Dornase alfa and progression of lung disease in cystic fibrosis

Abstract

Obstruction, infection, and inflammation lead to progressive and irreversible lung destruction in cystic fibrosis (CF). Neutrophil-derived DNA contributes to thick, viscous secretions. Dornase alfa hydrolyzes DNA, reducing the viscosity of CF sputum. Clinical trials have shown that dornase alfa improves forced expiratory volume in one second (FEV1). Immediate improvement is important, but long term survival requires slowing the rate of lung function decline. Demonstrating changes in rate of decline requires long term studies with many patients, which are impractical for clinical trials. Observational studies such as the Epidemiologic Study of Cystic Fibrosis (ESCF) can address rate of decline in lung function, and is being used to evaluate the long-term effectiveness of dornase alfa. CF patients age 8–38 years when initially treated with dornase alfa (index event) were compared to patients not treated (for 2 years before and 2 years after index). In a preliminary analysis, FEV1 at index for the dornase alfa group (n = 2,706) was 80.5% predicted, and for the comparator group (n = 3,991) 86.7% predicted. The estimated rate of FEV1 decline before index for the dornase alfa group was −2.81 and for the comparator group −0.85% predicted/year. After index, the rate of decline for the dornase alfa group was −1.53% predicted/year (46% reduction, P < 0.001), with no change in the comparator group. These preliminary results suggest that initiating dornase alfa is associated with both an acute improvement in FEV1 and a slowing of the rate of FEV1 decline. Analysis is ongoing to further evaluate this association. Pediatr Pulmonol. 2008; 43:S24–S28. © 2008 Wiley-Liss, Inc.