Monoclonal Antibody Bezlotoxumab for Prevention of Recurrent C.Diff

C. diff, or Clostridium Difficile, a bacterium that infects the bowel, is the most common cause of infectious diarrhea in hospitalized patients. Recurrences are common after antibiotic treatment, are a cause of re-admissions to hospital, and in some cases can be fatal.

Now researchers have found that the addition of a drug called bezlotoxumab to standard antibiotic treatment can reduce the risk of a repeat infection by 37 percent. Bezlotoxumab is a human monocalonal antibody and works by neutralizing a toxin produced by the C. diff bacteria that damages the gut wall.
For the study, doctors conducted a double-blind, randomized, placebo-controlled trial involving 2,655 adults across over 300 hospitals in 30 countries worldwide.

Background
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 C. difficile toxins A and B, respectively.

Methods
We conducted two 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 C. difficile infection. Participants received an infusion of bezlotoxumab (10 mg per kilogram of body weight), actoxumab plus bezlotoxumab (10 mg per kilogram each), or placebo; actoxumab alone (10 mg per kilogram) was given in MODIFY I but discontinued after a planned interim analysis. The primary end point was recurrent infection (new episode after initial clinical cure) within 12 weeks after infusion in the modified intention-to-treat population.

Results
In both trials, the rate of recurrent C. difficile infection was significantly lower with bezlotoxumab alone than with placebo. In prespecified subgroup analyses (combined data set), 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 rates of sustained cure (initial clinical cure without recurrent infection in 12 weeks) were 64%, 58%, and 54%, respectively. The rates of adverse events were similar among these groups; the most common events were diarrhea and nausea.

Conclusions
Among participants receiving antibiotic treatment for primary or recurrent C. 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.

References:
http://www.iadvanceseniorcare.com/news-item/infection-control/new-c-diff-treatment-reduces-recurrent-infections-40
http://www.nejm.org/doi/full/10.1056/NEJMoa1602615?query=featured_home