{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:35:39Z","timestamp":1790796939777,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T00:00:00Z","timestamp":1627257600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["headachejournal.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Headache"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate the long\u2010term effectiveness, safety, and tolerability of erenumab in a real\u2010world migraine population, looking for putative predictors of responsiveness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Erenumab proved to be effective, safe, and well tolerated in the prevention of episodic migraine (EM) and chronic migraine (CM) in long\u2010term extension studies of double\u2010blind, placebo\u2010controlled trials in patients with no more than two (EM) or three (CM) prior preventive treatment failures.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A 48\u2010week, multicenter, longitudinal cohort real\u2010life study was conducted at 15\u00a0headache centers across eight Italian regions between December 20, 2018 and July 31, 2020. We considered all consecutive patients with high\u2010frequency episodic migraine (HFEM) or CM aged 18\u201365\u00a0years. Each patient was treated with erenumab 70\u00a0mg, administered monthly. The dose was switched to 140\u00a0mg in nonresponders and in responders who had become nonresponders for at least 4\u00a0weeks. Change in monthly migraine days (MMDs) or monthly headache days (MHDs) at Weeks 45\u201348 compared with baseline was the primary efficacy endpoint. Secondary endpoints encompassed variation in monthly analgesic intake, achievement of a \u226550%, \u226575%, or 100% reduction in migraine or headache days, and any change in the Visual Analogue Scale (VAS) and Headache Impact Test\u20106 scores (HIT\u20106) during the same time interval.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 242 patients with migraine received at least one dose of erenumab 70\u00a0mg and were considered for safety analysis, whereas 221 received a monthly erenumab dose for \u226548\u00a0weeks and were included in the effectiveness and safety analysis set. All patients had previously been treated unsuccessfully with \u22653\u00a0migraine\u2010preventive medication classes. From baseline to Weeks 45\u201348, erenumab treatment reduced MMD by 4.3\u00a0\u00b1\u00a05.3\u00a0(mean\u00a0\u00b1\u00a0SD) in patients with HFEM, and MHD by 12.8\u00a0\u00b1\u00a08.9 (mean\u00a0\u00b1\u00a0SD) in subjects with CM. VAS and HIT\u20106\u00a0scores were decreased by 1.8\u00a0\u00b1\u00a01.9 (mean\u00a0\u00b1\u00a0SD) and 12.3\u00a0\u00b1\u00a011 (mean\u00a0\u00b1\u00a0SD) in HFEM, and by 3.0\u00a0\u00b1\u00a02.2 (mean\u00a0\u00b1\u00a0SD) and 13.1\u00a0\u00b1\u00a011.2 (mean\u00a0\u00b1\u00a0SD) in CM. Median monthly analgesic intake passed from 11.0 (interquartile range [IQR] 10.0\u201313.0) to 5 (IQR 2.0\u20138.0) in HFEM and from 20.0 (IQR 15.0\u201330.0) to 6.0 (IQR 3.8\u201310.0) in CM. The \u226550% responders were 56.1% (32\/57) in HFEM and 75.6% (124\/164) in CM; \u226575% responders were 31.6% (18\/57) and 44.5% (73\/164); and 100% responders were 8.8% (5\/57) and 1.2% (2\/164), respectively. At Week 48, 83.6% (137\/164) of patients with CM had reverted to EM. Erenumab was safe and well tolerated. Responsiveness to erenumab was positively associated with cutaneous allodynia (OR: 5.44, 95% CI: 1.52\u201319.41;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.009) in HFEM. In patients with CM, \u226550% responsiveness was positively associated with male sex (OR: 2.99, 95% CI: 1.03\u20138.7;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.044) and baseline migraine frequency (OR: 1.12, 95% CI: 1.05\u20131.20;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.001) and negatively associated with psychiatric comorbidities (OR: 0.37, 95% CI: 0.15\u20130.87;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.023) and prior treatment failures (OR: 0.77, 95% CI: 0.64\u20130.92;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.004).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Long\u2010term (48\u2010week) erenumab treatment provides sustained effectiveness, safety, and tolerability in real\u2010life patients with HFEM or CM with \u22653 prior preventive treatment failures. The dose of 140\u00a0mg was required in most patients along the study and should be taken into consideration as the starting dose. Allodynia (in HFEM), male sex, and baseline migraine frequency (in CM) might represent positive responsiveness predictors. Conversely, psychiatric comorbidities and multiple prior preventive treatment failures could be negative predictors in patients with CM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/head.14194","type":"journal-article","created":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T11:09:10Z","timestamp":1627297750000},"page":"1351-1363","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":83,"title":["Long\u2010term (48\u00a0weeks) effectiveness, safety, and tolerability of erenumab in the prevention of high\u2010frequency episodic and chronic migraine in a real world: Results of the EARLY 2 study"],"prefix":"10.1111","volume":"61","author":[{"given":"Piero","family":"Barbanti","sequence":"first","affiliation":[{"name":"Headache and Pain Unit IRCCS San Raffaele Pisana Rome Italy"},{"name":"San Raffaele University Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2658-2243","authenticated-orcid":false,"given":"Cinzia","family":"Aurilia","sequence":"additional","affiliation":[{"name":"Headache and Pain Unit IRCCS San Raffaele Pisana Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabina","family":"Cevoli","sequence":"additional","affiliation":[{"name":"IRCCS Istituto delle Scienze Neurologiche Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Egeo","sequence":"additional","affiliation":[{"name":"Headache and Pain Unit IRCCS San Raffaele Pisana Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Fofi","sequence":"additional","affiliation":[{"name":"Headache and Pain Unit IRCCS San Raffaele Pisana Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Messina","sequence":"additional","affiliation":[{"name":"Neurology Unit IRCCS San Raffaele Scientific Institute Vita\u2010Salute San Raffaele University Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Salerno","sequence":"additional","affiliation":[{"name":"San Giovanni Addolorata Hospital Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Torelli","sequence":"additional","affiliation":[{"name":"Unit of Neurology Department of Medicine and Surgery Headache Center University of Parma Parma Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Albanese","sequence":"additional","affiliation":[{"name":"Neurophysiopathology Unit Headache Center University Hospital of Rome \u201cTorVergata\u201d Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Carnevale","sequence":"additional","affiliation":[{"name":"San Filippo Neri Hospital Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Bono","sequence":"additional","affiliation":[{"name":"Center for Headache and Intracranial Pressure Disorders Neurology Unit A.O.U. Mater Domini Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"D'Amico","sequence":"additional","affiliation":[{"name":"Neuroalgology Unit Headache Center Fondazione IRCCS Istituto Neurologico \u201cCarlo Besta\u201d Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo","family":"Filippi","sequence":"additional","affiliation":[{"name":"Neurology Unit IRCCS San Raffaele Scientific Institute Vita\u2010Salute San Raffaele University Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5934-5535","authenticated-orcid":false,"given":"Claudia","family":"Altamura","sequence":"additional","affiliation":[{"name":"Headache and Neurosonology Unit Policlinico Universitario Campus Bio\u2010Medico Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Vernieri","sequence":"additional","affiliation":[{"name":"Headache and 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