Safety of repeated intermittent courses of aerosolized recombinant human deoxyribonuclease in patients with cystic fibrosis

• Published in: The Journal of pediatrics Vol. 131; no. 1; pp. 118 - 124
• Main Authors: Eisenberg, Jay D., Aitken, Moira L., Dorkin, Henry L., Harwood, Ivan R., Ramsey, Bonnie W., Schidlow, Daniel V., Wilmott, Robert W., Wohl, Mary Ellen, Fuchs, Henry J., Christiansen, David H., Smith, Arnold L.
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01-07-1997; Elsevier
• Subjects: Adolescent; Adult; Aerosols; Aged; Antibody Formation; Biological and medical sciences; Bronchial Hyperreactivity - chemically induced; Child; Cystic Fibrosis - drug therapy; Cystic Fibrosis - immunology; Cystic Fibrosis - physiopathology; Deoxyribonucleases - administration & dosage; Deoxyribonucleases - immunology; Deoxyribonucleases - therapeutic use; Drug Administration Schedule; Drug Hypersensitivity - etiology; Dyspnea - drug therapy; Errors of metabolism; Female; Follow-Up Studies; Forced Expiratory Volume - drug effects; Humans; Immunoglobulin G - biosynthesis; Immunoglobulin Isotypes - biosynthesis; Lung - drug effects; Lung - physiopathology; Male; Medical sciences; Metabolic diseases; Middle Aged; Miscellaneous hereditary metabolic disorders; Quality of Life; Recombinant Proteins; Safety; Vital Capacity - drug effects; FVC; rhDNase; CF; FEV 1; Human; Immunopathology; Allergy; Deoxyribonuclease; Enzyme; Antibody; Toxicity; Treatment efficiency; Cystic fibrosis; Esterases; Inhalation; Lung function; Treatment; Intermittent; Aerosols; Hydrolases
• ISSN: 0022-3476; 1097-6833
• DOI: 10.1016/S0022-3476(97)70134-3

Objectives: To determine the effect of repeated doses of aerosolized recombinant human deoxyribonuclease (rhDNase) on the development of anti-rhDNase antibodies, acute allergic reactions, and pulmonary function in patients with cystic fibrosis.
Design: A multicenter, open-label study in which 184 patients received 10 mg aerosolized rhDNase twice a day for 14 days followed by a 14-day washout period for a total of 6 treatment cycles. Serial determinations of anti-rhDNase antibodies and pulmonary functions were performed.
Results: Detectable anti-rhDNase antibodies developed in 16 (8.7%) patients. These patients had no changes in their symptoms from the time they entered the trial. Antibodies detected were all of the IgG isotype. Increases in both forced expired volume in 1 second and forced vital capacity were noted from the beginning to the end of each cycle of treatment returning to baseline during the off-treatment period of each cycle. Seropositivity to rhDNase was not associated with allergic reactions and had no relationship on improvement in pulmonary function.
Conclusions: Development of anti-rhDNase antibodies occurred in a small number of patients and was not associated 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 improved significantly during the 14-day cycles while rhDNase was administered and returned to baseline when rhDNase was discontinued. (J Pediatr 1997;131:118-24)