Recombinant human deoxyribonuclease (rhDNase) in cystic fibrosis

Background. The chronic inflammatory pulmonary disease in cystic fibrosis is associated with the influx of neutrophils which, as they die, release large quantities of deoxyribonucleic acid (DNA). These DNA strands contribute considerably to the viscosity of CF sputum. Results. Dornase alfa,the recombinant human deoxyribonuclease (rhDNase), has been shown in vitro to depolymerise DNA,to liquefy secretions and to decrease viscoelastic porperties of CF respiratory secretions. A comprehensive clinical development programme has established the efficacy and safety of dornase alfa in children, adolescents and adults with cystic fibrosis. Lung function improved in patients aged 5 years or older with a forced expiratory volume (FEV1)greater than or equal to 40% of predicted, and acute respiratory exacerbations were less frequent if patients inhaled rhDNase. Adverse drug effects are voice alterations, laryngitis and exanthema. Treatment is expensive with monthly costs of approx. 1200 Euro per patient. Response to treatment varies considerably, and no parameter has been identified which could predict a favourable outcome. A two to four week trial of rhDNase inhalation is therefore required to determine the response to treatment in an individual patient.