Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients.
Recurrences are common after antibiotic therapy.
Actoxumab and bezlotoxumab are human monoclonal antibodies against Clostridium difficile toxins A and B, respectively.
Dr Mark Wilcox conducted 2 double-blind, randomized, placebo-controlled, phase 3 trials, MODIFY I and MODIFY II, involving 2655 adults receiving oral standard-of-care antibiotics for primary or recurrent Clostridium difficile infection.
Participants received an infusion of bezlotoxumab, actoxumab plus bezlotoxumab, or placebo; actoxumab alone was given in MODIFY I but discontinued after a planned interim analysis.
The team's primary end point was recurrent infection within 12 weeks after infusion in the modified intention-to-treat population.
|The rates of initial clinical cure were 80% with bezlotoxumab alone|
|New England Journal of Medicine|
In both trials, the rate of recurrent Clostridium difficile infection was significantly lower with bezlotoxumab alone than with placebo, and was significantly lower with actoxumab plus bezlotoxumab than with placebo.
In a combined data set, the team found that rates of recurrent infection were lower in both groups that received bezlotoxumab than in the placebo group in subpopulations at high risk for recurrent infection or for an adverse outcome.
The rates of initial clinical cure were 80% with bezlotoxumab alone, 73% with actoxumab plus bezlotoxumab, and 80% with placebo.
The researchers observed that the rates of sustained cure were 64%, 58%, and 54%, respectively.
The rates of adverse events were similar among these groups.
The team noted that the most common events were diarrhea and nausea.
Dr Wilcox's team comments, "Among participants receiving antibiotic treatment for primary or recurrent Clostridium difficile infection, bezlotoxumab was associated with a substantially lower rate of recurrent infection than placebo, and had a safety profile similar to that of placebo."
"The addition of actoxumab did not improve efficacy."