MEDIUM-TERM TREATMENT OF STABLE STAGE CYSTIC-FIBROSIS WITH RECOMBINANT HUMAN DNASE-I

Background - A phase II multicentre double blind placebo controlled st udy in 1993 showed that short term treatment (10 days) with recombinan t human DNase I (rhDNase) was safe and improved pulmonary function in patients with cystic fibrosis with stable stage lung disease. A six mo nth open label treatment study was conducted in some of the patients w ho participated in the short term study to assess the medium term effe cts of rhDNase. Methods - Patients who completed the phase II study an d were stable for 14 days prior to treatment were eligible. They were treated with rhDNase 2.5 mg twice daily for six months and reviewed at regular intervals to assess safety and efficacy. Results - Fifty nine patients (31M, 28F) of age range 16-55 years were recruited. Mean bas eline values for forced expiratory volume in one second (FEV(1)) and f orced vital capacity (FVC) were 41.5% and 72.4% of predicted, respecti vely. The mean increase in FEV(1) over the first month of treatment wa s 13.1% (range 12-14.1%) and then stabilised at 6.2% (4.6-7.8%) for th e subsequent five months. FVC was similarly improved. Administration o f rhDNase improved the severity of dyspnoea, cystic fibrosis related s ymptoms, and the modified Taussig/NIH score (not statistically signifi cant). Fifty seven of the 59 patients completed the study; two died fr om progression of their pulmonary disease unrelated to treatment with rhDNase. The adverse events and intercurrent illnesses were no differe nt from those expected in a cystic fibrosis population. Pharyngitis wa s the only possible drug related adverse event which occurred at least once in 14% of patients during the six month period. Conclusions - Ad ministration of rhDNase was safe, well tolerated, and improved pulmona ry function in patients with cystic fibrosis. When rhDNase was stopped at day 169 there was a deterioration in pulmonary function and dyspno ea score.