Efficacy of Elaxacaftor/Tezacaftor/Ivacaftor after market authorization in pwCF

<bold>Background:</bold> The CFTR modulator Elaxacaftor/Tezacaftor/Ivacaftor (ETI) has been shown to remarkably improve health condition in people with CF (pwCF) in clinical studies. We assessed the efficacy of ETI in a registry-based pharmacovigilance project since its market introduction in 2021. <bold>Methods:</bold> Clinical outcomes of pwCF receiving ETI were assessed at baseline (before ETI start) and at subsequent follow-up medical visits (FUs) every three months in a longitudinal observational study on Swiss data from the European Cystic Fibrosis Society Patient Registry. Changes in sweat chloride concentration, BMI and FEV_1pp over time were analyzed using mixed-effects models for repeated measures and stratified according to age (6-11 vrs, 12-17 yrs, ≥18 yrs). Results are presented as means (95% CI). <bold>Results:</bold> 424 pwCF, including 127 children 6-17yrs, were involved. The majority had four FUs. Sweat chloride decreased from 97 mmol/l (96-99) to 45 mmol/l (43-47; p<0.001) after ETI introduction. Decrease was less pronounced in adults (−46 mmol/l; 44-48) compared to younger individuals (−38 mmol/l; 34-42; p<0.05). BMI increased over time by 1.2 kg/m² (1.0-1.5; p<0.001) which was comparable for all age groups. Improvement in FEV_1pp was highly significant between baseline and FU1 (+11.6%; 10.6-12.5; p<0.0001), and not significant between FU 1-4. FEV_1pp increase did not differ between age groups despite adults having a significant lower FEV1pp at baseline. <bold>Discussion:</bold> Introduction of ETI resulted in a significant decrease of sweat chloride concentration and a significant and sustainable increase of BMI and FEV_1pp independent of age. Real world evidence demonstrates equal efficacy of ETI throughout different age groups.