Outcomes and Factors Associated with Insufficient Effectiveness of Acute Treatments of Migraine in Japan: Results of the ObserVational survey of the Epidemiology, tReatment, and Care Of MigrainE (OVERCOME [Japan]) Study.

BACKGROUND: Knowledge of patient outcomes and treatment effectiveness associated with acute migraine treatments in Japan is lacking. OBJECTIVE: To describe patient-reported outcomes (PROs) and treatment effectiveness in three acute treatment groups from OVERCOME (Japan): over-the-counter (OTC) only, prescription nonsteroidal anti-inflammatory drugs/acetaminophen (Rx-NSAIDs/ACE) only, and triptans. METHODS: OVERCOME (Japan) was an observational, cross-sectional, population-based web survey of people with migraine (July-September 2020). PROs, including the Migraine-Specific Quality of Life Questionnaire (MSQ), Migraine Interictal Burden Scale (MIBS-4), Migraine Disability Assessment (MIDAS), and Work Productivity and Activity Impairment Questionnaire: Migraine (WPAI-M), were compared pairwise between treatment groups. Logistic regression was used to examine treatment effectiveness. RESULTS: The analysis included 9075 survey respondents (OTC only: n = 5791; Rx-NSAIDs/ACE only: n = 751; triptans: n = 2533). Triptan users reported the lowest MSQ scores, most severe disability (MIDAS: 20.7% versus 6.3% and 11.6%) and severe interictal burden (MIBS-4: 50.1% versus 21.2% and 19.8%), and greatest work impairment (WPAI-M: 50.4% versus 32.2% and 30.8%) compared with the OTC and Rx-NSAIDs/ACE groups, respectively. Treatment effectiveness was very poor-to-poor for 60.9%, 43.1%, and 47.6% of the triptan, OTC, and Rx-NSAIDs/ACE groups, respectively. Severe interictal burden was significantly associated with insufficient treatment effectiveness (odds ratios, severe versus no burden: 0.47 [95% confidence interval: 0.40-0.54], 0.56 [0.35-0.89], and 0.41 [0.32-0.52], for the OTC, Rx-NSAIDs/ACE, and triptan groups, respectively). CONCLUSION: People with high migraine burden used triptans for acute treatment, but many reported poor treatment effectiveness. Education may be required to promote better treatments, including earlier introduction of migraine-specific acute and preventive medications.

Discrete Choice Experiment to Understand Japanese Patients' and Physicians' Preferences for Preventive Treatments for Migraine.

INTRODUCTION: Self-injectable calcitonin gene-related peptide (CGRP) monoclonal antibody (mAb) auto-injectors and non-CGRP oral medications are currently available for migraine prevention in Japan. This study elicited the preferences for self-injectable CGRP mAbs and non-CGRP oral medications and determined differences in the relative importance of auto-injector attributes for patients and physicians in Japan. METHODS: Japanese adults with episodic (EM) or chronic (CM) migraine and physicians who treat migraine completed an online discrete choice experiment (DCE), asking participants to choose a hypothetical treatment they preferred between two self-injectable CGRP mAb auto-injectors and a non-CGRP oral medication. The treatments were described by seven treatment attributes, with attribute levels varying between questions. DCE data were analyzed using a random-constant logit model to estimate relative attribution importance (RAI) scores and predicted choice probabilities (PCP) of CGRP mAb profiles. RESULTS: A total of 601 patients (79.2% with EM, 60.1% female, mean age: 40.3 years) and 219 physicians (mean length of practice: 18.3 years) completed the DCE. About half (50.5%) of patients favored CGRP mAb auto-injectors, while others were skeptical of (20.2%) or averse (29.3%) to them. Patients most valued needle removal (RAI = 33.8%), shorter injection duration (RAI = 32.1%), and auto-injector base shape and need for skin pinching (RAI = 23.2%). Most physicians (87.8%) favored auto-injectors over non-CGRP oral medications. Physicians most valued less-frequent dosing RAI = 32.7%), shorter injection duration (30.4%), and longer storage outside the fridge (RAI = 20.3%). A profile comparable to galcanezumab showed a higher likelihood of being chosen by patients (PCP = 42.8%) than profiles comparable to erenumab (PCP = 28.4%) and fremanezumab (PCP = 28.8%). The PCPs of the three profiles were similar among physicians. CONCLUSION: Many patients and physicians preferred CGRP mAb auto-injectors over non-CGRP oral medications and preferred a treatment profile similar to galcanezumab. Our results may encourage physicians in Japan to consider patient preferences when recommending migraine preventive treatments.

Potential Unmet Needs in Acute Treatment of Migraine in Japan: Results of the OVERCOME (Japan) Study.

INTRODUCTION: Using data from the ObserVational survey of the Epidemiology, tReatment, and Care Of MigrainE study in Japan (OVERCOME [Japan]), we describe the current status of the acute treatment of migraine in Japan. METHODS: OVERCOME (Japan) was a cross-sectional, observational, population-based web survey of people with migraine in Japan (met modified International Classification of Headache Disorders criteria or had a physician diagnosis of migraine) conducted between July and September 2020. Respondents reported current acute medication use and effectiveness (assessed using the Migraine Treatment Optimization Questionnaire [mTOQ-4]). Cardiovascular history and risk factors of the respondents were also recorded. Potential unmet acute treatment needs were defined as insufficient effect of current acute treatments (mTOQ-4 score ≤ 5), a history of oral triptan use (and not currently taking any triptan), potential contraindications to triptans due to cardiovascular comorbidities, and/or cardiovascular risk factors. RESULTS: In total, 17,071 people with migraine in Japan completed the survey; 14,869 (87.1%) of these were currently using acute treatments. Poor effectiveness of current acute treatment was reported by 7170 respondents (42.0%), 900 respondents (5.3%) were former triptan users, 1759 (10.3%) had contraindications to triptans, and 9026 (52.9%) reported at least one cardiovascular risk factor. Overall, 12,649 (74.1%) of OVERCOME (Japan) respondents were categorized into one or more of these groups and were considered to have potential unmet acute treatment needs. CONCLUSION: Almost three-quarters of people with migraine in Japan may have potential unmet needs for acute treatment of migraine. There are substantial opportunities for improving care for people with migraine in Japan, including prescription of novel acute medications.

Burden of Migraine in Japan: Results of the ObserVational Survey of the Epidemiology, tReatment, and Care Of MigrainE (OVERCOME [Japan]) Study.

INTRODUCTION: The ObserVational survey of the Epidemiology, tReatment, and Care Of MigrainE study in Japan (OVERCOME [Japan]) assessed the impact and burden of migraine in Japan. METHODS: OVERCOME (Japan) was a cross-sectional, observational, population-based web survey of Japanese people with migraine conducted between July and September 2020. The burden and impact of migraine were assessed using the Migraine Disability Assessment (MIDAS), Migraine-Specific Quality-of-Life Questionnaire (MSQ), Migraine Interictal Burden Scale (MIBS-4), and Work Productivity and Activity Impairment-Migraine scale. Results were stratified by average number of monthly headache days (0-3, 4-7, 8-14, ≥ 15). RESULTS: In total, 17,071 Japanese people with migraine completed the survey. Of these, 14,033 (82.2%) met International Classification of Headache Disorders, 3rd edition criteria for migraine and 9667 (56.6%) reported a physician diagnosis of migraine. Overall, 20.7% of respondents experienced moderate-to-severe disability (MIDAS). Moderate-to-severe interictal burden (MIBS-4) was experienced by 41.5% of respondents. MSQ scores in all domains were lowest in respondents with the most frequent headaches (≥ 15 monthly headache days) and highest in those with the lowest frequency headaches (≤ 3 monthly headache days), indicating poorer quality of life in those with more frequent headaches. Work time missed due to migraine (absenteeism) increased with increasing headache frequency, from 3.8 to 6.2%; presenteeism affected 29.8-49.9% of work time. Although migraine burden was greatest in people with the most frequent headaches, those with the lowest headache frequency still experienced substantial disability, interictal burden, and impacts on productivity and quality of life. There was also substantial unmet need for migraine care: 36.5% of respondents had ever hesitated to seek medical care for their headaches, and 89.8% had never used preventive medication. CONCLUSION: In Japan, the burden of migraine and barriers to migraine care are substantial. Improving patient awareness and healthcare provider vigilance may help improve patient outcomes.

Comprehensive population-based survey of migraine in Japan: results of the ObserVational Survey of the Epidemiology, tReatment, and Care Of MigrainE (OVERCOME [Japan]) study.

OBJECTIVE: The ObserVational survey of the Epidemiology, tReatment, and Care Of MigrainE study in Japan (OVERCOME [Japan]) aimed to provide an up-to-date assessment of migraine epidemiology in Japan. METHODS: OVERCOME (Japan) was a cross-sectional, population-based web survey of Japanese adults recruited from consumer panels. People with active migraine (met modified International Classification of Headache Disorders, 3rd edition [ICHD-3] criteria or had a self-reported physician diagnosis of migraine) answered questions about headache features, physician consultation patterns, and migraine medication use. The burden and impact of migraine were assessed using Migraine Disability Assessment (MIDAS) and Work Productivity and Activity Impairment scales. RESULTS: In total, 231,747 respondents accessed the screener, provided consent, and were eligible for the survey. The migraine group included 17,071 respondents (mean ± SD age 40.7 ± 13.0 years; 66.5% female). ICHD-3 migraine criteria were met by 14,033 (82.2%) respondents; 9667 (56.6%) self-reported a physician diagnosis of migraine. The mean number of monthly headache days was 4.5 ± 5.7 and pain severity (0-10 scale) was 5.1 ± 2.2. In the migraine group, 20.7% experienced moderate to severe migraine-related disability (MIDAS score ≥ 11). Work productivity loss was 36.2% of work time missed, including 34.3% presenteeism. Only 57.4% of respondents had ever sought medical care for migraine/severe headache. Most respondents (75.2%) were currently using over-the-counter medications for migraine; 36.7% were using prescription nonsteroidal anti-inflammatory drugs, and only 14.8% were using triptans. Very few (9.2%) used preventive medications. CONCLUSIONS: Unmet needs for migraine health care among people with migraine in Japan include low rates of seeking care and suboptimal treatment.

Costs and resource use of community-dwelling patients with Alzheimer's disease in Japan: 18-month results from the GERAS-J study.

OBJECTIVE: To determine the longitudinal societal costs and burden of community-dwelling patients with Alzheimer's disease (AD) and their caregivers in Japan. METHODS: GERAS-J was an 18-month, prospective, longitudinal, observational study. Using the Mini-Mental State Examination (MMSE), patients routinely visiting memory clinics were stratified into groups based on AD severity at baseline (mild, moderate, and moderately severe/severe [MS/S]). Healthcare resource utilization and caregiver burden were assessed using the Resource Utilization in Dementia and Zarit "Caregiver" Burden Interview questionnaires, respectively. Total monthly societal costs were estimated using Japan-specific unit costs of services and products (patient direct healthcare use, patient social care use, and informal caregiving time). RESULTS: Overall, 553 patients (156 mild; 209 moderate; 188 MS/S) were enrolled. MMSE scores declined (1.73, 1.38, and 0.95 points for the mild, moderate, and MS/S AD groups, respectively) and caregiver burden and resource utilization increased over 18 months in each of the AD severity groups. Cumulative total societal costs per patient over 18 months were 3.1, 3.8, and 5.3 million Japanese yen (29,006, 35,662, and 49,725 USD) for mild, moderate, and MS/S AD, respectively. Both patient social care costs and caregiver informal care costs increased with baseline disease severity, with >50% of total costs due to caregiver informal care in each disease severity subgroup. CONCLUSIONS: Total treatment costs increased with AD severity over 18 months due to increases in both patient social care costs and caregiver informal care costs. Our data suggest current social care services in Japan are insufficient to alleviate the negative impact of AD on caregiver burden.

Long-Term Pain Management and Health Care Resource Use Among an Employed Population in Japan with Knee Osteoarthritis Combined with Low Back Pain.

OBJECTIVE: Assess long-term comorbidity burden and pain management patterns among working-age patients with knee osteoarthritis (KOA) only without low back pain (LBP) (KOA-noLBP) and patients with KOA plus LBP (KOA+LBP) in Japan. METHODS: Retrospective claims data analyses were conducted on data from the Japan Medical Data Center (JMDC) database. Adult patients (≥40 years) with a diagnosis of knee osteoarthritis (KOA) (January 1, 2011-December 31, 2012) and 5 years of follow-up were evaluated. The first claim with a KOA diagnosis defined the index date. Longitudinal pain management patterns were assessed in both cohorts. RESULTS: Overall, 1,828 patients met study criteria (717 with KOA-noLBP; 1,111 with KOA+LBP). The mean age of patients with KOA-noLBP was 52.1 years, and that of patients with KOA+LBP was 53.1 years, with more females in the KOA+LBP cohort (49.4% vs. 55.0%). Regardless of cohort, >90% of patients received pharmacological intervention during the 5-year follow-up period. The most common regimen first received was either topical or oral nonsteroidal anti-inflammatory drugs. A higher mean number of pharmaceutical treatments were received by patients in the KOA+LBP cohort (3.6) than by patients in the KOA-noLBP cohort (2.7) during the follow-up period. Regardless of cohort, most of the direct medical cost was derived from medication. CONCLUSION: This study demonstrates that a greater proportion of the JMDC population of working individuals with KOA were comorbid with LBP and received pain-related treatment in the long-term perspective relative to patients with KOA without LBP. Appropriate pain management for both KOA and LBP would be key for effective resource utilization in an aging society facing socioeconomic burdens.

Unmet Needs in Japanese Patients Who Report Insufficient Efficacy with Triptans for Acute Treatment of Migraine: Retrospective Analysis of Real-World Data.

INTRODUCTION: Migraine attacks notably impact people's daily lives, health-related quality of life (HRQoL), and ability to work. Triptans are widely used as acute medication for a migraine attack but are ineffective, poorly tolerated, or contraindicated in some patients. HRQoL and work productivity are therefore likely to pose particular problems for patients whose migraine attacks do not respond sufficiently to triptan acute treatment. This real-world study aimed to determine whether migraine-related HRQoL, disability, and work productivity differed between triptan insufficient responders (TIRs) and sufficient responders (TSRs) receiving this acute treatment for migraine in Japan. METHODS: This was a retrospective analysis of 2017 Adelphi Migraine Disease Specific Programme cross-sectional survey data collected from physicians and their consulting patients with migraine in Japan. Patients had to be receiving a triptan as their sole acute prescribed medication for migraine. TIRs were defined as patients who achieved headache pain freedom within 2 h of taking triptan acute treatment in no more than three of five migraine attacks. Differences in outcomes between TIRs and TSRs were examined in adjusted analyses using a multivariable general linear model. RESULTS: Of 200 patients receiving a triptan as their sole prescribed acute treatment for migraine, 88 (44.0%) were classed as TIRs. Migraine-Specific Quality of Life Questionnaire scores were significantly lower-indicating poorer HRQoL-among TIRs than TSRs, as were mean EuroQol 5-dimension utility and visual analog scale scores (p < 0.05 for comparisons). TIRs also reported significantly (p ≤ 0.003) greater impairment than TSRs across all Work Productivity and Activity Impairment domains, with the exception of work time missed. Migraine disability was higher among TIRs than TSRs. CONCLUSION: Migraine attacks had a negative impact on the HRQoL, disability, and work productivity of people with migraine in Japan reporting insufficient efficacy with acute triptan treatment, highlighting the need for more effective acute treatment options.

Social burden of people with the migraine diagnosis in Japan: evidence from a population-based cross-sectional survey.

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.

Longitudinal Assessment of Pain Management Among the Employed Japanese Population with Knee Osteoarthritis.

PURPOSE: To assess comorbidity burden and pain-management patterns among working-aged patients with knee osteoarthritis only (KOA/O) and patients with knee osteoarthritis plus osteoarthritis at another site (KOA/+) in Japan. PATIENTS AND METHODS: Retrospective claims data analysis was conducted using the Japan Medical Data Center database. Working-aged adults (aged 40 to 71 years) with 5 years of follow-up and diagnosed with knee osteoarthritis (KOA) between January 1, 2011, and December 31, 2012, were evaluated. The first claim with a KOA diagnosis defined the index date. Patients were divided into two mutually exclusive cohorts: KOA/O and KOA/+. Longitudinal pain-management patterns during each year of follow-up were analyzed. RESULTS: A total of 2542 patients met study criteria: 1575 KOA/O and 967 KOA/+. Mean age and number of comorbidities were higher among the KOA/+ versus KOA/O cohort. Pharmaceutical treatment was received by 91.5% of patients in the KOA/+ compared with 85.1% of patients in the KOA/O cohort during the first year of follow-up. The most common pharmacological treatment received during the first year of follow-up was either topical or oral nonsteroidal anti-inflammatory drugs for both cohorts. During each year of follow-up, the KOA/+ cohort had greater proportion of patients with at least one health-care encounter (ie, hospital admissions, outpatient and pharmacy visits) and higher direct medical costs compared with the KOA/O cohort. CONCLUSION: This study demonstrates that a greater proportion of the working population with KOA/+ received pain-related treatment compared with patients with KOA/O. Further studies are necessary to evaluate appropriate pain management for both KOA only and KOA with other sites.

Factors associated with insufficient response to acute treatment of migraine in Japan: analysis of real-world data from the Adelphi Migraine Disease Specific Programme.

BACKGROUND: Real-world data on sufficient/insufficient response, and predictors of insufficient response, to acute treatments for migraine are limited in Japan. This study aimed to identify factors associated with insufficient response to acute treatment of migraine by exploring significant differences between people with migraine who sufficiently/insufficiently respond to prescribed acute treatment in Japan. METHODS: This was a retrospective analysis of 2014 Adelphi Migraine Disease Specific Programme cross-sectional survey data collected from physicians and their consulting adult patients with migraine in Japan. Insufficient responders to prescribed acute treatment were patients who achieved headache pain freedom within 2 h of acute treatment in no more than three of their last five migraine attacks. Factors associated with insufficient response to prescribed acute migraine treatment were identified using backward logistic regression. RESULTS: Overall, 227/538 (42.2%) patients were classified as insufficient responders to prescribed acute migraine treatment. Significantly more insufficient responders than sufficient responders had consulted a neurologist or a migraine/headache specialist, and had chronic migraine or medication-overuse or tension-type headaches (p < 0.05). More insufficient responders than sufficient responders reported taking acute treatment when/after the pain started (77.0 vs. 68.9%) than at first sign of migraine (p < 0.05). Compared with sufficient responders, insufficient responders reported a significantly higher mean ± standard deviation (SD) Migraine Disability Assessment total score (12.7 ± 23.3 vs. 5.8 ± 10.4, p < 0.001) and lower quality of life (EuroQol-5 Dimensions utility score 0.847 ± 0.19 vs. 0.883 ± 0.16, p = 0.024). Factors significantly associated with insufficient response to acute treatment included seeing a neurologist versus an internist (odds ratio [OR] 1.93; 95% confidence interval [CI] 1.29-2.88; p = 0.002), taking acute medication when/after pain started versus at first sign of migraine (OR 1.65; 95% CI 1.05-2.60; p = 0.030), a higher MIDAS total score (OR 1.04; 95% CI 1.02-1.06; p < 0.001), and presence of comorbid cardiovascular disease (OR 0.53; 95% CI 0.28-0.98; p = 0.044). CONCLUSIONS: Many people with migraine in Japan struggle to adequately treat migraine attacks with prescribed acute medication and exhibit high levels of unmet need for acute treatment. Optimized management strategies utilizing existing therapeutic options as well as additional effective therapeutic options for migraine are required to improve symptoms and quality of life.

Costs and Resource Use Associated with Community-Dwelling Patients with Alzheimer's Disease in Japan: Baseline Results from the Prospective Observational GERAS-J Study.

BACKGROUND: As the Japanese population ages, caring for people with Alzheimer's disease (AD) dementia is becoming a major socioeconomic issue. OBJECTIVE: To determine the contribution of patient and caregiver costs to total societal costs associated with AD dementia. METHODS: Baseline data was used from the longitudinal, observational GERAS-J study. Using the Mini-Mental State Examination (MMSE) score, patients routinely visiting memory clinics were stratified into three groups based on AD severity. Health care resource utilizationwas recorded using the Resource Utilization in Dementia questionnaire. Total monthly societal costs were estimated using Japan-specific unit costs of services and products (patient direct health care use, patient social care use, and informal caregiving time). Uncertainty around mean costs was estimated using bootstrapping methods. RESULTS: Overall, 553 community-dwelling patients withADdementia (28.3% mild[MMSE21-26], 37.8% moderate[MMSE 15-20], and 34.0% moderately severe/severe [MMSE < 14]) and their caregivers were enrolled. Patient characteristics were: mean age 80.3 years, 72.7% female, and 13.6% living alone. Caregiver characteristics were: mean age 62.1 years, 70.7% female, 78.8% living with patient, 49.0% child of patient, and 39.2% sole caregiver. Total monthly societal costs of AD dementia (Japanese yen) were: 158,454 (mild), 211,301 (moderate), and 294,224 (moderately severe/severe). Informal caregiving costs comprised over 50% of total costs. CONCLUSION: Baseline results of GERAS-J showed that total monthly societal costs associated with AD dementia increased with AD severity. Caregiver-related costs were the largest cost component. Interventions are needed to decrease informal costs and decrease caregiver burden.

Migraine-Specific Quality-of-Life Questionnaire (MSQ) Version 2.1 Score Improvement in Japanese Patients with Episodic Migraine by Galcanezumab Treatment: Japan Phase 2 Study.

PURPOSE: Evaluate changes from baseline in health-related quality of life (QoL) in Japanese patients with episodic migraine receiving preventive treatment with galcanezumab (GMB). PATIENTS AND METHODS: Preventive treatments for migraine have been shown to improve QoL, but few clinical trials have examined QoL outcomes in Japanese patients. This phase 2, randomized, double-blind, placebo-controlled study was conducted at 40 centers in Japan. Patients aged 18-65 years with episodic migraine (4-14 monthly migraine headache days) received GMB 120 mg (n=115), 240 mg (n=114), or placebo (PBO, n=230) as monthly subcutaneous injections for 6 months. QoL was measured monthly using the Migraine-Specific Quality-of-Life Questionnaire (MSQ) version 2.1. Prespecified analyses were differences between GMB and PBO for change from baseline in all 3 domains of the MSQ and MSQ-Total, for each month and the average over Months 4-6. RESULTS: Treatment with GMB significantly increased MSQ scores from baseline vs PBO. Average change ± SE from baseline across Months 4-6 was 10.12±0.72 (PBO), 17.13±1.03 (GMB 120 mg; P<0.001), and 15.91±1.03 (GMB 240 mg; P<0.001) for MSQ Role Function-Restrictive; 4.80±0.65 (PBO), 9.64±0.93 (GMB 120 mg; P<0.001), and 8.35±0.93 (GMB 240 mg; P<0.05) for MSQ Role Function-Preventive (MSQ-RFP); 3.46±0.77 (PBO), 10.04±1.10 (GMB 120 mg; P<0.001), and 7.73±1.10 (GMB 240 mg; P<0.05) for MSQ Emotional Function, and 7.14±0.67 (PBO), 13.46±0.95 (GMB 120 mg; P<0.001), and 11.98±0.95 (GMB 240 mg; P<0.001) for MSQ-Total. Significantly greater improvement in scores in all MSQ domains and MSQ-Total was observed for both GMB doses vs PBO at Month 1 and was maintained for Months 1-6 (excluding Month 5 for MSQ-RFP). CONCLUSION: Preventive treatment with GMB 120 mg/240 mg improves MSQ scores in Japanese patients with episodic migraine. Improvements were seen within the first month and maintained for 6 months and are similar to those seen in global studies enrolling primarily Caucasian patients. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02959177 (registered November 7, 2016).

Prevalence, burden, and clinical management of migraine in China, Japan, and South Korea: a comprehensive review of the literature.

BACKGROUND: The objective of this review was to determine the unmet needs for migraine in East Asian adults and children. METHODS: We searched MEDLINE and EMBASE (January 1, 1988 to January 14, 2019). Studies reporting the prevalence, humanistic and economic burden, and clinical management of migraine in China (including Hong Kong and Taiwan), Japan, and South Korea were included. Studies conducted before 1988 (before the International Headache Society [IHS] first edition of the International Classification of Headache Disorders) were not included. RESULTS: We retrieved 1337 publications and 41 met the inclusion criteria (28 from China, 7 from Japan, and 6 from South Korea). The 1-year prevalence of migraine (IHS criteria) among adults ranged from 6.0% to 14.3%. Peak prevalence ranged from 11% to 20% for women and 3% to 8% for men (30- to 49-year-olds). For children, prevalence of migraine increased with age. Information on the economic burden and clinical management of migraine was limited, particularly for children. When reported, migraine was significantly associated with high levels of disability and negative effects on quality of life. Studies suggested low levels of disease awareness/diagnosis within each country. Of individuals with migraine from China, 52.9% to 68.6% had consulted a physician previously, 37.2% to 52.7% diagnosed with headache had not been diagnosed with migraine previously, and 13.5% to 18% had been diagnosed with migraine previously. Of individuals with migraine from Japan, 59.4% to 71.8% had never consulted a physician previously, 1.3% to 7.3% regularly consulted physicians for their headache, and only 11.6% of individuals with migraine were aware that they had migraine. In addition, studies suggested that over-the-counter medication use was high and prescription medication use was low in each country. CONCLUSIONS: This review suggests that there are unmet needs for migraine in terms of sufficient and appropriate diagnosis, and better management and therapies for treatment of migraine in East Asia. The findings are limited by a lack of recent information and significant gaps in the literature. More recent, population-based studies assessing disease burden and clinical management of migraine are needed to confirm unmet needs for migraine across East Asia.

Real-world treatment patterns and patient-reported outcomes in episodic and chronic migraine in Japan: analysis of data from the Adelphi migraine disease specific programme.

BACKGROUND: In Japan, detailed information on the characteristics, disease burden, and treatment patterns of people living with migraine is limited. The aim of this study was to compare clinical characteristics, disease burden, and treatment patterns in people with episodic migraine (EM) or chronic migraine (CM) using real-world data from clinical practice in Japan. METHODS: This was an analysis of data collected in 2014 by the Adelphi Migraine Disease Specific Programme, a cross-sectional survey of physicians and their consulting adult patients in Japan, using physician and patient questionnaires. We report patient demographics, prescribed treatment, work productivity, and quality-of-life data for people with CM (≥15 headache days/month) or EM (not fulfilling CM criteria). In descriptive analyses, continuous and categorical measures were assessed using t-tests and Chi-squared tests, respectively. RESULTS: Physicians provided data for 977 patients (mean age 44.5 years; 77.2% female; 94.5% with EM, 5.5% with CM). A total of 634/977 (64.9%) invited patients (600 with EM; 34 with CM) also provided data. Acute therapy was currently being prescribed in 93.7% and 100% of patients with EM and CM, respectively (p = 0.069); corresponding percentages for current preventive therapy prescriptions were 40.5% and 68.5% (p < 0.001). According to physicians who provided data, preventive therapy was used at least once by significantly fewer patients with EM than with CM (42.3% vs. 68.5%, respectively; p < 0.001). Among patients who provided physicians with information on issues with their current therapy (acute therapy: n = 668 with EM, n = 38 with CM; preventive therapy: n = 295 with EM, n = 21 with CM), lack of efficacy was the most frequently identified problem (acute therapy: EM 35.3%, CM 39.5% [p = 0.833]; preventive therapy: EM 35.3%, CM 52.4% [p = 0.131]). Moderate-to-severe headache-related disability (Migraine Disability Assessment total score ≥ 11) was reported by significantly fewer patients with EM than with CM (21.0% vs. 60.0%, respectively; p < 0.001) among patients who provided data. CONCLUSIONS: Preventive treatment patterns in people with EM versus CM differ in Japan, with both types of migraine posing notable disease burdens. Our findings demonstrate that more effective migraine therapies are required to reduce the burden of the disease.

Treatment satisfaction with pharmaceutical interventions in Japanese adults with osteoarthritis and chronic knee pain: an analysis of a web-based survey.

PURPOSE: Patient satisfaction is an important outcome in successful osteoarthritis (OA) treatment. The aim of this study was to evaluate treatment satisfaction for medication (TSM) in people with knee OA (KOA), identify the factors predictive of treatment satisfaction, and describe the burden of illness. PATIENTS AND METHODS: This cross-sectional, patient-reported study used an Internet-based survey and analyzed responses of respondents with KOA (N=400) on characteristics including pain sites and levels (including pain ratings using the Numerical Rating Scale and Short-Form McGill Pain Questionnaire), treatment satisfaction (Global, Effectiveness, and Convenience scores) based on the Treatment Satisfaction Questionnaire for Medication (TSQM-9), and quality of life (QoL; based on the Arthritis Impact Measurement Scale 2-Short Form). Respondents with only KOA (n=237) were compared with those having KOA and additional painful sites (KOA+; n=163). Factors predicting TSM were identified using multivariable linear regression analyses. RESULTS: Respondents with KOA were more likely to report intermittent pain for 3 months or more compared with those with KOA+ (58.6% vs 48.5%, respectively; P=0.044), while those with KOA+ were more likely to report consistent pain for 3 months or more (P=0.022). Respondents with KOA+ also had more difficulty due to their knee pain while sleeping (P=0.022) and resting (P=0.015). Reported TSM did not differ significantly across KOA vs KOA+ groups, with both groups reporting low satisfaction; all domains of QoL were worse for those with KOA+. Knee pain reduction by medication predicted higher satisfaction across domains, while lower pre-medication pain and post-medication pain matching expectations predicted higher TSQM-9 Global and Effectiveness scores. CONCLUSION: Medication treatment satisfaction rates were low among Japanese respondents with KOA. Given that lower pain, greater pain reduction post-medication, and meeting pain management expectations were predictive of higher satisfaction, treatment strategies that can better address pain may prove beneficial for overall patient satisfaction.

Detection, diagnosis, and treatment of Alzheimer's disease dementia stratified by severity as reported by caregivers in Japan.

BACKGROUND: Dementia of Alzheimer's disease (AD) imposes burdens on patients, caregivers, and society. This cross-sectional study examined caregiver-reported history of disease onset and AD dementia to inform efforts promoting early disease detection and diagnosis. METHODS: An online survey collected self-reported cross-sectional data - demographic characteristics, diagnosis, treatment experiences, and other information on disease detection, diagnosis, and treatment - from caregivers of patients with AD dementia. These characteristics were examined as a function of AD dementia severity. RESULTS: Three hundred patients with AD dementia were trichotomized by long-term care insurance levels reported by caregivers: 12.3% (n=37) as low severity, 63.7% (n=191) as medium severity, and 24.0% (n=72) as high severity. The Short-Memory Questionnaire and patient dependency scores both varied significantly across severity groups. AD dementia symptoms were most frequently first detected by a caregiver (58.7%) or the patient's family (45.7%). However, in 13.7% of cases, symptoms were detected by a health care provider during a routine visit. Memory problems were the most frequent first symptoms (77.3%), followed by repetition (55.7%). Patients (73.7%) were taking symptomatic treatment such as acetylcholinesterase inhibitors or memantine. High-severity patients were older, had been diagnosed with AD dementia for a longer time, had more frequent reports of memory problems as the first symptoms detected, and required more hours of care per day, compared with low-severity patients. CONCLUSION: Caregivers and families play an integral role in the identification of AD dementia patients, with memory problems being common first symptoms noticed by caregivers that led to a diagnosis of AD dementia. These results provide novel insight into the detection, diagnosis, and treatment of AD dementia in Japan and how these factors differ across the spectrum of disease severity.

Alzheimer's disease severity and its association with patient and caregiver quality of life in Japan: results of a community-based survey.

BACKGROUND: Alzheimer's disease (AD) dementia, a progressive neurodegenerative disease, exerts significant burden upon patients, caregivers, and healthcare systems globally. The current study investigated the associations between AD dementia patient disease severity and health-related quality of life (HRQoL) of both patients (proxy report) and their caregivers living in Japan, as well as caregiving-related comorbidities such as depression. METHODS: This cross-sectional study used self-reported data from caregivers of people diagnosed with AD dementia by a healthcare provider in Japan. Caregivers were identified via online panels and invited to participate in an online survey between 2014 and 2015. Caregivers completed survey items for themselves, in addition to providing proxy measures for patients with AD dementia for whom they were caring. Patient and caregiver HRQoL was measured using the EuroQoL 5-Dimension (EQ-5D). Additional outcomes for caregivers of AD dementia patients included the Patient Health Questionnaire (PHQ-9) of depressive symptomology, as well as comorbidities experienced since initiating caregiving for their AD dementia patients. These outcomes were examined as a function of AD dementia severity, as measured by long-term care insurance (LTCI) categories. Bivariate analyses between LTCI and outcomes were conducted using independent t-tests and chi-square tests. Multivariable analyses, controlling for potential confounders, were conducted using generalized linear models (GLMs) specifying a normal distribution. RESULTS: Across 300 caregiver respondents, multivariable results revealed that increasing AD dementia severity was significantly associated with poorer patient and caregiver EQ-5D scores and a high proportion of caregivers (30.0%) reported PHQ-9 scores indicative of major depressive disorder (MDD). The most frequent comorbidities experienced after becoming caregivers of AD dementia patients included hypertension (12.7%) and insomnia (11.0%). Depression and other comorbidities did not differ significantly by patient severity. CONCLUSIONS: The current study provides unique insight into the specific degree of incremental burden associated with increasing AD dementia severity among patients and caregivers alike. Importantly, greater disease severity was associated with poorer quality of life among both patients and caregivers. These results suggest that earlier detection and treatment of AD dementia may provide an opportunity to reduce the burden of disease for patients, caregivers, and society at large.

Epidemiology, associated burden, and current clinical practice for the diagnosis and management of Alzheimer's disease in Japan.

The burden of dementia in Japan is large and growing. With the world's fastest aging population, it is estimated that one in five elderly people will be living with dementia in Japan by 2025. The most common form of dementia is Alzheimer's disease (AD), accounting for around two-thirds of dementia cases. A systematic review was conducted to examine the epidemiology and associated burden of AD in Japan and to identify how AD is diagnosed and managed in Japan. English and Japanese language databases were searched for articles published between January 2000 and November 2015. Relevant Japanese sources, clinical practice guideline registers, and reference lists were also searched. Systematic reviews and cohort and case-control studies were eligible for inclusion, with a total of 60 studies included. The most recent national survey conducted in six regions of Japan reported the mean prevalence of dementia in people aged ≥65 years to be 15.75% (95% CI: 12.4, 22.2%), which is much higher than the previous estimated rate of 10% in 2010. AD was confirmed as the predominant type of dementia, accounting for 65.8% of all cases. Advancing age and low education were the most consistently reported risk factors for AD dementia. Japanese guidelines for the management of dementia were released in 2010 providing specific guidance for AD about clinical signs, image findings, biochemical markers, and treatment approaches. Pharmacotherapies and non-pharmacotherapies to relieve cognitive symptoms were introduced, as were recommendations to achieve better patient care. No studies reporting treatment patterns were identified. Due to population aging and growing awareness of AD in Japan, health care expenditure and associated burden are expected to soar. This review highlights the importance of early detection, diagnosis, and treatment of AD as strategies to minimize the impact of AD on society in Japan.

[Clinical Implications and Appropriate Use of Amyloid Imaging with florbetapir (18F) in Diagnosis of Patients with Alzheimer Disease].

florbetapir (18F) is a radiolabeled compound that can be used to visualize amyloid-beta (Aß) plaques in the brains of patients with cognitive dysfunction, who are suspected of having Alzheimer disease (AD). Knowing the status of Aß accumulation in the brain is beneficial to selecting therapeutic strategies or to planning of laboratory examinations, hence amyloid PET imaging is expected to be utilized more often in a clinical setting. Based on the results of a clinical study of florbetapir (18F), this review discusses the usefulness and clinical significance of amyloid PET imaging, and its appropriate use in Japan. (Received Octover 7, 2015; Accepted February 15, 2016; Published October 1, 2016).