{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T18:05:30Z","timestamp":1789236330652,"version":"build-2803163510"},"reference-count":49,"publisher":"SAGE Publications","issue":"11","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cephalalgia"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>This study aimed to evaluate the efficacy and tolerability of rimegepant for the prevention of episodic migraine in participants with a documented history of inadequate response to 2\u20134 categories of traditional oral preventive medication (OPM).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This multinational phase 4 trial consisted of an untreated 28-day observational phase (OP) and a 12-week double-blind treatment (DBT) phase. Participants with 4\u201314 monthly migraine days (MMDs), &lt;15 monthly headache days (&lt;7 non-migraine) and documented previous inadequate response to 2\u20134 traditional OPM categories were enrolled. Participants were randomized to rimegepant 75\u2005mg orally disintegrating tablet (ODT) or placebo every other day (EOD). The primary endpoint was mean change from the OP in MMDs through the 12-week DBT phase. Key secondary endpoints were tested hierarchically to control type I errors. Tolerance and safety were assessed throughout the DBT phase.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In total, 328 participants received rimegepant and 324 received placebo. The most common OPM categories with prior inadequate response were anticonvulsants (61%), beta-blockers (56%) and amitriptyline (51%). The mean \u00b1 SD number of MMDs in the OP was 8.4 \u00b1 2.4 and 8.3 \u00b1 2.3, respectively, in the rimegepant (n\u2009=\u2009324) and placebo (n\u2009=\u2009319) groups. Across the DBT phase, participants who received rimegepant had a significantly larger mean change from the OP in MMDs than those who received placebo (\u22122.1 vs. \u22120.5 days; difference\u2009=\u2009\u22121.6 days; 95% confidence interval (CI) = \u22122.1 to \u22121.2;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). All key secondary endpoints favored rimegepant: (i) percentage of participants with \u226550% reduction from the OP in MMDs with moderate or severe pain intensity across the DBT phase (difference: 20.1%; 95% CI = 13.7 to 26.5;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009&lt;\u20090.0001); (ii) mean change from the OP in MMDs in the first month of the DBT phase (difference: \u22121.7 days; 95% CI = \u22122.3 to \u22121.2;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009&lt;\u20090.0001); (iii) mean change from the OP in MMDs in the last month of the DBT phase (difference: \u22121.4 days; 95% CI = \u22122.1 to \u22120.8;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009&lt;\u20090.0001); (iv) mean change from baseline in Migraine-Specific Quality-of-Life Questionnaire v2.1 Restrictive Role Function domain score at week 12 of the DBT phase (difference: 6.6 points; 95% CI = 3.6 to 9.5;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009&lt;\u20090.0001); and (v) mean change from baseline in Migraine Interictal Burden Scale score at week 12 of the DBT phase (difference: \u22120.9 points; 95% CI = \u22121.4 to \u22120.4;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.0006). Rimegepant was well tolerated with a safety profile not notably different from placebo.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Rimegepant 75\u2005mg ODT EOD is efficacious and well tolerated for the prevention of episodic migraine in participants with a documented history of inadequate response to 2\u20134 categories of traditional OPM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>\n                      ClinicalTrials.gov, NCT05518123 (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/study\/NCT05518123\">https:\/\/clinicaltrials.gov\/study\/NCT05518123<\/jats:ext-link>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/03331024251391378","type":"journal-article","created":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T07:57:05Z","timestamp":1763539025000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":9,"title":["A phase 4, randomized, double-blind, placebo-controlled trial evaluating the efficacy and tolerability of rimegepant for the prevention of episodic migraine in adults with a history of inadequate response to traditional oral preventive medications"],"prefix":"10.1177","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0796-4702","authenticated-orcid":false,"given":"Patricia","family":"Pozo-Rosich","sequence":"first","affiliation":[{"name":"Headache Unit, Neurology Department, Vall d'Hebron University Hospital &amp; Headache and Neurological Pain Research Group, Vall d'Hebron Research Institute, Universitat Aut\u00f2noma de Barcelona, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7193-8016","authenticated-orcid":false,"given":"Jos\u00e9 Antonio Gien","family":"L\u00f3pez","sequence":"additional","affiliation":[{"name":"Star Medica Hospital, M\u00e9rida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawel","family":"Lisewski","sequence":"additional","affiliation":[{"name":"Tricals"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ay\u015fe Neslihan","family":"Aslan","sequence":"additional","affiliation":[{"name":"Pfizer Inc."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harpreet","family":"Seehra","sequence":"additional","affiliation":[{"name":"Pfizer R&D UK Ltd"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Thiry","sequence":"additional","affiliation":[{"name":"Pfizer Inc."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy","family":"Abraham","sequence":"additional","affiliation":[{"name":"Pfizer R&D UK Ltd"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luz M.","family":"Ramirez","sequence":"additional","affiliation":[{"name":"Pfizer Inc."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4105-1248","authenticated-orcid":false,"given":"Robert","family":"Fountaine","sequence":"additional","affiliation":[{"name":"Pfizer Inc."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terence","family":"Fullerton","sequence":"additional","affiliation":[{"name":"Pfizer Inc."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,11,18]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-022-00763-1"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/s10194-020-01208-0"},{"key":"e_1_3_4_4_2","first-page":"23","volume-title":"Handbook of clinical neurology","author":"Leonardi M","year":"2023","unstructured":"Leonardi M, Guastafierro E, Toppo C, et al. 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