Objective: To report survey results comparing the experiences of individuals with current versus previous high-frequency headache/migraine (HFM) with acute medication overuse (AMO) and to characterize self-reported experience with care in these groups. Background: Migraine is a disabling neurological disease that can negatively impact all aspects of life. Design/Methods: Respondents to this US, cross-sectional online survey qualified as living with migraine based on the validated "ID Migraine" screener. One group, labeled "current HFM+AMO," were having ≥8 headache/migraine days/month and using ≥10 days/month of acute headache medication, while the second group ("previous HFM+AMO") were now having ≤7 headache days/month with ≤9 days/month of acute headache medication use. Survey questions pertained to diagnosis, living with migraine, healthcare provider (HCP) communication, and treatment. Raw data were weighted to the US adult population. Results: US adults (N=550) were categorized as having current (n=440; mean age, 41.1yr; mean headache days/month, 15.2; mean acute headache medication days/month, 17.4 or previous (n=110; 47.2yr; 4.2days; 4.1days) HFM+AMO. Racial demographics (White [current, 57%; previous, 75%], Hispanic [24%; 13%], Black [11%; 4%]) are similar to the US population. Despite most respondents with HFM+AMO describing their overall health as "good" or "excellent" (current, 64%; previous, 72%; P=ns), 80% of current HFM+AMO) vs 66% of previous HFM+AMO expressed concern with their health (P<0.05). Of the current and previous HFM+AMO groups, 37% and 35%, respectively, wish their HCP better understood their mental/emotional health. Respondents wish HCPs discussed headache management goals with them (current, 66%; previous, 43%; P<0.05) and roughly half of both groups worry about asking too many questions (current, 47%; previous, 54%; P=ns). Current preventive treatment use was low (15–16%; P=ns), while acute medication (28–37%) and over-the-counter medication (57–59%) use was higher. Conclusions: This survey revealed several areas in which HCPs can improve care, including addressing mental health concerns and optimizing acute treatment. Disclosure: Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Axsome Therapeutics. Dr. Starling has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Lundbeck. Dr. Starling has received personal compensation in the range of $0-$499 for serving as a Consultant for Med-IQ. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Medscape. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Satsuma. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Neurolief. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Everyday Health. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Allergan. Dr. Starling has received personal compensation in the range of $500-$4,999 for serving as a Consultant for WebMD. Dr. Cady has received personal compensation for serving as an employee of Lundbeck. Dr. Cady has stock in Alder Biopharmaceutical. Dr. Buse has received personal compensation for serving as an employee of Vector Psychometric Group. Dr. Buse has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie-Allergan. Dr. Buse has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amgen. Dr. Buse has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lilly. Dr. Buse has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lundbeck. Dr. Buse has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Collegium. Dr. Buse has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lilly. Dr. Buse has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbvie-Allergan. Dr. Buse has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. Dr. Buse has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Current Pain and Headache Reports. The institution of Dr. Buse has received research support from Amgen. Mrs. Buzby has received personal compensation for serving as an employee of Coalition for Headache and Migraine Patients. Mrs. Buzby has a non-compensated relationship as a Advisor with Lundbeck that is relevant to AAN interests or activities. Mr. Spinale has received personal compensation for serving as an employee of The Harris Poll. Ms. Steinberg has received personal compensation for serving as an employee of The Harris Poll. Steven Kymes has received personal compensation for serving as an employee of Lundbeck. Steven Kymes has received personal compensation in the range of $0-$499 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for American Journal of Ophthalmology. Steven Kymes has received research support from Emmes Corporation.

To comprehensively evaluate the safety and tolerability of eptinezumab in patients with migraine.

To evaluate the effect of eptinezumab on time to next migraine and the 6-item Headache Impact Test (HIT-6) when administered during a moderate to severe migraine in patients considered candidates for preventive therapy.

To evaluate the efficacy and safety of the preventive migraine treatment, eptinezumab, initiated during a migraine attack.

May 8, 2019April 9, 2019Free AccessEptinezumab Increases Days Free from Canonical Migraine-Associated Symptoms Within 1 Month of Treatment in Patients with Chronic Migraine (P4.10-024)Jack Schim, Peter Goadsby, Eric Kassel, David Biondi, Joe Hirman, and Roger CadyAuthors Info & AffiliationsApril 9, 2019 issue92 (15_supplement)https://doi.org/10.1212/WNL.92.15_supplement.P4.10-024 Letters to the Editor

May 5, 2019April 9, 2019Free AccessEarly Impact of Eptinezumab on the Health-Related Quality of Life (HRQoL) of Patients with Episodic or Chronic Migraine: SF-36 Analysis Across the Spectrum of Migraine (P1.10-025)Merle Diamond, Richard Lipton, Ruslan Horblyuk, Joe Hirman, Roger Cady, and Eric KasselAuthors Info & AffiliationsApril 9, 2019 issue92 (15_supplement)https://doi.org/10.1212/WNL.92.15_supplement.P1.10-025 Letters to the Editor

Objective:To evaluate long-term prevention of episodic migraine with AMG334, a human anti-calcitonin gene-related peptide (CGRP) receptor monoclonal antibody. Background:CGRP plays a major role in migraine pathogenesis. Methods:Double-blind phase 2 study (NCT01952574) randomized adults (N=483) with episodic migraine to monthly subcutaneous injections of AMG334 (7-mg, 21-mg, or 70-mg) or placebo (2:2:2:3). Primary endpoint (change from baseline in monthly migraine days) and secondary endpoints (50[percnt] responder rate and change in monthly migraine attacks) were assessed at Week 12. After completing the double blind phase (12-week), patients could continue in an open-label extension (OLE) to receive 70-mg AMG334 up to 5 years. This interim analysis is based on available efficacy data up to week 52 from the ongoing OLE and safety data up to Week 76. Results:Baseline mean (SD) monthly migraine days was 8.7 (2.7). At Week 12, reductions from baseline in monthly migraine days were significantly greater with 70-mg AMG334 than placebo (-3.40 vs -2.28; p=0.021), but not with lower AMG334 doses (p>0.05). Responder rates (50[percnt]) were significantly higher with 70-mg AMG334 than placebo (47[percnt] vs 30[percnt]; p=0.011). Changes in monthly migraine attacks were not statistically significant from placebo. Of 395 eligible patients, 383 entered the OLE. At data cutoff, median exposure was 34.1 weeks. During the OLE, further reductions from baseline in mean monthly migraine days were sustained for at least 52 weeks. At Week 52, 62[percnt], 38[percnt] and 19[percnt] of patients experienced ≥50[percnt], ≥75[percnt], and 100[percnt] reduction from baseline in migraine days, respectively . There were no major safety findings during the double-blind phase; tolerability was similar between AMG334 and placebo. No new safety signals were identified during the OLE. Conclusions:AMG334 70-mg demonstrated sustained efficacy in prevention of episodic migraine. The safety/tolerability profile of AMG334 in this phase 2 study supports continued development.

Background This study explored whether antagonism of orexin receptors might be an effective mechanism for migraine prevention. Methods We conducted a randomized, double-blind, placebo-controlled, pilot trial. Patients experiencing four to 14 days with migraine during a one-month baseline period were randomized to the orexin receptor antagonist filorexant 10 mg nightly or placebo for three months. Efficacy was assessed by mean monthly migraine days (headache plus at least one associated migraine symptom) and headache days. Safety and tolerability were assessed by adverse event reports and laboratory tests. Results Of 120 patients treated with filorexant and 115 treated with placebo, 97 (81%) and 101 (88%), respectively, completed the trial. There was no statistically significant difference between treatments for change from baseline in mean monthly migraine days (filorexant = −1.7, placebo = −1.3, difference = −0.4 (95% CI: −1.3, 0.4)) or headache days (filorexant = −1.7, placebo = −1.2, difference = −0.5 (95% CI: −1.4, 0.4)). Filorexant was generally well tolerated but was associated with a higher proportion of patients who reported adverse events than placebo (47% vs 37%), particularly somnolence (13% vs 4%). Conclusions These data fail to provide evidence that antagonism of orexin receptors with filorexant, when administered at night, is effective for migraine prophylaxis.

OBJECTIVE: Assessment of a novel, non-invasive, portable VNS device for acute treatment of migraine. BACKGROUND: Despite many acute treatment options for migraine, substantial unmet need remains. VNS is promising, but relatively unexplored. DESIGN/METHODS: Participants with migraine with or without aura, as defined by the International Classification of Headache Disorders- second edition, were eligible for an open-label, single arm, multiple attack study. Participants acutely treated up to 4 migraine attacks with a portable VNS within 6 weeks. Treatment consisted of two, 90-second doses, at 15-minute intervals delivered to the right cervical branch of the vagus nerve. Subjects were asked to self-treat once pain became moderate or severe, or after 20 minutes of mild pain. RESULTS: Of 30 enrolled patients, (5M, 25F, average age 39), 26 eligibly treated 79 migraine headaches . At two hours, headache response rate (pain mild or absent at 2 hours) was 46/79 (58%), and 22/79 (28%) were pain free. Average initial pain level was a 1.84 (0-no pain, 1-mild, 2-moderate, 3-severe pain), and dropped 35%, to 1.20 (p CONCLUSIONS: These results suggest that nVNS may be an effective and well-tolerated acute treatment for migraine in a responsive subgroup. Randomized controlled trials are warranted. Supported by: ElectroCore, LLC. Disclosure: Dr. Goadsby has received personal compensation for activities with Allergan, Colucid, MAP pharmaceuticals, Merck, Sharpe and Dohme, eNeura, Neuroaxon, Autonomic Technologies Inc, Boston Scientific, Eli-Lilly, Medtronic, Linde gases, Arteaus, AlderBio and BristolMyerSquibb. Dr. Goadsby has received personal compensation in an editorial capacity for Journal Watch Neurology and for developing educational materials for the American Headache Society. Dr. Goadsby has received research support from GlaxoSmithKline, MAP, MSD, eNeura, and Amgen. Dr Lipton has received personal compensation for activities with Allergan, Inc., Boston Scientific, Bristol-Myers Squibb Company, Cognimed, Colucid, Eli Lilly & Company, eNeura Therapeutics, GlaxoSmithKline, Inc., MAP, Merck, Nautilus Neuroscience, Novartis, and NuPathe. Dr. Lipton holds stock and/or stock options in eNeura Therapeutics. Dr. Cady has received personal compensation for activities with Merck & Co., Inc. Dr. Cady has received research support from Merck & Co., Inc Dr. Mauskop has received personal compensation for activities with Allergan, Inc., and Merck & Co., Inc. Dr. Grosberg has received personal compensation for activities with Tribute Pharmaceutical and Zogenix. Dr. Grosberg has received research support from Allergan, Inc., Electrocore, and Novartis.

Tobias Kurth and Pamela Rist’s Migraine and Cognitive Decline: A Topical Review is a muchneeded comprehensive review of the literature that explores the potential relationship between migraine and dementia. Their conclusion suggests that despite studies that report increased risk of stroke and/or white matter lesions, migraineurs are no more likely to develop dementia in mature adulthood than nonmigraineurs. This is welcomed news for millions of people afflicted with migraine, as well as the health care professionals who care for them. We commend the authors for this important contribution to the medical literature. An interesting limitation in this review is in the challenge of defining the accumulated migrainerelated disease burden in the populations being studied. Several studies have found a significant drop in cognitive efficiency during acute episodic migraine (EM) that recovers within 2 hours with effective treatment. Cognitive disturbance has been observed in all phases of a migraine attack from the premonitory through the recovery (postdrome) phase, yet in EM, migraine cognition is assumed to normalize with termination of the attack. This is undoubtedly true if the nervous system has sufficient time between repeated episodes of migraine to recover fully. Thus, migraine-related cognitive impairment is assumed to be secondary to reversible physiological disruptions associated with pain and/or the pathophysiology of migraine rather than the structural changes that occur in the disease of dementia. An unanswered question is the level of cognitive impairment when migraine attacks are generated in the nervous system with such frequency that there is little or no physiological recovery time. This may well be the case in the population of migraineurs living with chronic migraine (CM). Given that CM can last for years, there could be an accumulated impact of cognitive impairment that is sustained and clinically meaningful.The pervasive nature of CM has already been suggested in the increased frequency of comorbidities associated with migraine chronification. One might speculate that the impact of cognitive impairment in people with long-duration CM might be substantial, last for extended periods of time, and possibly lead to changes in the central nervous system (CNS) that imparts a degree of permanence. These changes may not be reflected in population-based studies focused primarily on episodic migraineurs. Migraine is unique among most other chronic diseases, in that its medical relevancy is the cumulative attrition associated with repeated attacks rather than a catastrophic disease end point as is associated with diseases such as hypertension, hyperlipidemia, or type II diabetes. Further, unlike other chronic diseases, the natural history of migraine generally improves in later adult life.While historically migraine has been considered a vascular disease,more recent explanations of its pathogenesis are rooted in a concept of a hyperexcitable brain. Considering white matter lesions as structural vascular pathology would reasonably support a hypothesis that migraine leads to early dementia. Yet the biology of a hyperexcitable nervous system would suggest that vascular changes are secondary to neuronal changes in the CNS. From this perspective, cognitive changes associated with migraine may be functional rather than anatomical, and white matter lesions seen in migraineurs do not represent meaningful vascular pathology. Perhaps migraine’s relationship to cognition is not a terminal event, such as dementia, but rather a ISSN 0017-8748 doi: 10.1111/head.12059 Published by Wiley Periodicals, Inc. Headache © 2013 American Headache Society