S J Newsome1, R M Daniel2, S B Carr3, D Bilton4, R H Keogh5. 1. Department of Medical Statistics, London School of Hygiene & Tropical Medicine, London, UK. Electronic address: simon.newsome@lshtm.ac.uk. 2. Division of Population Medicine, Cardiff University, Cardiff, UK. 3. Department of Paediatric Respiratory Medicine, Royal Brompton & Harefield NHS Foundation Trust, London, UK. 4. Faculty of Medicine, National Heart & Lung Institute, Imperial College London, London, UK. 5. Department of Medical Statistics, London School of Hygiene & Tropical Medicine, London, UK.
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%.
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%.
Authors: Vincent D Giacalone; Brian S Dobosh; Amit Gaggar; Rabindra Tirouvanziam; Camilla Margaroli Journal: Int J Mol Sci Date: 2020-05-08 Impact factor: 5.923
Authors: Daniela K Schlüter; Josh S Ostrenga; Siobhán B Carr; Aliza K Fink; Albert Faro; Rhonda D Szczesniak; Ruth H Keogh; Susan C Charman; Bruce C Marshall; Christopher H Goss; David Taylor-Robinson Journal: Thorax Date: 2021-05-11 Impact factor: 9.139