The role of dornase alfa in the treatment of cystic fibrosis

OBJECTIVE: To review the current utility and proper role of dornase alfa (recombinant human DNase or rhDNAse), which has been approved for use in cystic fibrosis. Several aspects related to these issues are addressed including the drug's mechanism of action, administration, and dosing, and clinical safety and efficacy. We also critically examine the agent's role in the treatment of cystic fibrosis and consider the controversies involved with its use. DATA SOURCE: A MEDLINE search was conducted to identify pertinent literature, including review articles and clinical trials. STUDY SELECTION: Studies examining the efficacy and safety of dornase alfa in patients with cystic fibrosis. DATA EXTRACTION: Results from published, prospective, randomized trials are presented and critiqued. DATA SYNTHESIS: Production of viscous respiratory secretions is a hallmark phenomenon of cystic fibrosis, leading to a variety of symptoms. Dornase alfa targets this symptom and decreases the viscosity of these secretions. Clinical trials have indicated a small but statistically significant improvement in forced expiratory volume in 1 second and forced vital capacity. Enhancement in a patient's dyspnea and quality of life has varied between the trials, with few of the studies noting no statistically significant improvement. Adverse reactions are minimal and did not result in any patient withdrawals from the trials. A positive impact on infection rates, length of hospitalization, and need for intravenous antibiotic therapy was noted in one trial. However, reports of similar results have not yet been published, and thus the clinical significance of impact of this phenomenon is not fully understood. Moreover, results of more long-term use and in patients whose conditions are less stable have yet to undergo the scrutiny of peer/editorial review. Administration of the drug, which must be maintained continuously, is relatively expensive. CONCLUSIONS: Dornase alfa appears to produce small but sustained improvements in lung function in patients with cystic fibrosis. It may also slow the progression of pulmonary disease. Infection rates appear to be reduced, which may well have important long-term consequences. However, evidence to date has not clarified the most appropriate use of dornase alfa in the treatment of cystic fibrosis. Whether quality of life is affected in a meaningful and measurable way is yet to clarified. A trial of the drug in patients with cystic fibrosis who have obvious lung disease is reasonable, but continued treatment should be based on clear clinical response. Therefore, questions about the drug's exact role in the overall management of cystic fibrosis remain to be answered. Although benefits received may not prove to be cost-effective, long-term effects on disease progression may well justify use of this agent.