Elexacaftor-Tezacaftor- Ivacaftor improves sinonasal outcomes in cystic fibrosis

Background: Many individuals with cystic fibrosis (CF) have chronic rhinosinusitis resulting in nasal ob-struction, sinus infections, and repeated surgeries. Elexacaftor-tezacaftor-ivacaftor is a highly effective modulator therapy approved for individuals aged 6 years or older with CF who have at least one F508del allele or other responsive mutation. The current study tests the hypothesis that ELX/TEZ/IVA improves sinonasal disease in CF.Methods: The study was a pre/post, observational cohort study conducted at two sites. Participants un-derwent a study visit prior to starting ELX/TEZ/IVA and a second visit at a median of 9 months on ther-apy. Each visit included sinus CT scan, rigid nasal endoscopy, and sweat chloride measurement. Symp-toms were measured with the 22 item Sinonasal Outcome Test at scheduled intervals during the study. Regression models were used to test for improvement in symptoms, endoscopy, and CT scales.Results: The study enrolled 34 individuals, with a median age of 27 years (range 12-60). Symptoms im-proved within 7 days of therapy and plateaued by day 28. Endoscopic crusting resolved and nasal polypo-sis improved, with a decrease in size or resolution of polyps. Sinus opacification and mucosal thickening improved on CT radiographs with treatment.Conclusions: Sinonasal symptoms improved rapidly and durably for at least 180 days on ELX/TEZ/IVA therapy. Objective measures of disease including endoscopic and CT findings improved with ELX/TEZ/IVA.(c) 2022 The Author(s). Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society.This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )