2 YEARS EXPERIENCE WITH RECOMBINANT HUMAN DNASE-I IN THE TREATMENT OFPULMONARY-DISEASE IN CYSTIC-FIBROSIS

Recombinant human DNase I(rhDNase) has been shown to improve pulmonary function in patients treated for up to 6 months. A cohort of 52 cysti c fibrosis patients with a FVC > 40% predicted were enrolled into an o pen label study in order to evaluate longer-term effects of rhDNase. T hey received 2.5 mg rhDNase twice daily for 6 months followed by a 2-w eek wash-out period, and for the subsequent 18 months were treated wit h rhDNase once daily. Twenty-six male and 26 female patients with a me an FVC of 2.941 and FEV(1) of 1.471 were recruited. Thirteen patients did not complete the study; there were seven deaths, three patients wi thdrew consent and three patients were lost to follow-up. Improvement in pulmonary function was seen following treatment and changes were ev aluated as mean percent change from baseline. The maximum improvement occurred in the first month followed by a plateau at a lower level of improvement. The mean improvement in FEV, over the first month was 13. 3% (range 12-14.1%), followed by a plateau at around 7.1% (range 4.6-1 1.0%) for the subsequent 23 months. Mean FVC was improved by 12.03% (r ange 9.0-14.3%) over the first month and subsequently 4.2% (range - 2. 2-10.2%). The effects on pulmonary function were similar for both trea tment doses of rhDNase. There was also a steady improvement in weight from a mean of 54.2 kg to 55.7 kg at the end of the study. Analysis of the results of only those patients who completed the full 2-yr treatm ent period show that changes in pulmonary function and weight were sim ilar to those observed for the whole group. The death rate and adverse event profile were consistent with that seen in a cystic fibrosis pop ulation. This study confirms that longer-term treatment with rhDNase m aintains the improvement in lung function, is associated with weight g ain and has a good safety profile.