Real-world association between ivacaftor initiation and lung function variability: A registry study.

BACKGROUND

Increased variability in forced expiratory volume in 1 s of % predicted (FEV1pp) has been associated with accelerated lung function decline in individuals with cystic fibrosis (CF). Lung function variability is a leading predictor of decline, but the association between ivacaftor initiation and FEV1pp variability has not been characterized.

METHODS

We utilized the Cystic Fibrosis Foundation Patient Registry (2008-2020) to quantify this association and identify risk factors of increased variability. Linear mixed effects models were used to compare pre- and post-ivacaftor initiation periods for established outcome measures of FEV1pp variability: i) maximum and ii) median deviations from the best (highest) FEV1pp during each period; iii) maximum, iv) median, and v) standard deviation about the trendline of the FEV1pp trajectory in each period.

RESULTS

The analysis cohort included 527 individuals. Across outcomes, FEV1pp variability was reduced after ivacaftor initiation (median reduction: 1.85 % predicted). Reductions were robust with highest magnitudes of effect identified using maximum deviation from the best FEV1pp while most consistent findings were reached with trendline measures, particularly median deviation. Risk factors for increased FEV1pp variability differed between children and adults but were consistent between G551D and R117H subgroups. F508del homozygous patients followed contemporaneously exhibited minimal change in variability (median change: 0.25 % predicted). Reduced variability weakly correlated with changes in FEV1pp and slope, but higher levels of pre-ivacaftor variability were associated with greater reductions.

CONCLUSIONS

There was evidence that ivacaftor initiation reduces FEV1pp variability in people with CF. Quantifying FEV1pp variability may have utility as a marker of therapeutic effectiveness.