Adherence to cystic fibrosis transmembrane conductance regulator (CFTR) modulators: analysis of a national specialty pharmacy database

Background: There have been significant advances in Cystic Fibrosis (CF) treatment, with the introduction of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulators. Adherence is an important goal for CF management, as nonadherence is linked to poor health outcomes. Objective: To calculate the medication adherence in patients taking CFTR modulators using a national specialty pharmacy database. Methods: This retrospective observational cohort study utilized de-identified specialty pharmacy data from September 2017 to August 2018 to assess medication adherence for three CFTR modulators: ivacaftor, lumacaftor/ivacaftor, and tezacaftor/ivacaftor & ivacaftor. The primary outcome was proportion of days covered (PDC) for each medication, with mean PDC values compared across age groups and insurance characteristics. All analyses were performed using the SAS 9.4 University Edition (SAS Institute, Cary, NC). Results: A total of 2,548 patients were analyzed, including 1,289 (50.59%) patients on lumacaftor/ivacaftor, 784 (30.77%) on ivacaftor, and 475 (18.64%) on tezacaftor/ivacaftor & ivacaftor. The mean PDC value for all CFTR modulators was above 0.80. Tezacaftor/ivacaftor & ivacaftor had the highest overall PDC of 0.92, while PDC values for both lumacaftor/ivacaftor and ivacaftor were 0.84. Children/adolescents on lumacaftor/ivacaftor (p = 0.0001) and tezacaftor/ivacaftor & ivacaftor (p = 0.001) had significantly higher mean PDC values compared to adults but not for ivacaftor (p = 0.3744). No statistical differences were seen in PDC across insurance characteristics. Conclusion: To the best of our knowledge, this is the first study to assess the adherence of three CFTR modulators using a large nationwide specialty database. With high acquisition costs of CFTR modulator therapies, there is a need to improve rates of adherence in patients with CF.