Dose adjustments of Elexacaftor/Tezacaftor/Ivacaftor in response to mental health side effects in adults with cystic fibrosis

J Cyst Fibros. 2022 Nov;21(6):1061-1065. doi: 10.1016/j.jcf.2022.05.001. Epub 2022 May 16.

Abstract

Introduction: Deterioration in mental health has been reported in a minority of individuals with cystic fibrosis starting elexacafor/tezacaftor/ivacaftor (ELX/TEZ/IVA). We report our experience of using sweat chloride and markers of clinical stability to titrate dose reduction with the aim of minimising adverse events and maintaining clinical stability.

Method: Adults (n = 266) prescribed ELX/TEZ/IVA, were included. Adverse events, sweat chloride, lung function and clinical data were collected.

Results: Nineteen (7.1%) individuals reported anxiety, low mood, insomnia and "brain fog" with reduced attention and concentration span. Thirteen underwent dose reduction with sweat chloride remained normal (<30 mmol l-1) or borderline (30-60 mmol l-1) in six (46.2%) and seven (53.2%) cases respectively. Improvement or resolution of AEs occurring in 10 of the 13 cases.

Conclusion: Dose adjustment of ELX/TEZ/IVA was associated with improvement in mental health AEs without significant clinical deterioration. Sweat chloride concentration may prove useful as a surrogate marker of CFTR function.

MeSH terms

  • Adult
  • Aminophenols / adverse effects
  • Benzodioxoles / adverse effects
  • Chloride Channel Agonists / adverse effects
  • Chlorides
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis* / complications
  • Cystic Fibrosis* / diagnosis
  • Cystic Fibrosis* / drug therapy
  • Humans
  • Mental Health
  • Mutation

Substances

  • ivacaftor
  • tezacaftor
  • elexacaftor
  • Chloride Channel Agonists
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Chlorides
  • Aminophenols
  • Benzodioxoles