Clinical effect of lumacaftor/ivacaftor in F508del homozygous CF patients with FEV1 ≥ 90% predicted at baseline

J Cyst Fibros. 2020 Jul;19(4):654-658. doi: 10.1016/j.jcf.2019.12.015. Epub 2020 Jan 7.

Abstract

Objective: The first available CFTR modulator combination for homozygous F508del patients, lumacaftor/ivacaftor, has not been tested in patients with percentage predicted (pp)FEV1 > 90 in the phase III trials. The objective of this study is to share real life experience about treatment results in this group.

Methods: In this retrospective observational study, patients aged 6 years or older starting on lumacaftor/ivacaftor in standard care were in strict follow up. For these patients, data were obtained about FEV1, BMI, CFQ-R and sweat chloride before start and after 6 months of treatment, and data about FEV1 and BMI were recorded every 3 months. Exacerbations were recorded continuously.

Results: We identified 40 patients with a ppFEV1 ≥ 90 at the start of lumacaftor/ivacaftor who had been in follow up for at least 12 months. After 12 months, ppFEV1 was unchanged, whereas mean absolute change in BMI was +0.88 (p = 0.001) with a mean change in SDS for BMI of +0.26 (p = 0.014). Mean CFQ-R overall score at 6 months improved by 2.6% (p = 0.004) and mean decrease in sweat chloride was -27.3 mEq/L (p = 0.000). Exacerbation rate declined from 1.03 to 0.53/person/year (p = 0.003). One patient discontinued treatment in the first 12 months because of progression of CFRLD, two paused treatment but resumed later.

Conclusion: Homozygous F508del patients starting lumacaftor/ivacaftor at ppFEV1 ≥ 90 improved significantly in nutritional status, sweat chloride levels and exacerbation rate, but did not respond in ppFEV1. Treatment is well tolerated in this patient group. These effects make it worth considering to treat this group of patients with lumacaftor/ivacaftor.

Publication types

  • Observational Study

MeSH terms

  • Aminophenols* / administration & dosage
  • Aminophenols* / adverse effects
  • Aminopyridines* / administration & dosage
  • Aminopyridines* / adverse effects
  • Benzodioxoles* / administration & dosage
  • Benzodioxoles* / adverse effects
  • Child
  • Chloride Channel Agonists / administration & dosage
  • Chloride Channel Agonists / adverse effects
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics*
  • Cystic Fibrosis* / diagnosis
  • Cystic Fibrosis* / drug therapy
  • Cystic Fibrosis* / genetics
  • Cystic Fibrosis* / physiopathology
  • Drug Combinations
  • Female
  • Forced Expiratory Volume / drug effects
  • Homozygote
  • Humans
  • Male
  • Nutritional Status / drug effects*
  • Quinolones* / administration & dosage
  • Quinolones* / adverse effects
  • Respiratory Function Tests / methods
  • Retrospective Studies
  • Sweat / chemistry*
  • Treatment Outcome

Substances

  • Aminophenols
  • Aminopyridines
  • Benzodioxoles
  • Chloride Channel Agonists
  • Drug Combinations
  • Quinolones
  • lumacaftor, ivacaftor drug combination
  • Cystic Fibrosis Transmembrane Conductance Regulator