Effect of Hypertonic Saline on Lung Function as Add-on Treatment in People With Cystic Fibrosis Receiving Dornase Alfa: A Cystic Fibrosis Foundation Patient Registry Analysis

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Introduction of novel therapies for cystic fibrosis (CF), raises the question whether traditional treatments can be withdrawn. Nebulized hypertonic saline (HS) could potentially be discontinued in patients receiving Dornase alfa (DA). In the pre-modulator era, did people with CF who were F508del homozygous (CFF508del) and received DA and HS have better preserved lung function than those treated with DA only? Retrospective analysis of CF Foundation Patient Registry data (2006-2014). Among 13,406 CFF508del with data for at least 2 consecutive years, 1,241 CFF508del had spirometry results and were treated with DA for 1-5 years without DA or HS during the preceding (baseline) year. Absolute percent predicted FEV1 (ppFEV1) change while on DA and HS relative to DA only was the main outcome. A marginal structural model was applied to assess the effect of 1-5 years of HS while controlling for time-dependent confounding. Of 1,241 CFF508del, 619 (median baseline age 14.6 years; IQR 6-53) received DA only and 622 (14.55 years; IQR 6-48.1) were treated with DA and HS for 1-5 years. After 1 year, subjects receiving DA and HS had ppFEV1 that averaged 6.60% lower than ppFEV1 in those treated with DA only (95%CI: -8.54% to -4.66%; P<.001). Lower lung function in the former relative to the latter persisted throughout follow-up, highlighting confounding by indication. After accounting for baseline age, sex, race, DA use duration, baseline and previous year's ppFEV1 and time-varying clinical characteristics, DA and HS for 1-5 years were similar to DA only regarding ppFEV1 (year 1: mean ppFEV1 change +0.53% [95%CI: -0.66% to +1.71%; P=.38]; year 5: -1.82% [-4.01% to +0.36%; P=.10]. In the pre-modulator era, CFF508del had no significant difference in lung function when nebulized HS was added to DA for 1-5 years.