The cystic fibrosis transmembrane conductance regulator (CFTR) modulator compound, ivacaftor, reached its 10-year anniversary of US Food and Drug Administration (FDA) approval in 2022. This long-standing experience captured within US CF foundation patient registry (US CFFPR) data up to December 2019 was harnessed by Merlo and colleagues in this edition of the journal to provide further insight into its ability to improve health outcomes.

In the first study,1 the authors used US CFFPR data between 2010 and 2019 to examine health effects observed over a mean follow-up period of approximately 6 years (maximum 7.9 years), the longest follow-up to date in the literature. An ivacaftor-treated cohort of 736 people with cystic fibrosis (pwCF) with a gating mutation (excluding R117H) were compared with an age-matched comparator cohort with F508del and a minimal function CFTR variant who were CFTR modulator naïve. A greater than eight point difference in FEV1 percent predicted (ppFEV1) was observed between the cohorts, with the magnitude of difference increasing over time both within the overall cohort, and in each of the different age groups examined (6–11, 12–17 and ≥18 years). The greatest magnitude of change over time occurred among 12–17 year olds. Accompanying benefits were observed in body mass index, rates of pulmonary exacerbation (PEx) and all-cause hospitalisation. Rate of lung transplant and mortality rate were also lower in the ivacaftor-treated cohort.

When interpreting these results, two aspects are important to interrogate. First, the validity of the comparison group. The molecular consequence of minimal function variants are felt to be similar to that of F508del,2 and US CFFPR-based …