In individuals with cystic fibrosis (CF), treatment with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) has been shown to halt lung function decline over 2 years, according to a recent analysis published in the Journal of Cystic Fibrosis.

The analysis compared participants with CF from 2 phase 3 clinical studies and an open-label extension study with a matched group of patients with CF from the US Cystic Fibrosis Foundation Patient Registry (CFFPR).

The researchers sought to characterize the effect of the CF transmembrane conductance regulator (CFTR) modulators ELX/TEZ/IVA on decline in pulmonary function over time by comparing the annualized rate of change in percent predicted forced expiratory volume in 1 second (ppFEV1) with that of a propensity score-matched historical cohort of controls from the US CFFPR who had not received CFTR modulators.

Patients who had received ELX/TEZ/IVA in the phase 3 studies 445-102 (NCT03525444) and 445-103 (NCT03525548) or the open-label extension study 445-105 (NCT03525574) and who had at least 3 ppFEV1 measurements over at least 6 months were propensity score matched with up to 5 patients from the CFFPR who were aged 12 years or more with the F/MF or F/F genotype.

In the present study, 468 ELX/TEZ/IVA-treated patients (367 with the F/MF genotype and 101 with the F/F genotype) were matched with 1714 CFTR modulator-untreated controls (1242 with the F/MF genotype and 472 with the F/F genotype). The baseline mean ppFEV1 values were 61.05±15.69 percentage points in the ELX/TEZ/IVA arm and 62.60±9.61 percentage points in the control arm.

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Results showed that patients treated with ELX/TEZ/IVA had a mean annualized rate of change in ppFEV1 of +0.39 percentage points (95% CI, -0.06 to 0.85) compared with -1.92 percentage points (95% CI, -2.16 to -1.69) in the matched control group (mean difference, 2.32 percentage points; P <.001). At year 2, the between-group difference in ppFEV1 was 16.91 percentage points (95% CI, 15.56 to 18.27; P <.001).

In the F/MF subgroup, the estimated annualized rate of change in ppFEV1 was +0.32 percentage points (95% CI, -0.19 to 0.82) in the ELX/TEZ/IVA arm vs -1.85 percentage points (95% CI, -2.13 to 1.58) in the untreated control arm (mean difference, 2.17 percentage points; P <.001). In the F/F subgroup, the estimated annualized rate of change in ppFEV1 was +0.74 percentage points (95% CI, -0.28 to 1.75) in the ELX/TEZ/IVA group vs -2.08 percentage points (95% CI,
-2.54 to -1.63) in the control group (mean difference, 2.82 percentage points; P <.001).

The authors concluded that “ELX/TEZ/IVA is the first CF therapy shown to halt lung function decline over an extended follow-up period of 2 years, suggesting that ELX/TEZ/IVA treatment has a significant impact on the progression and trajectory of CF lung disease.”

Reference

Lee T, Sawicki GS, Altenburg J, et al. Effect of elexacaftor/tezacaftor/ivacaftor on annual rate of lung function decline in people with cystic fibrosis. J Cyst Fibros. Published online December 27, 2022. doi:10.1016/j.jcf.2022.12.009