Ivacaftor (Kalydeco) with tezacaftor / ivacaftor (Symkevi) for the treatment of cystic fibrosis in people aged 12 years and over who have a homozygous F508del mutation

Ivacaftor (trade name: Kalydeco) with the fixed-dose combination of ivacaftor / tezacaftor (trade name: Symkevi) has been approved in Germany since October 2018 for the treatment of cystic fibrosis in teenagers aged 12 years and over and adults who have a homozygous F508del mutation. In 2019, the Institute for Quality and Efficiency (IQWiG, Germany) looked into whether ivacaftor in combination with tezacaftor / ivacaftor has any advantages or disadvantages in the treatment of cystic fibrosis in these people compared to the standard treatment of lumacaftor / ivacaftor.

The manufacturer provided data from an indirect comparison. The results of this kind of comparison are generally less reliable than those of a direct comparison. In this case, one study compared ivacaftor plus the fixed-dose combination of tezacaftor / ivacaftor with a placebo, and two other studies compared lumacaftor / ivacaftor at various doses with a placebo as well. Everyone in the studies had treatment for their cystic fibrosis symptoms too. Only people with a homozygous F508del mutation participated. These were the results after about half a year:

What are the advantages of ivacaftor?

Rashes: The indirect comparison suggests that ivacaftor has an advantage here.

What are the disadvantages of ivacaftor?

Hospital stays due to cystic fibrosis episodes affecting the airways: The indirect comparison suggests that ivacaftor has a disadvantage here.

No difference

Life expectancy: None of the participants passed away during the study.

There were also no differences between the two groups in terms of the following:

  • Health-related quality of life
  • Acute cystic fibrosis episodes affecting the airways
  • Weight problems
  • Gastrointestinal (stomach and bowel) problems
  • Treatment stopped due to side effects

What remains unanswered?

The manufacturer didn't provide any suitable data about severe side effects.

Labels: E84, Ivacaftor, Kalydeco