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We conducted a targeted literature review on patient burden during the interictal period of migraine. The results of the literature review revealed that: (1) migraine-associated burden persists into the interictal period and is not confined to the headache episodes themselves; (2) anxiety over the possible recurrence of headache episodes is a factor that reduces daily activities and quality of life (QOL); and (3) prophylactic treatment with calcitonin gene-related peptide (CGRP) antibody drugs may reduce the burden during the interictal period. From these findings, it is considered important in migraine treatment to identify the unmet needs of patients, including the burden during the interictal period, and to select an appropriate treatment method based on the burden experienced by individual patients.

Introduction: Migraine-related stigma (MiRS) and social burden is increasingly recognized. We assessed perspectives and attitudes toward migraine in people with and without migraine in Japan., Methods: OVERCOME (Japan) was a cross-sectional, population-based web survey of people with and without migraine (July-September 2020). People with migraine were individuals who met the modified International Classification of Headache Disorders criteria or had self-reported physician-diagnosed migraine. People without migraine were selected per quota sampling to represent the Japanese adult population. People with migraine reported their experiences on stigma and social burden and answered how frequently they experienced stigma using the MiRS questionnaire. Associations between MiRS and disability and MiRS and interictal burden were examined using the migraine disability assessment and Migraine Interictal Burden Scale-4. People without migraine reported their experiences and attitudes toward people with migraine by answering an 11-item attitudinal migraine questionnaire., Results: A total of 17,071 and 2008 people with and without migraine, respectively, completed the survey. Overall, 11,228 (65.8%) respondents with migraine reported that they have never experienced stigma or burden; however, of the 12,383 employed respondents, 5841 (47.2%) reported that their current employers are not "extremely" or "very" understanding about their conditions. Moreover, ∼30%-40% of respondents "sometimes," "often," or "very often" hid their migraine from others. The proportion of respondents who experienced stigma often or very often, as assessed by MiRS, was 16.5%; this increased with the increasing number of monthly migraine headache days. The proportion of respondents with moderate-to-severe disability and interictal burden increased with increasing stigma. Among respondents without migraine, the proportion holding a stigmatizing attitude toward those with migraine was low (<15%); ∼80% had never experienced work- or family-related stigma or burden., Conclusion: MiRS and burden exist but may be hidden and underrecognized in Japan. Disease awareness and education may be important to prevent and reduce stigma and burden., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

Background: Surveys using questionnaires to collect epidemiologic data may be subject to misclassification. Here, we analyzed a headache questionnaire to evaluate which questions led to a classification other than migraine., Methods: Anonymized surveys coupled with medical claims data from individuals 19-74 years old were obtained from DeSC Healthcare Inc. to examine proportions of patients with primary headache disorders (i.e.; migraine, tension-type headache, cluster headache, and "other headache disorders"). Six criteria that determined migraine were used to explore how people with other headache disorders responded to these questions., Results: Among the 21480 respondents, 7331 (34.0%) reported having headaches. 691 (3.2%) respondents reported migraine, 1441 (6.7%) had tension-type headache, 21 (0.1%) had cluster headache, and 5208 (24.2%) reported other headache disorders. Responses of participants with other headache disorders were analyzed, and the top 3 criteria combined with "Symptoms associated with headache" were "Site of pain" (7.3%), "Headache changes in severity during daily activities" (6.4%), and the 3 criteria combined (8.8%). The symptoms associated with headache were "Stiff shoulders" (13.6%), "Stiff neck" (9.4%), or "Nausea or vomiting" (8.7%), Photophobia" (3.3%) and "Phonophobia" (2.5%)., Conclusions: Prevalence of migraine as diagnosed by questionnaire was much lower than expected while the prevalence of "other headache" was higher than expected. We believe the reason for this observation was due to misclassification, and resulted from the failure of the questionnaire to identify some features of migraine that would have been revealed by clinical history taking. Questionnaires should, therefore, be carefully designed, and doctors should be educated, on how to ask questions and record information when conducting semi-structured interviews with patients, to obtain more precise information about their symptoms, including photophobia and phonophobia., (© 2024. The Author(s).)

Background: Migraine is a highly prevalent, disabling, misunderstood, underdiagnosed, and undertreated neurological disease. It is a leading cause of productivity loss in the workplace., Methods: This is the first large-scale company-wide headache education and evaluation program in the workplace., Results: 73,432 (90.5%) Fujitsu employees participated. The prevalence of migraine was 16.7%, tension-type headache 40.7%, and cluster headache 0.5%. After completing the training, 82.9% of participants without headache said they would change their attitude towards colleagues with headache disorders and 72.5% of total participants said their understanding of headache changed. The proportion of employees who thought that headache had a significant impact on people's lives increased from 46.8% to 70.6%; 2971 (4.1%) of all participants were interested in a virtual consultation with a headache specialist as part of the program, more than half of whom had not previously consulted for headache. Approximately 14.7 days per year of full productivity per employee with headache were gained resulting in an annual productivity saving per employee of US$4531., Conclusion: This unique headache workplace program was associated with a high level of participation, an improvement in the understanding of migraine and attitude towards colleagues with migraine, reduction in disability and increased employee productivity, and decreased costs of lost productivity due to migraine. Workplace programs for migraine should be considered for all industry sectors.

Background: Perimenstrual migraine attacks in women with menstrual migraine is difficult to treat. This post-hoc analysis evaluated the efficacy of lasmiditan, a high affinity and selective 5-HT 1F receptor agonist, for perimenstrual attacks., Methods: Patients from two randomized, double-blind, placebo-controlled clinical trials (MONONOFU and CENTURION) were instructed to treat an attack with a single dose of study medication within four hours of pain onset. After dosing, the proportion of patients who achieved freedom from migraine-related head pain, most bothersome symptom, and disability was reported at baseline up to 48 hours after dose and pooled data were evaluated., Results: A total of 303 patients (MONONOFU N = 78; CENTURION N = 225) treated perimenstrual migraine attacks with lasmiditan 50 mg (N = 24), 100 mg (N = 90), 200 mg (N = 110), and placebo (N = 79). More patients achieved migraine-related head pain freedom with lasmiditan 200 mg versus placebo at all time points assessed. At 2 hours, 33.6% of patients in the 200-mg group (p < 0.001), and 16.7% of patients in the 100-mg (p = 0.11) and 50-mg (p = 0.19) groups were pain free, compared with 7.6% in the placebo group., Conclusions: Lasmiditan treatment of perimenstrual migraine attacks was associated with freedom from migraine-related head pain at two hours, early onset of efficacy, and sustained efficacy. Clinical Trial registration: NCT03962738 and NCT03670810.

Background: Migraine is a chronic disease characterized by episodic headache attacks. No recent studies have, however been conducted on the epidemiology of migraine or the treatment landscape in Japan. This study was conducted as a fact-finding survey using medical claims data and an online survey on migraine and headaches, conducted among members of health insurance associations with the objective of gaining an understanding of migraine prevalence and the treatment status in Japan., Methods: The study methodology utilized a unique approach of combined data sources. The data sources used in this study are medical claims data and linked online survey data provided by DeSC Healthcare Inc (DeSC). The primary outcomes (from survey responses) were: the overall number and proportion of migraine patients; and the overall prevalence of migraine, stratified by age and sex. The secondary outcomes (from survey responses) were use of medical care; and clinical features/headache symptoms. The analysis population included all individuals who had response data for surveys conducted by DeSC. The online survey data and medical claims data were summarized., Results: The data population comprised 21,480 individuals. On the basis of the survey results, including probable cases, the overall prevalence of migraine was 3.2%. The highest prevalence of migraine was observed in patients aged 30-39 years. The prevalence of migraine in women was 4.4 times higher than in men. The percentage of migraine patients who had not been seen by a doctor was 81.0%. More than 80% of patients were taking over-the-counter drugs and 4.8% took prescription medicines only. Approximately 52.9% of patients considered that the intensity of pain symptoms was severe. Moreover, the majority of patients (72.9%) considered that the impairment of daily life activities was of moderate or severe degree., Conclusions: In Japan, the percentage of people with migraine who did not receive medical attention is as high as 80%. Additionally, the majority of patients tend to endure symptoms and continue with everyday activities. With innovative treatment approaches becoming available it is necessary to disseminate information that migraine is not a simple headache but an illness that requires medical treatment and consultation., (© 2022. The Author(s).)

Objective: To determine the efficacy and safety of fremanezumab administration in Japanese and Korean patients with chronic migraine (CM)., Background: Available preventive treatments for CM are limited by various efficacy and safety issues. Fremanezumab, a monoclonal antibody that targets the calcitonin gene-related peptide pathway involved in migraine pathogenesis, has been shown to be effective and well tolerated in large-scale, international Phase 3 trials., Methods: Randomized, placebo-controlled trial of patients with CM who received subcutaneous fremanezumab monthly (675 mg at baseline and 225 mg at weeks 4 and 8), fremanezumab quarterly (675 mg at baseline and placebo at weeks 4 and 8), or matching placebo. Primary endpoint was the mean change from baseline in the monthly (28-day) average number of headache days of at least moderate severity during the 12 weeks after the first dose., Results: Among 571 patients randomized (safety set, n = 569; full analysis set, n = 566), the least-squares mean (±standard error [SE]) reduction in the average number of headache days of at least moderate severity per month during 12 weeks was significantly greater with fremanezumab monthly (-4.1 ± 0.4) and fremanezumab quarterly (-4.1 ± 0.4) than with placebo (-2.4 ± 0.4). The difference from the placebo group in the mean change (95% confidence interval [CI]) was -1.7 days (-2.54, -0.80) for the fremanezumab monthly group and -1.7 days (-2.55, -0.82) for the fremanezumab quarterly group (p < 0.001 vs. placebo for both fremanezumab groups). The percentage of patients with a ≥50% reduction in the average number of headache days of at least moderate severity per month (response rate) was higher with fremanezumab monthly (29.0%) and fremanezumab quarterly (29.1%) than with placebo (13.2%) in addition to other improvements in secondary endpoints, including reduction of acute medication use (mean change from baseline during 12-week period ± SE: fremanezumab monthly, -3.7 ± 0.4; fremanezumab quarterly, -3.9 ± 0.4; placebo, -2.4 ± 0.4) and improvements in disability scores (mean change from baseline in six-item Headache Impact Test score at 4 weeks after third injection ± SE: fremanezumab monthly, -8.1 ± 0.7; fremanezumab quarterly, -8.0 ± 0.7; placebo, -6.5 ± 0.7). Fremanezumab was well tolerated with a similar incidence of adverse events including injection-site reactions as placebo (patients with at least one treatment-emergent adverse event: fremanezumab total, n = 232 [61.4%]; placebo, n = 118 [61.8%])., Conclusion: Fremanezumab effectively prevents CM in Japanese and Korean patients and was well tolerated. No safety signal was detected., (© 2021 The Authors. Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.)

Objectives: To assess the impacts of social situation changes due to the coronavirus disease 2019 (COVID-19) pandemic on headache-related disability and other symptoms in patients with migraine in Japan., Methods: We conducted a multicentre, cross-sectional study including 659 outpatients with migraine diagnosed by headache specialists. The participants were asked about the impacts of the first wave of the COVID-19 pandemic on headache-related disability, headache days, headache intensity, stress, physical activity, hospital access and their work and home lives. For headache-related disability, the total Migraine Disability Assessment (MIDAS) score and part A and B scores were analysed. Multivariate stepwise linear regression analysis was performed to identify the clinical predictors of changes in the total MIDAS score before and during the COVID-19 pandemic. Logistic regression analysis was performed to determine the factors related to new-onset headache during the COVID-19 pandemic., Results: Finally, 606 migraine patients (73 M/533 F; age, 45.2 ± 12.0 years) were included in the study, excluding those with incomplete data. Increased stress, substantial concern about COVID-19 and negative impacts of the first wave of the COVID-19 pandemic on daily life were reported in 56.8 %, 55.1 and 45.0 % of the participants, respectively. The total MIDAS and A and B scores did not significantly change after the first wave of the COVID-19 pandemic. New-onset headache, which was observed in 95 patients (15.7 %), was associated with younger age and worsened mood and sleep in the logistic regression analysis. The multivariate stepwise linear regression analysis of changes in the total MIDAS score before and during the first wave of COVID-19 pandemic identified worsened sleep, increased acute medication use, increased stress, medication shortages, comorbidities, the absence of an aura and new-onset headache were determinants of an increased total MIDAS score during the first wave of the COVID-19 pandemic., Conclusions: In this multicentre study, clinical factors relevant to headache-related disability, such as new-onset headache, stress and sleep disturbances, were identified, highlighting the importance of symptom management in migraine patients during the first wave of the COVID-19 pandemic.

Background: Because of the burden of migraine in Japan, there is a need for safe and effective preventive treatments. This study assessed the long-term safety and tolerability of galcanezumab in Japanese patients with episodic (EM) or chronic (CM) migraine., Research Design and Methods: In this 12-month open-label study, adult patients with EM who previously completed a 6-month, double-blind, placebo-controlled trial were newly randomized to either galcanezumab dose from placebo or continued their assigned galcanezumab doses (all: 120 mg, n = 120; 240 mg, n = 126). Newly enrolled patients with CM were randomized to 120-mg (n = 32) or 240-mg (n = 33) galcanezumab. The primary outcome was long-term safety and tolerability., Results: The incidence of TEAEs was similar between treatment groups. Nasopharyngitis was the most common TEAE, followed by injection site reactions. The discontinuation rate was low (EM = 9.3%; CM = 15.4%) and no deaths were reported. Patients with EM who received galcanezumab in the placebo-controlled trial had sustained efficacy. Both doses reduced the number of migraine headache days in patients with CM., Conclusions: Long-term treatment with 120-mg or 240-mg galcanezumab was safe and effective in Japanese patients with EM or CM., Trial Registration: https://clinicaltrials.gov, identifier: NCT02959190.

Objectives: To quantify the social burden among Japanese migraine patients in the context of currently available migraine treatments, by comparison with non-migraine controls, and comparison of migraine patients currently taking prescription medication versus not taking prescription medication., Design: Cross-sectional analysis., Setting: Data from the population-based online self-administered Japan National Health and Wellness Survey (NHWS) 2017., Participants: Respondents to the NHWS (n=30 001) were ≥18 years. Migraine patients were respondents with self-reported experience and physician diagnosis of migraine. Non-migraine controls reported no migraine experience. Migraine patients were subgrouped into currently taking prescription medication for migraine (Rx) and currently not taking prescription medication (non-Rx)., Methods: One-way analysis of variance tests were performed to compare health-related quality of life (HRQoL), work productivity and activity impairment and healthcare resource utilisation between migraine patients and matched non-migraine controls selected by 1:1 propensity score matching. Generalised linear models were used to compare outcomes and migraine related characteristics between Rx and non-Rx., Results: Compared with matched controls, migraine patients (n=1265) had significantly lower HRQoL in terms of lower Physical Component Summary (48.36 vs 51.29, p<0.001), Mental Component Summary (44.65 vs 48.31, p<0.001), Role/Social Component Summary (41.78 vs 46.18, p<0.001) and mean EuroQol 5-Dimension index (0.77 vs 0.86, p<0.001) scores. Migraine patients experienced significantly higher absenteeism (6.95% vs 3.07%, p<0.001), presenteeism (32.73% vs 18.94%, p<0.001), work productivity loss (34.82% vs 20.03%, p<0.001) and daily activity impairment (35.70% vs 22.04%, p<0.001) and visited healthcare professionals more often (8.38 vs 4.57, p<0.001) than controls. No significant differences in these outcomes were found when comparing Rx (n=587) and non-Rx (n=678) patients., Conclusions: There is an unmet need for improved HRQoL and work productivity in Japanese migraine patients despite the currently available prescription medications, which are important factors to consider for future development of migraine therapies., Competing Interests: Competing interests: HI reports personal fees for consulting, lectures and speaker's honorarium from Pfizer, Eisai, Otsuka Pharmaceutical, Kyowa Kirin, Takeda Pharmaceutical, Amgen Astellas BioPharma, and Eli Lilly, outside the submitted work. KU, TK and ZC are full-time employees of Eli Lilly Japan KK. and share holders of Eli Lilly & Company. SJ and YC are full-time employees of Kantar, Health Division., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Cefaly (Cefaly Technology, Seraing, Belgium) is a device that stimulates the bilateral supraorbital nerve transcutaneously. A previous study in Europe proved that Cefaly was an effective and safe device as a preventive therapy for migraine. However, there have been no studies on this device in Asia. We examined the safety and preventive effect of Cefaly for migraine. One-hundred patients were prospectively collected from four headache units in Japan. The inclusion criteria were as follows: 18-75 years of age, migraine with and without aura, and at least 2 attacks per month. A 4-week baseline period was followed by 12-week treatment period. The primary end point was the change from baseline in the number of migraine days at 12 weeks. The secondary end points include the changes of the number of migraine attacks, all headache days, acute medicine consumption days and headache severity. After treatment, a questionnaire survey on the satisfaction of the treatment was administered to the patients. The Friedmann test was used to assess the changes between baseline period and after treatment, and Mann-Whitney U test was used for the comparison of efficacy between chronic migraine and episodic migraine, with and without prophylactic treatment or medication overuse. After 12 weeks of treatment, Cefaly use significantly decreased the number of migraine days (8.16 vs. 6.84; p = 0.0036). Only three subjects (3.0%) dropped out due to the adverse effects; however, no serious adverse events were observed. The compliance of this study was very high at 90.0%. Furthermore, a significant decrease was observed in the number of migraine attacks (5.33 vs. 3.94; p = 0.0002) and the intake of acute antimigraine drugs (8.75 vs. 7.83; p = 0.0166). Cefaly is considered to be a safe and highly tolerable effective device for Japanese patients. Trial registration: This study was retrospectively registered to UMIN-CTR(UMIN000033333) on 10 July 2018.

Objectives: The prevalence rate of migraines is 8.4%; it is mostly diagnosed in women at 20s to 40s, and is known to cause major physical and mental disruption to daily life. This study was conducted on women aged between their 20s and 40s, in order to investigate the possible differences in the features of the occlusal state between a migraine and a non-migraine (control) group., Methods: Age-matched female patients with migraine (n = 60) diagnosed by headache specialists and healthy controls (n = 57) were enrolled. Dental casts were used to evaluate some features., Results: The maxillary and mandibular dentition casts from the migraine group showed significantly characteristic findings in their Angle's classification, overjet, and deviation in the anterior tooth midline, compared to the control group., Discussion: The results relating occlusal state to both tension-related headaches and migraines, which have different pathogeneses, suggest the possibility of dental intervention to improve the symptoms of primary headaches.

Objectives: Details on grinding patterns and types of contact during sleep bruxism in association with migraine headache have not yet been elucidated. This study compared the characteristics of sleep bruxism between patients with migraine and controls., Methods: The study included 80 female patients who had been diagnosed with migraine and 52 women with no history of migraine. Grinding patterns were measured using the BruxChecker® (Scheu Dental, Iserlohn, Germany)., Results: There was a significant difference between the two groups in the distribution of grinding patterns at the laterotrusive side (p < 0.001). When the anterior teeth and premolar and molar regions in the two groups were compared, the proportion of the grinding area at all sites was significantly larger in the migraine group than in the control group (p < 0.001)., Discussion: The BruxChecker® showed that there was substantial grinding over a large area among migraine patients, particularly in the molar region.

The Japanese Headache Society and the Japanese Society of Neurology has published the 2013 guidelines for the diagnosis and treatment of chronic headache. A new CQ has been set up in the guidelines on the topic of "How to treat chronic migraine." In the past, lomerizine was the only prophylactic medication of migraine that was eligible under insurance coverage. However, afterward in 2010, valproate was added to the list of antimigraine medications approved under insurance coverage, followed by propranolol, amitriptyline, and verapamil, with rapid advances in the treatment of migraine. Valproate, topiramate (not approved under insurance coverage until date), and amitriptyline could potentially be used in the treatment of chronic migraine in Japan; further, considering the clinical outcomes thus far, lomerizine could also be added to the list. As a drug for migraine prophylaxis, valproate is contraindicated in pregnant women and needs to be used with caution.

Migraine is a common neurological disorder that produces substantial disability for sufferers. Chronic migraine (≥ 15 headache days/month; CM) was significantly more disabling than episodic migraine (< 15 headache days/month; EM). CM was associated with greater impairment of occupational and social aspects of quality of life. Lost productivity time was substantially higher among CM participants than persons with EM. Full time employment was lower in CM participants because of medical leave. The medical costs were two or three times higher for CM than EM. These results suggest that migraine chronification is associated with substantial economic burden.

The aim of prophylactic treatment of migraine is to reduce the frequency and severity of migraine attacks. Identifying relevant trigger factors can help reduce the frequency of migraine attacks. The headache diary is useful to identify trigger factors and pattern of headaches and to assess the efficacy of medication. Prophylactic drugs should be considered when attacks are frequent or severe and the acute treatments such as triptans or NSAIDs are not effective. Lomerizine, propranolol, valproate and amitriptyline are useful. Lomerizine is recommended as the first-line prophylactic drug because it is licensed as a preventive drug for migraine in Japan. If attacks has not improved after using a prophylactic drug for 2 months, the drug can be changed to another drug. Propranolol is particularly useful if a patient has hypertension. Amitriptyline is useful if there is associated depression and/or tension-type headache. Valproate is considered if attacks are frequent. Patients should be informed benefits and potential side-effects of the medicine.

We developed and tested a version of the migraine-specific quality of life (MSQOL) instrument for use in Japan. The MSQOL was translated into Japanese, evaluated by physicians and nurses who has experienced migraine headaches, 'backtranslated', approved by the author of the original version, and tested in 70 out-patients with migraine. There were no ceiling or floor effects. All three subscales were found to be internally consistent: alpha > or = 0.76. The patients' scores were similar to those reported in the user's manual, with the exception of a difference of about 11 points on the Avoidance Behaviors subscale. Some correlations between MSQOL scores and SF-36 scores were statistically significant, although none exceeded 0.52. Linear associations between some measures of symptoms and some MSQOL scales were statistically significant, but those associations were consistent neither for the two kinds of symptom reports (severity and frequency) nor across all MSQOL subscales. Low MSQOL scores in early 1999 correlated with more return visits for medication and with greater amounts of triptan (anti-migraine) medication in 2001 and 2002. Overall, we interpret these results as indicating that, while they cannot be used as substitutes for reports of symptoms, scores on the Japanese version of the MSQOL can be used to assess the impact of migraine headaches on patients' lives.

This study presents the first nationwide survey of migraine in Japan. A representative sample of 4029 subjects aged 15 years or older was selected from the Japanese population according to the quota method. A combination of telephone interview and mailed questionnaire methods was used. Diagnosis of migraine was based on the International Headache Society (IHS) Classification. The overall prevalence of migraine in the past year was 8.4%; 5.8% was migraine without aura and 2.6% was migraine with aura. Significant correlation was found between the prevalence of migraine and such variables as gender, age and district of residence. Doctor attendance rate was very low and 69.4% with migraine had never consulted a physician for headache. Yet, 74.2% complained that migraine headache impaired their daily activity significantly. Only 11.6% were aware that their headache was migraine and 56.9% were using only the over-the-counter drugs. The study revealed a comparably high prevalence of migraine in the general population of Japan compared with other countries. A genetic factor was speculated as the cause of regional difference in migraine prevalence.

A preliminary study was undertaken to provide clinical evidence to support the hypothesis that: "Migraine with aura, migraine without aura and aura alone are the same condition, which differ in degree rather than pathophysiology." At the City of London Migraine Clinic, 50 patients consecutively attending the clinic with a past or present history of migraine with aura were questioned. Of the 50 patients questioned 36 (70%) had a combination of migraine with aura, migraine without aura and/or aura alone; i.e. 70% had had more than one type of migraine attack. The duration, severity and frequency of attacks did not differ between migraine with and migraine without aura. Conclusion--the results support the hypothesis that migraine with and migraine without aura, and aura alone are not separate conditions, because: (1) most patients suffer from more than one type of migraine attack; (2) there are no significant differences in the characteristics of the migraine attacks in the different groups; (3) there are no significant differences in the characteristics of the subjects.

Magnetic resonance imaging (MRI) was studied in 91 patients with migraine and in 98 controls. Risk factors known to cause MRI lesions were carefully examined. In 36 patients with migraine (39.6%), small foci of high intensity on T2-weighted and proton-density-weighted images were seen in the white matter. Of patients with migraine who were less than 40 years old and without any risk factor, 29.4% showed lesions on MRI; this was significantly higher than the 11.2% for the group of age-matched controls (n = 98). The lesions were distributed predominantly in the centrum semiovale and frontal white matter in young patients, but extended to the deeper white matter at the level of basal ganglia in the older age group. The side of the MRI lesions did not always correspond to the side of usual aura or headache. Migraine-related variables such as type of migraine, frequency, duration or intensity of headache or consumption of ergotamine showed no significant correlation with the incidence of MRI abnormalities. Our data indicated that migraine may be associated with early pathologic changes in the brain.

Hisaka Igarashi,1 Mamoru Shibata,2 Akichika Ozeki,3 Kathleen Ann Day,4 Taka Matsumura3 1Department of Internal Medicine, Fujitsu Clinic, Kawasaki, Japan; 2Department of Neurology, Tokyo Dental College Ichikawa General Hospital, Ichikawa, Japan; 3Eli Lilly Japan K.K., Kobe, Japan; 4Eli Lilly and Company, Indianapolis, IN, USACorrespondence: Taka MatsumuraMedical Science, Medicines Development Unit Japan, Eli Lilly Japan K.K., 4-15-1 Akasaka, Akasaka Garden City 13F, Minato-ku, Tokyo, 107-0052, JapanTel +81 3 5574 9169Fax +81 3 5574 9979Email matsumura_taka@lilly.comPurpose: This study aimed to extensively evaluate the onset and maintenance effect of galcanezumab compared with placebo for the prevention of episodic migraine in Japanese patients.Patients and Methods: This was a post-hoc analysis of a Phase 2, multicenter, randomized, double-blind, placebo-controlled study conducted between December 2016 and January 2019 (ClinicalTrials.gov: NCT02959177). Patients aged between 18 and 65 years with episodic migraine were randomized to receive a monthly injection of galcanezumab (120 mg: N = 115, 240 mg: N = 114) or placebo (N = 230) for 6 months. Outcome measures included onset of effect at weekly and daily intervals—assessed by change from baseline in the number of migraine headache days and the proportion of patients with migraine headache—with galcanezumab versus placebo. To further confirm the onset and maintenance effect, the 50% response rate was also evaluated.Results: The mean change from baseline in weekly migraine headache days was significantly reduced with galcanezumab (– 0.97 days) compared with placebo (– 0.10 days) at week 1 (p ≤ 0.0001), which was maintained at all subsequent weeks up to week 4 (all p ≤ 0.0001 vs placebo). A significantly smaller proportion of galcanezumab-treated patients had migraine headache compared with placebo-treated patients at day 1 after the first injection (13.6% vs 31.4%, respectively; p ≤ 0.0001), which was also maintained at all subsequent days during the first week after the first injection. Furthermore, the 50% response rate was significantly higher with galcanezumab compared with placebo from week 1 through month 6.Conclusion: The onset of the migraine preventive effect of galcanezumab was rapid compared with placebo, starting from day 1 after the first injection in Japanese patients with episodic migraine. The effect was maintained during the first week and first month, and throughout 6 months of monthly injections of galcanezumab. Galcanezumab is a promising preventive treatment in Japanese patients with episodic migraine.Keywords: calcitonin gene-related peptide, galcanezumab, Japan, migraine disorders, onset of effect, maintenance effect