DNase trials in cystic fibrosis.

Cystic fibrosis (CF) is a disease with a high morbidity and mortality from pulmonary disease. Sputum from CF patients contains high levels of deoxyribonucleic acid (DNA), which contribute to its viscoelasticity. Recombinant deoxyribonuclease (rhDNase) has been developed and in vitro studies have showed reduction in the viscoelasticity of CF sputum. This article reviews the in vivo clinical trials conducted to determine the safety and efficacy of this treatment. Phase 1 studies showed preliminary safety data and some evidence of clinical benefit. The two Phase 2 short-term studies showed improvement in pulmonary function and important safety data. The Phase 3 study, which included 968 patients, showed improvement in forced expiratory volume in one second (FEV1) of 5.8% and 5.6% in patients treated once and twice daily, respectively. The risk of developing an exacerbation of infection was reduced by 28% with once daily and 37% with twice daily treatment, compared to placebo. The drug was safe and there was some improvement in quality of life data. Longer-term open labelled studies, the results of intermittent administration, administration to severely ill patients, and the use of different delivery systems are reviewed. In conclusion, recombinant deoxyribonuclease is a new treatment which has been shown to benefit patients with cystic fibrosis when used in conjunction with conventional treatment.