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MODIFY: Zinplava reduces C. diff recurrence regardless of antibiotic choice
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NEW ORLEANS — Zinplava prevented recurrent Clostridium difficile infection regardless of which standard of care antibiotics patients received, according to a prespecified analysis of the MODIFY trials presented at IDWeek 2016.
Zinplava (bezlotoxumab, Merck) is a fully human IgG1 monoclonal antibody that neutralizes the effects of C. difficile toxin B. It was recently approved by the FDA for the prevention of recurrent C. difficile infection (CDI) in high-risk adults receiving antibiotic therapy for CDI, and Merck expects it will be available in the first quarter of 2017, according to a press release.
Erik R. Dubberke
“It’s a novel non-antibiotic approach to prevention of CDI recurrence when given in addition to standard of care antibiotics for [CDI],” Erik R. Dubberke, MD, MSPH, of the division of infectious diseases, Washington University School of Medicine, said during his presentation. “Its efficacy was demonstrated in two randomized placebo controlled trials: MODIFY I and MODIFY II.”
To determine whether the choice of standard of care antibiotic — metronidazole, vancomycin or fidaxomicin — influenced CDI recurrence after bezlotoxumab therapy, MODIFY investigators stratified randomization based on antibiotic treatment for a pre-specified analysis.
Among 781 CDI patients who received bezlotoxumab and 773 who received placebo, 48.5% received oral metronidazole, 48.5% received oral vancomycin alone or with IV metronidazole, and 3.6% received oral fidaxomicin alone or with IV metronidazole. Recurrent CDI patients were more likely to receive vancomycin (71%) while primary CDI patients were more likely to receive metronidazole (60%).
“Patients receiving vancomycin were older and sicker, and had more risk factors for recurrent [CDI],” Dubberke noted.
Rates of clinical cure — defined as absence of diarrhea for at least 2 consecutive days after completion of no more than 2 weeks of standard of care antibiotics — were comparable between treatment and placebo groups regardless of antibiotic type, which was consistent with overall study results (80% vs. 80.3%). Moreover, the bezlotoxumab group had a lower CDI recurrence rate compared with placebo in all three antibiotic subgroups (16.5% vs. 26.6% overall).
“Bezlotoxumab had no impact on the proportion of patients that achieved clinical cure regardless of the stratum, and overall 80% of subjects achieved clinical cure. However ... 10% fewer [patients who received bezlotoxumab] had recurrence compared to those on placebo in the metronidazole arm, 15% fewer in the vancomycin stratum and 12% fewer in the fidaxomicin stratum, for a 12% reduction in recurrence amongst those people who received bezlotoxumab compared to placebo overall in the trial, and the results for metronidazole, vancomycin and all subjects were statistically significant,” Dubberke said. “Bezlotoxumab did not affect the initial clinical response at the end of standard of care therapy, and bezlotoxumab reduced the proportion of subjects with [CDI] recurrence regardless of the standard of care antibiotic given for treatment of the presenting episode.” – by Adam Leitenberger
Reference:
Dubberke ER, et al. Abstract #838. Presented at: IDWeek; Oct. 25-30, 2016; New Orleans.
Disclosures: Dubberke reports financial relationships with Rebiotix, Merck, Sanofi Pasteur and Summit. Please see the full study for a list of all other researchers’ relevant financial disclosures.