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

Background: 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. Methods: 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 FEVI (ppFEVI) and investigated whether the effect differed by ppFEVI at treatment initiation or by age. Results: Considering the population as a whole, there was no significant effect of one-year's use of DNase; change in ppFEVI 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 ppFEVI < 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). Conclusions: 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 ppFEV 1 > 70%. (C) 2018 The Authors. Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society. This is an open access article under the CC BY NC-ND license.