{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T01:05:55Z","timestamp":1790903155157,"version":"4.1.0"},"reference-count":16,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Cephalalgia"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To evaluate whether initiation of calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) was non-inferior to initiation of onabotulinumtoxinA with respect to the hazard of ischemic stroke or transient ischemic attack (IS + TIA) in a real-world cohort of adults with migraine.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective, active-comparator, new-user pharmacoepidemiology study using the NIH All of Us Research Program Registered Tier Dataset (v8). Adults with migraine initiating CGRP mAbs (erenumab, fremanezumab, galcanezumab, eptinezumab) were compared with initiators of onabotulinumtoxinA from January 2018 through September 2023. The primary outcome was IS\u2009+\u2009TIA occurring more than 90 days after treatment initiation. Inverse probability of treatment weighting (IPTW) with stabilized propensity scores was used to adjust for 23 baseline covariates. Non-inferiority was assessed on the hazard ratio (HR) scale using a prespecified margin of 1.5, with non-inferiority concluded if the upper bound of the 95% confidence interval (CI) was less than 1.5. Prespecified subgroup analyses included migraine with aura and without aura. Prespecified sensitivity analyses included a per-protocol analysis, a crossover-excluded analysis, and an IS-only analysis. Fracture was used as a negative control outcome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 16,147 patients with migraine in the cohort, the primary comparison included 1,581 CGRP mAb initiators and 947 onabotulinumtoxinA initiators. IPTW achieved a good covariate balance for the primary comparison (maximum standardized mean difference 0.016). For the primary outcome, 14 IS\u2009+\u2009TIA events occurred among CGRP mAb initiators and 22 among onabotulinumtoxinA initiators. The hazard ratio for IS\u2009+\u2009TIA was 0.524 (95% CI 0.263\u20131.046), which met the prespecified statistical criterion for non-inferiority because the upper confidence bound was below 1.5; however, the estimate was imprecise because of the small number of events. In the migraine with aura subgroup, the estimate also met the non-inferiority criterion (HR 0.419, 95% CI 0.163\u20131.080), whereas the migraine without aura subgroup, per-protocol analysis, and major adverse cardiovascular events analysis were inconclusive for non-inferiority. For major adverse cardiovascular events the HR was 1.068 (95% CI 0.589\u20131.935). The fracture negative control was also not significantly different (HR, 1.175; 95% CI, 0.692\u20131.993; p\u2009=\u20090.551), arguing against systematic healthy-user confounding. A formal adjusted comparison with untreated patients was not feasible due to structural confounding inherent to the stepped-care treatment pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this real-world diverse cohort, initiation of CGRP mAbs met the prespecified statistical criterion for non-inferiority relative to onabotulinumtoxinA for the primary IS\u2009+\u2009TIA outcome. However, this finding was based on few events and wide CIs and should be interpreted cautiously as limited evidence against a large relative increase in incident IS + TIA risk, rather than as definitive evidence of equivalent safety, absence of modest harm, or a protective effect. Several secondary, subgroup, and supportive analyses remained inconclusive for non-inferiority. Larger adequately powered comparative safety studies are needed.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/03331024261464438","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T18:24:31Z","timestamp":1783016671000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["Cerebrovascular risk with calcitonin gene-related peptide monoclonal antibodies versus onabotulinumtoxinA in patients with migraine: A real-world pharmacoepidemiologic study in the National Institutes of Health All of Us Research Program"],"prefix":"10.1177","volume":"46","author":[{"given":"Sedat","family":"G\u00fcl","sequence":"first","affiliation":[{"name":"Neurological Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6507-1967","authenticated-orcid":false,"given":"Bradley","family":"Ong","sequence":"additional","affiliation":[{"name":"Neurological Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"Trudeau","sequence":"additional","affiliation":[{"name":"Neurological Institute"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio, USA"},{"name":"Center for Outcomes Research &amp; Evaluation, Neurological Institute, Cleveland Clinic, Cleveland, Ohio, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4536-9974","authenticated-orcid":false,"given":"Hsiangkuo","family":"Yuan","sequence":"additional","affiliation":[{"name":"Thomas Jefferson University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.b3914"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/head.70008"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000008591"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1177\/0333102418759786"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1705848"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1708226"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1097\/AJP.0000000000001136"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/head.14153"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000213852"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2024.4537"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMsr1809937"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-147-8-200710160-00010-w1"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12874-021-01440-5"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02744-3"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.7172"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/head.70136"}],"container-title":["Cephalalgia"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/03331024261464438","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/03331024261464438","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/03331024261464438","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T06:17:22Z","timestamp":1783232242000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/03331024261464438"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7]]},"references-count":16,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1177\/03331024261464438"],"URL":"https:\/\/doi.org\/10.1177\/03331024261464438","relation":{},"ISSN":["0333-1024","1468-2982"],"issn-type":[{"value":"0333-1024","type":"print"},{"value":"1468-2982","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7]]},"article-number":"03331024261464438"}}