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

J Pediatr. 1997 Jul;131(1 Pt 1):118-24. doi: 10.1016/s0022-3476(97)70134-3.

Abstract

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.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aerosols
  • Aged
  • Antibody Formation
  • 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
  • Female
  • Follow-Up Studies
  • Forced Expiratory Volume / drug effects
  • Humans
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin Isotypes / biosynthesis
  • Lung / drug effects
  • Lung / physiopathology
  • Male
  • Middle Aged
  • Quality of Life
  • Recombinant Proteins
  • Safety
  • Vital Capacity / drug effects

Substances

  • Aerosols
  • Immunoglobulin G
  • Immunoglobulin Isotypes
  • Recombinant Proteins
  • Deoxyribonucleases