Nine in Ten Eligible Migraine Patients in Japan Have Never Tried CGRP Preventive Antibodies

Approximately 90 percent of people with migraine in Japan who met the eligibility criteria for calcitonin gene-related peptide monoclonal antibodies (CGRP mAbs) had never received this preventive therapy, according to a nationwide, population-based analysis of the OVERCOME (Japan) 2nd study. The findings, drawn from a cross-sectional online survey of 19,590 adults with migraine, reveal a substantial treatment gap at the population level, where most prior evidence on these drugs had come from clinics and insurance claims databases that capture only people already engaged with the healthcare system.

Of the 19,590 respondents with migraine, 1,484 (7.6 percent) met these eligibility criteria at the time of the survey. Within this eligible group, only 78 respondents were current CGRP mAb users and 58 had discontinued the therapy, leaving 1,348 people — 90.8 percent — who had never used the drugs. Among the 18,106 respondents classified as ineligible based on their symptoms at survey time, 110 were current users and 176 had discontinued, a pattern the authors attribute to symptom improvement during treatment: because eligibility was judged on current symptoms, patients whose migraines improved on CGRP mAbs could fall below the thresholds. Accounting for this, the researchers estimate the true untreated proportion among potentially eligible individuals likely lies between 76.2 and 90.8 percent.

Treatment patterns differed sharply between users and nonusers. CGRP mAb-experienced respondents in both eligibility groups were far more likely to have visited departments authorized to prescribe the drugs, at rates of 63.6 to 88.5 percent, compared with 19.5 to 56.9 percent among those without experience. Among eligible current users, 40.5 percent had consulted headache specialists, and triptan use was high, with 84.6 percent having ever used these acute medications and 73.1 percent using them currently. Average monthly headache days over the past 90 days ranged from 10.4 to 10.9 among eligible respondents, and 22.4 to 28.2 percent of eligible participants had chronic migraine.

Awareness emerged as a striking barrier. Among eligible respondents who had never used CGRP mAbs, 78.0 percent reported never having heard of the drug class, 11.6 percent recognized the name, and only 10.4 percent knew what kind of medication it was. Even more telling, only 4.2 percent of eligible nonusers had ever been introduced to CGRP mAbs by a physician. Among the small subgroup of 56 eligible nonusers whose doctors had mentioned the therapy, cost concerns dominated the reasons for declining: 37.5 percent cited worry about the cost, and 30.4 percent said they were unsure whether the treatment would be worth the expense, followed by concerns about side effects and uncertainty about whether the effect would surpass their current treatment.

Patient perceptions of headache also diverged by treatment status. Between 60.3 and 67.9 percent of eligible respondents viewed headache as a disease that can only be endured until symptoms subside, and eligible nonusers were less likely to discuss treatment goals with their physicians — 33.2 percent reported never doing so, compared with 14.9 percent of eligible current users. Current users, by contrast, more frequently perceived their symptoms as improvable with medication or lifestyle changes, and 61.5 percent expressed a desire to consult a doctor and change how they manage treatment.

In multivariate logistic regression among eligible respondents, CGRP mAb treatment experience was most strongly associated with prior triptan use (odds ratio 9.38, 95 percent confidence interval 5.94 to 14.80) and consultation at a CGRP mAb-prescribable department (odds ratio 7.20, 95 percent confidence interval 3.60 to 14.37). History of medication-overuse headache, diabetes, and hypertension were also significantly associated with treatment experience. In a sensitivity analysis restricted to respondents who had visited a medical institution in the past year, visiting a prescribable department and discussing treatment goals with a physician remained significant. The authors note that the cross-sectional design cannot establish causation, and that cardiovascular comorbidities may reflect both triptan contraindications steering patients toward CGRP mAbs and greater healthcare engagement overall.

The study also documented real-world patterns of stopping and restarting therapy. Among 234 respondents who discontinued CGRP mAbs, the most common reasons overall were that a doctor advised stopping (14.5 percent), that the injection did not work or no longer worked (13.2 percent), and information from the internet (12.0 percent). Among 256 respondents who suspended and resumed treatment, the leading reasons for resumption were headaches returning (16.8 percent) and increased attack frequency (15.6 percent), with physician recommendation also playing a role — underscoring the clinician’s central role throughout the treatment course.

The authors place their findings in international context, noting that an analysis of the OVERCOME (US) study reported 95.0 percent of people with migraine had never used CGRP mAbs, though direct comparison is limited by differing eligibility frameworks, drug pricing, reimbursement policies, and survey methodology. Female respondents showed lower odds of CGRP mAb treatment experience despite migraine’s higher prevalence among women in Japan, a pattern the authors flag as a potential sex-based disparity in access that warrants further research.

The survey carries important limitations. All data were self-reported, medical diagnoses were not confirmed against records, and the online format may have excluded older adults and those with limited digital access, likely making the treatment-gap estimate conservative. Prior oral preventive failure was operationalized as prior use of physician-prescribed oral preventives rather than strict guideline-defined failure, potentially misclassifying eligibility in both directions. The survey also predates the October 2025 position statement from the Japanese Headache Society recommending CGRP-targeting therapies, including monoclonal antibodies and gepants, as first-line migraine prevention — a guideline change the authors suggest may improve access, though its real-world effect remains to be evaluated.

Subject of Research: Population-level utilization and treatment gaps of CGRP monoclonal antibodies among people with migraine in Japan

Article Title: Calcitonin Gene-Related Peptide Monoclonal Antibody Utilization and Treatment Gaps in People with Migraine in Japan: Results from the OVERCOME (Japan) 2nd Study

Article References: Hanaoka, Y., Takizawa, T., Ishii, R., Danno, D., Hamakawa, M., Ueda, K., Tanizawa, Y., Osaga, S., Tharappel, L. J. P., & Hashimoto, C. (2026). Calcitonin Gene-Related Peptide Monoclonal Antibody Utilization and Treatment Gaps in People with Migraine in Japan: Results from the OVERCOME (Japan) 2nd Study. Drugs – Real World Outcomes, 13(3), 431-450. https://doi.org/10.1007/s40801-026-00571-9

Image Credits: AI Generated

DOI: 10.1007/s40801-026-00571-9

Keywords: migraine, CGRP monoclonal antibodies, Japan, OVERCOME study, treatment gap, preventive treatment, headache specialists, cross-sectional survey, patient awareness, physician-patient communication, triptans, healthcare access