Assessment of efficacy and tolerability of elexacaftor-tezacaftor-ivacaftor in an observational cohort study of "aged" people with cystic fibrosis.

BACKGROUND: Therapeutic advancements utilizing modulators of the cystic fibrosis transmembrane conductance regulator (CFTR) have revolutionized the treatment of people with cystic fibrosis (pwCF). Elexacaftor-Tezacaftor-Ivacaftor (ETI) is a highly effective modulator therapy and has been shown to improve health outcomes in people with CF (PwCF). Due to these therapeutic advancements, many pwCF are getting older, but little is known regarding the safety and efficacy of ETI in pwCF at a more advanced age. OBJECTIVES: We aimed to determine the effect of ETI on clinical outcomes in older pwCF. DESIGN: This study was a single-center, retrospective analysis of pwCF who received open-label ETI following FDA approval and were over the age of 40 at the time of ETI initiation. METHODS: Data were obtained from the electronic medical record from a large CF center in the United States of America between November 2019 and January 2021, including body mass index (BMI), lung function as % predicted FEV1 before ETI initiation, and approximately 3 months and one a follow-up visit within 9-15 months post-ETI initiation. The exacerbation frequency over 12 months was recorded before and after ETI initiation. RESULTS: Forty-two patients met the inclusion criteria. Mean age at time of ETI initiation was 47.9, 23 patients (54.8%) were male, and 11 (26.2%) were homozygous for the F508del mutation. Linear mixed effects models suggest a monthly increase of 0.24 (95% CI 0.08-0.41, p = 0.003) for ppFEV1 and 0.03 (95% CI 0.002-0.06, p = 0.036) for BMI post-ETI, resulting in a 2.96 (95% CI 0.98-4.95) increase in ppFEV1 and 0.39 (95% CI 0.03-0.76) increase in BMI approximately 1-year post-ETI. In addition, a significant decline in pulmonary exacerbations was seen in the year following ETI initiation (1.5 ± 1.3 exacerbations/year prior vs 0.5 ± 0.7 exacerbations/year post; p < 0.0001). CONCLUSION: Treatment with ETI in this unique cohort of pwCF was safe. Whereas ETI affected BMI in a subtle way, initiation of ETI was associated with stabilization of lung disease with a significant but moderate increase in lung function and a decline in the number of exacerbations in the follow-up period. Longer and larger studies will be needed to analyze the effect of ETI on an aging CF population.