Patients with cystic fibrosis (CF) who received elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) generally saw no loss in pulmonary function after 2 years, while those not receiving the intervention saw a decrease in lung function. These were among study findings published in the Journal of Cystic Fibrosis.
Researchers evaluated the effect of ELX/TEZ/IVA on the rate of lung function decline over time in individuals with CF. To accomplish this, the researchers, compared the annualized rate of change in percent predicted forced expiratory volume in 1 second (ppFEV1) in patients who received ELX/TEZ/IVA in phase 3 trials vs a matched group of people with CF from the US Cystic Fibrosis Foundation Patient Registry (CFFPR) who were not eligible for CF transmembrane conductance regulator (CFTRm) modulator therapy.
Intervention group participants had received ELX/TEZ/IVA in 2 previous phase 3 clinical studies or an open-label extension study and had at least 3 ppFEV1 measurements for at least 6 months. These participants were propensity score-matched with as many as 5 patients from the CFFPR with F/MF or F/F genotypes, who constituted the control group. Participants in this cohort were at least 12 years old, had no evidence of CFTRm use at baseline or in the analysis period, had at least 3 FEV1 records from at least 6 months from baseline through the 2-year follow-up, and had at least 1 stableencounter in the baseline year with valid nutritional and pulmonary function test data.
A mixed model was used to estimate the annualized mean rate of change in ppFEV1 using all available ppFEV1 measures up to 120 weeks, excluding those during the first 21 days of ELX/TEZ/IVA to avoid inclusion of acute lung function improvement.
A total of 468 patients (mean [SD] age, 26.41 [10.66] years; 49.6% female) who received ELX/TEZ/IVA (n=367 F/MF; n=101 F/F) were matched with 1714 CFTRm-untreated control individuals (mean age, 25.77 [5.65] years; 49.4% female; n=1242 F/MF; n=472 F/F). The ELX/TEZ/IVA and CFTRm-untreated control cohorts were well balanced regarding baseline characteristics after matching.
The patients who received ELX/TEZ/IVA had a mean annualized rate of change in ppFEV1 of +0.39 percentage points (95% CI, −0.06 to 0.85) vs -1.92 percentage points (95% CI, -2.16 to -1.69) for the matched control individuals (mean difference, 2.32 percentage points; P <.001). At year 2, the between-group difference in ppFEV1 was 16.91 percentage points (95% CI, 15.56-18.27; P <.001).
In a subgroup analysis for participants with the F/MF genotype, the estimated annualized rate of change in ppFEV1 was +0.32 percentage points (95% CI, -0.19 to 0.82) for those who received ELX/TEZ/IVA vs -1.85 percentage points (95% CI, -2.13 to -1.58) in CFTRm-untreated control individuals (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) for patients who received ELX/TEZ/IVA compared with -2.08 percentage points (95% CI, -2.54 to -1.63) in CFTRm-untreated control individuals (mean difference, 2.82 percentage points; P <.001).
Among several limitations, the use of noncontemporaneous control individuals may have introduced temporal bias owing to changes in clinical care, and baseline characteristics used for matching may reflect benefits of CFTRm treatment. Also, data on education and insurance were not available and not included in the propensity score model. Furthermore, some data was taken from an open-label extension study that took place during the COVID-19 global pandemic, when social distancing and mask use likely led to a decrease in pulmonary exacerbations.
“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,” concluded the investigators.
Disclosure: This work was supported by Vertex Pharmaceuticals Incorporated. The study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
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