Efficacy and Safety of Monoclonal Antibodies Against Clostridioides difficile Toxins for Prevention of Recurrent Clostridioides difficile Infection: A Systematic Review and Meta-Analysis.

ABSTRACT

BACKGROUND: Clostridioides difficile infection is one of the most common health care-associated infections. To reduce the recurrent Clostridioides difficile infection (rCDI), monoclonal antibodies against Clostridioides difficile toxin A (actoxumab) and toxin B (bezlotoxumab) were developed. In the present study, we performed a systematic review and meta-analysis to assess their efficacy and safety. MATERIALS AND METHODS: An electronic database was searched for relevant randomized controlled trials assessing bezlotoxumab and/or actoxumab. Outcomes included rate of rCDI and adverse events including cardiovascular and gastrointestinal events. RESULTS: Four randomized controlled trials comparing antitoxin antibodies (n=1916) versus placebo (n=889) were identified. rCDI was significantly reduced by bezlotoxumab plus actoxumab (risk ratio=0.54, 95% confidence interval=0.41-0.70, P<0.001) and bezlotoxumab monotherapy (risk ratio=0.62, 95% confidence interval=0.51-0.76, P<0.001) compared with placebo. Subgroup analysis showed that bezlotoxumab plus actoxumab was remarkably preventive for patients with the following high-risk features inpatients, vancomycin treatment, and BI/NAP/027 strain. Regarding safety, there was no difference in cardiovascular and gastrointestinal events as well as all-cause mortality between bezlotoxumab-treated patients and placebo. CONCLUSIONS: The results of our meta-analysis demonstrated the effectiveness and safety of bezlotoxumab for the prevention of rCDI. Bezlotoxumab may be a good therapeutic option for severe C. difficile infection rather than mild cases.