Impact of pulmonary exacerbations and lung function on generic health-related quality of life in patients with cystic fibrosis

Caitlyn T. Solem, Montserrat Vera-Llonch, Sizhu Liu, Marc Botteman, Brenda Castiglione

The analysis aimed to examine the impact of pulmonary exacerbations (PEs) and lung function on generic measures of HRQL in patients with cystic fibrosis (CF) using trial-based data. In a 48-week randomized, placebo-controlled study of ivacaftor in patients ≥12 years with CF and a G551D-CFTR mutation the relationship between PEs, PE-related hospitalizations and percent predicted forced expiratory volume in one second (ppFEV1) with EQ-5D measures (index and visual analog scale [VAS]) was examined in post-hoc analyses. Multivariate mixed-effects models were employed to describe the association of PEs, PE-related hospitalizations, and ppFEV1 on EQ-5D measures. One hundred sixty one patients (age: mean 25.5 [SD 9.5] years; baseline ppFEV1: 63.6 [16.4]) contributed 1,214 observations (ppFEV1: no lung dysfunction [n = 157], mild [n = 419], moderate [n = 572], severe [n = 66]). Problems were most frequently reported on pain/discomfort, anxiety/depression, and usual activities EQ-5D items. The mean (SE) EQ-5D index nominally decreased (worsened) with worsening severity of lung dysfunction (P = 0.070): 0.931 (0.023); mild: 0.923 (0.021); moderate: 0.904 (0.018); severe: 0.870 (0.020). 146 PEs were experienced by 72 patients, including 52 PEs (35.6 %) that required hospitalization. Mean EQ-5D index and VAS scores were lowest (worst) within 1 week (before or after PE start) for PEs requiring hospitalization. Pulmonary exacerbations, PE-related hospitalizations, and ppFEV1 were significant predictors of EQ-5D index and VAS. In a clinical study of patients with CF (≥12 years of age and a G551D-CFTR mutation), PEs, primarily those requiring hospitalization, were associated with low EQ-5D index and VAS scores. The impact of ppFEV1 was relatively smaller. Reducing PEs, in particular those requiring hospitalization, would likely improve HRQL among these patients. ClinicalTrials.gov, NCT00909532 ; URL: clinicaltrials.gov, May 26, 2009.