Bezlotoxumab, a human monoclonal antibody against Clostridioides difficile toxin B, was found to prevent recurrence of infection as well as C difficile-associated rehospitalizations, according to the results of an analysis recently published in the European Journal of Clinical Microbiology & Infectious Diseases.
The phase 3 MODIFY I and II trials (ClinicalTrials.gov Identifiers: NCT01241552 and NCT01513239) demonstrated that when given during standard-of-care antibiotic treatment for an active C difficile infection, bezlotoxumab significantly reduced the incidence of recurrent infection in high-risk adults. However, as healthcare practices and reimbursement methods differ across European countries, as do C difficile strains isolated from European and North American participants, a post hoc analysis was conducted to assess the efficacy of bezlotoxumab in preventing recurrent C difficile infection, as well as other secondary efficacy outcomes, in a subgroup of European participants enrolled in the MODIFY I and II trials.
In total, 606 European participants from the MODIFY trials (bezlotoxumab 10 mg/kg single intravenous infusion, n=313; placebo, n=293) were included in the analysis. Data from both groups were compared to assess initial clinical cure, recurrent C difficile infection, all-cause and C difficile infection-associated rehospitalizations within 30 days of discharge, and mortality through 12 weeks postinfusion.
Results were consistent with those seen in the MODIFY I and II trials. Baseline characteristics between the 2 treatment groups analyzed were generally similar, with more immunocompromised participants in the bezlotoxumab group than in the placebo group (27.2% vs 20.1%). The overall rate of initial clinical cure was similar between the 2 groups. The rate of recurrent C difficile infection in the bezlotoxumab group was lower compared with the placebo group; this was also observed among participants with at least 1 risk factor for recurrent C difficile infection. A reduction in the rate of 30-day C difficile infection-associated rehospitalizations was noted in the bezlotoxumab group vs the placebo group.
“[I]t is reasonable to consider the use of bezlotoxumab as an adjunct to standard of care antibacterial therapy in European patients with one or more risk factors for [recurrent C difficile infection],” the authors report. In addition, “…the differences in strain types and the differences in their distribution between North America and Europe did not appear to impact the efficacy of bezlotoxumab in reducing the rate of [recurrent C difficile infection] in the European population compared with the global population enrolled in the MODIFY trials.”
Bouza E, Cornely OA, Ramos-Martinez A, et al. Analysis of C. difficile infection-related outcomes in European participants in the bezlotoxumab MODIFY I and II trials [published online June 6, 2020]. Eur J Clin Microbiol Infect Dis. doi:10.1007/s10096-020-03935-3.