Paediatric patients with heterozygous familial hypercholesterolaemia treated with evolocumab for 80 weeks (HAUSER-OLE): a single-arm, multicentre, open-label extension of HAUSER-RCT.

Autor:	Santos RD; Lipid Clinic Heart Institute, University of São Paulo Medical School Hospital and Hospital Israelita Albert Einstein, São Paulo, Brazil., Ruzza A; Global Clinical Development, Amgen, Thousand Oaks, CA, USA., Hovingh GK; Department of Vascular Medicine, Amsterdam University Medical Center, Amsterdam, Netherlands., Stefanutti C; Department of Molecular Medicine, Umberto I Hospital, Sapienza University of Rome, Rome, Italy., Mach F; Cardiology Department, Geneva University Hospitals, Geneva, Switzerland., Descamps OS; Department of Internal Medicine, Pole Hospitalier Jolimont, Reseau HELORA, La Louviere, Belgium., Bergeron J; Department of Medicine, Centre Hospitalier Universitaire de Québec-Université Laval, Québec, QC, Canada., Wang B; Biostatistics Department, Amgen, Thousand Oaks, CA, USA., Bartuli A; Rare Diseases and Medical Genetics Unit, Bambino Gesù Children's Hospital IRCCS, Rome, Italy., Buonuomo PS; Rare Diseases and Medical Genetics Unit, Bambino Gesù Children's Hospital IRCCS, Rome, Italy., Greber-Platzer S; Division of Pediatric Pulmonology, Allergology and Endocrinology, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria., Luirink I; Department of Paediatrics, Amsterdam University Medical Center, Amsterdam, Netherlands., Bhatia AK; Global Clinical Development, Amgen, Thousand Oaks, CA, USA., Raal FJ; Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa., Kastelein JJP; Department of Vascular Medicine, Amsterdam University Medical Center, Amsterdam, Netherlands., Wiegman A; Department of Paediatrics, Amsterdam University Medical Center, Amsterdam, Netherlands., Gaudet D; Clinical Lipidology and Rare Lipid Disorders Unit, Community Genomic Medicine Centre and Department of Medicine and ECOGENE-21, Université de Montreal, Chicoutimi, Québec, QC, Canada. Electronic address: daniel.gaudet@umontreal.ca.
Jazyk:	angličtina
Zdroj:	The lancet. Diabetes & endocrinology [Lancet Diabetes Endocrinol] 2022 Oct; Vol. 10 (10), pp. 732-740. Date of Electronic Publication: 2022 Sep 05.
DOI:	10.1016/S2213-8587(22)00221-2
Abstrakt:	Background: The HAUSER-RCT study showed that 24 weeks of evolocumab (a proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitor) in paediatric patients with heterozygous familial hypercholesterolaemia was safe and improved lipid parameters compared to placebo. Here, we aimed to evaluate the safety and efficacy of evolocumab in this population for an additional 80 weeks. Methods: HAUSER-OLE was an 80-week, single-arm, open-label extension of HAUSER-RCT, a randomised controlled trial, and was conducted at 46 centres in 23 countries. Paediatric patients aged 10-17 years with heterozygous familial hypercholesterolaemia who completed 24 weeks of monthly treatment with subcutaneously administered placebo or 420 mg evolocumab in HAUSER-RCT with no serious treatment-emergent adverse events were eligible to enrol in HAUSER-OLE. All patients received open-label subcutaneous evolocumab 420 mg monthly with background statins with or without ezetimibe for 80 additional weeks. The primary endpoint was treatment-emergent adverse events. Efficacy was evaluated by changes in lipids from the baseline of HAUSER-RCT to the end of HAUSER-OLE (104 weeks). This study is registered with ClinicalTrials.gov (NCT02624869) and is now completed. Findings: Between Sept 10, 2016, and Nov 25, 2019, 157 patients were enrolled in HAUSER-RCT and received randomised treatment; 150 continued to HAUSER-OLE, received evolocumab treatment, and were included in the full analysis set, presented here. 146 (97%) of 150 patients completed the open-label extension. The incidence of treatment-emergent adverse events in HAUSER-OLE was 70% (105 of 150). Overall, the most common treatment-emergent adverse events were nasopharyngitis (22 [15%] of 150), headache (14 [9%]), and influenza-like illness (13 [9%]). Serious treatment-emergent adverse events occurred in four (3%) of 150 patients (perforated appendicitis and peritonitis, wrist fracture, anorexia nervosa, and headache); none was considered related to evolocumab. No treatment-emergent adverse events led to treatment discontinuation. At week 80, the mean percentage change from baseline in LDL cholesterol was -35·3% (SD 28·0). Interpretation: After 80 weeks of treatment, evolocumab was safe, well tolerated, and led to sustained reductions in LDL cholesterol in paediatric patients with heterozygous familial hypercholesterolaemia. When lipid goals cannot be achieved with conventional treatments, evolocumab is an effective add-on therapy in paediatric patients. Funding: Amgen. Translations: For the French, Spanish, Spanish, Portuguese, Italian and Dutch translations of the abstract see Supplementary Materials section. Competing Interests: Declaration of interests RDS reports receiving consulting fees and lecture fees from AstraZeneca, Aché, Amryt, Libbs, Hoffmann-La Roche, and Novo Nordisk; grant support, consulting fees, and lecture fees from Amgen and Sanofi-Regeneron Pharmaceuticals; lecture fees from Getz Pharma, Eli Lilly, Hypera, PTC Therapeutics, and Pfizer; fees for coordinating a research protocol from Esperion; grant support from Kowa; and consulting fees from Abbott, Novartis, and Hypera. AR is a former employee and a stockholder of Amgen and is an inventor on the pending patent application 63/032451 on PCSK9 inhibitors and methods of use thereof to treat cholesterol-related disorders. GKH reports study funding from Amgen and grants or contracts from Vidi Grant (zonMW) and Klinkerpad Fonds. GKH also reports being employed by Novo Nordisk. OSD reports receiving grants or contracts from Amgen, Daiichi Sankyo, Novartis, Novo Nordisk, and Viatris; consulting fees from Amgen, Daiichi Sankyo, Merck Sharp & Dohme, and Sanofi; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Amgen, Daiichi Sankyo, Merck Sharp & Dohme, Mylan, Sanofi, and Viatris; support for attending meetings from Sanofi and Daiichi Sankyo; and participation on a data safety monitoring board or advisory board from Sanofi and Daiichi Sankyo. JB reports receiving advisory board fees or lecture fees from Amgen, HLS Therapeutics, Medison, and Novartis; and grant or contract support from Amgen, Arrowhead, LIB Therapeutics, Novartis, Regeneron Pharmaceuticals, Sanofi, and The Medicines Company. BW and AKB are employees and stockholders of Amgen. SG-P reports receiving study funding from Amgen. FJR reports grants or contracts from Regeneron, Novartis, and LIB Therapeutics; fees for advisory board presentations and lectures from Amgen, Sanofi-Aventis, Regeneron, and Novartis; and travel support to attend the 2022 European Atherosclerosis Society (EAS) Congress from EAS. JJPK reports grants or contracts from NewAmsterdam Pharma; a leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid from NewAmsterdam Pharma; stock or stock options from NewAmsterdam Pharma; and patents planned, issued, or pending from NewAmsterdam Pharma. JJPK also reports consulting fees from CSL Behring, Esperion, Madrigal Pharmaceuticals, Novartis, and Pfizer; and participation on a data safety monitoring board or advisory board for CSL Behring, North Sea Therapeutics, Silence Therapeutics, and Scribe Therapeutics. DG reports receiving grants or contracts from Amgen, Aegerion (Amryt), Eli Lilly, Esperion, Ionis, Pfizer, Regeneron, Sanofi, and The Medicines Company; payments or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Amgen, Aegerion (Amryt), and Regeneron; and participation on a data safety monitoring board or advisory board for Amgen, Aegerion (Amryt), Arrowhead, Eli Lilly, Pfizer, Regeneron, Sanofi, and Verve Therapeutics. AW reports payment or honoraria for lectures, presentations, speakers' bureaus, manuscript writing or educational events from Novartis and Algorithm; participation on a data safety monitoring board or advisory board for Amryt; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid for Novartis; and research support for pharmaceutical trials from Amgen, Regeneron, Novartis, and Silence Therapeutics. CS, FM, AB, PSB, and IL declare no competing interests. (Copyright © 2022 Elsevier Ltd. All rights reserved.)
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