Effects of elexacaf tor/tezacaf tor/ivacaf tor therapy in children with cystic fibrosis - a comprehensive assessment using lung clearance index, spirometry, and functional and structural lung MRI

Background: With improvement in supportive therapies and the introduction of cystic fibrosis transmem-brane conductance regulator (CFTR)-modulator treatment in patients with cystic fibrosis (CF), milder disease courses are expected. Therefore, sensitive parameters are needed to monitor disease course and effects of CFTR-modulators. Functional lung MRI using matrix-pencil decomposition (MP-MRI) is a promising tool for assessing ventilation and perfusion quantitatively. This study aimed to assess the treatment effect of elexacaftor/tezacaftor/ivacaftor combination regimen (ELX/TEZ/IVA) on measures of structural and functional lung abnormalities.Methods: 24 children with CF underwent lung function tests (multiple breath washout, spirometry), functional and structural MRI twice (one year apart) before and once after at least two weeks (mean 4.7 & PLUSMN; 2.6 months) on ELX/TEZ/IVA. Main outcomes were changes ( A) upon ELX/TEZ/IVA in lung function, defect percentage of ventilation (VDP) and perfusion (QDP), defect distribution index of ventilation and perfusion (DDIV, DDIQ), and Eichinger score. Statistical analyses were performed using paired t-tests and multilevel regression models with bootstrapping.Results: We observed a significant improvement in lung function, structural and functional MRI param-eters upon ELX/TEZ/IVA treatment (mean; 95%-CI): ALCI2.5 (TO)-0.84 (-1.62 to-0.06); AFEV1 (z-score) 1.05 (0.56 to 1.55); AVDP (% of impairment)-6.00 (-8.44 to-3.55); AQDP (% of impairment)-3.90 (-5.90 to-1.90); ADDIV-1.38 (-2.22 to-0.53); ADDIQ-0.31 (-0.73 to 0.12); AEichinger score-3.89 (-5.05 to-2.72).Conclusions: Besides lung function tests, functional and structural MRI is a suitable tool to monitor treat-ment response of ELX/TEZ/IVA therapy, and seems promising as outcome marker in the future.& COPY; 2022 Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society.