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: 23 April 2018.

Study characteristics

We included 19 trials with 2565 people with cystic fibrosis; 15 trials (2447 people) compared dornase alfa to placebo (a dummy treatment with no active medication) or no dornase alfa treatment; two trials (32 people) compared daily dornase to hypertonic saline; one trial (48 people) compared daily dornase alfa with hypertonic saline and alternate day dornase alfa; and one trial (38 people) compared dornase alfa to mannitol and the combination of both drugs. People from all age groups (infants through to adults) took part in the trials which lasted from six days to three years.

Key results

Dornase alfa compared to placebo or no treatment

We found 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 (eight trials; 1708 participants). There were also fewer exacerbations (flare up of lung inflammation) in these longer trials. One trial found that the cost savings from dornase alfa offset 18% to 38% of the medication costs.

Dornase alfa - daily versus alternate day

One trial (43 children) found no differences between treatment schedules for lung function, quality of life or pulmonary exacerbations.

Dornase alfa compared to other medications that improve airway clearance

The results from trials comparing dornase alfa to hypertonic saline or mannitol were mixed. One trial (43 children) showed a greater improvement in lung function with dornase alfa compared to hypertonic saline and one trial (23 participants) reported no difference in lung function between dornase alfa and mannitol or dornase alfa and dornase alfa plus mannitol. In one trial (23 participants) quality of life scores were better with dornase alfa alone than with dornase alfa plus mannitol; other drug comparisons found no difference between treatments for quality of life. No trials in any comparison of treatments reported any difference between groups in the number of pulmonary exacerbations.

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.

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 from 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 other hyperosmolar agents in improving lung function.

Read the full 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 strategy: 

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: 23 April 2018.

Clinicaltrials.gov and the International Clinical Trials Registry Platform were also searched to identify unpublished or ongoing trials. Date of most recent search: 07 June 2018.

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. GRADE was used to assess the level of evidence.

Main results: 

The searches identified 69 trials, of which 19 (2565 participants) met our inclusion criteria. Fifteen trials compared dornase alfa to placebo or no dornase alfa (2447 participants); two compared daily dornase to hypertonic saline (32 participants); one compared daily dornase alfa to 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.

Dornase alfa compared to placebo or no treatment

Dornase alfa improved forced expiratory volume at one second at one month (four trials, 248 participants), three months (one trial, 320 participants; moderate-quality evidence), six months (one trial, 647 participants; high-quality evidence) and two years (one trial, 410 participants). Limited low-quality evidence showed no difference between groups for changes in quality of life. There was a decrease in pulmonary exacerbations with dornase alfa in trials of up to two years (moderate-quality evidence). 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.

Dornase alfa: daily versus alternate day

One cross-over trial (43 children) found no differences between treatment regimens for lung function, quality of life or pulmonary exacerbations (low-quality evidence).

Dornase alfa compared to other medications that improve airway clearance

Results for these comparisons were mixed. One trial (43 children) showed a greater improvement in forced expiratory volume at one second for dornase alfa compared to hypertonic saline (low-quality evidence), and one trial (23 participants) reported no difference in lung function between dornase alfa and mannitol or dornase alfa and dornase alfa plus mannitol (low-quality evidence). One trial (23 participants) found a difference in quality of life favouring dornase alfa when compared to dornase alfa plus mannitol (low-quality evidence); other comparisons found no difference in this outcome (low-quality evidence). No trials in any comparison reported any difference between groups in the number of pulmonary exacerbations (low-quality evidence).

When all comparisons are assessed, dornase alfa did not cause significantly more adverse effects than other treatments, except voice alteration and rash.

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