(126) Change in Pulmonary Function after Introduction of Elexacaftor/tezacaftor/ivacaftor: Results from the National CF-cohort in Denmark

Background: Triple modulator treatment has shown remarkable improvement in lung function in cystic fibrosis (CF) patients after just few months of treatment. Initially introduced through trials and compassionate use programs from May 2018, Denmark was among the first countries to attain market authorization in September 2020, and elexacaftor/tezacaftor/ivacaftor was rolled out in the months to follow. The country has the highest prevalence of F508del mutation in Europe (96 % homo- or heterozygote) with the vast majority of the CF patients being eligible for treatment with triple modulators. Routine CF care involves close monitoring with spirometry data obtained at every consultation. This provides high-resolution data for monitoring disease progression in short time spans as well as pre-modulator observation time for longitudinal evaluation. Our objective was to evaluate changes in percent predicted forced expiratory volume in 1 second (ppFEV1) during 12 months after implementation of elexacaftor/tezacaftor/ivacaftor in the Danish CF population.

Methods: A national observational cohort study at the two Danish CF Centers in a real-world set-up to evaluate the impact of elexacaftor/tezacaftor/ivacaftor on lung function. The study participants include all CF patients in Denmark, including Greenland and the Faroe Islands, eligible for CF transmembrane conductance (CFTR) triple modulator treatment. The inclusion criteria are age above 12 years, at least one F508del mutation, not solid organ transplanted, and CF diagnosis and F508del status verified by sweat test and gene sequencing. The primary endpoint is ppFEV1. Subgroup analyses include prior modulator treatment, chronic lung infection and birth cohort, respectively. FEV1 was obtained at study visits at treatment initiation and 1, 3, 6, 9 and 12 months follow-up in addition to monthly routine contacts. Spirometry was performed with CareFusion Jaeger Vyntus Spiro Spirometer. The ppFEV1 was calculated using the Global Lung Initiative reference equations.

For the statistical analysis patients will contribute individual observation time and impact of treatment will be assessed using a longitudinal mixed-effect model.

Results: Preliminary Results

Ultimo September 2022, 300 patients (male n=145) will have been treated for 12 months of whom 194 (65%) have switched from prior modulator treatment. At treatment initiation, median age was 26 years [IQR 18; 35], mean BMI was 21.4 (SD 3.6), mean ppFEV1 was 74.9 % (SD 25.3). 221 (74%) were homozygote for F508del. At the time of abstract submission, a total of 1,780 FEV1 measurements after initiation of triple modulator treatment had been collected (per subject: Mean=6.0, SD 2.3). In addition, 10,258 (per subject: Mean=34.0, SD 15.8) FEV1 measurements are available for analysis of observation time prior to treatment with elexacaftor/tezacaftor/ivacaftor. All eligible patients for triple modulator therapy have completed baseline data collection.

Conclusions: The final data at one-year follow-up will have been collected and analyzed for the conference.

Acknowledgements:

References: