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.

Background: Limited studies have measured the burden of migraine in Japan. This study aimed at estimating the disease burden of migraine in Japan and identifying factors associated with the burden using the 2017 National Health and Wellness Survey. Methods: Migraine patients were defined by ICHD-3 like criteria with ≥4 monthly headache days (MHDs), and non-migraine respondents were selected using 1:4 propensity score matching. Multivariate analyses were conducted to compare Health-related Quality of Life (HRQoL), work productivity and activity impairment (WPAI), healthcare resource utilization (HRU) and costs between the two groups, and to identify factors associated with these outcomes in migraine patients. Results: In 30,001 respondents, 378 migraine patients were identified. Compared to matched controls (N = 1512), migraine patients had lower physical (45.17 vs. 49.89), mental (42.28 vs. 47.71) and role/social (37.91 vs. 44.19) component summary scores (p < 0.001). Migraine patients had higher absenteeism (6.4% vs. 2.2%), presenteeism (40.2% vs. 22.5%), total work productivity impairment (44.3% vs. 24.5%), total activity impairment (45.0% vs. 23.9%), indirect costs (1,492,520 JPY vs. 808,320 JPY) and more visits to healthcare providers in the past 6 months (7.23 vs. 3.96) (p < 0.001). More MHDs was associated with worse HRQoL, and higher HRU and indirect costs. Conclusions: Japanese migraine patients experience an incremental burden. This demonstrates the unmet needs among Japanese migraine patients.

Objectives This study aims to examine the association between migraine and various psychiatric and somatic comorbidities in Japan. Design Cross-sectional study using existing data of the 2017 Japan National Health and Wellness Survey (NHWS). Setting Nationally representative sample of persons (in terms of age and gender) living in the general community aged 18 years or older in Japan. Participants Out of a sample of 30 001 NHWS respondents, 378 respondents were identified as migraine patients and 25 209 were identified as non-migraine patients. After propensity score (PS) matching (1:4), 1512 matched non-migraine respondents were identified. Primary and secondary outcome measures Prevalence and PS-matched prevalence ORs (PORs) were assessed for each psychiatric and somatic comorbidity among migraine patients and matched non-migraine respondents (including migraine patients with less than 15 monthly headache days (MHDs) and migraine patients with more than 15 MHDs). Results Migraine patients were predominately female and had significantly higher prevalence than matched non-migraine respondents to have psychiatric and somatic comorbidities. Psychiatric comorbidities with >5% prevalence among migraine patients included depression, post-traumatic stress disorder and anxiety disorders, while gastrointestinal disorders were the most prevalent somatic comorbidity category. Other somatic comorbidities included allergies, insomnia, premenstrual syndrome and anaemia. Migraine patients with more than 15 MHDs tended to have higher point estimates for POR. Conclusion Psychiatric and somatic conditions were more prevalent in migraine patients than matched non-migraine respondents, some being novel associations not previously reported in Japan. This study provided insights on comorbidities, which could complicate care, clinical practice and outcomes among migraine patients.

Background: Sodium valproate is a standard drug for first‐line prophylactic treatment of migraine. However, little information is available of its use in Japanese patients.Aim: To evaluate the effectiveness and safety of an extended‐release tablet of sodium valproate in the prophylactic treatment for Japanese patients with migraine by postmarketing surveillance.Methods: This was a prospective, multicenter and non‐interventional observation study in routine clinical practice. A total of 1222 patients with migraine of all age groups (aged <10 to ≤80 years) and both sexes (17.3% men and 82.7% women) from 169 sites were enrolled.Results: Migraine frequency during a 4‐week period was reduced from 10.2 ± 6.0 days in 1040 patients to 5.0 ± 4.6 days in 944 patients (P < 0.001): 70.8% of patients experienced remission of migraine by ≥30%, 59.0% by ≥50% and 11.8% by ≥100%. Multivariate analysis and stratification sampling showed that this sodium valproate tablet was the most effective in patients with more migraine days, and complete remission was observed in 29% of patients whose migraine days were less than 3 days per 4 weeks at baseline. The extended‐release tablet of sodium valproate reduced migraine intensity and duration of migraine attacks. The incidence of adverse drug reactions was 6.3% (67/1070 patients) and well tolerated. However, four pregnancies were discovered in this survey.Conclusions: This first large observation study in Japan suggests that an extended‐release tablet of sodium valproate is effective and safe for the prophylactic treatment of patients with migraine in routine clinical practice.