Comparing the efficacy and safety of faecal microbiota transplantation with bezlotoxumab in reducing the risk of recurrent Clostridium difficile infections: a systematic review and Bayesian network meta-analysis of randomised controlled trials.

OBJECTIVES: The risk of recurrent Clostridium difficile infections (RCDIs) is high when treated with standard antibiotics therapy (SAT) alone. It is suggested that the addition of faecal microbiota transplantation (FMT) or bezlotoxumab after SAT reduces the risk of RCDI. In the absence of head-to-head randomised controlled trials (RCTs), this review attempts to compare the efficacy and safety of bezlotoxumab with FMT in reducing the risk of RCDI in hospitalised patients.

DESIGN: A systematic review and Bayesian network meta-analysis.

DATA SOURCE: A comprehensive search from inception to 30 February 2019 was conducted in four databases (Medline/PubMed, Embase, Scopus, ClinicalTrials.gov).

ELIGIBILITY CRITERIA: RCTs reporting the resolution of diarrhoea associated with RCDI without relapse for at least 60 days after the end of treatments as the primary outcome.

DATA EXTRACTION AND SYNTHESIS: We extracted author, year of publication, study design and binomial data that represented the resolution of diarrhoea or adverse events of monoclonal antibodies and FMT infusion. Random-effects models were used for resolution rate of RCDI and adverse events. The Cochrane Risk of Bias tool was used to assess the quality of included RCTs.

RESULTS: Out of 1003 articles identified, seven RCTs involving 3043 patients contributed to the review. No difference was reported between single or multiple infusions of FMT and bezlotoxumab in resolving RCDI, (OR 1.53, 95% credible interval (CrI) 0.39 to 5.16) and (OR 2.86, 95% CrI 1.29 to 6.57), respectively. Patients treated with SAT alone or bezlotoxumab with SAT showed significantly lower rates of diarrhoea than FMT (OR 0, 95% CrI 0 to 0.09) and (OR 0, 95% CrI 0 to 0.19), respectively. There was no difference in terms of other adverse events.

CONCLUSIONS: This is the first network meta-analysis that has compared the recently Food and Drug Administration-approved monoclonal antibody bezlotoxumab with FMT for resolving RCDI. The quality of the included RCTs was variable. The findings of this study suggested no difference between single or multiple infusions of FMT and bezlotoxumab. However, FMT was associated with a higher rate of non-serious diarrhoea as opposed to SAT used alone or in combination with bezlotoxumab.