMT was superior to placebo for induction of clinical remission (OR 2.80; 95% CI 1.50–5.23) and response (OR 2.53; 95% CI 1.53–4.20). No indirect comparisons between FMT and licensed treatments reached statistical significance for efficacy outcomes. On SUCRA analysis, FMT (SUCRA 0.57, 0.58) had comparable SUCRA values with golimumab (SUCRA 0.53, 0.39) and vedolizumab (SUCRA 0.58, 0.61) in terms of clinical remission and response respectively. Infliximab (SUCRA 0.71, 0.93) and tofacitinib (SUCRA 0.85, 0.75) were ranked highest while adalimumab (SUCRA 0.23, 0.21) was ranked lowest. There was no increase in the rates of any AEs for FMT and licensed therapies and no differences in indirect comparisons. Vedolizumab (SUCRA 0.81) was the safest option, followed by tofacitinib (SUCRA 0.55). FMT (SUCRA 0.38) had comparable SUCRA values with adalimumab (SUCRA 0.37) and golimumab (SUCRA 0.47). Only tofacitinib increased the incidence of infections compared with placebo (OR 1.51; 95%CI 1.05–2.19). Based on SUCRAs, FMT (SUCRA 0.83) was the safest in terms of infections. Vedolizumab had lower incidence of serious AEs compared with FMT and placebo, while FMT was ranked as the least safe treatment. In subgroup analysis, FMT through the lower gastrointestinal (GI) tract was superior to placebo (OR 3.92; 95%CI 1.94–7.92) and performed numerically better than FMT through the upper GI tract (OR 0.29; 95%CI 0.08–1.13). Conclusion Evidence suggests that FMT could be an efficacious and safe alternative induction therapy for refractory UC. Lower GI delivery of FMT might be more effective. Due to the absence of head-to-head trials and the limited size of FMT trials, conclusions must be interpreted with caution.