Impact of age at ivacaftor initiation on pulmonary outcomes among people with cystic fibrosis

Abstract

Background Ivacaftor (IVA) improves lung function and other extrapulmonary outcomes in people with cystic fibrosis (CF). However, the effect of initiating IVA at earlier versus later ages has not been studied. Methods We conducted an observational cohort study of people in the US CF Foundation Patient Registry aged ≥6 years with ≥1 CF transmembrane conductance regulator–gating mutation to compare the effects of initiating IVA at earlier ages on per cent predicted forced expiratory volume in 1 s (ppFEV1) and pulmonary exacerbation (PEx) outcomes. People with CF were grouped by age at IVA initiation (ages 6–10, 11–15, 16–20 and 21–25 years) to perform three analyses of younger versus older IVA initiation (6–10 vs 11–15, 11–15 vs 16–20 and 16–20 vs 21–25 years). For each analysis, baseline characteristics assessed over 1-year periods at the same age prior to IVA initiation were balanced by standardised mortality/morbidity ratio (SMR) weighting. For each analysis, outcomes were compared over a 5-year outcome assessment period when both groups were in the same age range and receiving IVA. Findings Baseline characteristics were well balanced between younger and older IVA initiator groups after SMR weighting. In the outcome assessment period, younger IVA initiators had significantly higher mean ppFEV1 than older initiators across all comparisons, and those initiating IVA between ages 6–10 and 11–15 years had significantly lower PEx rates. Interpretation Study findings showed the importance of early IVA initiation in people with CF. Data are available upon reasonable request. The data that support the findings of this study are available from the US Cystic Fibrosis Foundation Patient Registry at . The US Cystic Fibrosis Foundation Patient Registry collects and manages its own data and maintains processes for researchers to request summarised data. Restrictions may apply to the availability of these data, which were used under a license agreement for this study.