Patients with cystic fibrosis and advanced lung disease benefit from lumacaftor/ivacaftor treatment.

Background: Several studies have assessed safety and efficacy outcomes for lumacaftor/ivacaftor therapy. We report on lumacaftor/ivacaftor's impact on lung function, physical performance, and health-related quality of life (HRQOL) in a subpopulation of Danish people with Cystic Fibrosis (CF; PWCF) with advanced pulmonary disease who would not fulfill inclusion criteria for these studies.

Methods: This follow-up study examined lumacaftor/ivacaftor's effect in a highly selected CF population. Inclusion criteria included low percent predicted forced expiratory volume in one second (ppFEV ), fast deteriorating ppFEV , low body mass index (BMI), and difficult-to-treat infections. Primary endpoints included change in ppFEV slope, cardiopulmonary exercise testing (CPET), and all domains of the Cystic Fibrosis Questionnaire-Revised (CFQ-R). Secondary outcomes included change in ppFEV , BMI Z-score, and sweat chloride concentration.

Results: A total of 21 patients homozygous for the F508del mutation and a median ppFEV of 38.7 were included. We found significant improvements in ppFEV (+4.2 p < .01, +5.8 p < .01, +4.8 p < .01 and +3.8 p = .03 ppFEV after 3, 6, 9, and 12 months of treatment compared to baseline), ppFEV slope (+6.84 ppFEV /year between the year before and the year after treatment initiation; p = .02), and saturation at CPET initiation (+1.4%, p < .02) and termination (+2.6%, p < .01) after 6 months of treatment. Finally, HRQOL improved significantly in all CFQ-R domains except Emotion and Treat.

Conclusions: Our findings suggest that lumacaftor/ivacaftor reduces lung function decline, improves lung function, physical performance, and HRQOL to a greater extent in PWCF with severe lung disease than previously recognized.