LONG -TERM DORNASE ALFA THERAPY IN CHILDREN WITH CF

D. Sands, A. Nowakowska, R. Piotrowski, A. Milanowski

Institute of Mother and Child, Warsaw, Poland

OBJECTIVE: Cystic fibrosis (CF) is the most common recessively inherited disease of white races. Most of the morbidity and of mortality is due to bronchopulmonary complications. Current disease management strategies focus on the maintenance of pulmonary function promoting clearance of airway secretions, reducing inflammation, infection and improving nutritional status. One of the contributory factors to the viscid nature of CF sputum is its high content of DNA. Treatment with recombinent human (rh) DNase was shown to improve pulmonary functions and reduce the risk of respiratory tract infections in patients with CF. The aim of our study was to evaluate the long -term effects of dornase alfa and its tolerance in CF children.

METHODS: Dornase alfa was given to 32 children with CF (15 girls, 17 boys; aged 5-18 years, mean age 10,7 years, FVC >40%). They received 2,5 mg dornase alfa daily by nebulisation for 36 months. Recordings of FVC and FEV1 (both corrected for height, sex and age) were taken at the start of dornase alfa therapy and then subsequently at 2 weeks, 3 months, 6 months and every 3 months until 36 months of treatment. The number of respiratory exacerbations requiring intravenous anti-biotic therapy was determined during the period of dornase alfa treatment and compared with the same period before therapy. Radiological changes in lungs were evaluated using Brasfield scoring system.

RESULTS: 1. Quick improvement after 2 weeks of dornase alfa treatment. FEV1 increased by mean 12,47%, FVC by 9,4 %. Improvement was maintained during 36 months of treatment. 2. No progression in lung, x-rays in 70% of treated patients 3. Smaller number of infections in the period of dornase alfa therapy (mean 38 days of intravenous antibiotic a year vs 52 days before treatment. 4.Correlation between early (3 months) and 24 months FEV1 responses to treatment (r=0,6, p=0,0001)

CONCLUSIONS: Dornase alfa treatment improves the quality of life ofCF children by reducing the number of infections, improving pulmonary functions and patients well - being. A 3 month trial of dornase alfa therapy is predictive of long - term benefit.