Elexacaftor-Tezacaftor- Ivacaftor improves sinonasal outcomes in cystic fibrosis

• Published in: Journal of cystic fibrosis 2022-09, Vol.21 (5), p.792-799
• Main Authors: Stapleton, Amanda L., Kimple, Adam J., Goralski, Jennifer L., Nouraie, S. Mehdi, Branstetter, Barton F, Shaffer, Amber D, Pilewski, Joseph M, Senior, Brent A, Lee, Stella E, Zemke, Anna C.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aminophenols; Benzodioxoles; Child; Chloride Channel Agonists; Chlorides; Cystic fibrosis; Cystic Fibrosis - complications; Cystic Fibrosis - diagnosis; Cystic Fibrosis - drug therapy; Cystic Fibrosis Transmembrane Conductance Regulator - genetics; Highly effective modulator therapy; Humans; Indoles; Middle Aged; Mutation; Pyrazoles; Pyridines; Pyrrolidines; Quinolones; Sinus disease; Sinusitis; Sinusitis - diagnosis; Sinusitis - drug therapy; Young Adult
• ISSN: 1569-1993; 1873-5010
• DOI: 10.1016/j.jcf.2022.03.002

•HEMT improves symptoms of chronic rhinosinusitis within a week.•Improvement of symptoms lasts out to at least 6 months.•HEMT improves sinus opacification on CT scan.•HEMT improves nasal polyposis and improving of crusting on endoscopic exam. Many individuals with cystic fibrosis (CF) have chronic rhinosinusitis resulting in nasal obstruction, 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. The study was a pre/post, observational cohort study conducted at two sites. Participants underwent a study visit prior to starting ELX/TEZ/IVA and a second visit at a median of 9 months on therapy. Each visit included sinus CT scan, rigid nasal endoscopy, and sweat chloride measurement. Symptoms 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. The study enrolled 34 individuals, with a median age of 27 years (range 12–60). Symptoms improved within 7 days of therapy and plateaued by day 28. Endoscopic crusting resolved and nasal polyposis improved, with a decrease in size or resolution of polyps. Sinus opacification and mucosal thickening improved on CT radiographs with treatment. 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.