vx-770 and Paranasal-Sinus-Diseases

Elexacaftor-tezacaftor-ivacaftor is a highly effective modulator for cystic fibrosis (CF) patients homozygous or heterozygous for F508del. Effects of the drug on sinonasal symptoms have not been studied.. Adult participants were prospectively evaluated at baseline and after three months of treatment using validated questionnaires assessing sinonasal symptoms (SNOT-22) and CF-related quality of life (CFQ-R).. Forty-three participants completed the study; 23 were taking other CF transmembrane conductance (CFTR) modulators at the time of study participation. There was a significant improvement in mean SNOT-22 from 34.8 (29.4-40, 95% confidence interval) to 24.4 (19.9-29.0) (p = 0.000003) and in the Respiratory domain of the CFQR from 60.6 (57.1-64.1) to 83.3 (79.4-87.2) (p = 0.0000002), both achieving a minimal clinically important difference. Patients previously taking CFTR modulators experienced a greater benefit in sinonasal and respiratory symptoms.. Elexacaftor-tezacaftor-ivacaftor is associated with significant improvement in sinonasal symptoms; previous use of CFTR modulators is associated with greater benefit.

Topics: Adult; Aminophenols; Benzodioxoles; Chloride Channel Agonists; Cystic Fibrosis; Drug Combinations; Female; Humans; Indoles; Male; Paranasal Sinus Diseases; Prospective Studies; Pyrazoles; Pyridines; Pyrrolidines; Quality of Life; Quinolones

Most patients with Cystic fibrosis (CF) have chronic sinus disease which may require multiple sinus surgeries and antibiotic courses. Ivacaftor can improve lung function, lower sweat chloride levels and improve weight by targeting the primary defect, a faulty gene and its protein product, cystic fibrosis transmembrane conductance regulator (CFTR) in patients with the G551D mutation. Its role in improving sinus disease has not been evaluated.. The objective of this study was to evaluate efficacy of ivacaftor in improving CF related sinus disease.. Observational study.. Twelve patients with cystic fibrosis and a G551D-CFTR mutation.. Twelve patients with a G551D-CFTR mutation were monitored for at least one year before and after starting ivacaftor.. Sinus disease progression was monitored by comparing computed tomography (CT) of sinuses before and at one year on therapy. Hospital admissions, pulmonary exacerbations, weight, BMI and lung function were also compared.. Median age was 17 years (range 10-44). Weight, BMI, FEV1 significantly increased and sweat chloride significantly decreased by six months on ivacaftor therapy. CT of the sinuses in all patients improved. Seven patients had severe sinus disease, improved to moderate in three and mild in remaining four. Four patients had moderate disease which improved to mild in all. One patient had normal sinus CT before and after the therapy.. Patients with CF and G551D mutation, within 6 months of starting ivacaftor had significant improvements in weight, BMI and mean % FEV1. Significant lessening of underlying sinus disease measured by CT scan was noted, suggesting a disease modifying effect.

Topics: Adolescent; Adult; Aminophenols; Child; Cohort Studies; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Female; Genotype; Humans; Male; Mutation; Paranasal Sinus Diseases; Quinolones; Tomography, X-Ray Computed; Treatment Outcome; Young Adult

In patients with Cystic Fibrosis and a type III mutation, ivacaftor (Kalydeco(®), Vertex) can increase the opening time of the CFTR channel and improve chloride transport. Research showed significant improvement of lung function and increase in weight following ivacaftor use. However, ivacaftor showed to have adverse events on the sinonasal system as well, such as upper respiratory tract infections, nasal congestion and headaches. This case report showed a positive effect of ivacaftor on the sinonasal pathology in a 17 year old patient with CF. After 5 months of ivacaftor use, the CT-sinus showed complete resolution of the opacification of the paranasal sinuses and a decrease in symptoms of sinonasal disease. This positive effect of ivacaftor on sinonasal pathology seems promising, therefore more research is needed to evaluate the effect of ivacaftor on the upper airways in CF.

Topics: Adolescent; Aminophenols; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; DNA; Female; Forced Expiratory Volume; Genotype; Humans; Ion Transport; Mutation; Paranasal Sinus Diseases; Paranasal Sinuses; Quinolones; Tomography, X-Ray Computed

Topics: Acetates; Adult; Aminophenols; Androstadienes; Anti-Allergic Agents; Cyclopropanes; Cystic Fibrosis; Female; Fluticasone; Humans; Leukotriene Antagonists; Paranasal Sinus Diseases; Quinolines; Quinolones; Rhinitis, Allergic, Perennial; Sulfides; Treatment Outcome; Young Adult