Is Bezlotoxumab Efficacy Affected by Concomitant Antibiotics for C. diff?
NEW ORLEANS, LA—Patients given bezlotoxumab exhibited significantly less Clostridium difficile infection (CDI) recurrence regardless of choice of standard of care (SoC) antibiotics, according to a study presented at IDWeek.
Two global, randomized, double-blind, placebo-controlled trials—MODIFY I and MODIFY II—evaluated the safety and efficacy of bezlotoxumab, an anti-C. difficile toxin B monoclonal antibody for the prevention of CDI recurrence in adults receiving SoC antibiotics (metronidazole, vancomycin, or fidaxomicin) for primary or recurrent CDI.
Bezlotoxumab represents a novel, non-antibiotic approach to prevent CDI recurrence. In 2013, the Centers for Disease Control and Prevention declared C. difficile "an urgent public health threat." The ubiquitous spore-forming bacterium has become the leading cause of hospital-associated infection in the United States, and incidence of community-associated CDI is also increasing. An estimated 453,000 initial episodes of CDI occurred in 2011; recurrent episodes numbered 83,000 and there were 29,000 CDI-associated deaths.
Erik R. Dubberke, MD, MSPH, from Washington University School of Medicine, St. Louis, MO, and colleagues conducted a pre-specified analysis to assess clinical cure (initial clinical response) and CDI recurrence based on SoC antibiotic received. Their rationale: CDI recurrence (primary end point) might be influenced by the SoC antibiotic selected.
Bezlotoxumab or placebo (normal saline) was given with SoC antibiotics chosen by the treating physician. The primary end point was defined as a new episode of diarrhea (at least 3 unformed stools within 24 hours) and positive stool test for toxigenic C. difficile after clinical cure of the baseline CDI episode. Clinical cure was defined as SoC antibiotics administered for up to 14 days and no diarrhea for 2 days after completing SoC. CDI recurrence was defined as a new episode of diarrhea and a positive stool test following clinical cure of a baseline CDI episode. Data from MODIFY I and MODIFY II were pooled to provide increased precision for estimating treatment effects.
The most common SoC antibiotics administered were oral metronidazole (48% of subjects) or oral vancomycin (alone or with intravenous metronidazole, 48%). Oral fidaxomicin (alone or with intravenous metronidazole) was given to 4% of study patients.
As seen with overall study data, clinical cure rates were similar in both the bezlotoxumab and placebo groups regardless of SoC antibiotic received. "Bezlotoxumab did not affect the initial clinical response at the end of SoC therapy," Dr. Dubberke said. However, "patients receiving vancomycin had more risk factors for CDI recurrence."
Rates of CDI recurrence were lower among patients who received bezlotoxumab vs. placebo across all 3 SoC subgroups: metronidazole (18.2% vs. 28.0%), vancomycin (22.9% vs. 38.4%), and fidaxomicin (23.1% vs. 35.0%), all of which were statistically significant vs. placebo. For all subjects, CDI recurrence was 20.6% in the bezlotoxumab arm and 33.2% in the placebo arm.
"Bezlotoxumab reduced the proportion of subjects with CDI recurrence regardless of the SoC antibiotic given for treatment of the presenting episode," he concluded.
The study was funded by Merck & Co., Inc.