Long-term non-pulmonary outcomes of Elaxacaftor-Tezacaftor-Ivacaftor (ETI) in pwCF

Résumé fourni par la source

Objectives: In a registry-based pharmacovigilance study we assessed non-pulmonary outcomes in pwCF over a period of 2 yrs after ETI start. Methods: Sweat chloride, BMI, use of pancreatic enzymes and insulin, and incidence of DIOS from Swiss pwCF registered in the ECFSPR were collected every 3 months over a period of 2 yrs before and 2 yrs after ETI start. Changes over time were assessed using mixed-effects models (sweat chloride, BMI) and generalized estimated equations (drug utilization, DIOS). Subgroup analyses were performed by gender, age (6-11, 12-17, ≥18 yrs), CFTR variants (F/F, F/other), and severity of lung disease (mild FEV1pp >80%, severe FEV1pp <40%). Results: 636 pwCF, including 260 children, were included. Sweat chloride concentration decreased from 98 mmol/L (CI 96.2-99.7) before to 44.5 mmol/L (CI 42.8-46.3) after ETI start (p<0.0001) and was more pronounced in <18 yrs and F/F variants. BMI z-scores increased by 0.34 (CI 0.28-0.4; p<0.0001) over 2 yrs after ETI start, with the largest gain in severe lung disease (0.6; CI 0.5-0.8), but also significant improvements in mild lung disease and 6-11 yrs. No difference was found by gender or CFTR variants. Pancreatic enzyme use remained around 94% from 2 years before to 2 years after ETI start, with no significant change over time and no age-related differences. Insulin utilization (about 26% in ≥18 yrs) was equally unchanged, and DIOS incidence remained low (around 2.5%) and stable over the observation time. Conclusion: ETI significantly and sustainably improved sweat chloride and BMI in all groups over a period of 2 yrs, whereas no significant changes were observed for prevalence of pancreatic enzymes or insulin and for incidence of DIOS.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.