"Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection" The New England Journal of Medicine. 2017. 376:305-317. PubMed
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Does bezlotoxumab, a monoclonal antibody against Clostridium difficile toxin B, reduce the recurrence of C. difficile infection in adults receiving antibiotics for primary or recurrent infection?
Among adults receiving standard-of-care antibiotics for C. difficile infection, bezlotoxumab decreased the recurrence of infection and had a safety profile similar to that of placebo. Actoxumab, an antibody against toxin A, provided no additional benefit when used with bezlotoxumab.
Clostridium difficile infection is a significant cause of diarrhea in hospitalized patients, and recurrence of infection is common post-antibiotic treatment. Bezlotoxumab, a human monoclonal antibody against C. difficile toxin B, was evaluated for its efficacy in preventing recurrence when administered alongside standard antibiotics.
As of the latest update, no guidelines have been published that reflect the results of this trial.
- MODIFY I and MODIFY II: Two double-blind, randomized, placebo-controlled, phase 3 trials. - N=2,655 adults with primary or recurrent C. difficile infection. - Intervention groups: bezlotoxumab (10 mg/kg), actoxumab plus bezlotoxumab (10 mg/kg each), placebo; actoxumab alone given in MODIFY I but discontinued after an interim analysis. - Setting: 322 sites in 30 countries. - Enrollment: November 1, 2011, through May 22, 2015. - Analysis: Intention-to-treat. - Primary efficacy outcome: recurrent infection within 12 weeks after infusion in the modified intention-to-treat population. - Safety outcome: adverse events during a 12-week follow-up period.
- Adults with primary or recurrent C. difficile infection receiving oral standard-of-care antibiotics. - Inclusion criteria: Diarrhea with a positive stool test for toxigenic C. difficile. - Exclusion criteria: Symptomatic ventricular arrhythmias, non-sustained ventricular tachycardia (NSVT) ≥15 PVCs per hour at a rate of ≥120 bpm.
- Participants were stratified according to standard-of-care antibiotics and hospitalization status. - Randomly assigned to receive a single infusion of bezlotoxumab, actoxumab plus bezlotoxumab, placebo, or actoxumab alone.
- Recurrent C. difficile infection rate was significantly lower with bezlotoxumab alone (17% in MODIFY I, 16% in MODIFY II) and with actoxumab plus bezlotoxumab (16% in MODIFY I, 15% in MODIFY II) than with placebo (28%). - Initial clinical cure rates were 80% with bezlotoxumab alone and actoxumab plus bezlotoxumab, and 80% with placebo; sustained cure rates were 64%, 58%, and 54%, respectively. - Adverse events were similar across the groups, with diarrhea and nausea being the most common.
- Standard-of-care antibiotic selection was not standardized. - Efficacy of bezlotoxumab unaffected by choice of standard-of-care antibiotic. - Assessed time from infusion to onset of symptoms was broad, limiting the assessment of antitoxin effect on severity and duration of baseline episode. - Potentially serious but low-frequency toxic effects difficult to detect due to relatively small number of patients.
The study was funded by Merck.
- Wilcox MH, et al. "Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection: A Randomised, Double-Blind, Placebo-Controlled Trial". Lancet. 2017;389(10066): 276-287. - Full text of the MODIFY I and MODIFY II trials available at NEJM.org.