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

J Cyst Fibros. 2019 Jan;18(1):110-117. doi: 10.1016/j.jcf.2018.08.004. Epub 2018 Aug 29.

Abstract

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 FEV1 (ppFEV1) and investigated whether the effect differed by ppFEV1 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 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).

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 ppFEV1 > 70%.

Keywords: DNase; Long-term treatment effect; Patient registry; UK Cystic Fibrosis Registry.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Cystic Fibrosis / drug therapy*
  • Cystic Fibrosis / physiopathology
  • Deoxyribonuclease I / therapeutic use*
  • Female
  • Follow-Up Studies
  • Forced Expiratory Volume / drug effects
  • Forced Expiratory Volume / physiology*
  • Humans
  • Lung / drug effects
  • Lung / physiopathology*
  • Male
  • Recombinant Proteins / therapeutic use
  • Registries*
  • Respiratory Function Tests
  • Retrospective Studies
  • Time Factors
  • Treatment Outcome
  • Young Adult

Substances

  • Recombinant Proteins
  • Deoxyribonuclease I
  • dornase alfa