Effects of CFTR modulators throughout life with cystic fibrosis

Abstract

In the last decade, the care for cystic fibrosis (CF) has transformed from symptomatic treatment to causative treatment, with agents acting directly on the defective CF transmembrane conductance regulator (CFTR) protein. These CFTR modulators have been highly effective, and the most successful drug of this class to date, elexacaftor/tezacaftor/ivacaftor (ETI), is now available for approximately 90% of the people with CF from the age of two years, improving prospects in this group. Life expectancy estimates have increased from 30–40 years to 50–70 years. Lung function, nutritional status, somatic growth, pancreatic exocrine function, and fertility have all improved. ETI can prevent or reduce characteristic events of CF disease including meconium ileus, pulmonary exacerbations and mitigate against chronic infection and inflammation. The benefits begin with the foetus and extend throughout infancy, childhood, and adult life. A new era of CF care raises challenges like equity, long-term safety, and comorbidities in an aging CF population, but also raises possibilities including antenatal prevention of CF disease, eliminating intensive treatments, and increasing the likelihood of parenthood for people with CF.