Unlocking growth potential: Ivacaftor therapy and developmental gains in lung and height in a cohort study of children and young adults with cystic fibrosis

Rationale Cystic fibrosis (CF) is historically characterized by impaired lung function and stunted growth due to variants in Cystic Fibrosis Transmembrane conductance Regulator ( CFTR ). CFTR modulators, like ivacaftor, have revolutionized treatment. Short-term benefits are well-documented. Objective To evaluate the long-term effect of ivacaftor on height and lung function. Methods We conducted a retrospective cohort analysis using data from the Cystic Fibrosis Foundation Patient Registry from 2012 to 2020. This study included 18 193 individuals aged 6–20 years, comparing those who received ivacaftor monotherapy (n=1794) to a control group not receiving any modulator therapy (n=16 399). Longitudinal analyses assessed height and lung function (Forced Vital Capacity, FVC) over time, stratified by age, sex, and CFTR variant class. Mixed-effects models evaluated the relationship between ivacaftor, height, and lung function. Results Children and young adults treated with ivacaftor demonstrated accelerated height and lung function growth and final height and FVC attainment compared to those not receiving ivacaftor. At age 20, ivacaftor-treated males and females had a higher mean FVC of 662 and 530 milliliters (p<0.0001), respectively. The effects were more pronounced in children and young adults with severe CFTR variants. Ivacaftor's contribution to FVC was evident across all ages and mediated predominantly through its impact on height, though it also had height-independent effects. Conclusions Ivacaftor therapy is associated with faster growth and greater height and lung function attainment. These findings support early initiation of CFTR modulators to optimize peak lung function and growth, which could impact long-term respiratory and non-respiratory morbidity and mortality.