A case-controlled study with dornase alfa to evaluate impact on disease progression over a 4-year period

Background: Chronic endobronchial sepsis and profuse airway secretions domi nate pulmonary disease in cystic fibrosis. Recombinant human DNase I (dorna se alfa) reduces the viscoelasticity of airway secretions and hence may imp rove clearance of airway secretions. Objectives: To evaluate the long-term influence of dornase alfa on disease progression by performing a case-contr olled study with dornase alfa over a period of 4 years. Methods: A cohort o f patients with cystic fibrosis who have been treated with dornase alfa wer e matched with a control group of patients with cystic fibrosis who had not received treatment with dornase alfa. The patients were matched by pulmona ry function, age, and then sex. All available measurements of forced expira tory volume in one second (FEV1), height, weight and sputum bacteriology we re collected for periods when the patients were free from respiratory exace rbations. Results: Thirty-eight patients were matched. Slopes of median cha nges in FEV1 were -2.19 (-3.32, -1.06) in the control group and -0.75 (-1.8 7, 0.36) in the dornase alfa-treated group (p = 0.076). There were more inf ective exacerbations per patient year in the control group [3.13 (1.25-4.25 )] in comparison to the dornase alfa group [1.25 (0.63-3.0), p = 0.035] ove r the 4-year treatment period. Antibiotic requirements were also greater wi th a median 43.75 (17.5-60.0) days of intravenous antibiotic use per patien t year in the control group and 16.25 (8.5-44.0) days in the dornase alfa g roup (p = 0.034). Conclusions: The trends suggest that dornase alfa may hav e some influence on disease progression but in view of the limitations of t he current study the need for further long-term studies in larger cohorts o f patients is emphasised. Copyright (C) 2001 S. Karger AG, Basel.