A Six-Month Real-World Effectiveness Investigation of Elexacaftor/Tezacaftor/Ivacaftor According to Baseline Lung Function in People with Cystic Fibrosis

Background: Highly effective CFTR modulator therapy has substantially changed the clinical course of cystic fibrosis (CF), but the magnitude of treatment response may vary according to baseline lung function. We evaluated the real-world effects of elexacaftor/tezacaftor/ivacaftor (ETI) in people with CF aged >6 years across a broad range of baseline lung function. Methods: In this observational study, 62 people with CF (23 male; age range 7.8–36.8 years) who were eligible for ETI according to genotype underwent assessment at treatment initiation and after 6 months. Assessments included spirometry, respiratory oscillometry, body composition and biochemical measurements. Results: Mean ppFEV1 increased from 94% at baseline to 108% after 6 months (p < 0.001), while mean FEF25–75 increased from 77% to 100% predicted (p < 0.001). Lower baseline ppFEV1 was associated with a greater ppFEV1 response (r = −0.596, p < 0.001), and baseline ppFEV1 remained the only significant factor associated with ppFEV1 change in multivariable analysis (β = −0.21, p = 0.006). Improvement was greater among participants with baseline ppFEV1 < 90%, although a measurable increase was also observed in those with ppFEV1 ≥ 90%. BMI increased significantly. HDL and LDL cholesterol increased (p = 0.007 and p = 0.011, respectively), whereas C-reactive protein decreased (p < 0.001). Changes in oscillometry were modest and provided limited additional information beyond spirometry in this cohort. Conclusions: ETI was associated with significant improvements in lung function in people with CF aged >6 years, including those with preserved baseline spirometry. The magnitude of ppFEV1 improvement was greatest in participants with lower baseline ppFEV1. These findings support measurable physiological benefit from ETI across a broad spectrum of baseline lung function, while highlighting the need for longer-term studies of outcomes in people with near-normal spirometry.