Review of CFTR Modulators 2020

Abstract

CFTR (cystic fibrosis transmembrane conductance regulator) modulators are small molecules that directly change the CFTR protein, improving function of the CFTR chloride channel. Beginning in 2012 with the FDA approval of the first CFTR modulator, ivacaftor, this class of medication has had largely positive effects on many outcomes in people with cystic fibrosis (pwCF), including lung function, quality of life, and growth. There have been continued exciting developments in the current research on CFTR modulators, expanding beyond original studies. This first part of a three-part Cystic Fibrosis (CF) Year in Review 2020 will focus on research on CFTR modulators. Subsequent parts of the CF year in review will cover pulmonary and infectious inflammatory aspects, and the multisystem effects of CF in the 2020 literature. The review focuses on articles from Pediatric Pulmonology, but it includes articles from other journals that are of particular interest to clinicians. New developments in CF research continue to be brought forth to the CF community, deepening the understanding of this disease and improving clinical care.

State-of-the-art review of lung imaging in cystic fibrosis with recommendations for pulmonologists and radiologists from the “iMAging managEment of cySTic fibROsis” (MAESTRO) consortium

“…Using the lung clearance index (LCI) as a parameter, decline is defined as annual drop of 17% and 15% in CF patients younger and older than 12 years of age, respectively [21,22]. "Improving lung function" is the sub-scenario in CF patients on treatment with new CF transmembrane conductance regulator (CFTR) modulator therapies [23]. In young children who cannot perform lung function tests, decline was defined by clinically integrated evaluation which included the presence of chronic respiratory symptoms, frequency of respiratory exacerbation and antibiotic therapy [24,25].…”

Elexacaftor/tezacaftor/ivacaftor in children aged 6–11 years with cystic fibrosis, at least one F508DEL allele, and advanced lung disease: A 24‐week observational study

“…It has been shown that ivacaftor, lumacaftor, and tezacaftor (used singly or in combination) are safe and efficacious in children aged 6–11 years 5 . Furthermore, the results of a 24‐week, Phase‐III open‐label trial of ETI have shown that the treatment was as safe and effective in CF patients aged 6–11 years with at least one F508del allele as in adults and adolescents 6 .…”

Non‐pulmonary CFTR‐related symptom improvement with ivacaftor in p.Phe508del/p.Arg117His (7T) cystic fibrosis

“…There are over 2000 known mutations across a number of mutation classes that result in a heterogenous phenotype, ranging from classic pancreatic insufficient CF to CFTR related diseases and even no evidence of disease despite mutations in each allele 1 . The diagnosis of CF can be challenging for those who do not have typical symptoms, and this can raise issues about how they should be managed and whether it is appropriate to use CFTR modulators 2,3 …”