WS11.03 Positive and negative impacts of elexacaftor/tezacaftor/ivacaftor: healthcare providers’ observations across US Centres

Objectives: Treatment of cystic fibrosis (CF) has been transformed by the advent of CF transmembrane conductance regulator (CFTR) modulators, which have been associated with unprecedented clinical improvements. However, negative side-effects with implications for safety and well-being have been reported in several case series, including neuropsychiatric changes. This study aimed to better characterize the emerging positive and negative impacts of elexacaftor/tezacaftor/ivacaftor (ETI). Methods: The CF Foundation’s Mental Health Advisory Committee developed a 26-item survey distributed in May 2022 to multidisciplinary US CF care teams to assess observations of their patients’ experiences with ETI. Survey responses estimated the prevalence and degree of impact of ETI on functioning across 5 domains: 1) positive physical and psychological effects of ETI, 2) sleep difficulties, 3) cognitive difficulties, 4) worsening mental health, and 5) concerns about the future, including finances. Results: Seventy-five health care providers treating pediatric and/or adult people with CF completed the survey. Positive physical effects of ETI and increased optimism were reported in the upper to highest quartile (50%-100%) and were rated as having a significant impact on daily functioning. Sleep and cognitive difficulties were rated as occurring in 1–24% of patients, with a slight impact on daily functioning. Psychological symptoms (e.g., increased stress, depression, anxiety) and new psychiatric medications were reported in 1–24% of patients, with a moderate effect on daily functioning. Concerns about the future were reported in 1–24%, with minimal impact. Conclusion: Positive physical effects of ETI were reported most often by providers across US programs, however, a variety of negative impacts were also observed, including sleep disruptions and negative psychological symptoms. Additional research is needed to assess the prevalence and consequences of these side-effects.