Dornase alfa for cystic fibrosis.
BACKGROUND
Dornase alfa is currently used to treat pulmonary disease (the major cause of morbidity and mortality) in cystic fibrosis.


OBJECTIVE
To determine whether the use of dornase alfa 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.


METHODS
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 Cystic Fibrosis Register: 17 July 2009.


METHODS
All randomised and quasi-randomised controlled trials where dornase alfa was compared to placebo, standard therapy or another mucolytic.


METHODS
Authors independently assessed trials for inclusion criteria; the lead author and a colleague carried out analysis of methodological quality and data extraction.


RESULTS
The searches identified 43 trials, of which 15 met our inclusion criteria, including a total of 2469 participants. Three additional studies examined the healthcare cost from one of the clinical trials. Twelve studies compared dornase alfa to placebo or no dornase alfa treatment; one compared daily dornase alfa with hypertonic saline and alternate day dornase alfa; and two compared daily dornase alfa to hypertonic saline. Study duration varied from six days to two years. The number of deaths was not significant between treatment groups. Spirometric lung function improved in the treated groups, with significant differences at one month, three months, six months and two years, there was a non-significant difference at three years. 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.


CONCLUSIONS
There is evidence to show that therapy with dornase alfa 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 FEV(1) 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.
Institute of Child Health, University of Liverpool, Alder Hey Children's NHS Foundation Trust, Eaton Road, Liverpool, Merseyside, UK, L12 2AP.
Ashley P
AP
Jones
Colin
C
Wallis
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000188:drug therapy*; D003850:Deoxyribonuclease I / Q000009:adverse effects / Q000627:therapeutic use*; D005100:Expectorants / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007223:Infant; D016032:Randomized Controlled Trials as Topic; D012462:Saline Solution, Hypertonic / Q000627:therapeutic use
D005100:Expectorants; D012462:Saline Solution, Hypertonic; C085693:DNASE1 protein, human; D003850:Deoxyribonuclease I