Clinical use of dornase alfa is associated with a slower rate of FEV 1 decline in cystic fibrosis

Objectives Randomized controlled trials of dornase alfa have shown forced expiratory volume in 1 sec (FEV 1 ) to improve in patients with cystic fibrosis (CF) but have not assessed change in the rate of lung function decline. We assessed the relationship of dornase alfa use and FEV 1 decline using the Epidemiologic Study of Cystic Fibrosis (ESCF). Methodology Patients aged 8–38 years who had been enrolled in ESCF for 2 years when initially treated with dornase alfa were selected if they remained on treatment during the following 2 years. A comparator group included patients aged 8–38 who were not yet reported to have received dornase alfa. For each patient we estimated the annual rate of decline in FEV 1 % predicted before and after the index using a mixed‐effects model adjusted for age, gender, pulmonary exacerbations, respiratory therapies, and nutritional supplements. Results The dornase alfa group (n = 2,230) had a lower FEV 1 % predicted at index and a more rapid decline during the pre‐index period. The mean rate of FEV 1 decline improved for the dornase alfa group; the improvement was similar in adults and children 8–17 years old but was not statistically significant in adults. The comparator group (n = 5,970) showed no change among adults and an increased rate of decline among children 8–17 years old. Conclusions The use of dornase alfa for a 2‐year period is associated with a reduction in the rate of FEV 1 decline. These results also demonstrate the value of using an observational study to assess the association of instituting new therapies in the clinical setting with changes in the rate of FEV 1 decline in patients with CF. Pediatr. Pulmonol. 2011; 46:545–553. © 2011 Wiley‐Liss, Inc.