2115. Efficacy of Bezlotoxumab (bezlo) in Prevention of C. difficile infection Recurrence (rCDI) in Patients Receiving Concomitant Systemic Antibiotics (CAs)
Session: Poster Abstract Session: Clostridium difficile: Therapeutics
Saturday, October 29, 2016
Room: Poster Hall
Posters
  • mccolgam_192470-0001-ID_Week_Poster_v1.04FINAL.pdf (906.0 kB)
  • Background:  Treatment guidelines recommend stopping CAs in patients with CDI but this is not always possible.  MODIFY I and MODIFY II were global, randomized, double-blind, placebo-controlled trials of the efficacy and safety of the anti-C. difficile toxin B monoclonal antibody bezlo for the prevention of rCDI in adults receiving standard of care (SOC) antibiotic treatment for primary or recurrent CDI.  Patients receiving CAs were not excluded from the trials, and patients requiring CAs for other infections during the 12-week follow-up period were continued in the study and assessed for rCDI.  Because rCDI has been associated with receipt of CAs, the efficacy of bezlo was evaluated among patients who received CAs as a post-hoc analysis.

    Methods:  rCDI was defined as a new episode of diarrhea (≥3 unformed stools in 24 hours) and positive stool test for toxigenic C. difficile following clinical cure (CC) of the baseline CDI episode.  CC was defined as SOC antibiotics given for ≤14 days, and no diarrhea for 2 consecutive days after SOC completion.  The proportion of subjects who achieved CC and/or experienced rCDI was calculated for subjects who received at least one dose of CAs during SOC.  A second analysis was conducted for subjects who achieved CC and later received CAs during the post-SOC follow-up period.  Data from MODIFY I and MODIFY II were combined to provide increased precision.

    Results:  During SOC treatment, 37% of bezlo subjects and 41% of placebo subjects received CAs. Among subjects who achieved CC, 33% in each treatment group received CAs during the post-SOC follow-up period. While overall CC at the end of SOC was 80% in both treatment groups, in those who received CAs, CC was reduced equally to 74% (Table). Of those receiving CAs during SOC, rCDI occurred in 18% of bezlo subjects and 28% of placebo subjects. In the post-SOC follow-up period, rCDI among subjects who received CAs occurred in 22% and 34% of the bezlo and placebo groups, respectively. The differences in rCDI between the bezlo and placebo groups in subjects receiving CAs were generally of the same magnitude as those in the overall (FAS) population.

    Conclusion:  Efficacy of bezlo (prevention of rCDI) was maintained in subjects receiving CAs during treatment of the initial episode and during the follow-up period. 

    Kathleen Mullane, DO, FIDSA1, Mark Wilcox, MD2, Yoav Golan, MD MS, FIDSA3, Yoshihiko Murata, MD PhD4, Keri Shoemaker, MS4, Michelle Kelly, MS4, Alison Pedley, PhD4 and Mary Beth Dorr, PhD4, (1)Medicine, University of Chicago Medicine, Chicago, IL, (2)Leeds Teaching Hospitals, Leeds, United Kingdom, (3)Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, MA, (4)Merck & Co., Inc., Kenilworth, NJ

    Disclosures:

    K. Mullane, Merck: Investigator and Scientific Advisor , Consulting fee , Research support and Speaker honorarium
    Ansun: Investigator , Research support
    Astellas: Investigator , Scientific Advisor and Speaker's Bureau , Consulting fee , Research support and Speaker honorarium
    Chimerix: Investigator and Scientific Advisor , Consulting fee and Research support
    Gilead: Investigator , Research support
    Oxford Immunotec: Investigator , Research support
    Rebiotix: Investigator , Research support
    Seres: Investigator and Scientific Advisor , Consulting fee and Research support

    M. Wilcox, MERCK: Grant Investigator , Scientific Advisor and Speaker's Bureau , Consulting fee , Research support and Speaker honorarium
    PFIZER: Grant Investigator , Scientific Advisor and Speaker's Bureau , Consulting fee , Research support and Speaker honorarium
    SUMMIT: Grant Investigator and Scientific Advisor , Consulting fee and Research support
    SERES: Grant Investigator , Scientific Advisor and Speaker's Bureau , Consulting fee , Research support and Speaker honorarium
    DA VOLTERRA: Grant Investigator and Scientific Advisor , Consulting fee and Research support
    BIOMERIEUX: Investigator and Scientific Advisor , Consulting fee and Research support
    ALERE: Grant Investigator , Scientific Advisor and Speaker's Bureau , Consulting fee , Research support and Speaker honorarium
    ACTELION: Grant Investigator and Scientific Advisor , Consulting fee and Research support

    Y. Golan, Merck: Investigator , Scientific Advisor and Speaker's Bureau , Consulting fee , Research grant and Speaker honorarium
    Pfizer: Speaker's Bureau , Speaker honorarium
    The Medicines Company: Speaker's Bureau , Speaker honorarium
    Allergan: Investigator , Scientific Advisor and Speaker's Bureau , Consulting fee , Research grant and Speaker honorarium

    Y. Murata, Merck: Employee , Salary and stock options

    K. Shoemaker, Merck & Co., Inc.: Employee and Shareholder , Salary

    M. Kelly, None

    A. Pedley, Merck & Co: Employee and Shareholder , Salary

    M. B. Dorr, Merck & Co., Inc.: Employee and Shareholder , Salary

    Findings in the abstracts are embargoed until 12:01 a.m. CDT, Wednesday Oct. 26th with the exception of research findings presented at the IDWeek press conferences.