Effectiveness and safety of elexacaftor/tezacaftor/ivacaftor in patients with cystic fibrosis and advanced lung disease with the Phe508del/minimal function genotype

Respir Med. 2021 Nov-Dec:189:106646. doi: 10.1016/j.rmed.2021.106646. Epub 2021 Oct 12.

Abstract

Background: Elexacaftor/tezacaftor/ivacaftor (E/T/I) is a cystic fibrosis transmembrane conductance regulator (CFTR) triple combination therapy used for the treatment of cystic fibrosis (CF) in patients aged ≥12 years who have at least one copy of the Phe508del mutation (F) in the CFTR gene or another mutation that is responsive to treatment with E/T/I. This study determined the effectiveness and safety of E/T/I treatment in a cohort of CF patients.

Methods: This retrospective cohort study collected data from the first 6 months of treatment of patients with CF, compound heterozygotes for the F and a minimal function (MF) mutations, enrolled in an E/T/I compassionate use program only available to patients having ppFEV1<40 or who are considered for lung transplantation. Forty-seven patients were included. Follow-up was performed after 1, 3, and 6 months from the beginning of therapy, assessing lung function, body mass index (BMI), sweat chloride concentration (SCC), quality of life (QoL), and safety.

Results: After 6 months of treatment, the mean (standard deviation (SD)) SCC decreased from 91.1 (19.3) mmol/L to 46.2 (24.2) mmol/L. The decrease of SCC was accompanied by improvement of lung function (mean (95% Confidence Interval (CI) absolute increase in ppFEV1 was 10.69 (8.05,13.33) after 1 month and 14.16 (11.43, 16.89) after 6 months of treatment), nutrition (mean (SD) BMI increased from 20.7 (3.0) kg/m2 at baseline to 22.6 (3.1) after 6 months), and QoL. No safety concerns were observed.

Conclusions: E/T/I was clinically effective and safe in patients with advanced CF lung disease with an F/MF genotype.

Keywords: CFTR; Cystic fibrosis; Elexacaftor/tezacaftor/ivacaftor; Minimal function.

MeSH terms

  • Adolescent
  • Adult
  • Aminophenols / therapeutic use
  • Benzodioxoles / therapeutic use
  • Chloride Channel Agonists / therapeutic use*
  • Cystic Fibrosis / drug therapy*
  • Cystic Fibrosis / genetics*
  • Cystic Fibrosis / physiopathology
  • Drug Therapy, Combination
  • Female
  • Genotype
  • Humans
  • Indoles / therapeutic use
  • Male
  • Middle Aged
  • Pyrazoles / therapeutic use
  • Pyridines / therapeutic use
  • Pyrrolidines / therapeutic use
  • Quinolones / therapeutic use
  • Respiratory Function Tests
  • Retrospective Studies

Substances

  • Aminophenols
  • Benzodioxoles
  • Chloride Channel Agonists
  • Indoles
  • Pyrazoles
  • Pyridines
  • Pyrrolidines
  • Quinolones
  • tezacaftor
  • ivacaftor
  • elexacaftor