Introduction

Bezlotoxumab (trade name: Zinplava) has been approved in Germany since January 2017 for the prevention of recurring Clostridium difficile infection (CDI) in adults with increased risk. It is used during treatment with antibiotics.

Clostridium difficile is a type of gut bacteria that is harmless to healthy humans. Certain antibiotics that interfere with the gut flora can allow Clostridium difficile to multiply excessively, though. The bacteria produce proteins (toxins) that can cause a bowel inflammation with very severe diarrhea, fever and abdominal cramps. The severity of the condition differs from person to person. It might also keep coming back. This is referred to as recurrent CDI.

Bezlotoxumab is an antibody against the toxins that are released. It is used to try to prevent repeated bowel inflammations caused by Clostridium difficile.

Application

Bezlotoxumab is given only once, as an infusion (IV drip) into a vein. The dose is determined based on the person’s body weight. The infusion takes about one hour.

Other treatments

People at high risk of repeated infection with Clostridium difficile usually don’t receive preventive treatment but are actively monitored. Treatment is started at the onset of symptoms.

Assessment

In 2018, the Institute for Quality and Efficiency in Health Care (IQWiG, Germany) wanted to find out whether bezlotoxumab has any advantages or disadvantages for people at high risk of repeated infection with Clostridium difficile when compared with active monitoring.

The manufacturer provided two studies. The researchers at IQWiG were able to use the data of 1,175 patients in the analysis. One half of the patients had treatment with bezlotoxumab, while the other half received a placebo (fake medication) as an infusion (IV drip). All participants had additional treatment with antibiotics.

The following results were found after 12 weeks:

What are the advantages of bezlotoxumab?

  • Recurrence of infection with Clostridium difficile: Here, the studies show an advantage of bezlotoxumab: 21 out of 100 people who received both bezlotoxumab and antibiotics had a recurrence, compared to 33 out of 100 people who only received antibiotics.

What are the disadvantages of bezlotoxumab?

  • The combination of bezlotoxumab and antibiotics was found to have no disadvantages compared to treatment with antibiotics only.

No difference

  • Life expectancy: There was no difference here: 8 to 9 out of 100 people passed away in each group.
  • Serious side effects: There were no differences here either.
  • Treatment stopped due to side effects: There was no difference here either. Only one person stopped treatment due to side effects.

What remains unanswered?

  • The manufacturer provided no suitable data on the following:
    • Pain
    • Hospital admissions due to CDI
    • Health-related quality of life

It also remains unclear whether bezlotoxumab causes side effects in the gastrointestinal tract (stomach or bowel).

More information

This information summarizes the main results of a review produced by the Institute for Quality and Efficiency in Health Care (IQWiG, Germany). The review was commissioned by the German Federal Joint Committee (G-BA) as part of the “early benefit assessment of medications.” On the basis of this review and the hearings received, the G-BA passed a resolution on the added benefit of bezlotoxumab (Zinplava).