ADHERENCE PATTERNS AND THEIR DETERMINANTS TO CFTR MODULATORS IN FRANCE.

Cystic fibrosis transmembrane conductance regulator modulators (CFTRm) represent a major therapeutic advance for patients with cystic fibrosis (pwCF). Given their oral administration and high efficacy, they may be better suited than other cystic fibrosis treatments to optimize long-term adherence, which is crucial to ensuring effectiveness. To examine adherence patterns to CFTRm and their determinants, we conducted a population-based retrospective cohort study using data from the French CF Registry linked to the French National Health Data System. We included pwCF (>6 years) who initiated at least one CFTRm (ivacaftor or lumacaftor/ivacaftor) between 2012 and 2020 and were treated for at least six months. Implementation was measured using the continuous multiple-interval measure of medication availability version 7 (CMA-7), and longitudinal K-means clustering identified adherence trajectories based on monthly CMA-7 values over one-year follow-up. Multinomial logistic regression assessed associations between adherence patterns and sociodemographic and clinical characteristics. Among 1362 patients, three adherence trajectories were identified: optimal adherence (68%), gradual decline (16%), and initial drop-off followed by return to optimal adherence after 3-5 months (16%). Compared to optimal adherence, gradual decline trajectory was associated with age 15-25 years (reference: >25), while drop-off and rebound trajectory was linked to being younger than 15 and P. aeruginosa bronchial colonization. Socioeconomic disadvantage was also associated with nonoptimal adherence. This study highlights the need for age-tailored interventions to support long-term adherence, revealing a decline among adolescents and young adults, along with a specific pattern among children, which may relate to prescribing practices at treatment initiation.