Bezlotoxumab Reduces Rates of Recurrent C. Diff Infection

By Will Boggs MD

January 17, 2020

NEW YORK (Reuters Health) - The monoclonal antibody bezlotoxumab reduces the rate of recurrent Clostridioides difficile infection, according to findings from the MODIFY II trial.

"We found that many of the patients (16% to 32%) who were tested at 6, 9, or 12 months after they were treated for C. difficile infection (CDI) still had a toxigenic strain of C. difficile in their stool," said Dr. Mary Beth Dorr of Merck and Company, Inc., in Kenilworth, New Jersey.

"Despite this relatively high incidence of colonization, only a few of these patients exhibited symptoms of disease during this period," she told Reuters Health by email.

Patients who mount immune responses against C. difficile toxins A and B have lower rates of recurrent CDI. The monoclonal antibody actoxumab neutralizes toxin A, and bezlotoxumab neutralizes toxin B, and their combination and bezlotoxumab alone were superior to placebo in preventing recurrent CDI through 12 weeks of the MODIFY I/II trials.

In the current study, Dr. Dorr and colleagues evaluated results from 295 MODIFY II participants who were followed for 12 months to assess the long-term rates of recurrent CDI and C. difficile colonization following antitoxin infusion.

The recurrent CDI incidence rates during the core study for these patients were 25.3% with actoxumab plus bezlotoxumab, 18.8% with bezlotoxumab alone, and 50.0% with placebo.

The 12-month incidence rates of recurrent CDI among the 168 patients who had achieved a sustained clinical cure during the core study were 27.6% with actoxumab plus bezlotoxumab, 18.8% with bezlotoxumab alone, and 51.5% with placebo, the researchers report in Clinical Infectious Diseases.

In the bezlotoxumab group, there were no cases of recurrent CDI in the nine-month extension period.

Colonization rates were similar across treatment groups at each follow-up visit: 18%-25% in the actoxumab plus bezlotoxumab group, 16%-24% in the bezlotoxumab group and 19%-32% in the placebo group.

Bezlotoxumab has an elimination half-life of around 19 days and remains detectable in serum at clinically important concentrations up to six months after treatment.

"Bezlotoxumab is indicated for prevention of C. difficile recurrence in patients at high risk for recurrence," Dr. Dorr said. "Known risk factors for recurrence include advanced age (65 years and older), recurrent disease, immunosuppression, and need for treatment with high-risk systemic antibiotics that disrupt the gut microbiota."

"Bezlotoxumab is given as a single dose of 10 mg/kg," she said. "It is available as a 1,000-mg single-use vial which costs $3,800."

Dr. Kiki Chung of Leiden University Medical Center, in the Netherlands, who recently reviewed antibody-mediated therapy for the treatment and prevention of CDI, highlighted the "persistent colonization of C. difficile in the intestinal tract after 12 months of treatment with bezlotoxumab or placebo in 20% of the patients."

"The effect seems to be a sustainable one (for 12 months at least)," she told Reuters Health by email. "But this effect is also seen in the placebo group that has an almost equal lack of recurrent CDI in months 4-12."

"After 12 weeks, recurrent CDI is rare, even though colonization is common (in all patients, regardless of treatment)," said Dr. Chung, who was not involved in the study. "The increase of sustained clinical cure (of 12 weeks) when using actoxumab-bezlotoxumab or bezlotoxumab, compared to placebo, is due to prevention rather than delay."

Merck Sharp and Dohme Corp., a subsidiary of Merck and Company, Inc., funded the study and employed several of the authors.

SOURCE: Clinical Infectious Diseases, online December 23, 2019.