Long-term durability of ivacaftor (IVA) treatment benefit in people with cystic fibrosis (PwCF)

Abstract

<b>Background:</b> IVA has been shown to reduce the rate of change (ROC) in lung function over 3 years; longer term durability of this benefit is unknown. <b>Objective:</b> To compare the ROC in lung function in pwCF aged ≥6 years with&nbsp;<i>CFTR</i>&nbsp;gating mutations treated with IVA with the ROC in pwCF with&nbsp;<i>F508del</i>&nbsp;and a minimal function mutation (comparator cohort) over 2-5 years. <b>Methods:</b> US CF Foundation Patient Registry data from 2010-2019 were used. Annualized ROC was estimated using mixed models for repeated measures among pwCF with ≥3 ppFEV1 measures spanning ≥6 months between 1 month after index (IVA cohort: IVA initiation date, comparator cohort: closest visit date within 6 months of matched IVA index) and 24, 36, 48, and 60 months. Clinical and demographic characteristics during the baseline period (2 years prior to index) were balanced between cohorts using standardized mortality ratio (SMR) weighting. <b>Results:</b> After SMR weighting, the mean age at index and mean baseline ppFEV1 in the year prior to index were 18.7 years and 80.6 in the IVA cohort (n=548), and 18.6 years and 79.6 in the comparator cohort (n=541) for the 5-year follow-up cohort. Table illustrates that ROC in lung function in the IVA cohort was consistent over time, and ROC in the IVA vs. comparator cohorts was significantly lower over 3-5 years of follow-up. <b>Conclusion:</b> IVA has a durable treatment benefit over time. <b>Sponsor:</b> Vertex Pharmaceuticals Inc.