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

Abstract

Background:

Bezlotoxumab 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.

Methods:

The 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.

Results:

The 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.

Conclusions:

The 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 Registration:

NCT01241552 (MODIFY I) and NCT01513239 (MODIFY II).

• Authors: Dale N Gerding, Ciaran P Kelly, Galia Rahav, Christine Lee, Erik R Dubberke, Princy N Kumar, Bruce Yacyshyn, Dina Kao, Karen Eves, Misoo C Ellison, Mary E Hanson, Dalya Guris, Mary Beth Dorr
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 67 Issue 5 Pg. 649-656 (08 16 2018) ISSN: 1537-6591 [Electronic] United States
• PMID: 29538686 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Antibodies, Monoclonal
• Antibodies, Neutralizing
• Broadly Neutralizing Antibodies
• Metronidazole
• bezlotoxumab
• Vancomycin
• Fidaxomicin

Topics

• Adolescent
• Adult
• Age Factors
• Aged
• Aged, 80 and over
• Anti-Bacterial Agents (therapeutic use)
• Antibodies, Monoclonal (therapeutic use)
• Antibodies, Neutralizing (therapeutic use)
• Broadly Neutralizing Antibodies
• Clostridioides difficile (drug effects)
• Clostridium Infections (mortality, prevention & control)
• Fecal Microbiota Transplantation
• Female
• Fidaxomicin (administration & dosage)
• Humans
• Male
• Metronidazole (administration & dosage)
• Middle Aged
• Patient Readmission
• Recurrence
• Risk Factors
• Secondary Prevention
• Vancomycin (administration & dosage)
• Young Adult