Recombinant human deoxyribonuclease for cystic fibrosis

Recombinant human deoxyribonuclease (rhDNase) is currently used to treat pulmonary disease (the major cause of morbidity and mortality) in cystic fibrosis.

To determine whether the use of rhDNase in cystic fibrosis is associated with improved mortality and morbidity compared to placebo or other mucolytics and to identify any adverse events associated with its use.

We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group trials register which comprises references identified from comprehensive electronic database searches, handsearching relevant journals and abstracts from conferences. Date of the most recent search of the Group's register: January 2003.

All randomized and quasi-randomized controlled trials where rhDNase was compared to either placebo, standard therapy or another mucolytic.

Trials were independently assessed for inclusion criteria and the lead reviewer and a colleague carried out analysis of methodological quality and data extraction.

The searches identified 38 trials, of which 12 trials met our inclusion criteria, including a total of 2294 participants. Three additional studies examined the health care cost from one of the clinical trials. Ten studies compared rhDNase to placebo; one compared daily rhDNase with hypertonic saline and alternate day rhDNase; and one compared daily rhDNase to hypertonic saline. Study duration varied from six days to two years. The number of deaths was not significant between treatment groups. Lung function improved in the treated groups, with significant differences at one month, three months, six months and two years. The mean percentage change in FEV1in the two largest trials were 5.80 (95% CI 3.99 to 7.61) and 3.24 (95% CI 1.03 to 5.45). There was no excess of adverse effects except voice alteration (and rash, which were reported more frequently in one trial in the treated groups. Insufficient data were available to analyse differences in antibiotic treatment, inpatient stay and quality of life.

There is evidence to show that therapy with rhDNase over a one month period is associated with an improvement in lung function in CF, results from a trial lasting six months also showed the same effect. Therapy over a two year period (based on one trial) significantly improved FEV1 in children and there was a non-significant reduction in the risk of infective exacerbations. Voice alteration and rash appear to be the only adverse events reported with increased frequency in randomised controlled trials.