Medication adherence to cystic fibrosis transmembrane conductance regulator (CFTR) modulators: Analysis on the French cystic fibrosis population from 2012 to 2020.

BACKGROUND

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators, ivacaftor and lumacaftor/ivacaftor, were introduced in France in 2012 and 2015, respectively, and transformed treatment landscape. Real-world data on medication adherence to these treatments remains limited, although crucial for effectiveness. We evaluated 1-year and 2-year medication adherence (persistence and implementation) using linked data from the French Cystic Fibrosis Registry and the French National Health Data System (SNDS), and examined determinants.

METHODS

We conducted a retrospective cohort study including all French cystic fibrosis patients aged 6 years and more, initiating ivacaftor or lumacaftor/ivacaftor between 2012 and 2020, and treated for at least 6 months. Medication adherence was measured as persistence (time to discontinuation fixed to 84-day gap) and implementation (continuous multiple-interval measure of medication availability version 7; CMA-7). It was calculated over 1-year and 2-year following treatment initiation. Determinants of non-persistence (treatment discontinuation) were identified using a Cox proportional hazards model. Determinants of optimal implementation (CMA7≥0.8) were assessed with multivariate logistic regressions.

RESULTS

Among 1362 patients, 95 initiated ivacaftor and 1267 initiated lumacaftor/ivacaftor, with a mean age of 19 years and 53% male. Mean time to discontinuation was 653 ± 141 days. Proportion of patients with optimal implementation at 1 year and 2 years were 79% and 75%, respectively. Age <18 years, higher socio-economic level, higher number of cotherapies, and lower percent predicted forced expiratory volume in 1 s (ppFEV1%) were associated with better treatment implementation at both 1-year and 2-years.

CONCLUSIONS

Most patients on CFTR modulators showed optimal implementation with persistence declining over time, potentially affecting long-term outcomes.