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This systematic review and meta-analysis assessed the efficacy and safety of calcitonin gene-related peptide antagonists in adults with Cluster headache.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We searched PubMed, Web of Science, Cochrane CENTRAL, ClinicalTrials.gov, and EBSCO for randomized controlled and single-arm trials involving episodic and chronic cluster headache. Safety outcomes evaluate the treatment-emergent adverse events, serious adverse events, and treatment discontinuations, while efficacy outcomes included the change from baseline in the mean number of weekly attacks, the proportion of participants achieving a\u2009\u2265\u200950% or\u2009\u2265\u200930% reduction in weekly attack frequency, and those reporting a \u201cmuch improved\u201d or \u201cvery much improved\u201d status on the Patient Global Impression of Change scale.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Four randomized controlled trials and two single-arm trials were included. Calcitonin gene-related peptide antagonists reduced weekly attacks by a mean of -7.23 (95% CI:\u2009\u2212\u20099.86 to\u2009\u2212\u20094.60).\u2009\u2265\u200950% responder rate was 46% (95% CI: 26%-67%) and\u2009\u2265\u200930% responder rate was 59% (95% CI: 45%-73%). Efficacy effects were larger in episodic than in chronic Cluster headache. The pooled proportion of patients experiencing at least one TEAE was 60% (95% CI: 35%-82%). SAEs (4%, 95% CI: 1%-9%) and discontinuations (3%, 95% CI: 1%-7%) were uncommon.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Calcitonin gene\u2013related peptide antagonists provide preventive benefit with acceptable safety in cluster headache. These findings should be interpreted as supportive but less definitive. Larger, long-term, placebo-controlled randomized trials are needed to confirm efficacy and guide clinical use.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12883-026-04733-8","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T04:34:44Z","timestamp":1771475684000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Safety and efficacy of calcitonin gene-related peptide antagonists for cluster headache: a systematic review and meta-analysis"],"prefix":"10.1186","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-5680-8842","authenticated-orcid":false,"given":"Ro\u2019ya","family":"Khanfar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eithar","family":"Radwan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sama","family":"Hattab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"issue":"1","key":"4733_CR1","first-page":"10","volume":"101","author":"PJ Goadsby","year":"2001","unstructured":"Goadsby PJ. 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