{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T18:27:39Z","timestamp":1793730459746,"version":"4.6.1"},"reference-count":60,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,3,15]],"date-time":"2026-03-15T00:00:00Z","timestamp":1773532800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,15]],"date-time":"2026-03-15T00:00:00Z","timestamp":1773532800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["headachejournal.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Headache"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Calcitonin gene\u2010related peptide (CGRP) inhibitors, including monoclonal antibodies (mAbs) and small\u2010molecule antagonists (gepants), have transformed migraine treatment. Although clinical trials established their efficacy and initial safety, post\u2010marketing surveillance is essential for understanding their real\u2010world safety profile in a broader population. Therefore, this study aims to systematically review and synthesize findings from published pharmacovigilance studies that analyze potential safety signals for CGRP inhibitors using major international databases, including the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), the World Health Organization's (WHO's) VigiBase, and EudraVigilance, in order to establish a comprehensive real\u2010world safety profile to guide clinical practice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A systematic search was conducted in major electronic databases for studies published up to September 2025. Study selection, data extraction, and quality assessment were performed by two independent researchers. We included original research articles analyzing FAERS, VigiBase, or EudraVigilance for AEs associated with erenumab, galcanezumab, fremanezumab, eptinezumab, rimegepant, ubrogepant, atogepant, or zavegepant. Data on key signals of disproportionate reporting (SDRs) and quantitative measures of disproportionality were extracted and synthesized thematically.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The search identified 30 eligible studies. For mAbs, consistent SDRs included injection site reactions, alopecia (e.g., fremanezumab reporting odds ratio (ROR) ranging from 2.73 to 6.9), constipation (primarily for erenumab, RORs ranging from 4.92 to 17.94), and a range of cardiovascular events. For gepants, common SDRs included nausea and fatigue or somnolence, with highly specific SDRs for severe constipation for atogepant (ROR\n                      <jats:sub>025<\/jats:sub>\n                      \u2009=\u200919.99) and dysgeusia for zavegepant (ROR\n                      <jats:sub>025<\/jats:sub>\n                      \u2009=\u2009212.07), linked to its nasal administration. A critical divergence was observed for rare but serious cerebrovascular events: SDRs for reversible cerebral vasoconstriction syndrome (RCVS [erenumab ROR 9.43, 95% confidence interval {CI} 4.5\u201319.8]) and cervical artery dissection (CeAD [galcanezumab ROR 14.0, 95% CI 6.22\u201331.4]) were associated with certain mAbs. Conversely, no such SDRs have been detected for gepants to date, although this distinction requires confirmation as real\u2010world exposure increases. However, a class\u2010level SDR for cerebrovascular diseases as a whole was identified for CGRP inhibitors as a group (ROR 1.22, 95% CI 1.12\u20131.33). Also notable were shared SDRs for Raynaud's phenomenon and alopecia across both subclasses. Finally, concerning safety in pregnancy, the data are complex: while comprehensive class\u2010level analyses did not identify a disproportionality signal compared to triptans, some analyses of individual drugs have identified reporting patterns that warrant cautious interpretation, underscoring the need for further dedicated pharmacovigilance studies to fully clarify the safety profile in this population.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This systematic review confirms that CGRP inhibitors have a manageable yet complex safety profile. It distinguishes rare, serious cerebrovascular events (RCVS, CeAD) associated with some mAbs but not with gepants, as well as shared adverse effects such as Raynaud's phenomenon and alopecia. Significant heterogeneity in safety profiles\u2014from erenumab's pronounced constipation SDR to zavegepant's unique dysgeusia\u2014challenges the view of CGRP inhibitors as a monolithic category. These findings provide a clear rationale for personalized risk assessment, enabling clinicians to tailor treatment to individual patient profiles.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/head.70081","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T04:57:11Z","timestamp":1773637031000},"page":"1128-1147","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Post\u2010marketing safety of\n                    <scp>CGRP<\/scp>\n                    monoclonal antibodies and gepants: A systematic review of spontaneous reporting system data"],"prefix":"10.1111","volume":"66","author":[{"given":"Martina","family":"Giacon","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences University of Piemonte Orientale  Novara 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