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

Abstract

BackgroundIvacaftor (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.MethodsWe 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.FindingsBaseline 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 ppFEV1than older initiators across all comparisons, and those initiating IVA between ages 6–10 and 11–15 years had significantly lower PEx rates.InterpretationStudy findings showed the importance of early IVA initiation in people with CF.