{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T01:36:51Z","timestamp":1790127411674,"version":"4.0.1"},"reference-count":33,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,3,11]],"date-time":"2024-03-11T00:00:00Z","timestamp":1710115200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Evolocumab is a humanized immunoglobulin G2 monoclonal antibody, directed against Proprotein Convertase Subtilisin\/Kexin type 9 (PCSK9), prescribed in hypercholesterolemic patients. The safety profile of this drug is currently defined by the data of pre-authorization clinical trials. The purpose of this study is to update knowledge of the safety of evolocumab through an analysis of post-marketing real-world data on suspected adverse reactions (SARs), reported by the EudraVigilance database system. Methods: The public version of the EudraVigilance database has been used, and only serious SARs signals were included. Results: Musculoskeletal system disorders, flu-like symptoms, injection-site reactions, skin reactions, and metabolism and nutrition disorders are observed in the post-marketing surveillance, as well as being found in the pre-authorization studies. Not previously signaled in the pre-marketing studies, diarrhea was reported. Furthermore, signals related to cardiac adverse reactions, more frequently at the expense of adults in comparison to elders, were found. Conclusions: The post-marketing safety profile of evolocumab emerging from an analysis of the EudraVigilance data system indicates it is sufficiently safe but suggests the necessity for caution when it is prescribed to hyperlipidemic patients affected by heart diseases.<\/jats:p>","DOI":"10.3390\/ph17030364","type":"journal-article","created":{"date-parts":[[2024,3,11]],"date-time":"2024-03-11T11:05:10Z","timestamp":1710155110000},"page":"364","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Adverse Reactions to Evolocumab: Analysis of Real-World Data from EudraVigilance"],"prefix":"10.3390","volume":"17","author":[{"given":"Fabrizio","family":"Calapai","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1292-6284","authenticated-orcid":false,"given":"Carmen","family":"Mannucci","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Dental Sciences and Morphological and Functional Imaging, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariaconcetta","family":"Curr\u00f2","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7286-5674","authenticated-orcid":false,"given":"Luigi","family":"Cardia","sequence":"additional","affiliation":[{"name":"Department of Human Pathology of Adult and Childhood \u201cGaetano Barresi\u201d, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2663-6387","authenticated-orcid":false,"given":"Emanuela","family":"Esposito","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8116-4821","authenticated-orcid":false,"given":"Gioacchino","family":"Calapai","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4075-8065","authenticated-orcid":false,"given":"Ilaria","family":"Ammendolia","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy"},{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3622","DOI":"10.2174\/1381612824666181010144823","article-title":"Pharmacology of PCSK9 Inhibitors: Current Status and Future Perspectives","volume":"24","author":"Tsouka","year":"2018","journal-title":"Curr. Pharm. Des."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/s41586-020-2911-7","article-title":"Inhibition of PCSK9 potentiates immune checkpoint therapy for cancer","volume":"588","author":"Liu","year":"2020","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Picard, C., Poirier, A., B\u00e9langer, S., Labont\u00e9, A., Auld, D., Poirier, J., and PREVENT-AD Research Group (2019). Proprotein convertase subtilisin\/kexin type 9 (PCSK9) in Alzheimer\u2019s disease: A genetic and proteomic multi-cohort study. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0220254"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1007\/s11255-017-1505-2","article-title":"PCSK9 in chronic kidney disease","volume":"49","author":"Pavlakou","year":"2017","journal-title":"Int. Urol. Nephrol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.abb.2017.06.001","article-title":"Hypercholesterolemia: The role of PCSK9","volume":"625\u2013626","author":"Melendez","year":"2017","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1007\/s40262-017-0620-7","article-title":"Clinical Pharmacokinetics and Pharmacodynamics of Evolocumab, a PCSK9 Inhibitor","volume":"57","author":"Kasichayanula","year":"2018","journal-title":"Clin. Pharmacokinet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1210\/endrev\/bnab035","article-title":"The Multifaceted Biology of PCSK9","volume":"43","author":"Seidah","year":"2022","journal-title":"Endocr. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"189","DOI":"10.2147\/CEOR.S347085","article-title":"Prevalence and Patient Outcomes of Adult Primary Hypercholesterolemia and Dyslipidemia in the UK: Longitudinal Retrospective Study Using a Primary Care Dataset from 2009 to 2019","volume":"14","author":"Bilitou","year":"2022","journal-title":"Clin. Outcomes Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1056\/NEJMoa1316222","article-title":"A 52-week placebo-controlled trial of evolocumab in hyperlipidemia","volume":"370","author":"Blom","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_10","unstructured":"(2024, February 10). Summary of Product Characteristics. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/repatha-epar-product-information_en.pdf."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1161\/CIRCULATIONAHA.113.007012","article-title":"Efficacy and safety of longer-term administration of evolocumab (AMG 145) in patients with hypercholesterolemia: 52-week results from the Open-Label Study of Long-Term Evaluation Against LDL-C (OSLER) randomized trial","volume":"129","author":"Koren","year":"2014","journal-title":"Circulation"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2132","DOI":"10.1016\/j.jacc.2019.08.1024","article-title":"Long-Term Efficacy and Safety of Evolocumab in Patients with Hypercholesterolemia","volume":"74","author":"Koren","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1080\/14740338.2019.1681395","article-title":"Efficacy and safety of PCSK9 monoclonal antibodies","volume":"18","author":"Iqbal","year":"2019","journal-title":"Expert. Opin. Drug Saf."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1002\/cpt.1193","article-title":"Adverse Events Associated With PCSK9 Inhibitors: A Real-World Experience","volume":"105","author":"Schreuder","year":"2019","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_15","first-page":"163","article-title":"Clinical efficacy and safety of evolocumab for low-density lipoprotein cholesterol reduction","volume":"12","author":"Henry","year":"2016","journal-title":"Vasc. Health Risk Manag."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"5317","DOI":"10.1111\/bcp.15460","article-title":"Adverse event profiles of PCSK9 inhibitors alirocumab and evolocumab: Data mining of the FDA adverse event reporting system","volume":"88","author":"Ji","year":"2022","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"894685","DOI":"10.3389\/fphar.2022.894685","article-title":"Real-world safety of PCSK9 inhibitors: A pharmacovigilance study based on spontaneous reports in FAERS","volume":"13","author":"Feng","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1536\/ihj.22-052","article-title":"Effect of the Early Application of Evolocumab on Blood Lipid Profile and Cardiovascular Prognosis in Patients with Extremely High-Risk Acute Coronary Syndrome","volume":"63","author":"Hao","year":"2022","journal-title":"Int. Heart J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1111\/bcp.15494","article-title":"Ocular disorders associated with PCSK9 inhibitors: A pharmacovigilance disproportionality analysis","volume":"89","author":"Zhao","year":"2023","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"9866486","DOI":"10.1155\/2022\/9866486","article-title":"Musculoskeletal Adverse Events Associated with PCSK9 Inhibitors: Disproportionality Analysis of the FDA Adverse Event Reporting System","volume":"2022","author":"Ding","year":"2022","journal-title":"Cardiovasc. Ther."},{"key":"ref_21","first-page":"62","article-title":"Muscle-Related Adverse Events Associated with PCSK9 Inhibitors in a Veteran Population","volume":"40","author":"Cencetti","year":"2023","journal-title":"Fed. Pract."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1177\/2047487320902750","article-title":"LDL-cholesterol lowering with evolocumab, and outcomes according to age and sex in patients in the FOURIER Trial","volume":"28","author":"Sever","year":"2021","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e111","DOI":"10.1016\/j.clinthera.2021.02.002","article-title":"Effectiveness, Safety, and Adherence to Treatment of Proprotein Convertase Subtilisin\/Kexin Type 9 Inhibitors in Real Practice","volume":"43","year":"2021","journal-title":"Clin. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1056\/NEJMoa1615664","article-title":"Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease","volume":"376","author":"Sabatine","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_25","first-page":"e15467","article-title":"Atrial Fibrillation as a Possible Adverse Reaction to Evolocumab","volume":"13","author":"Abdelmaseih","year":"2021","journal-title":"Cureus"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e01127","DOI":"10.1002\/prp2.1127","article-title":"Response to \u201cEvaluating Adverse Events in Databases\u201d","volume":"11","author":"Calapai","year":"2023","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Calapai, F., Ammendolia, I., Cardia, L., Curr\u00f2, M., Calapai, G., Esposito, E., and Mannucci, C. (2023). Pharmacovigilance of Risankizumab in the Treatment of Psoriasis and Arthritic Psoriasis: Real-World Data from EudraVigilance Database. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15071933"},{"key":"ref_28","unstructured":"(2024, February 10). EudraVigilance Database. Available online: https:\/\/www.ema.europa.eu\/en\/human-regulatory-overview\/research-and-development\/pharmacovigilance-research-and-development\/eudravigilance."},{"key":"ref_29","unstructured":"(2016). MedDRA and pharmacovigilance: A complex and little-evaluated tool. Prescrire Int., 25, 247\u2013250."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1186\/s12911-023-02374-2","article-title":"Lessons learned from annotation of VAERS reports on adverse events following influenza vaccination and related to Guillain-Barr\u00e9 syndrome","volume":"23","author":"Sankaranarayanapillai","year":"2024","journal-title":"BMC Med. Inform. Decis. Mak."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1016\/j.cjca.2023.08.003","article-title":"New Biological Therapies for Low-Density Lipoprotein Cholesterol","volume":"39","author":"Gill","year":"2023","journal-title":"Can. J. Cardiol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Calapai, F., Mannucci, C., McQuain, L., and Salvo, F. (2023). Pharmacological Evaluation of Signals of Disproportionality Reporting Related to Adverse Reactions to Antiepileptic Cannabidiol in VigiBase. Pharmaceuticals, 16.","DOI":"10.20944\/preprints202308.1495.v1"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.therap.2019.01.006","article-title":"Case-non-case studies: Principle, methods, bias and interpretation","volume":"74","author":"Faillie","year":"2019","journal-title":"Therapies"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/3\/364\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:12:03Z","timestamp":1760105523000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/17\/3\/364"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,11]]},"references-count":33,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["ph17030364"],"URL":"https:\/\/doi.org\/10.3390\/ph17030364","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,11]]}}}