Treatment adherence and mental health in people with cystic fibrosis and advanced lung disease treated with elexacaftor/tezacaftor/ivacaftor.

INTRODUCTION

Advanced lung disease (ALD) is a leading cause of mortality in cystic fibrosis (CF). Although Elexacaftor/Tezacaftor/Ivacaftor (ETI) provides significant clinical benefits, little is known about long-term adherence, health-related quality of life (HRQoL), and neuropsychological side-effects in people with CF (PWCF) and ALD. This study evaluated adherence, HRQoL, mental health, and ETI-related side-effects.

METHODS

In this longitudinal study, PWCF and ALD enrolled in an ETI compassionate use program were assessed cross-sectionally after approximately 30 months of ETI therapy using the Treatment Adherence Questionnaire-CF (TAQ-CF), CFQ-R, PHQ-9, GAD-7, and an ad-hoc neuropsychological side-effects survey. Clinical parameters (ppFEV1, BMI, sweat chloride) and CFQ-R scores were followed from baseline to 36 months.

RESULTS

Thirty-three PWCF and ALD were included. From baseline to 36 months, sweat chloride decreased by 57.4 mmol/L, while ppFEV1 and BMI increased by 19.4% and 1.6 kg/m2, respectively. HRQoL improved significantly across most CFQ-R domains. Mean overall adherence was 75.6%; 45.2% of participants reported high and 51.6% moderate adherence. No significant associations were found between adherence and clinical or mental health outcomes. Concentration difficulties and insomnia were reported by 25.8% and 32.3% of participants, respectively. Anxiety was associated with memory and concentration difficulties and insomnia.

CONCLUSION

Approximately 30 months after ETI initiation, PWCF and ALD maintained moderate-to-high adherence, potentially reflecting disease severity and treatment burden. ETI provided sustained pulmonary and HRQoL benefits, although persistent neuropsychological side-effects occurred in a subset of participants and were associated with anxiety. Comprehensive ALD management should address both physical and mental health.