{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T12:27:53Z","timestamp":1789820873908,"version":"4.0.1"},"reference-count":11,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T00:00:00Z","timestamp":1714521600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2024,5]]},"abstract":"\n BACKGROUND:<\/jats:title>\n Pediatric patients with homozygous familial hypercholesterolemia (HoFH) have an increased risk of atherosclerotic cardiovascular disease and difficulty meeting low-density lipoprotein cholesterol (LDL-C) goals. In this post hoc analysis, we evaluated pooled safety and efficacy data from 3 studies in pediatric patients with HoFH treated with the PCSK9 (proprotein convertase subtilisin\/kexin type 9) monoclonal antibody inhibitor evolocumab.<\/jats:p>\n <\/jats:sec>\n \n METHODS:<\/jats:title>\n Patients with HoFH aged 10 to 17 years received treatment with open-label evolocumab 420 mg subcutaneously monthly or biweekly in the TAUSSIG, RAMAN, or HAUSER-OLE clinical studies. All patients received background statins with or without ezetimibe. Study duration ranged from 12 to 260 weeks. The primary end point was treatment-emergent adverse events per 100 patient-years. Efficacy end points were changes from baseline to week 12 in lipids and PCSK9.<\/jats:p>\n <\/jats:sec>\n \n RESULTS:<\/jats:title>\n \n Of the 39 patients in the pooled analysis, 69.2% were males, median age was 13.0 years, and 79.5% (31\/39) had genotyped HoFH with\n LDLR<\/jats:italic>\n pathogenic variants. Overall, median exposure to evolocumab was 18.2 (Q1, Q3: 3.0, 18.5) months. Treatment-emergent adverse events with an exposure-adjusted patient incidence rate of \u22655% were upper respiratory tract infection (6.6%), influenza (5.2%), and acne (5.0%) per 100 patient-years. Exposure-adjusted patient incidence of serious treatment-emergent adverse events was 13.3% per 100 patient-years. Excluding 4 patients receiving lipoprotein apheresis, week 12 median percentage change from baseline in LDL-C was \u22122.9% (Q1, Q3: \u221221.7, 1.5); however, 42.9% (15\/35) of patients achieved \u226515% reduction in LDL-C from baseline. Residual LDLR (LDL receptor) activity was not associated with a reduction in LDL-C.\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSIONS:<\/jats:title>\n In this pooled data analysis from 3 studies in pediatric patients with HoFH, evolocumab was well tolerated, with no new safety signals reported. These safety findings are consistent with findings from previous studies of evolocumab. Patients showed marked variability in LDL-C reduction. Results from this pooled analysis support guidelines suggesting a trial of PCSK9 inhibitor therapy regardless of estimated residual LDLR function.<\/jats:p>\n <\/jats:sec>\n \n REGISTRATION:<\/jats:title>\n \n URL:\n https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n ; Unique identifier: NCT01624142, NCT03403374, and NCT02624869.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/atvbaha.123.320268","type":"journal-article","created":{"date-parts":[[2024,3,28]],"date-time":"2024-03-28T05:01:38Z","timestamp":1711602098000},"page":"1156-1164","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":20,"title":["Evolocumab Treatment in Pediatric Patients With Homozygous Familial Hypercholesterolemia: Pooled Data From Three Open-Label Studies"],"prefix":"10.1161","volume":"44","clinical-trial-number":[{"clinical-trial-number":"nct02624869","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct01624142","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03403374","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Frederick J.","family":"Raal","sequence":"first","affiliation":[{"name":"Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa (F.J.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2861-5325","authenticated-orcid":true,"given":"Robert A.","family":"Hegele","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biochemistry, Robarts Research Institute, University of Western Ontario, London, Canada (R.A.H., J.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6827-0718","authenticated-orcid":true,"given":"Andrea","family":"Ruzza","sequence":"additional","affiliation":[{"name":"Global Development (A.R., J.A.G.L., A.K.B.), Amgen Inc., Thousand Oaks, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8604-5549","authenticated-orcid":true,"given":"J. Antonio G.","family":"L\u00f3pez","sequence":"additional","affiliation":[{"name":"Global Development (A.R., J.A.G.L., A.K.B.), Amgen Inc., Thousand Oaks, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajay K.","family":"Bhatia","sequence":"additional","affiliation":[{"name":"Global Development (A.R., J.A.G.L., A.K.B.), Amgen Inc., Thousand Oaks, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johnny","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Medicine and Biochemistry, Robarts Research Institute, University of Western Ontario, London, Canada (R.A.H., J.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huei","family":"Wang","sequence":"additional","affiliation":[{"name":"Global Biostatistics (J.W., H.W.), Amgen Inc., Thousand Oaks, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5185-3666","authenticated-orcid":true,"given":"Daniel","family":"Gaudet","sequence":"additional","affiliation":[{"name":"Clinical Lipidology and Rare Lipid Disorders Unit, Community Genomic Medicine Centre and ECOGENE-21, Department of Medicine, Universit\u00e9 de Montreal, Chicoutimi, Quebec, Canada (D.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6223-5671","authenticated-orcid":true,"given":"Albert","family":"Wiegman","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Amsterdam UMC, Location AMC, the Netherlands (A.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6759-0522","authenticated-orcid":true,"given":"Jian","family":"Wang","sequence":"additional","affiliation":[{"name":"Global Biostatistics (J.W., H.W.), Amgen Inc., Thousand Oaks, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raul D.","family":"Santos","sequence":"additional","affiliation":[{"name":"Lipid Clinic Heart Institute (InCor), University of Sao Paulo Medical School Hospital and Hospital Israelita Albert Einstein, Sao Paulo, Brazil (R.D.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehad197"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61374-X"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(17)30044-X"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2019.12.020"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2020.05.027"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.117.310217"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2021.10.003"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(22)00221-2"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.gim.2021.09.012"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.11.002"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61350-5"}],"container-title":["Arteriosclerosis, Thrombosis, and Vascular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/ATVBAHA.123.320268","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T14:41:53Z","timestamp":1748529713000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/ATVBAHA.123.320268"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5]]},"references-count":11,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5]]}},"alternative-id":["10.1161\/ATVBAHA.123.320268"],"URL":"https:\/\/doi.org\/10.1161\/atvbaha.123.320268","relation":{"is-referenced-by":[{"id-type":"doi","id":"10.1007\/s11883-025-01305-y","asserted-by":"object"}]},"ISSN":["1079-5642","1524-4636"],"issn-type":[{"value":"1079-5642","type":"print"},{"value":"1524-4636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5]]},"assertion":[{"value":"2023-10-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}