{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:51:25Z","timestamp":1787014285368,"version":"build-2736575974"},"reference-count":41,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T00:00:00Z","timestamp":1748476800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["headachejournal.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Headache"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives\/Background<\/jats:title>\n                    <jats:p>This study was undertaken to evaluate the postmarketing safety of monoclonal antibodies (mAbs) targeting the calcitonin gene\u2010related peptide pathway used for migraine prophylaxis through pharmacovigilance data analysis by examining suspected adverse events reported in Europe. Migraine is one of the most prevalent and debilitating neurological disorders globally. The introduction of mAbs targeting the calcitonin gene\u2010related peptide pathway has transformed migraine prophylaxis. However, their safety profiles in real\u2010world settings are not fully established, and ongoing safety monitoring is essential, as clinical trials may not capture all potential adverse drug reactions associated with new therapies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A disproportionality analysis was carried out by analyzing postmarketing pharmacovigilance data from the EudraVigilance database, focusing on four mAbs: eptinezumab, fremanezumab, galcanezumab, and erenumab. Descriptive and statistical analyses were performed on data retrieved from the date of marketing authorization of each medicine up to June 16, 2024. The reporting odds ratio (ROR), information component, and empirical Bayes geometric mean were calculated to detect signals of disproportionate reporting comparing their safety profiles to topiramate, a standard preventive migraine treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 14,285 reports had emerged; most of them were from females and concerned patients aged 18\u201364\u2009years. The most frequently reported adverse drug reactions were primarily nonserious, aligning with literature and previously established safety profiles, such as fatigue and injection site reactions. The statistical analysis revealed 15 significant disproportionality signals: 11 for eptinezumab and four for galcanezumab. Eptinezumab highlighted potential new safety signals such as palpitations (ROR\u2009=\u20096.93, 95% confidence interval [CI] =\u20093.39\u201314.18), oropharyngeal pain (ROR\u2009=\u20097.19, 95% CI\u2009=\u20093.40\u201315.24), and erythema (ROR\u2009=\u200912.31, 95% CI\u2009=\u20094.58\u201333.12). These findings suggest a potential class effect, warranting further investigations and highlighting the importance of continued monitoring regarding the long\u2010term safety of mAbs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Almost all of the most reported and statistically significant adverse events were nonserious and consistent with the existing literature. Given the chronic nature of migraine treatment, continuous pharmacovigilance monitoring is essential to ensure their constant safe use in clinical practice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/head.14962","type":"journal-article","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T07:59:31Z","timestamp":1748505571000},"page":"1080-1094","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Postmarketing safety of migraine prophylactic monoclonal antibodies: An\n                    <scp>EudraVigilance<\/scp>\n                    database analysis of eptinezumab, fremanezumab, galcanezumab, and erenumab"],"prefix":"10.1111","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0089-3043","authenticated-orcid":false,"given":"Victoria","family":"Nikitina","sequence":"first","affiliation":[{"name":"Unit of Pharmacology, Department of Medical and Surgical Sciences Alma Mater Studiorum University of Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7897-2956","authenticated-orcid":false,"given":"Greta","family":"Santi Laurini","sequence":"additional","affiliation":[{"name":"Unit of Pharmacology, Department of Medical and Surgical Sciences Alma Mater Studiorum University of Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5710-8077","authenticated-orcid":false,"given":"Nicola","family":"Montanaro","sequence":"additional","affiliation":[{"name":"Alma Mater Studiorum University of Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6253-4014","authenticated-orcid":false,"given":"Domenico","family":"Motola","sequence":"additional","affiliation":[{"name":"Unit of Pharmacology, Department of Medical and Surgical Sciences Alma Mater Studiorum University of Bologna  Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,29]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"World Health Organization.Regulation and Prequalification \u2013 Pharmacovigilance.2025. Accessed February 5 2025.https:\/\/www.who.int\/teams\/regulation\u2010prequalification\/regulation\u2010and\u2010safety\/pharmacovigilance#:~:text=In%20addition%20to%20their%20benefits other%20medicine%2Fvaccine%20related%20problem"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40264-014-0240-1"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.j337"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40264-016-0491-0"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-20195-0_17"},{"key":"e_1_2_11_7_1","unstructured":"Eudravigilance \u2013 European Database of Suspected Adverse Drug Reaction Reports.2024. Accessed June 16 2024.http:\/\/www.adrreports.eu\/"},{"key":"e_1_2_11_8_1","unstructured":"The European Medicines Agency.Human Regulatory. EudraVigilance.2024. Accessed October 28 2024.https:\/\/www.ema.europa.eu\/en\/human\u2010regulatory\/researchdevelopment\/pharmacovigilance\/eudravigilance"},{"key":"e_1_2_11_9_1","unstructured":"The European Medicines Agency.Human Regulatory. Guideline on Detection and Management of Duplicate Individual Cases and Individual Case Safety Reports (ICSRs).2025. Accessed February 5 2025https:\/\/www.ema.europa.eu\/en\/documents\/regulatory\u2010procedural\u2010guideline\/draft\u2010guideline\u2010detection\u2010and\u2010management\u2010duplicate\u2010individual\u2010cases\u2010and\u2010individual\u2010case\u2010safety\u2010reports_en.pdf"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.2165\/00002018-199920020-00002"},{"key":"e_1_2_11_11_1","unstructured":"The Medical Dictionary for Regulatory Activities\u2010MedDRA.2024. Accessed September 16 2024.https:\/\/www.meddra.org\/how\u2010to\u2010use\/basics\/hierarchy"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cct.2008.02.004"},{"key":"e_1_2_11_13_1","unstructured":"Introductory Guide MedDRA Version 27.2024. Accessed September 16 2024.https:\/\/admin.meddra.org\/sites\/default\/files\/guidance\/file\/intguide_27_0.pdf"},{"key":"e_1_2_11_14_1","unstructured":"Vyepti\u00ae INN\u2010eptinezumab\u2010 European Medicines Agency.Summary of Product Characteristics.2024. Accessed September 16 2024.https:\/\/www.ema.europa.eu\/en\/documents\/product\u2010information\/vyepti\u2010epar\u2010product\u2010information_en.pdf"},{"key":"e_1_2_11_15_1","unstructured":"European Medicines Agency.Aimovig\u00ae INN\u2010erenumab\u2010 Summary of product characteristics.2024. Accessed September 16 2024.https:\/\/www.ema.europa.eu\/en\/documents\/product\u2010information\/aimovig\u2010epar\u2010product\u2010information_en.pdf"},{"key":"e_1_2_11_16_1","unstructured":"Ajovy\u00ae INN\u2010fremanezumab\u2010European Medicines Agency.Summary of Product Characteristics.2024. Accessed September 16 2024.https:\/\/www.ema.europa.eu\/en\/documents\/product\u2010information\/ajovy\u2010epar\u2010product\u2010information_en.pdf"},{"key":"e_1_2_11_17_1","unstructured":"European Medicines Agency.Emgality\u00ae INN\u2010Galcanezumab\u2010Summary of Product Characteristics.2024. Accessed September 16 2024.https:\/\/www.ema.europa.eu\/en\/documents\/product\u2010information\/emgality\u2010epar\u2010product\u2010information_en.pdf"},{"issue":"2","key":"e_1_2_11_18_1","first-page":"S1","article-title":"Canadian Headache Society guideline for migraine prophylaxis","volume":"39","author":"Pringsheim T","year":"2012","journal-title":"Can J Neurol Sci"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1468-1331.2006.01411.x"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182535d20"},{"key":"e_1_2_11_21_1","unstructured":"The European Medicines Agency.Human Regulatory. Screening for Adverse Reactions in EudraVigilance.2024. Accessed June 30 2024.https:\/\/www.ema.europa.eu\/en\/documents\/other\/screening\u2010adverse\u2010reactions\u2010eudravigilance_en.pdf"},{"key":"e_1_2_11_22_1","unstructured":"The REporting of A Disproportionality analysis for drUg Safety Signal Detection Using Individual Case Safety Reports in PharmacoVigilance \u2013 READUS\u2010PV Chechlist.2025. Accessed February 5 2025.https:\/\/readus\u2010statement.org\/readus\u2010statement\/"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1177\/2042098620938595"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2005.02504.x"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-4356(02)00450-X"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0080-623420140000400023"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/j.pain.0000000000002275"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1526-4610.2011.01900.x"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-021-01253-3"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1257282"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1177\/03331024241297673"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-023-01640-y"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.14679"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000201008"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-023-07167-z"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.13596"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/ccr3.4625"},{"key":"e_1_2_11_38_1","unstructured":"The European Medicines Agency.Summary of Risk Management Plan for VYEPTI\u00ae (Eptinezumab).2024. Accessed September 28 2024.https:\/\/www.ema.europa.eu\/en\/documents\/rmp\u2010summary\/vyepti\u2010epar\u2010risk\u2010management\u2010plan\u2010summary_en.pdf"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-020-02681-6"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-020-01186-3"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2004.01.006"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12455620"}],"container-title":["Headache: The Journal of Head and Face Pain"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/headachejournal.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/head.14962","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T08:44:53Z","timestamp":1762073093000},"score":1,"resource":{"primary":{"URL":"https:\/\/headachejournal.onlinelibrary.wiley.com\/doi\/10.1111\/head.14962"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,29]]},"references-count":41,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1111\/head.14962"],"URL":"https:\/\/doi.org\/10.1111\/head.14962","archive":["Portico"],"relation":{},"ISSN":["0017-8748","1526-4610"],"issn-type":[{"value":"0017-8748","type":"print"},{"value":"1526-4610","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,29]]},"assertion":[{"value":"2024-11-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-03-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}