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Observational Study
. 2024 Nov 30;203(1):9.
doi: 10.1007/s00408-024-00768-1.

Lung Clearance Index Improves in People with Cystic Fibrosis not Achieving a Clinical Important Difference in Forced Expiratory Volume in One Second After Elexacaftor/Tezacaftor/Ivacaftor Therapy

Valeria Daccò  1 , Andrea Gramegna  2   3 , Chiara Rosazza  1 , Alessandra Mariani  1 , Arianna Biffi  1 , Chiara Lanfranchi  1 , Laura Zazzeron  1 , Federica Bellante  1 , Francesco Blasi  2   3 , Gianfranco Alicandro  4   5
Affiliations
Observational Study

Lung Clearance Index Improves in People with Cystic Fibrosis not Achieving a Clinical Important Difference in Forced Expiratory Volume in One Second After Elexacaftor/Tezacaftor/Ivacaftor Therapy

Valeria Daccò et al. Lung. .

Abstract

Purpose: In people with cystic fibrosis (pwCF), elexacaftor/tezacaftor/ivacaftor (ETI) therapy is associated with an average improvement in FEV1 of 10-14%. However, a subset of individuals fails to achieve a clinically meaningful increase in spirometric indicators. In this study, we aimed to assess whether the lung clearance index (LCI2.5), a more sensitive indicator of lung involvement, improves following ETI initiation in this population.

Methods: We conducted a prospective observational study in a specialized CF center in Italy. PwCF performed a spirometry and a multiple breath nitrogen washout test the day they initiated ETI therapy and after 6 and 12 months. They were grouped according to the 12-month change in FEV1 into two groups: Individuals who experienced a change in FEV1 ≥ a minimal clinically important difference (MCID) of 3% and those who did not. Mean changes in LCI2.5 were estimated using generalized estimating equations.

Results: The study included 129 pwCF who initiated ETI at our center (Age Range: 12-36 years). In 20 subjects (15.5%), the FEV1 change was < MCID. These individuals had better baseline pulmonary function than those with FEV1 changes ≥ MCID (Median FEV1: 102.5 vs 87.0%), with the majority (90%) having FEV1 values ≥ 90%. Mean changes in LCI2.5 at 12-month follow-up visit were - 1.44 units (95% CI: - 2.12; - 0.75) in individuals with changes in FEV1 < MCID and - 2.64 units (95% CI: -3.05; -2.23) in those with values ≥ MCID.

Conclusion: LCI2.5 is a useful measure to monitor the effectiveness of ETI in pwCF with normal spirometry and limited FEV1 change following treatment initiation.

Keywords: CFTR modulators; Cystic fibrosis; Elexacaftor/tezacaftor/ivacaftor; Heterogeneity of response; Lung clearance index; Personalised medicine; Response to treatment.

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Conflict of interest statement

Declarations. Conflict of interest: A.G., V.D. and F.B. reported honoraria for lectures from Vertex; A.G. reported honoraria for lectures from Zambon, Foodar, Insmed; F.B. reported honoraria for lectures from Viatris, Zambon, Foodar, Chiesi, Insmed; A.G. and V.D. reported travel support from Neupharma; A.G. and F.B. reported travel support from Viatris. Ethical Approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of the Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy (protocol number 594_2016). Consent to Participate: Written informed consent was obtained from all individuals and their parents if the participant was under 18 years old.

References

    1. Accurso FJ, Rowe SM, Clancy JP et al (2010) Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation. N Engl J Med 363:1991–2003. https://doi.org/10.1056/NEJMOA0909825 - DOI - PubMed - PMC
    1. Heijerman HGM, McKone EF, Downey DG et al (2019) Efficacy and safety of the elexacaftor/tezacaftor/ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial. Lancet (London, England) 394:1940. https://doi.org/10.1016/S0140-6736(19)32597-8 - DOI - PubMed
    1. Gramegna A, Contarini M, Aliberti S et al (2020) From ivacaftor to triple combination: a systematic review of efficacy and safety of CFTR modulators in people with cystic fibrosis. Int J Mol Sci 21:1–23. https://doi.org/10.3390/IJMS21165882 - DOI
    1. Zolin A, Orenti A, Jung A, et al (2023) European Cystic Fibrosis Society Patient Registry (ECFSPR) - Annual Report 2021. www.ecfs.eu/ecfspr . Accessed 14 May 2024
    1. Sutharsan S, Dillenhoefer S, Welsner M et al (2023) Impact of elexacaftor/tezacaftor/ivacaftor on lung function, nutritional status, pulmonary exacerbation frequency and sweat chloride in people with cystic fibrosis: real-world evidence from the German CF Registry. Lancet Reg Heal Eur. https://doi.org/10.1016/J.LANEPE.2023.100690 - DOI

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