As noted above, the exclusion of patients with major vascular events within 12 months before each study was a limitation of the analysis, but this is typical for most studies of migraine treatment or prevention. of acute migraine-specific medication use or vascular risk factors at baseline, AE incidence was similar across the placebo and erenumab treatment groups. Hypertension AEs were reported for 0.9% (placebo), 0.8% (erenumab 70 mg), and 0.2% (erenumab 140 mg) of patients. Vascular AEs, which were similar across double-blind and open-label treatment, generally were confounded, with plausible alternative etiologies. In 18 patients with events reviewed by the independent committee, 4 events Conteltinib were positively adjudicated as cardiovascular in origin: 2 deaths and 2 vascular events. All 4 positively adjudicated cardiovascular events occurred during open-label erenumab treatment. Conclusion Selective blockade of the Conteltinib canonical calcitonin gene-related peptide receptor with erenumab for migraine prevention had a vascular safety profile comparable to that of placebo over 12 weeks, with no increased emergence of events over time. Further study of long-term safety of erenumab in Rabbit Polyclonal to ELOA3 patients with migraine is needed. Clinicaltrials.gov identifiers “type”:”clinical-trial”,”attrs”:”text”:”NCT02066415″,”term_id”:”NCT02066415″NCT02066415, “type”:”clinical-trial”,”attrs”:”text”:”NCT02456740″,”term_id”:”NCT02456740″NCT02456740, “type”:”clinical-trial”,”attrs”:”text”:”NCT01952574″,”term_id”:”NCT01952574″NCT01952574, “type”:”clinical-trial”,”attrs”:”text”:”NCT02483585″,”term_id”:”NCT02483585″NCT02483585, “type”:”clinical-trial”,”attrs”:”text”:”NCT02174861″,”term_id”:”NCT02174861″NCT02174861, and “type”:”clinical-trial”,”attrs”:”text”:”NCT01723514″,”term_id”:”NCT01723514″NCT01723514. Classification of evidence This analysis provides Class II evidence that for patients with migraine, erenumab does not increase the risk of vascular AEs. Migraine affects over 1 billion people worldwide1 and 15%C20% of Americans.2 More than 25% of adults with migraine are candidates for preventive therapy,3 but fewer than 30% of candidates receive it.4,5 Over 80% of patients with chronic migraine discontinue oral preventive therapy within the first year.6 There is an unmet need for an effective, well-tolerated therapy to prevent migraine. Calcitonin gene-related peptide (CGRP) plays a key role in migraine pathophysiology.7,8 Monoclonal antibodies have recently been developed that bind to either CGRP or the canonical CGRP receptor to prevent migraine. Because CGRP can mediate vasodilation,9 inhibition of the CGRP pathway could theoretically attenuate compensatory vasodilation during ischemic conditions, but the relative importance of the CGRP receptor pathway compared with other vasodilatory pathways during ischemia (e.g., myocardial) has not been established.9,C11 In addition, patients with migraine have an increased risk of vascular events, including stroke and myocardial ischemia,12,13 and acute migraine-specific medications such as triptans and ergotamine have known vasoconstrictive effects.14,15 Thus, it is important to examine vascular safety, particularly over the longer term, in patients treated with therapies that block the effects of CGRP. Erenumab (in the Conteltinib United States, erenumab-aooe) is a fully human monoclonal antibody that specifically targets and blocks the canonical CGRP receptor to prevent migraine.16 Administered subcutaneously once monthly, erenumab has been shown to be effective for migraine prevention.17,C20 This pooled analysis of vascular safety in clinical studies of erenumab for migraine prevention included vascular (cardiovascular, cerebrovascular, or peripheral) adverse events (AEs) that were reported by investigators, events that were adjudicated across all studies by an independent committee of clinical experts, and a pooled analysis of blood pressure (BP) measurements. This report also includes results of a 24-hour ambulatory BP monitoring study that assessed the potential cardiovascular effects of erenumab in healthy controls. Methods The primary research questions for this pooled analysis were to examine if the rates of vascular (cardiovascular or cerebrovascular) AEs were higher in the erenumab group vs the placebo group of controlled clinical studies, both overall and in subgroups of patients at a higher risk of vascular AEs, as well as the effect of erenumab treatment on BP. This analysis provides Class II evidence that for patients with migraine, erenumab does not increase the risk of vascular AEs. Design Information about AEs was collected as reported by the patient, either spontaneously or in response to the investigator’s nondirected questioning, per standard procedures in clinical.