The MODIFY I and MODIFY II trials were designed to evaluate monoclonal antibody bezlotoxumab (which provides passive immunity to toxin B), actoxumab (which provides passive immunity to toxin A), and the combination of these agents in comparison with placebo among participants who were receiving standard-of-care therapy with oral vancomycin, metronidazole, or fidaxomicin (the actoxumab-only regimen was discontinued after an interim analysis and was included only in MODIFY I).
According to a commentary, a possible advantage of bezlotoxumab is that it provides passive immunity to a microbial product and therefore is not subjected to the risk of antibiotic resistance, though C. difficile resistance to standard antibiotic therapy has not been problematic, despite extensive use of these agents. It adds that there are several important issues that are unresolved and need to be addressed, particularly relative risk stratification and product cost. It notes that the relative benefits and risks associated with each combination of standard antibiotic with bezlotoxumab not fully understand-the assessment of bezlotoxumab combined with fidaxomicin is particularly important, since this agent has already been shown to have substantial clinical success and cost effectiveness for preventing relapses of C. difficile infection in patients with primary infection. In addition, stool transplantation has proved highly successful for patients with relapsing C. difficile infection, but this treatment is generally reserved for patients who have had multiple relapses.
Bezlotoxumab has now been approved by the FDA for the management of C. difficile infection. In November 2016, the European Medicines Agency issued a positive opinion on the marketing authorisation application for bezlotoxumab for the prevention of recurrence of C. difficile infection in adults at high risk for recurrence.