Evolocumab in paediatric heterozygous familial hypercholesterolaemia: cognitive function during 80 weeks of open-label extension treatment.

Autor:	Santos RD; Lipid Clinic Heart Institute (InCor), University of Sao Paulo Medical School Hospital and Hospital Israelita Albert Einstein, Av. Dr Enéas C. Aguiar 44, Sao Paulo 05403-900, Brazil., Ruzza A; Global Development, Amgen, Thousand Oaks, CA, USA., Wang B; Biostatistics Department, Amgen, Thousand Oaks, CA, USA., Maruff P; Cogstate Ltd., Melbourne, VIC, Australia., Schembri A; Cogstate Ltd., Melbourne, VIC, Australia., Bhatia AK; Global Development, Amgen, Thousand Oaks, CA, USA., Mach F; Cardiology Department, Geneva University Hospital, Geneva, Switzerland., Bergeron J; Lipid Clinic, Department of Medicine, Centre Hospitalier Universitaire de Québec-Université Laval, Quebec, QC, Canada., Gaudet I; Department of Health Sciences, Université du Quebec à Chicoutimi, and ECOGENE-21, Chicoutimi, QC, Canada., St Pierre J; Department of Pediatrics, Faculty of Medicine, McGill University, Montréal, QC, Canada., Kastelein JJP; Department of Vascular Medicine, Amsterdam UMC, Amsterdam, Netherlands., Hovingh GK; Department of Vascular Medicine, Amsterdam UMC, Amsterdam, Netherlands., Wiegman A; Department of Pediatrics, Amsterdam UMC, Amsterdam, Netherlands., Gaudet D; The Clinical Lipidology and Rare Lipid Disorders Unit, Community Genomic Medicine Centre and ECOGENE-21, Department of Medicine, Université de Montréal, Chicoutimi, QC, Canada., Raal FJ; Division of Endocrinology and Metabolism, Department of Medicine Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Jazyk:	angličtina
Zdroj:	European journal of preventive cardiology [Eur J Prev Cardiol] 2024 Feb 15; Vol. 31 (3), pp. 302-310.
DOI:	10.1093/eurjpc/zwad332
Abstrakt:	Aims: PCSK9 inhibition intensively lowers low density lipoprotein cholesterol and is well tolerated in adults and paediatric patients with familial hypercholesterolaemia (FH). HAUSER-RCT showed that 24 weeks of treatment with evolocumab in paediatric patients did not affect cognitive function. This study determined the effects of 80 additional weeks of evolocumab treatment on cognitive function in paediatric patients with heterozygous FH. Methods and Results: HAUSER-OLE was an 80-week open-label extension of HAUSER-RCT, a randomized, double-blind, 24-week trial evaluating the efficacy and safety of evolocumab in paediatric patients (ages 10-17 years) with FH. During the OLE, all patients received monthly 420 mg subcutaneous evolocumab injections. Tests of psychomotor function, attention, visual learning, and executive function were administered at baseline and Weeks 24 and 80 of the OLE. Changes over time were analysed descriptively and using analysis of covariance. Cohen's d statistic was used to evaluate the magnitude of treatment effects. Analysis of covariance results indicated no decrease in performance across visits during 80 weeks of evolocumab treatment for Groton Maze Learning, One Card Learning accuracy, Identification speed, or Detection speed (all P > 0.05). Performance on all tasks was similar for those who received placebo or evolocumab in the RCT (all P > 0.05). For all tests, the least square mean differences between patients who received placebo vs. evolocumab in the parent study were trivial (all Cohen's d magnitude < 0.2). Conclusion: In paediatric patients with FH, 80 weeks of open-label evolocumab treatment had no negative impact on cognitive function. Registration: ClinicalTrials.gov identifier: NCT02624869. Competing Interests: Conflict of interest: R.D.S. reports receiving the following: consulting fees and lecture fees from Abbott, Amgen, Amryt, AstraZeneca, Aché, Biolab, Getz Pharma, Eli Lilly, Libbs, Merck, PTC Therapeutics, Novo Nordisk, Novartis, and Sanofi-Regeneron Pharmaceuticals; grant support from Amgen, Kowa, Esperion, Novartis, and Sanofi-Regeneron Pharmaceuticals. A.R. reports former employment with and holding stock in Amgen. He is a current employee of GSK. He holds a pending patent application PCT/US2021/034489 on PCSK9 inhibitors and methods of use thereof to treat cholesterol-related disorders. B.W. and A.K.B. report employment with and holding stock in Amgen. P.M. and A.S. are employees of Cogstate Ltd., the company that provided the cognitive tests in this study. J.B. reports receiving lecture fees from Amgen and HLS Therapeutics Inc.; grant support from Amgen, Arrowhead Pharmaceuticals, Amryt, Eli Lilly, Ionis Pharmaceuticals, Kowa, LIB Therapeutics, New Amsterdam Pharma, Novartis, Novo Nordisk, Regeneron Pharmaceuticals, Sanofi, and The Medicines Company; and serving on advisory boards for Amgen, Novartis, and Ultragenyx. J.S.P. reports grants from Novo Nordisk and Bausch Health. J.J.P.K. reports consulting fees from AstraZeneca, CiVi Biopharma, CSL Behring, Draupnir Bio, Esperion, Gemphire Therapeutics, Madrigal Pharmaceuticals, Matinas BioPharma, NorthSea Therapeutics, Novo Nordisk, Novartis, Regeneron Pharmaceuticals, REGENXBIO, Staten Biotechnology, 89bio, OMEICOS Therapeutics, Serometrix. G.K.H. reports employment with Novo Nordisk; consulting and speakers bureau fees from Aegerion Pharmaceuticals, Amgen, Regeneron Pharmaceuticals, and Sanofi; grant support from Aegerion Pharmaceuticals, Amgen, AstraZeneca, Eli Lilly, Genzyme, Ionis Pharmaceuticals, Kowa, Pfizer, Regeneron Pharmaceuticals, Roche, Sanofi, and The Medicines Company; and serving on advisory boards for Aegerion Pharmaceuticals, Amgen, Regeneron Pharmaceuticals, and Sanofi. A.W. reports research support for pharmaceutical trials of lipid-lowering agents from Amgen, Regeneron, Novartis, and Silence Therapeutics; and is member of a safety board for Amryt. D.G. reports receiving consulting fees from HDL Therapeutics, Regeneron Pharmaceuticals, and Sanofi; and grant support from Esperion, Gemphire Therapeutics, HDL Therapeutics, Pfizer, Regeneron Pharmaceuticals, Sanofi, and The Medicines Company. F.J.R. has received research grants, honoraria, or consulting fees for professional input and/or lectures from Sanofi, Regeneron, Amgen, and Novartis. The remaining authors have nothing to disclose. (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)
Databáze:	MEDLINE
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