{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T16:24:17Z","timestamp":1790267057575,"version":"4.1.0"},"reference-count":21,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,12,18]],"date-time":"2021-12-18T00:00:00Z","timestamp":1639785600000},"content-version":"vor","delay-in-days":17,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Teva Branded Pharmaceutical Products R&D, Inc."}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Headache Pain"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Migraine prevalence is age and sex dependent, predominating in women in early and middle adulthood; however, migraine also represents a substantial burden for men and adults of all ages. Thus, understanding this burden and the efficacy of migraine preventive medications in both sexes and across age groups is critical. The randomized, placebo-controlled, double-blind, phase 3b FOCUS study demonstrated the safety and efficacy of fremanezumab, a fully humanized monoclonal antibody (IgG2\u2206a) that selectively targets calcitonin gene-related peptide as a migraine preventive treatment for individuals with migraine and prior inadequate response to 2 to 4 migraine preventive medication classes. Here, we assessed the efficacy of fremanezumab in participants from FOCUS subgrouped by age (18\u201345\u2009years and\u2009&gt;\u200945\u2009years) and sex.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>In the FOCUS study, eligible participants were randomized (1:1:1) to 12\u2009weeks of double-blind treatment with quarterly fremanezumab, monthly fremanezumab, or matched monthly placebo. In this post hoc analysis, we evaluated changes from baseline in monthly migraine days (primary endpoint of FOCUS) and other secondary and exploratory efficacy outcomes in prespecified age (18\u201345 and\u2009&gt;\u200945\u2009years) and sex subgroups.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The modified intention-to-treat population (received \u2265 1 dose of study drug and had \u2265 10\u2009days of postbaseline efficacy assessments for the primary endpoint) totaled 837 participants (18\u201345\u2009years, <jats:italic>n<\/jats:italic>\u2009=\u2009373; &gt;\u200945\u2009years, <jats:italic>n<\/jats:italic>\u2009=\u2009464; male, <jats:italic>n<\/jats:italic>\u2009=\u2009138; female, <jats:italic>n<\/jats:italic>\u2009=\u2009699). Consistent reductions in monthly average number of migraine days during 12\u2009weeks were observed, regardless of age (18\u201345\u2009years: quarterly fremanezumab, \u2212\u20094.1\u2009days; monthly fremanezumab, \u2212\u20094.7\u2009days; placebo, \u2212\u20090.9\u2009days; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001; &gt;\u200945\u2009years: quarterly fremanezumab, \u2212\u20093.6\u2009days; monthly fremanezumab, \u2212\u20093.7\u2009days; placebo, \u2212\u20090.3\u2009days; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) and sex (male: quarterly fremanezumab, \u2212\u20094.1\u2009days; monthly fremanezumab, \u2212\u20094.6\u2009days; placebo, \u2212\u20090.3\u2009days; <jats:italic>P\u2009&lt;<\/jats:italic>\u00a00.001; female: quarterly fremanezumab, \u2212\u20093.6\u2009days; monthly fremanezumab, \u2212\u20093.9\u2009days; placebo, \u2212\u20090.6\u2009days; <jats:italic>P\u2009&lt;<\/jats:italic>\u00a00.001). Fremanezumab also reduced monthly headache days of at least moderate severity, monthly days of acute medication use, and improved Migraine Disability Assessment scores across subgroups.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>These results demonstrate the efficacy of fremanezumab in patients with difficult-to-treat migraine for reducing migraine and headache days, acute medication use, and disability, regardless of age or sex.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link> Identifier <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT03308968\">NCT03308968<\/jats:ext-link> (FOCUS), registered October 13, 2017.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s10194-021-01336-1","type":"journal-article","created":{"date-parts":[[2021,12,18]],"date-time":"2021-12-18T09:02:39Z","timestamp":1639818159000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Impact of age and sex on the efficacy of fremanezumab in patients with difficult-to-treat migraine: results of the randomized, placebo-controlled, phase 3b FOCUS study"],"prefix":"10.1186","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7176-126X","authenticated-orcid":false,"given":"Antoinette","family":"MaassenVanDenBrink","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisela M.","family":"Terwindt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua M.","family":"Cohen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve","family":"Barash","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena Ramirez","family":"Campos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Galic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoping","family":"Ning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikko","family":"K\u00e4rpp\u00e4","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,12,18]]},"reference":[{"key":"1336_CR1","doi-asserted-by":"publisher","unstructured":"GBD 2016 Headache Collaborators (2018) Global, regional, and national burden of migraine and tension-type headache, 1990\u20132016: a systematic analysis for the Global Burden of Disease Study 2016. 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All participants provided written informed consent prior to participation in the study. The study protocol and consent form were reviewed and approved by the relevant independent ethics committee or institutional review board at participating study sites.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Antoinette MaassenVanDenBrink: Research\/consultancy\/speaker support from Allergan, Amgen\/Novartis, Lilly, and Teva; independent support from the Dutch Research Council and the Dutch Heart and Brain Foundations.Gisela M. Terwindt: Consultancy support from Novartis, Allergan, Lilly, and Teva; independent support from the Dutch Organization for Scientific Research, the Dutch Heart & Brain Foundations, the International Retinal Research Foundation, and Dioraphte.Joshua M. Cohen: Employee and\/or stockholder of Teva Branded Pharmaceutical Products R&D, Inc.Steve Barash: Employee and\/or stockholder of Teva Branded Pharmaceutical Products R&D, Inc.Verena Ramirez Campos: Employee and\/or stockholder of Teva Branded Pharmaceutical Products R&D, Inc.Maja Galic: Employee and\/or stockholder of Teva Branded Pharmaceutical Products R&D, Inc.Xiaoping Ning: Employee and\/or stockholder of Teva Branded Pharmaceutical Products R&D, Inc.Mikko K\u00e4rpp\u00e4: Received research compensation from Teva and Amgen.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"152"}}