Real-world data on the efficacy and safety of tezacaftor-ivacaftor in adults living with cystic fibrosis homozygous for F508del and heterozygous for F508del and a residual function mutation.

BACKGROUND: To examine safety and efficacy of tezacaftor-ivacaftor (TEZ/IVA) in a real-life setting in adults living with cystic fibrosis. METHODS: A multicentre retrospective observational study, including adults living with cystic fibrosis (pwCF) eligible for TEZ/IVA, with assessments at baseline, 3 months (visit3mo) and 6 months (visit6mo) after start of treatment. Outcomes included change in FEV1, LCI, FeNO, CFQ-R, estimated number of annual acute exacerbations, BMI, dosage of pancreatic enzyme replacement therapy (PERT) and airway microbiology. We also assessed safety. RESULTS: Forty-eight adult pwCF (mean (±SD) age 33 (±12) years; mean FEV1 65 (±19) %P) were included. Three subgroups were identified: pwCF F/F CFTR modulator-naive (n = 28; 58%), pwCF F/F previously treated with lumacaftor-ivacaftor (n = 11; 23%) and pwCF F/RF (n = 9; 19%). Adverse events were described in 3 pwCF (6%) during the 6-month observation period (in one leading to treatment interruption). At visit3mo, FEV1 had improved in all subgroups. In the entire group, mean FEV1 had increased from 66 (±2.9) %P to 72 (±2.9) %P (p < 0.0001). Similarly, LCI improved by approximately one unit at visit3mo (p = 0.02). At visit6mo mean annual acute exacerbation rate decreased significantly (p = 0.02). Only in the CFQ-R social functioning domain score, a significant improvement was observed at visit6mo (p < 0.01). CONCLUSIONS: We showed that TEZ/IVA is safe, well tolerated and effective in terms of improvement of lung function, ventilation inhomogeneity, health-related social functioning, and reduction of estimated annual acute exacerbation rate, in adult pwCF F/F and F/RF. Results in this real-life study reflect those observed in RCTs.

The roles and experiences of adolescents with cystic fibrosis and their parents during transition: A qualitative interview study.

PURPOSE: Inadequate participation of Adolescents and Young Adults (AYAs) and parents are well-established barriers of transition. Shifts in roles are mandatory with increasing responsibilities for AYAs and decreasing involvement of parents in care. This study explores the shifts in roles of AYAs and their parents and its association with the subjective experience of transition. METHODS: We conducted in-depth semi-structured interviews with AYAs living with Cystic Fibrosis and parents. Participants were recruited through patient organizations via convenience sampling and questioned on which roles they assumed during transition. Three authors performed an interpretative phenomenological analysis, establishing separate code trees for AYAs and parents. Data saturation was achieved. RESULTS: 18 AYAs (age 21y±2.9) and 14 parents (age 50y±2.0) were included. We identified five common themes: (1) the reciprocal reliance between AYAs and parents, (2) the policies of physicians and hospitals, (3) the AYAs' changing appeal and need for support, (4) the identification of parents as co-patients, and (5) the enforced changes in the roles of parents. AYAs primarily addressed roles related to self-management, while parents discussed family functioning. CONCLUSIONS: This study identified motives underlying the assumption of roles by AYAs and parents. Both AYAs and parents addressed similar themes, highlighting their mutual challenges and needs. In contrast to AYAs, parents' desired roles were undefined and a latent sense of responsibility was identified as an important motive. Healthcare providers should acknowledge parents' challenging position and communicate transparently about changing roles. Additionally, healthcare providers should recognize that imposing restrictive roles may result in parental resistance, but can also foster AYAs' skill development. Future research should examine the short- and long-term impact of role-management interventions in AYAs and their parents.