Lung function improvement on triple modulators: high-resolution, nationwide data from the Danish Cystic Fibrosis...

Area of Science:

• Pulmonology
• Pharmacology
• Genetics

Background:

• Denmark provided early, universal access to elexacaftor/tezacaftor/ivacaftor triple modulator therapy for cystic fibrosis patients.
• A nationwide, unselected population aged 6 years and above was monitored to evaluate treatment impact.

Purpose of the Study:

• To assess the real-world impact of elexacaftor/tezacaftor/ivacaftor on lung function and disease progression in cystic fibrosis.
• To analyze treatment effects across diverse subgroups including age, disease severity, and prior treatment history.

Main Methods:

• Linear mixed-effect models were used to analyze changes in lung function parameters (ppFEV1, ppFVC, ppFEF25-75%) pre- and post-treatment.
• Data from 392 individuals with cystic fibrosis, including spirometry measurements, were analyzed.
• Subgroup analyses examined effects based on prior modulator use, disease severity, age, and birth cohort.

Main Results:

• Elexacaftor/tezacaftor/ivacaftor treatment led to a mean improvement of 13.0% in ppFEV1 after 12 months.
• The annual rate of change in ppFEV1 shifted from -1.4% pre-treatment to +2.7% during treatment.
• Significant improvements were also observed in ppFVC (+8.0%) and ppFEF25-75% (+19.5%).

Conclusions:

• Real-world data demonstrate substantial lung function improvements with elexacaftor/tezacaftor/ivacaftor across all analyzed subgroups.
• The study highlights a new phase of consistent lung function gains for cystic fibrosis patients on this therapy.