SAFETY OF REPEATED INTERMITTENT COURSES OF AEROSOLIZED RECOMBINANT HUMAN DEOXYRIBONUCLEASE IN PATIENTS WITH CYSTIC-FIBROSIS

Objectives: To determine the effect of repeated doses of aerosolized r ecombinant human deoxyribonuclease (rhDNase) on the development of ant i-rhDNase antibodies, acute allergic reactions, and pulmonary function in patients with cystic fibrosis. Design: A multicenter, open-label s tudy in which 184 patients received 10 mg aerosolized rhDNase mice a d ay for 14 days followed by a 14-day washout period for a total of 6 tr eatment cycles. Serial determinations of anti-rhDNase antibodies and p ulmonary functions were performed. Results: Detectable anti-rhDNase an tibodies developed in 16 (8.7%) patients. These patients had no change s in their symptoms from the time the entered the trial. Antibodies de tected were all of the Ige isotype. Increases in both forced expired v olume in 1 second and forced vital capacity were noted from the beginn ing to the end of each cycle of treatment returning to baseline during the off-treatment period of each cycle. Seropositivity to rhDNase mas not associated with allergic reactions and had no relationship on imp rovement in pulmonary function. Conclusions: Development of anti-rhDNa se antibodies occurred in a small number of patients and was not assoc iated with side effects. Intermittent administration of rhDNase for 24 weeks to patients with cystic fibrosis was well tolerated and was not associated with anaphylaxis in any patient. Pulmonary function improv ed significantly during the 14-day cycles while rhDNase was administer ed and returned to baseline when rhDNase was discontinued.