The clinical effectiveness of elexacaftor/tezacaftor/ivacaftor (ETI) for people with CF without a F508del variant: A systematic review and meta-analysis.

Autor: Lupas D; Schulich School of Medicine, Western University, London, Ontario, Canada., Chou FY; Division of Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, BC, Canada., Hakani MAA; Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada., Kuthiala I; Schulich School of Medicine, Western University, London, Ontario, Canada., Srikrishnaraj A; Schulich School of Medicine, Western University, London, Ontario, Canada., Li X; Centre for Heart Lung Innovation, University of British Columbia, Vancouver, BC, Canada., Potter N; Centre for Heart Lung Innovation, University of British Columbia, Vancouver, BC, Canada., Quon BS; Centre for Heart Lung Innovation, University of British Columbia, Vancouver, BC, Canada; Division of Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, BC, Canada. Electronic address: bradley.quon@hli.ubc.ca.
Jazyk: angličtina
Zdroj: Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society [J Cyst Fibros] 2024 Sep; Vol. 23 (5), pp. 950-958. Date of Electronic Publication: 2024 Jul 23.
DOI: 10.1016/j.jcf.2024.07.012
Abstrakt: Background: Access to elexacaftor/tezacaftor/ivacaftor (ETI) for people with cystic fibrosis (PwCF) without a F508del variant is limited due to lack of clinical data supporting efficacy.
Methods: In this systematic review and meta-analysis, we examined patient-level data from studies reporting the clinical response to ETI for PwCF with non-F508del CFTR variants. We searched electronic data sources including Embase, MEDLINE, and CENTRAL from January 1st, 2019 to May 14th, 2024.
Findings: Our search results identified 4,795 studies and 20 met the eligibility criteria. 120 of 164 (73 %) individuals had a positive clinical response to ETI, defined by a sweat chloride (SwCl) decrease of ≥10 mmol/L or percent-predicted FEV1 (ppFEV1) improvement of ≥5 %. 51 unique ETI-responsive variants were represented across these 120 individuals and 27 of these variants (53 %) have not been previously approved by the U.S. FDA. For variants with at least 10 individuals treated with ETI to date, a consistent positive clinical response was observed for N1303K and G85E. For N1303K (n = 48), the median increase in ppFEV1 was 16 % (IQR: 8 %, 29 %), with a median decrease in SwCl of -9 (IQR: -4, -22) mmol/L. For G85E (n = 16), the median increase in ppFEV1 was 13.5 % (IQR: 8 %, 19 %) with a median decrease in SwCl of -46 (IQR: -39, -66) mmol/L.
Conclusion: Additional ETI-responsive variants were identified following a comprehensive review of ETI clinical use in PwCF without F508del. This data can be used by the CF community in efforts to expand the labelled indications or to help advocate for off-label ETI reimbursement.
Competing Interests: Declaration of competing interest BSQ has participated in Vertex Pharmaceuticals sponsored clinical trials as site PI and has received honoraria for speaking engagements organized by Vertex Pharmaceuticals.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: