Triple modulator therapy effects in children and young adults with cystic fibrosis

<bold>Introduction:</bold> Cystic fibrosis (CF) is a multisystem genetic recessive autosomic disease. Elexacaftor–tezacaftor–ivacaftor (ETI) is an innovative modulator therapy for CF patients. Italian drug agency approved ETI for CF children from 6 years old with at least one F508del mutation in September 2022. We aimed to investigate one year ETI effects in a cohort of CF patients. <bold>Methods:</bold> We collected pulmonary function tests, sweat chloride tests, pulmonary exacerbations rate, chronic infections and otorhinolaryngeal evaluations at one year before, at the time of starting ETI, 6 and 12 months after. <bold>Results:</bold> 96 patients were enrolled from 6 to 26 years old. 43% of patients were homozygous for F508del and 22 patients were transitioned to ETI from a prior modulator therapy. Pulmonary function tests improved after 12 months (%FEV1 81%±20 vs 90%±22, p<0,01). It was seen a significant correlation between the increase of weight and the pulmonary function test improvement (p<0,05, r² 0,3). Sweat chloride decreased at 12 months (117 mg vs 47 mg, p<0,001). Positive airway culture tests percentage for <italic>P. aeruginosa</italic> and <italic>methicillin-resistant S. aureus</italic> and hospital admissions for pulmonary exacerbations decreased in the year following the start of therapy (both p<0,001). In a subgroup of patients, sinunasal symptoms and nasal endoscopic score decreased 6 months after starting ETI (p<0,01). Only two cases withdrawn from ETI due to adverse events. <bold>Conclusion:</bold> Triple therapy had beneficial clinical effects and a good safety profile in eligible CF patients, both children and young adults. A longer monitoring period is needed to demonstrate that improvements are clinically significant and enduring without adverse effects.