{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T08:02:10Z","timestamp":1790928130192,"version":"4.1.0"},"reference-count":25,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cephalalgia"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Women show increased prevalence and severity of migraine compared to men. Whether small molecule calcitonin gene-related peptide receptor (CGRP-R) antagonists (i.e., gepants) and monoclonal antibodies targeting either the CGRP-R or the CGRP peptide might show sexually dimorphic outcomes for acute and preventive therapy has not been established.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a subpopulation analysis of available published data from FDA reviews to evaluate potential sex differences in the response rates of ubrogepant, rimegepant and zavegepant for acute migraine therapy. Available data from FDA reviews of erenumab, fremanezumab, galcanezumab and eptinezumab, approved CGRP-R and CGRP monoclonal antibodies and of atogepant were examined for prevention outcomes based on patient sex. Preventive outcomes were analyzed separately for patients with episodic migraine and chronic migraine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In women, the three approved gepants produced statistically significant drug effects regardless of dose tested on the FDA mandated co-primary endpoints, the proportion of patients achieving two-hour pain-freedom and the proportion of patients free of their most bothersome symptom at two hours post-dose. In women, the average placebo-subtracted two-hour pain-freedom proportion was 9.5% (CI: 7.4 to 11.6) and the average numbers needed to treat was 11. The free from most bothersome symptom at two hours outcomes were also significant in women. The gepant drugs did not reach statistically significant effects on the two-hour pain-freedom endpoint in the men, with an average drug effect of 2.8% (CI: \u22122.5 to 8.2) and an average number needed to treat of 36. For freedom from most bothersome symptom at two hours post-dose endpoint, differences were not significant in male patients. The treatment effect in each of the gepant studies was always numerically greater in women than in men. In evaluation of prevention outcomes with the antibodies or atogepant using the change from the specified primary endpoint (e.g., monthly migraine days), the observed treatment effect for episodic migraine patients almost always favored drug over placebo in both women and men. For chronic migraine patients the treatment effects of antibodies were similar in men and women and always favored the drug treated group. Conclusion\/Interpretation: Small molecule CGRP-R antagonists are effective in acute migraine therapy in women but available data do not demonstrate effectiveness in men. CGRP-targeting therapies are effective for migraine prevention in both male and female episodic migraine patients but possible sex differences remain uncertain. In male and female chronic migraine patients, CGRP\/CGRP-R antibodies were similarly effective. The data highlight possible differential effects of CGRP targeted therapies in different patient populations and the need for increased understanding of CGRP neurobiology in men and women.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/03331024241238153","type":"journal-article","created":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T06:09:47Z","timestamp":1710310187000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":52,"title":["Evaluation of outcomes of calcitonin gene-related peptide (CGRP)-targeting therapies for acute and preventive migraine treatment based on patient sex"],"prefix":"10.1177","volume":"44","author":[{"given":"Frank","family":"Porreca","sequence":"first","affiliation":[{"name":"Department of Pharmacology, University of Arizona, Tucson, USA"},{"name":"Mayo Clinic Arizona, Phoenix, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edita","family":"Navratilova","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Arizona, Tucson, USA"},{"name":"Mayo Clinic Arizona, Phoenix, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe","family":"Hirman","sequence":"additional","affiliation":[{"name":"Pacific Northwest Statistical Consulting, Woodinville, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoinette Maassen","family":"van den Brink","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Pharmacology, Vascular Medicine and Metabolic Diseases, Erasmus MC University Medical Center Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2652-2897","authenticated-orcid":false,"given":"Richard B","family":"Lipton","sequence":"additional","affiliation":[{"name":"Departments of Neurology, Psychiatry and Behavioral Science, and Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W","family":"Dodick","sequence":"additional","affiliation":[{"name":"Mayo Clinic Arizona, Phoenix, USA"},{"name":"Atria Academy of Science and Medicine, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2024,3,13]]},"reference":[{"key":"bibr1-03331024241238153","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-021-00328-4"},{"key":"bibr2-03331024241238153","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(21)00409-9"},{"key":"bibr3-03331024241238153","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32504-8"},{"key":"bibr4-03331024241238153","doi-asserted-by":"publisher","DOI":"10.1177\/0333102418821662"},{"key":"bibr5-03331024241238153","doi-asserted-by":"publisher","DOI":"10.1016\/j.maturitas.2020.12.012"},{"key":"bibr6-03331024241238153","doi-asserted-by":"publisher","DOI":"10.1177\/0333102417739584"},{"key":"bibr7-03331024241238153","doi-asserted-by":"publisher","DOI":"10.1177\/0333102418786266"},{"key":"bibr8-03331024241238153","doi-asserted-by":"publisher","DOI":"10.1111\/head.13407"},{"key":"bibr9-03331024241238153","unstructured":"Ubrogepant \u2013 New drug application (NDA); Center for Drug Evaluation and Research (CDER); 211765 \u2013 Orig1s000 \u2013 Clinical Review(s), https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2019\/211765Orig1s000MedR.pdf (2019, accessed 13 June 2023)"},{"key":"bibr10-03331024241238153","unstructured":"Jawidzik L. Rimegepant \u2013 New drug application (NDA); Center for Drug Evaluation and Research (CDER); 212728 \u2013 Orig1s000 \u2013 Clinical Review(s), https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2020\/212728Orig1s000MedR.pdf (2020, accessed 13 June 2023)."},{"key":"bibr11-03331024241238153","unstructured":"Kau R. Zavegepant \u2013 New drug application (NDA); Center for Drug Evaluation and Research (CDER); 216386 \u2013 Orig1s000 \u2013 Clinical Review(s), https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2023\/216386Orig1s000MedR.pdf (2023, accessed 13 June 2023)."},{"key":"bibr12-03331024241238153","doi-asserted-by":"publisher","DOI":"10.2307\/2530643"},{"key":"bibr13-03331024241238153","first-page":"719","volume":"22","author":"Mantel N","year":"1959","journal-title":"J Natl Cancer Inst"},{"key":"bibr14-03331024241238153","unstructured":"Freilich ER. Eptinezumab \u2013 New drug application (NDA); Center for Drug Evaluation and research (CDER); 761119 \u2013 Orig1s000 \u2013 Clinical Review(s), https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2020\/761119Orig1s000MedR.pdf (2019, accessed 07 July 2023)."},{"key":"bibr15-03331024241238153","unstructured":"Villalba ML. Galcanezumab \u2013 New drug application (NDA); Center for Drug Evaluation and research (CDER); 761063 \u2013 Orig1s000 \u2013 Clinical Review(s), https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2018\/761063Orig1s000MedR.pdf (2018, accessed 07 July 2023)."},{"key":"bibr16-03331024241238153","unstructured":"Fitter H. Fremanezumab \u2013 New drug application (NDA); Center for Drug Evaluation and research (CDER); 761089 \u2013 Orig1s000 \u2013 Clinical Review(s), https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2018\/761089Orig1s000SumR.pdf (2018, accessed 07 July 2023)."},{"key":"bibr17-03331024241238153","unstructured":"Fitter H. Erenumab \u2013 New drug application (NDA); Center for Drug Evaluation and research (CDER); 761077 \u2013 Orig1s000 \u2013 Clinical Review(s), https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2018\/761077Orig1s000SumR.pdf (2017, accessed 07 July 2023)."},{"key":"bibr18-03331024241238153","unstructured":"Abbvie Inc. Atogepant \u2013 New drug application (NDA); Center for Drug Evaluation and research (CDER); 215206 \u2013 Orig1s000 \u2013 Clinical Review(s), https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2021\/215206Orig1s000IntegratedR.pdf (2021, accessed 10 November 2023)."},{"key":"bibr19-03331024241238153","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/187103"},{"key":"bibr20-03331024241238153","doi-asserted-by":"publisher","DOI":"10.1007\/s11916-022-01052-8"},{"key":"bibr21-03331024241238153","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000011216"},{"key":"bibr22-03331024241238153","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.774341"},{"key":"bibr23-03331024241238153","unstructured":"Caronna E, Gallardo VJ, Alpuente A, et\u00a0al. European multicenter study on the use of anti-CGRP monoclonal antibodies in real life for migraine prevention: study cohort description.\n                      Presented at the International Headache Congress 2023\n                      (14\u201317 September 2023, Seoul, Republic of Korea), LBAPO-023."},{"key":"bibr24-03331024241238153","unstructured":"Caronna E, Gallardo VJ, Alpuente A, et\u00a0al. Sex differences in the response and tolerability to anti-CGRP monoclonal antibodies for migraine prevention in real life: results from a European multicenter observational study.\n                      Presented at the International Headache Congress 2023\n                      (14\u201317 September 2023, Seoul, Republic of Korea), LBAPO-025."},{"key":"bibr25-03331024241238153","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21897"}],"updated-by":[{"DOI":"10.1177\/03331024241254952","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2024,6,21]],"date-time":"2024-06-21T00:00:00Z","timestamp":1718928000000}}],"container-title":["Cephalalgia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/03331024241238153","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/03331024241238153","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/03331024241238153","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T14:46:16Z","timestamp":1777387576000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/03331024241238153"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3]]},"references-count":25,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1177\/03331024241238153"],"URL":"https:\/\/doi.org\/10.1177\/03331024241238153","relation":{},"ISSN":["0333-1024","1468-2982"],"issn-type":[{"value":"0333-1024","type":"print"},{"value":"1468-2982","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3]]},"article-number":"03331024241238153"}}