Efficacy of Bezlotoxumab in Trial Participants Infected With Clostridioides difficile Strain BI Associated With Poor Outcomes

Abstract Background Bezlotoxumab reduced rates of recurrent Clostridioides difficile infection (rCDI) vs placebo in Monoclonal Antibodies for C. difficile Therapy (MODIFY) I/II trial participants receiving antibacterial drug treatment for CDI. A secondary objective of MODIFY I/II was to assess bezlotoxumab’s efficacy against C. difficile strains associated with increased rates of morbidity and mortality. Methods In this post-hoc analysis of pooled MODIFY I/II data, efficacy endpoints were assessed in participants infected with restriction endonuclease analysis BI and non-BI strains of C. difficile at study entry. Treatment outcomes were compared between participants receiving bezlotoxumab (alone or with actoxumab [B, B+A]) and those receiving no bezlotoxumab (placebo or actoxumab [P, A]). Results From 2559 randomized participants, C. difficile was isolated from 1588 (67.2%) baseline stool samples. Participants with BI strains (n = 328) were older and had more risk factors for rCDI than non-BI strain participants (n = 1260). There were no differences in initial clinical cure rate between BI and non-BI strains in either group. The rCDI rate for BI strains treated with bezlotoxumab was lower than for the no bezlotoxumab group (B, B+A vs P, A: 23.6% vs 43.9%) and was also lower for the non-BI strains (B, B+A vs P, A: 21.4% vs 36.1%). Rates of 30-day CDI-associated rehospitalization were greater with BI vs non-BI strains in both groups. Conclusions Infection with BI strains of C. difficile predicted poor outcomes in the MODIFY I/II trials. Bezlotoxumab (alone or with actoxumab) treatment was effective both in BI and non-BI subpopulations. Bezlotoxumab (alone or with actoxumab), alongside antibacterial drug treatment for Clostridioides difficile infection (CDI), was similarly effective at reducing CDI recurrence in both phase 3 trial participants infected with BI strain and in those infected with non-BI C. difficile strains.