Efficacy of bezlotoxumab in trial participants infected with Clostridioides difficile strain BI associated with poor outcomes.

BACKGROUND Bezlotoxumab reduced rates of recurrent Clostridioides difficile infection (rCDI) versus placebo in 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 (REA) 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 rates 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 re-hospitalization were greater with BI versus non-BI strains in both groups. CONCLUSIONS Infection with BI strains of C. difficile predicted poor outcomes in the MODIFY I/II trials. Bezlotoxumab (B, B+A) treatment was effective both in BI and non-BI subpopulations.