A new study in Clinical Infectious Disease reported that bezlotoxumab, given with antibacterials for Clostridium difficile, could be effective as a preventive treatment for C difficile infection (CDI). A multinational group of investigators from the United States and Germany conducted the MODIFY I and MODIFY II clinical trials to evaluate the safety and efficacy of bezlotoxumab, a human monoclonal antibody to C diffiicile, and found that participants given active treatment had reduced rates of rehospitalization at 30 days.
Recurrences of CDI occur in up to 25% of patients who have successfully completed antibiotic therapy, with a 38% chance of a second recurrence.1-3 These 2 trials were able to show a 6% reduction in total CDI-related hospital readmissions at 30 days, and an 8% reduction in high-risk populations, including patients 65 and older or who had severe CDI.
Study co-investigator, Vimalanand S. Prabhu, BE, MMgmt, PhD, director, Outcomes Research at Merck & Co. Inc. Center for Real World and Observational Studies (CORE) in Chapel Hill, North Carolina, explained to Infectious Disease Advisor, “Studying high-risk populations should help define those patients who are most likely to benefit from bezlotoxumab. By determining how many of their recurrences result in a hospitalization, we can then extrapolate how many readmissions can be averted for these high-risk groups. This is very important to show in real-world settings outside the clinical trials.”
The MODIFY I and II trials were global, multicenter, randomized, placebo-controlled trials conducted at 322 sites in 30 countries from November 2011 to May 2015. A total of 530 of 781 (67.9%) participants treated with one dose of bezlotoxumab (10 mg/kg) were hospitalized at the time of randomization, as were 520 of 773 (67.3%) individuals treated with placebo (0.9% saline).
At the end of 30 days, participants taking bezlotoxumab were not only less likely to be re-hospitalized due to CDI (absolute difference, −6.1%; 95% CI, −9.5 to −2.8; relative difference, −53.4%), they were also less likely to be readmitted for other causes (absolute difference, −3.7%; 95% CI, −9.0 to 1.5; relative difference, −12.1%).
Even small reductions in hospital readmission rates can have significant consequences. The healthcare costs associated with CDI in 2014 were estimated at $5.4 billion, the majority of which were hospital-related. “Readmissions have a very significant impact on healthcare utilization, so even if only half of recurrences result in readmission, this would still have a significant impact on reducing healthcare resource utilization,” Dr. Prabhu said.
The investigators considered ways to increase the benefits of bezlotoxumab on readmissions by specifically targeting frailer and high-risk patients who have a lower threshold for hospitalization. Dr Prabhu noted, “This is seen in the sub-group analysis that shows that these patients have higher rates of readmissions compared to the overall population. These high-risk groups have a greater chance of recurrence, as well as being more likely to be readmitted given a recurrence, so reducing recurrence in these patients has even more impact.”
The study may have underestimated the real preventive rates of bezlotoxumab on CDI recurrence, Dr Pradhu pointed out, explaining “The percent of responders is also likely to be a higher in real-world settings, as clinical trials typically have a healthier patient population.” Delays in assessing CDI severity until after treatment may have also contributed to underestimating this feature.
- Prabhu VS, Cornely OA, Golan Y, et al. Thirty-day readmissions in hospitalized patients who received bezlotoxumab with antibacterial drug treatment for Clostridium difficile infection [published online August 11, 2017]. Clin Infect Dis. doi:10.1093/cid/cix523
- Johnson S, Louie TJ, Gerding DN, et al; Polymer Alternative for CDI Treatment (PACT) investigators. Vancomycin, metronidazole, or tolevamer for Clostridium difficile infection: results from two multinational, randomized, controlled trials. Clin Infect Dis 2014;59:345-354.
- Louie TJ, Miller MA, Mullane KM, et al; OPT-80-003 Clinical Study Group. Fidaxomicin versus vancomycin for Clostridium difficile infection. N Engl J Med 2011;364:422-431.
- Sheitoyan-Pesant C, Abou Chakra CN, et al. Clinical and healthcare burden of multiple recurrences of Clostridium difficile infection. Clin Infect Dis 2016;62:574-580.