{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T12:13:23Z","timestamp":1771503203014,"version":"3.50.1"},"reference-count":16,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T00:00:00Z","timestamp":1618531200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T00:00:00Z","timestamp":1618531200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006259","name":"Teva Pharmaceuticals","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100006259","id-type":"DOI","asserted-by":"crossref"}]}],"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>The FOCUS study evaluated the efficacy of migraine preventive medications across different countries within the same patient population, particularly for patients with difficult-to-treat migraine. These prespecified subgroup analyses evaluated efficacy by country in the FOCUS study of fremanezumab in adults with episodic migraine or chronic migraine and documented inadequate response to 2 to 4 migraine preventive medication classes.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Overall, 838 participants were enrolled in the FOCUS study, a randomized, double-blind, placebo-controlled, parallel-group, phase 3b study performed at 104 sites. For 12\u2009weeks of double-blind treatment, patients were randomized (1:1:1) to quarterly fremanezumab, monthly fremanezumab, or matched placebo. The primary efficacy endpoint was the mean change from baseline in monthly average migraine days over 12\u2009weeks of double-blind treatment, evaluated by country in these subgroup analyses.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Of 14 countries contributing data, the Czech Republic (<jats:italic>n<\/jats:italic>\u2009=\u2009188\/838; 22%), the United States (<jats:italic>n<\/jats:italic>\u2009=\u2009120\/838; 14%), and Finland (<jats:italic>n<\/jats:italic>\u2009=\u200985\/838; 10%) enrolled the most patients. Changes from baseline in monthly average migraine days over 12\u2009weeks were significantly greater with fremanezumab versus placebo for patients in these countries: Czech Republic (least-squares mean difference versus placebo [95% confidence interval]: quarterly fremanezumab, \u2212\u20091.9 [\u2212 3.25, \u2212 0.47]; <jats:italic>P<\/jats:italic>\u2009=\u20090.009; monthly fremanezumab, \u2212\u20093.0 [\u2212\u20094.39, \u2212\u20091.59]; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001), the United States (quarterly fremanezumab, \u2212\u20093.7 [\u2212 5.77, \u2212 1.58]; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001; monthly fremanezumab, \u2212\u20094.2 [\u2212 6.23, \u2212 2.13]; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001), and Finland (quarterly fremanezumab, \u2212\u20093.0 [\u2212\u20095.32, \u2212\u20090.63]; <jats:italic>P<\/jats:italic>\u2009=\u20090.014; monthly fremanezumab, \u2212\u20093.9 [\u2212\u20096.27, \u2212\u20091.44]; <jats:italic>P<\/jats:italic>\u2009=\u20090.002). Results were comparable for the remaining 9 countries, with the least-squares mean difference versus placebo ranging from \u2013 5.6 to \u2013 2.4 with quarterly fremanezumab and from \u2212\u20095.3 to \u2212\u20091.5 with monthly fremanezumab. Incidences of serious adverse events and adverse events leading to discontinuation were low and comparable across countries and treatment groups.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Monthly and quarterly fremanezumab significantly reduced the monthly average number of migraine days versus placebo regardless of country and continent (North America versus Europe) in migraine patients with documented inadequate response to 2 to 4 migraine preventive medication classes.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p>ClinicalTrials.gov 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>.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s10194-021-01232-8","type":"journal-article","created":{"date-parts":[[2021,4,16]],"date-time":"2021-04-16T14:34:10Z","timestamp":1618583650000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Efficacy and safety of fremanezumab in patients with migraine and inadequate response to prior preventive treatment: subgroup analyses by country of a randomized, placebo-controlled trial"],"prefix":"10.1186","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5074-5869","authenticated-orcid":false,"given":"Egilius L. 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All participants provided written informed consent before participation in the study.","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":"As an investigator involved in the study, ELHS received research grants from Teva Pharmaceuticals and is a member of Teva\u2019s Speakers Bureau. MK received research compensation from Amgen, Eisai, and Teva Pharmaceuticals. XN, JMC, and VRC are employees of Teva Pharmaceuticals. RY is a former employee of Teva Pharmaceuticals. UR has received personal compensation from Allergan, Amgen, Eli Lilly, Medscape, Novartis, StreaMedUp, and Teva Pharmaceuticals.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"26"}}