english.prescrire.org > Spotlight > Archives : 2018 > Bezlotoxumab (Zinplava°) and recurrence of C. difficile infection: No proven effect against serious complications, and cardiotoxicity

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Bezlotoxumab (Zinplava°) and recurrence of C. difficile infection: No proven effect against serious complications, and cardiotoxicity

FEATURED REVIEW Given the serious complications associated with Clostridium difficile infection, treatment that safely reduces the risk of recurrences in high-risk patients would constitute a therapeutic advance. Bezlotoxumab's ability to deliver this advance has not been demonstrated. Full review (2 pages) available for download by subscribers.

Abstract

  • After a first episode of Clostridium difficile infection, despite appropriate antibiotic therapy, the recurrence rate is about 20% to 30% and increases with the number of recurrences.
     
  • Bezlotoxumab is a monoclonal antibody that binds to toxin B, secreted by C. difficile. It has been authorised in the European Union for the prevention of recurrence of C. difficile infection in adults considered at high risk for recurrence. Bezlotoxumab is the first drug authorised in this indication. It is administered as a single intravenous infusion during antibiotic treatment for the episode of C. difficile infection.
     
  • Two comparative, randomised, double-blind trials evaluated addition of a bezlotoxumab infusion to antibiotic therapy in about 1600 patients whose main risk factor for recurrence was age over 65 years. In these trials, recurrence of a diarrhoeal episode with a positive stool culture for C. difficile within 3 months after the infusion was observed in about 16% of patients who received bezlotoxumab versus about 27% in the placebo groups. No effect was demonstrated on mortality or on the incidence of serious complications of C. difficile infection.
     
  • At this stage of the evaluation, in which only about 800 patients have been exposed to bezlotoxumab, its adverse effects appear to mainly consist of infusion reactions and cardiotoxicity. It is better to avoid exposing patients with heart failure to bezlotoxumab due to the increased incidence of cardiac adverse effects and mortality in these patients.
  •  NOT ACCEPTABLE  In patients undergoing antibiotic therapy for an episode of Clostridium difficile infection, the addition of a single infusion of bezlotoxumab reduces the risk of recurrence of C. difficile-associated diarrhoea within 3 months from about 27% with placebo to about 16%. Bezlotoxumab has not been properly evaluated in patients at high risk of recurrence. It increases the risk of heart failure. Given that bezlotoxumab has not been shown to have a beneficial effect against the serious complications of C. difficile infection, its harm-benefit balance is unfavourable and does not justify its use outside clinical research.

©Prescrire 1 October 2018

"Bezlotoxumab (Zinplava°) and recurrence of Clostridium difficile infection" Prescrire Int 2018; 27 (197): 229-232. (Pdf, subscribers only)

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 NOT ACCEPTABLE