Clinical Use of Dornase Alfa Is Associated With a Slower Rate of FEV1 Decline in Cystic Fibrosis

Objectives: Randomized controlled trials of dornase alfa have shown forced expiratory volume in 1 sec (FEV1) 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 FEV1 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 FEV1% 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 FEV1% predicted at index and a more rapid decline during the pre-index period. The mean rate of FEV1 decline improved for the dornase alfa group; the improvement was similar in adults and children 817 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 FEV1 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 FEV1 decline in patients with CF. Pediatr Pulmonol. 2011; 46:545-553. (C) 2011 Wiley-Liss, Inc.