Dornase alfa for cystic fibrosis
Abstract
Background
Dornase alfa is currently used as a mucolytic to treat pulmonary disease (the major cause of morbidity and mortality) in cystic fibrosis. It reduces mucus viscosity in the lungs, promoting improved clearance of secretions. This is an update of a previously published review.
Objectives
To determine whether the use of dornase alfa in cystic fibrosis is associated with improved mortality and morbidity compared to placebo or other medications that improve airway clearance, and to identify any adverse events associated with its use.
Search 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: 30 November 2015.
Clinicaltrials.gov was also searched to identify unpublished or ongoing trials. Date of most recent search: 28 November 2015.
Selection criteria
All randomised and quasi‐randomised controlled trials comparing dornase alfa to placebo, standard therapy or other medications that improve airway clearance.
Data collection and analysis
Authors independently assessed trials against the inclusion criteria; two authors carried out analysis of methodological quality and data extraction.
Main results
The searches identified 54 trials, of which 19 (including a total of 2565 participants) met our inclusion criteria. Three additional papers examined the healthcare cost from one of the clinical trials. Fifteen trials compared dornase alfa to placebo or no dornase alfa treatment (2447 participants); two compared daily dornase to hypertonic saline (32 participants); one compared daily dornase alfa with hypertonic saline and alternate day dornase alfa (48 participants); one compared dornase alfa to mannitol and the combination of both drugs (38 participants). Trial duration varied from six days to three years.
Compared to placebo, forced expiratory volume at one second improved in the intervention groups, with significant differences at one, three, six months and two years. There was also a significant improvement in lung clearance index at one month. There was a decrease in pulmonary exacerbations compared to placebo in trials of longer duration. The quality of the evidence from placebo‐controlled trials was moderate to high for outcomes of lung function and pulmonary exacerbations. Limited, low quality evidence was available for changes in quality of life from baseline. One trial that examined the cost of care, including the cost of dornase alfa, found that the cost savings from dornase alfa offset 18% to 38% of the medication costs.
The results for trials comparing dornase alfa to other medications that improve airway clearance (hypertonic saline or mannitol) were mixed, with one trial showing a greater improvement in forced expiratory volume at one second for dornase alfa compared to hypertonic saline, and three trials finding no difference between medications. In the only trial to assess the combination of dornase alfa with another medication compared to dornase alone, there was no benefit seen with the combination of dornase alfa and mannitol. Evidence of dornase alfa compared to other medications was limited and the open‐label design of the trials may have induced bias, therefore the quality of the evidence was judged to be low.
Dornase alfa did not cause significantly more adverse effects, except voice alteration and rash.
Authors' conclusions
There is evidence to show that, compared with placebo, therapy with dornase alfa improves lung function in people with cystic fibrosis in trials lasting one month to two years. There was a decrease in pulmonary exacerbations in trials of six months or longer. Voice alteration and rash appear to be the only adverse events reported with increased frequency in randomised controlled trials. There is not enough evidence to firmly conclude if dornase alfa is superior to hyperosmolar agents in improving lung function.
PICOs
Plain language summary
Dornase alfa, an inhaled drug, for treating lung disease in cystic fibrosis
Review question
We reviewed the evidence about the effect of using inhaled dornase alfa for treating lung disease in people with cystic fibrosis.
Background
Cystic fibrosis is an inherited condition which affects the movement of salt across cells in the body and affects, for example, the sweat glands, airways, pancreas and male reproductive system. Lung disease is the most common cause of death in people with cystic fibrosis and although the average life expectancy has increased over the last 30 years, it is still only 48.5 years in developed countries. People with cystic fibrosis develop chronic lung disease because of thick mucus that builds up in the lungs which causes infections and inflammation. Dornase alfa was developed to thin out this mucus, so it is easier for people to cough it up from their lungs; this in turn should decrease the number of infections and amount of inflammation and prevent chronic lung disease.
Search date
The evidence is current to: 28 November 2015.
Study characteristics
We included 19 trials in the review with a total of 2565 people with cystic fibrosis. Fifteen trials compared dornase alfa to placebo (a dummy treatment with no active medication) or no dornase alfa treatment (2447 people); two compared daily dornase to hypertonic saline (32 people); one compared daily dornase alfa with hypertonic saline and alternate day dornase alfa (48 people); and one compared dornase alfa to mannitol and the combination of both drugs (38 people). People from all age groups (infants through to adults) took part in the trials which lasted from six days to three years.
Key results
The review found evidence that dornase alfa improves lung function within one month when compared to a placebo or no treatment and this improvement was also seen in longer trials lasting from six months to two years; there were also fewer flare ups of the condition in these longer trials. One trial found that the cost savings from dornase alfa offset 18% to 38% of the medication costs.
The results from trials comparing dornase alfa to hypertonic saline or mannitol were mixed. One trial showed a greater improvement in lung function with dornase alfa compared to hypertonic saline, and three trials found no difference between medications. In the only trial to assess the combination of dornase alfa with another medication compared to dornase alfa alone, there was no benefit seen with the combination of dornase alfa and mannitol.
Overall, no serious side effects were reported, with only rash and a change in voice seen more frequently in those people taking dornase alfa. However, it is not definitively clear from the current evidence if dornase alfa is better than other medications such as hypertonic saline or mannitol.
Quality of the evidence
The quality of evidence from the trials comparing dornase alfa to placebo or no treatment was moderate to high for lung function results, but only one trial reported any changes in quality of life so the evidence for this outcome is limited.
Also, there were few trials comparing different treatment schedules of dornase alfa (e.g. once a day versus twice a day) or comparing dornase alfa to other medications which help with clearing secretions, so current evidence from these trials is limited and of low quality.
