WS18.04 Change in markers of systemic inflammation after elexacaftor/tezacaftor/ivacaftor initiation: results from 18 months follow-up in the Danish cystic fibrosis cohort

Objectives: Since the implementation of elexacaftor/tezacaftor/ivacaftor (ETI) in cystic fibrosis (CF), a reduction of purulent expectorated sputum and a decrease in hospitalizations and use of antibiotics has been observed in clinical practice. In the present study, we aim to assess the effect of ETI on markers of systemic inflammation. Methods: The study includes all Danish persons with CF aged ≥12 years who initiated ETI before July 2021. Demographic and clinical characteristics, including sex, age, pulmonary function, CF mutation, chronic pulmonary infection, antibiotic consumption, and co-morbidities were collected before treatment initiation (baseline) along with inflammation markers including leucocytes, differential counts, immunoglobulin G (IgG), and C-reactive protein (CRP). Follow-up data are collected at months 1, 3, 6, 9, 12 and 18 after treatment initiation. Preliminary results: Data collection is ongoing and will be concluded February 2023, ultimately including about 303 patients. Preliminary analyses (baseline vs 12 months follow-up) demonstrate significant declines in all inflammatory markers. Tabled 1Inflammation markernBaseline mean (SD) or median (IQR)12 months follow-up mean (SD) or median (IQR)p-value; test of significanceLeucocytes (×109 cells/L)1917.8 (2.7)6.8 (2.4)p < 0.001; paired t-testNeutrophiles (×109 cells/L)505.0 (3.3; 7.2)3.7 (2.9; 5.2)p = 0.03; paired WilcoxonIgG (g/L)14112.7 (4.0)10.9 (2.8)p < 0.001; paired t-testCRP (log(mg/L))1781.3 (1.2)0.9 (1.2)p = 0.003; paired t-test Open table in a new tab Conclusion: Preliminary results demonstrate a decline in markers of systemic inflammation. The reduction in the total number of circulating leucocytes seems to be primarily driven by a decrease in circulating neutrophils. These results indicate a reduction in systemic bacterial load, most likely driven by a reduced pulmonary bacterial load. As chronic inflammation, particularly in the lungs, is associated with developing irreversible lung damage and co-morbidities such as metabolic and autoimmune diseases and cancer, a normalization in systemic inflammation may have extensive health benefits for persons with CF.