Investigating the effects of long-term dornase alfa use on lung function using registry data

Dornase alfa (DNase) is one of the commonest cystic fibrosis (CF) treatments and is often used for many years. However, studies have not evaluated the effectiveness of its long-term use. We aimed to use UK CF Registry data to investigate the effects of one-, two-, three-, four- and five-years of DNase use on lung function to see if the benefits of short-term treatment use are sustained long term.

We analysed data from 4,198 people in the UK CF Registry from 2007 to 2015 using g-estimation. By controlling for time-dependent confounding we estimated the effects of long-term DNase use on percent predicted FEV₁ (ppFEV₁) and investigated whether the effect differed by ppFEV₁ at treatment initiation or by age.

Considering the population as a whole, there was no significant effect of one-year's use of DNase; change in ppFEV₁ over one year was -0.1% in the treated compared to the untreated (p = 0.51) and this did not change with long-term use. However, treatment was estimated to be more beneficial in people with lower lung function (p < 0.001); those with ppFEV₁ < 70% at treatment initiation, showed an increase in lung function over one year that was sustained out to five years. The estimated effect of DNase did not depend on age (p = 0.35).

DNase improved lung function in individuals with reduced lung function, bringing a step-change in lung function, but no change in the slope of decline. There was no evidence for a benefit in lung function in those initiating treatment with ppFEV₁ > 70%.