Secondary analyses indicate that bezlotoxumab is more effective in reducing C diff recurrence in patients with pre-specified risk factors.
In a presentation at the 6th International C diff Awareness Conference and Health EXPO on November 8, 2018, in Philadelphia, Pennsylvania, Mary Beth Dorr, PhD, clinical director and product development team lead for bezlotoxumab (Zinplava, Merck), presented data from secondary analyses indicating that the antibody was found to be more effective in reducing Clostridium difficile recurrence in patients with pre-specified risk factors. Following her presentation, Dr. Dorr sat down with Contagion® to discuss the conclusions of the analyses and explain how bezlotoxumab can help prevent recurrence of C diff in patients at a higher risk.
Bezlotoxumab is an antibody that is given when a patient with C diff is receiving antibiotics for treatment. The antibody has a long-half life and provides a passive immunity during the period of time when a patient's microbiota is disrupted, and it gives the body time to replenish the microbiota while preventing the symptoms of C diff recurrence.
The primary endpoint of the phase 3 trials were to reduce C diff infection recurrence in enrolled patients. The overall results indicated a 10% reduction in recurrence when bezlotoxumab was administered, but when looking at subgroups with a higher risk of C diff recurrence, the difference was larger, with an up to 25% reduction in C diff recurrence in patients with 3 or more risk factors.
Because of this, Dr. Dorr and a team of investigators set out to provide further detail about the factors that are considered high-risk for recurrence of infection.
In her interview, she discussed the MODIFY I trial, which consisted of 4 treatment arms: 1 in which patients received bezlotoxumab alone, another in which patient received actoxumab alone, 1 in which patients received a combination of bezlotoxumab and actoxumab, and a placebo arm. All patients received antibiotic treatment; the study drugs were given on top of active antibiotic therapy for the C diff infection.
The patients were followed by investigators for 90 days and asked to keep a diary to record any diarrhea. If diarrhea occurred, the patients were required to call their treating physician who would collect stool samples to determine if the diarrhea was caused by C diff infection.
The results indicated a 10% reduction in recurrence in patients who received either the combination treatment or bezlotoxumab alone. Patients in the actoxumab arm did not show a difference in recurrence from placebo. The investigators also looked at the combination arm in comparison with the bezlotoxumab arm and found that adding actoxumab to bezlotoxumab was not necessary for efficacy.
The investigators observed that in patients who had at least 1 risk factor, there was a 16% reduction in C diff recurrence when bezlotoxumab was administered. In patients with 3 or more risk factors, the difference increased to as high as 25%. These pre-specified risk factors included prior episodes of C diff infection, being over 65 years, being immunocompromised, having severe C diff infection, and infection with C diff strains associated with poor outcomes.
“We further looked at the impact of the number of risk factors, and what we saw is if you have just 1 risk factor, there was a sizeable difference [in recurrence] and the recurrence rate was high in the placebo group,” Dr. Dorr told Contagion®. “As the number of risk factors went up, the placebo rate of recurrence also went up. [The recurrence rate] was highest in patients who had 3 or more risk factors.”
Dr. Dorr continued to explain that knowing these risk factors can help clinicians identify patients at risk for C diff recurrence which can be beneficial in selecting appropriate treatments and preventative strategies.
Future research on bezlotoxumab will focus on determining the reason for recurrence in individuals who do not have these risk factors. Additionally, the team will conduct more analyses to determine if there are additional risk factors present in the phase 3 data. A published paper on analysis evaluating the presence of renal impairment in the study is forthcoming.