Bezlotoxumab for the Prevention of Recurrent Clostridioides difficile Infection: 12-Month Observational Data From the Randomized Phase III Trial, MODIFY II.

Published on Aug 14, 2020in Clinical Infectious Diseases9.079
路 DOI :10.1093/CID/CIZ1151
Ellie J. C. Goldstein66
Estimated H-index: 66
,
Diane M. Citron57
Estimated H-index: 57
+ 5 AuthorsMary Beth Dorr15
Estimated H-index: 15
(MSD: Merck & Co.)
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Abstract
From Monoclonal Antibodies for C. difficile Therapy II, no participants (n = 0/69) with a sustained clinical cure through 12 weeks following bezlotoxumab infusion experienced recurrent Clostridioides difficile infection (rCDI) after 9 months (versus actoxumab + bezlotoxumab, n = 2/65; versus placebo, n = 1/34). Bezlotoxumab's efficacy appears to be due to prevention rather than delayed onset of rCDI. CLINICAL TRIALS REGISTRATION: NCT01513239.
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References5
Newest
#1Ka Lai Yee (MSD: Merck & Co.)H-Index: 11
#2Huub Jan KleijnH-Index: 6
Last. Rebecca E. Wrishko (MSD: Merck & Co.)H-Index: 5
view all 7 authors...
ABSTRACT The fully human monoclonal antibody bezlotoxumab is indicated for preventing the recurrence of Clostridioides difficile (formerly Clostridium difficile) infection (CDI) in adults who receive antibacterial treatment for CDI and who are at high risk for a CDI recurrence. The efficacy and safety of 10-mg/kg of body weight bezlotoxumab were demonstrated in two phase 3 trials: the MODIFY I (ClinicalTrials.gov registration number NCT01241552) and MODIFY II (ClinicalTrials.gov registration num...
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#1Mark H. WilcoxH-Index: 104
#2Dale N. GerdingH-Index: 105
Last. Mary Beth DorrH-Index: 15
view all 21 authors...
BackgroundClostridium difficile is the most common cause of infectious diarrhea in hospitalized patients. Recurrences are common after antibiotic therapy. Actoxumab and bezlotoxumab are human monoclonal antibodies against C. difficile toxins A and B, respectively. MethodsWe conducted two double-blind, randomized, placebo-controlled, phase 3 trials, MODIFY I and MODIFY II, involving 2655 adults receiving oral standard-of-care antibiotics for primary or recurrent C. difficile infection. Participan...
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#1Lorraine D. Hernandez (MSD: Merck & Co.)H-Index: 9
#2Fred Racine (MSD: Merck & Co.)H-Index: 12
Last. Alex G. Therien (MSD: Merck & Co.)H-Index: 20
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Clostridium difficile infections (CDIs) are the leading cause of hospital-acquired infectious diarrhea and primarily involve two exotoxins, TcdA and TcdB. Actoxumab and bezlotoxumab are human monoclonal antibodies that neutralize the cytotoxic/cytopathic effects of TcdA and TcdB, respectively. In a phase II clinical study, the actoxumab-bezlotoxumab combination reduced the rate of CDI recurrence in patients who were also treated with standard-of-care antibiotics. However, it is not known whether...
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#1Martijn P. Bauer (LEI: Leiden University)H-Index: 20
#2Peter H. Nibbering (LEI: Leiden University)H-Index: 56
Last. J. T. Van Dissel (LEI: Leiden University)H-Index: 38
view all 5 authors...
Low serum concentrations of antibodies directed against the toxins TcdA and TcdB have been associated with a higher risk of recurrence of Clostridium difficile infection (CDI) after successful antibiotic treatment. However, there are conflicting reports. Herein, we compared serum levels of antibodies of patients with a single episode of CDI with those of patients who subsequently suffered a recurrence. We used a serum bank from patients who received an experimental whey protein product following...
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#1Lorraine Kyne (BIDMC: Beth Israel Deaconess Medical Center)H-Index: 35
#2Michel Warny (BIDMC: Beth Israel Deaconess Medical Center)H-Index: 22
Last. Ciaran P. Kelly (BIDMC: Beth Israel Deaconess Medical Center)H-Index: 91
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Summary Background We have reported that symptom-free carriers of Clostridium difficile have a systemic anamnestic immune response to toxin A. The aim of this study was to determine whether an acquired immune response to toxin A, during an episode of C difficile diarrhoea, influences risk of recurrence. Methods We prospectively studied 63 patients with nosocomial C difficile diarrhoea. Serial serum IgA, IgG, and IgM concentrations against C difficile toxin A, toxin B, or non-toxin antigens were ...
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Cited By3
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#1Srishti Saha (Mayo Clinic)H-Index: 10
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Last. Sahil Khanna (Mayo Clinic)H-Index: 40
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BACKGROUND Fecal microbiota transplantation (FMT) is highly effective for preventing recurrent Clostridioides difficile infection (CDI). Durability (no recurrence despite additional risk factor exposure) of FMT protection is largely unknown. We studied the durability of FMT in patients with recurrent CDI. METHODS A retrospective study of adults undergoing FMT for recurrent CDI was conducted. Data collected included demographics, CDI risk factors (comorbidities, healthcare exposure, systemic non-...
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#1Tanner M. Johnson (University of Colorado Hospital)H-Index: 1
#2Kyle C Molina (University of Colorado Hospital)H-Index: 4
Last. Matthew A Miller (University of Colorado Hospital)H-Index: 6
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BACKGROUND Bezlotoxumab (BEZ) is a monoclonal antibody used to prevent recurrent Clostridioides difficile infection (rCDI). This study investigates BEZ effectiveness in relation to rCDI and patient-specific risk factors in a real-world setting. METHODS A matched, retrospective cohort study was conducted from 2015 to 2019 to compare BEZ to historical standard of care (SoC) therapy with vancomycin or fidaxomicin. The primary outcome was incidence of 90-day rCDI. Secondary outcomes were incidence o...
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#1Ravina KullarH-Index: 22
#2Mai-Chi N Tran (SC: University of Southern California)H-Index: 1
Last. Ellie J. C. GoldsteinH-Index: 66
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Clostridioides difficile infection (CDI) is a major cause of nosocomial diarrhea that is deemed a global health threat. C. difficile strain BI/NAP1/027 has contributed to the increase in the mortality, severity of CDI outbreaks and recurrence rates (rCDI). Updated CDI treatment guidelines suggest vancomycin and fidaxomicin as initial first-line therapies that have initial clinical cure rates of over 80%. Unacceptably high recurrence rates of 15-30% in patients for the first episode and 40% for t...
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