2114. Efficacy of Bezlotoxumab in Patients Infected with Strains of Clostridium difficile Associated with Poor Outcomes
Session: Poster Abstract Session: Clostridium difficile: Therapeutics
Saturday, October 29, 2016
Room: Poster Hall
Posters
  • mccolgam_192434-0001-ID_Week_Poster_DiNubile_v1.04_FINAL (2).pdf (468.6 kB)
  • Background:  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 bezlotoxumab (bezlo) for the prevention of CDI recurrence in adults receiving standard of care antibiotic treatment (metronidazole, vancomycin, or fidaxomicin) for primary or recurrent CDI. A secondary objective was to assess the efficacy of bezlo against C. difficile strains associated with increased rates of morbidity and mortality (REA group BI, or ribotypes 027, 078 or 244).

    Methods:  Subjects provided a stool sample within 72 hours of randomization and at the time of a new episode of diarrhea. Stool samples with a positive culture at the central laboratory were sent to reference laboratories for REA and PCR ribotyping. CDI recurrence was defined as a new episode of diarrhea (≥3 unformed stools in 24 hours) and positive stool test for toxigenic C. difficile after clinical cure of the baseline CDI episode. Data from MODIFY I and MODIFY II were combined for a pre-specified pooled efficacy analysis, providing increased precision for estimating treatment effects.

    Results:  Across all treatment groups in MODIFY I+II, 1597 subjects (63% of the Full Analysis Set) had a positive baseline culture for C. difficile.  A BI strain was identified in 328 (20.5%) and ribotypes 027, 078, or 244 were identified in 337 baseline cultures (21.1%).  Overall, 84.8% of BI strains were ribotype 027. CDI recurrence rates by strain type for the bezlo and placebo groups are shown below (table).  CDI recurrence rates were lower in subjects who received bezlo compared with those who received placebo in the overall population, in subjects with a positive baseline culture, and in subjects infected with a strain associated with poor outcomes.  Although the study was not powered to demonstrate significant recurrence reduction according to strain type, the magnitude of the reduction for recurrent infections due to these strains was similar to the reduction in the overall population.

    Conclusion:  Neutralization of C. difficile toxin B by the monoclonal antibody bezlotoxumab, in subjects receiving standard of care antibiotics for CDI, reduces CDI recurrence in subjects infected with strains associated with poor outcomes.

     

    Stuart Johnson, MD, FIDSA1,2, Susan Sambol, MT1,2, Emma Best, PhD3, Mark Wilcox, MD3,4, Dale Gerding, MD, FIDSA5, Karen Eves, BS6, Alison Pedley, PhD6, Nicholas Kartsonis, MD6 and Mary Beth Dorr, PhD6, (1)Edward Hines, Jr. VA Hospital, Hines, IL, (2)Loyola University Chicago Stritch School of Medicine, Maywood, IL, (3)Leeds Teaching Hospitals, Leeds, United Kingdom, (4)University of Leeds, Leeds, United Kingdom, (5)Loyola University and Hines VA Hospital, Hines, IL, (6)Merck & Co., Inc., Kenilworth, NJ

    Disclosures:

    S. Johnson, Merck: Grant Investigator , Research grant
    Bio-K+: Scientific Advisor , Consulting fee
    Summit Therapeutics: Scientific Advisor , Consulting fee
    Seres Therapeutics: Scientific Advisor , Consulting fee

    S. Sambol, None

    E. Best, None

    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

    D. Gerding, Merck: Scientific Advisor , Consulting fee
    ViroPharma/Shire: Consultant , Consulting fee
    Pfizer: Consultant , Consulting fee
    Actelion: Scientific Advisor , Consulting fee
    Summit: Scientific Advisor , Consulting fee
    DaVolterra: Consultant , Consulting fee
    Sanofi Pasteur: Consultant , Consulting fee
    Rebiotix: Scientific Advisor , Consulting fee
    Seres Therapeutics: Grant Investigator , Research grant

    K. Eves, Merck & Co.: Employee and Shareholder , Salary

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

    N. Kartsonis, Merck and Co., Inc.: Member and Shareholder , Salary and Stock

    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.