Efficacy of Bezlotoxumab in Participants Receiving Metronidazole, Vancomycin, or Fidaxomicin for Treatment of Clostridioides (Clostridium) difficile Infection

Abstract

In phase 3 MODIFY I/II trials, bezlotoxumab significantly reduced recurrence of Clostridioides (Clostridium) difficile infection (rCDI) over 12 weeks. Choice of CDI antibacterial treatment may affect CDI-related outcomes; therefore, this prespecified analysis assessed if the magnitude of bezlotoxumab-induced rCDI reduction was influenced by the antibiotic administered. In MODIFY I/II (NCT01241552/NCT01513239), participants received a single infusion of bezlotoxumab (10 mg/kg) or placebo during anti-CDI treatment. Using pooled data from MODIFY I/II, initial clinical cure (ICC) and rCDI were assessed in metronidazole-, vancomycin-, and fidaxomicin-treated subgroups. Of 1554 participants in MODIFY I/II, 753 (48.5%) received metronidazole, 745 (47.9%) vancomycin, and 56 (3.6%) fidaxomicin. Fewer participants receiving metronidazole had a prior CDI episode in the previous 6 months (12.9%) or ≥1 risk factor for rCDI (66.0%) vs participants receiving vancomycin (41.2% and 83.6%, respectively) and fidaxomicin (55.4% and 89.3%, respectively). ICC rates were similar in the bezlotoxumab (metronidazole, 81.0%; vancomycin, 78.5%; fidaxomicin, 86.7%) and placebo groups (metronidazole, 81.3%; vancomycin, 79.6%; fidaxomicin, 76.9%). In placebo-treated participants, the rCDI was lower in the metronidazole subgroup vs the vancomycin and fidaxomicin subgroups (metronidazole, 28.0%; vancomycin, 38.4%; fidaxomicin, 35.0%). When analyzed by subsets based on history of CDI, rCDI rates were similar in the metronidazole and vancomycin groups. rCDI rates were lower in all antibiotic subgroups for bezlotoxumab vs placebo (metronidazole: rate difference [RD], –9.7%; 95% confidence interval [CI], –16.4% to –3.1%; vancomycin: RD, –15.4%; 95% CI, –22.7% to –8.0%; fidaxomicin: RD, –11.9%; 95% CI, –38.1% to 14.3%). Bezlotoxumab reduces rCDI vs placebo in participants receiving metronidazole and vancomycin, with a similar effect size in participants receiving fidaxomicin.