Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection in Patients at Increased Risk for Recurrence

Abstract

BackgroundBezlotoxumab is a human monoclonal antibody against Clostridium difficile toxin B indicated to prevent C. difficile infection (CDI) recurrence (rCDI) in adults at high risk for rCDI. This post hoc analysis of pooled monocolonal antibodies for C.difficile therapy (MODIFY) I/II data assessed bezlotoxumab efficacy in participants with characteristics associated with increased risk for rCDI.MethodsThe analysis population was the modified intent-to-treat population who received bezlotoxumab or placebo (n = 1554) by risk factors for rCDI that were prespecified in the statistical analysis plan: age ≥65 years, history of CDI, compromised immunity, severe CDI, and ribotype 027/078/244. The proportion of participants with rCDI in 12 weeks, fecal microbiota transplant procedures, 30-day all cause and CDI-associated hospital readmissions, and mortality at 30 and 90 days after randomization were presented.ResultsThe majority of enrolled participants (75.6%) had ≥1 risk factor; these participants were older and a higher proportion had comorbidities compared with participants with no risk factors. The proportion of placebo participants who experienced rCDI exceeded 30% for each risk factor compared with 20.9% among those without a risk factor, and the rCDI rate increased with the number of risk factors (1 risk factor: 31.3%; ≥3 risk factors: 46.1%). Bezlotoxumab reduced rCDI, fecal microbiota transplants, and CDI-associated 30-day readmissions in participants with risk factors for rCDI.ConclusionsThe risk factors prespecified in the MODIFY statistical analysis plan are appropriate to identify patients at high risk for rCDI. While participants with ≥3 risk factors had the greatest reduction of rCDI with bezlotoxumab, those with 1 or 2 risk factors may also benefit.Clinical Trials RegistrationNCT01241552 (MODIFY I) and NCT01513239 (MODIFY II).

Real-world efficacy of bezlotoxumab for prevention of recurrent Clostridium difficile infection: a retrospective study of 46 patients in five university hospitals in Finland

“…Patients with more than or equal to three risk factors experienced the greatest reduction in CDI recurrence with BEZ (− 24.8% [range − 39.1%, − 9.3%]), suggesting a potential targeted patient population for the drug. One limitation of these data is that several of the risk factors are loosely defined, including immunocompromised patients, which was based on clinical criteria [21]. …”

Recommendations for the diagnosis and treatment of Clostridioides difficile infection: An official clinical practice guideline of the Spanish Society of Chemotherapy (SEQ), Spaish Society of Internal Medicine (SEMI) and the working group of Postoperative Infection of the Spanish Society of Anesthesia and Reanimation (SEDAR)

“…The patients to be selected are obviously those in whom a high risk of recurrence is predictable. In this sense, the best-known elements of risk associated to the host are advanced age (≥65 years), the need to maintain antibiotic treatment for baseline infection, deficiencies in humoral immunity response, serious underlying diseases and the need to continue taking proton pump inhibitors, among others [185]. As the microorganism is concern, it seems clear that strains with high toxin production, as is the case with many of those grouped as 027, are associated with an increased risk of recurrence [186][187][188][189].…”

“…Interestingly, these scoring systems show us that certain patients in the first episode of CDI have a higher risk of recurrence than other patients in the second episode [185].…”

Modern approach to the therapy of infections caused by Clostridium difficile

“…The addition of actoxumab (human monoclonal antibody against CD toxin A) did not result in enhanced effectiveness of bezlotoxumab 7 . After additional analysis of aggregatedata from MODIFY I and II studies, based on stratification of risk for recurrence, bezlotoxumab showed not onlysignificant reduction of recurrent events, but also FMT was used to a lesser degree and lower readmission rate to hospital at 30 days due to CDI was registered in comparison to placebo 20 . Taking into account the latter results, it was recommended that patients who have 3 or more risk factors for recurrent CDI can benefit most from adding bezlotoxumab to standard antibiotic treatment, and this could also be useful for those with fewer risk factors 20 .…”

“…After additional analysis of aggregatedata from MODIFY I and II studies, based on stratification of risk for recurrence, bezlotoxumab showed not onlysignificant reduction of recurrent events, but also FMT was used to a lesser degree and lower readmission rate to hospital at 30 days due to CDI was registered in comparison to placebo 20 . Taking into account the latter results, it was recommended that patients who have 3 or more risk factors for recurrent CDI can benefit most from adding bezlotoxumab to standard antibiotic treatment, and this could also be useful for those with fewer risk factors 20 . However, this shortlived protective effect of bezlotoxumab requires further investigations that would deal with its possible long-term positive influence on incidence of recurrent CDIs.…”