Effects of elexacaftor/tezacaftor/ivacaftor therapy in children with cystic fibrosis – a comprehensive assessment using lung clearance index, spirometry, and functional and structural lung MRI

• Published in: Journal of cystic fibrosis 2023-07, Vol.22 (4), p.615-622
• Main Authors: Streibel, Carmen, Willers, Corin C., Pusterla, Orso, Bauman, Grzegorz, Stranzinger, Enno, Brabandt, Ben, Bieri, Oliver, Curdy, Marion, Bullo, Marina, Frauchiger, Bettina Sarah, Korten, Insa, Krüger, Linn, Casaulta, Carmen, Ratjen, Felix, Latzin, Philipp, Kieninger, Elisabeth
• Format: Article
• Language: English
• Subjects: CFTR modulator therapy; Children; Cystic fibrosis; Elexacaftor/tezacaftor/ivacaftor therapy; Functional lung MRI; Lung clearance index; Lung disease; Lung function; Multiple breath washout
• ISSN: 1569-1993; 1873-5010
• DOI: 10.1016/j.jcf.2022.12.012

•Structural and functional MP-MRI, LCI and FEV1 were compared after ETI treatment.•Ventilation and perfusion impairment assessed by MP-MRI improved upon ETI therapy.•MP-MRI adds information on ETI treatment effects complementary to FEV1 and LCI.•MP-MRI is a suitable and sensitive tool to monitor CFTR-modulator treatment effects. With improvement in supportive therapies and the introduction of cystic fibrosis transmembrane 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. 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 ± 2.6 months) on ELX/TEZ/IVA. Main outcomes were changes (Δ) 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. We observed a significant improvement in lung function, structural and functional MRI parameters upon ELX/TEZ/IVA treatment (mean; 95%-CI): ΔLCI2.5 (TO) -0.84 (-1.62 to -0.06); ΔFEV1 (z-score) 1.05 (0.56 to 1.55); ΔVDP (% of impairment) -6.00 (-8.44 to -3.55); ΔQDP (% of impairment) -3.90 (-5.90 to -1.90); ΔDDIV -1.38 (-2.22 to -0.53); ΔDDIQ -0.31 (-0.73 to 0.12); ΔEichinger score -3.89 (-5.05 to -2.72). Besides lung function tests, functional and structural MRI is a suitable tool to monitor treatment response of ELX/TEZ/IVA therapy, and seems promising as outcome marker in the future.