Treatment options for progressive MS (PMS) are limited in numbers and efficacy, which is most pronounced in patients with inflammatory disease activity. Immunoglobulin M (IgM) oligoclonal bands (OCBs) may identify a subset of PMS with more active inflammatory disease. The effects of natalizumab and methylprednisolone on intrathecal inflammation and the association of IgM OCBs with other biomarkers in PMS is uncertain. In the current study, we investigated the cerebrospinal fluid (CSF) proteome of untreated patients with PMS, effects of natalizumab and methylprednisolone, and associations of IgM OCBs with disease activity and CSF biomarkers. We found a reduction of BCMA, SLAMF7, granzyme A, IgG, and desmoglein-2 with both therapies, as well as natalizumab-specific reductions of VCAM-1, CD48, MDC, MMP-9, sE-selectin, and CHIT1, and methylprednisolone-specific reductions of DR3, IgD, RTN4, and increases of sCD206, LYVE1, sCD163 and MMP-3. IgM OCBs were associated with reduced levels of PIGR, higher levels of NFL and VEGF, and more contrast-enhancing lesions. The study suggests T and B cell activity biomarkers as treatment-responsive CSF biomarkers in PMS. Additionally, we found natalizumab to reduce adhesion molecules and methylprednisolone to increase myeloid biomarkers. Lastly, we confirm that IgM OCBs are associated with a more inflammatory MRI and CSF profile.

People with migraine may prefer over-the-counter (OTC) drugs because of multiple reasons, but their overuse can cause medication overuse headaches. This analysis of the ObserVational survey of the Epidemiology, tReatment, and Care Of MigrainE (OVERCOME [Japan]) 2nd study describes the real-world use of OTC headache drugs and the challenges that potentially prevent people with migraine from accessing appropriate medical management in Japan. This analysis of the cross-sectional, population-based, nationwide online survey included adults with migraine. Respondents reported their experiences with prescription and OTC drugs for migraine, migraine-specific drug awareness, and attitude towards migraine. Subgroup analyses were performed based on the number of monthly headache days (MHD) and the frequency of OTC drug use/month. The 19,590 respondents with migraine (68.8

Migraine adversely affects many aspects of daily life. In addition to burdens during headaches (ictal period), burdens between headaches (interictal period) are increasingly recognized. In this analysis of the ObserVational survey of the Epidemiology, tReatment, and Care Of MigrainE in Japan (OVERCOME [Japan]) 2nd study, we evaluated the contribution of interictal burden to daily activities, quality of life, work, family, costs, and medical treatment. The OVERCOME (Japan) 2nd study was a cross-sectional, web-based survey of 19,590 adults in Japan with migraine conducted between June and August 2023. Questionnaires included Headache Impact Test-6 (HIT-6), Migraine Interictal Burden Scale-4 (MIBS-4), Migraine Disability Assessment (MIDAS), Allodynia Symptom Checklist-12 (ASC-12), Migraine-Specific Quality-of-Life Questionnaire (MSQ), Impact of Migraine on Partners and Adolescent Children Scale (IMPAC), Work Productivity and Activity Impairment Questionnaire-Migraine (WPAI-M), and Migraine Treatment Optimization Questionnaire-6 (mTOQ-6). Additional questions asked about costs, frequency of migraine concerns between headaches, and experience with medical treatment. Analyses were conducted on subgroups based on HIT-6 and MIBS-4 scores: Severe (HIT-6 ≥ 60, MIBS-4 ≥ 3; n = 6854), High Interictal Burden (HIT-6 < 60, MIBS-4 ≥ 3; n = 2368), High Ictal Burden (HIT-6 ≥ 60, MIBS-4 < 3; n = 4253), and Milder (HIT-6 < 60, MIBS-4 < 3; n = 6115). Number of monthly headache days, total MIDAS score, and pain severity score were higher, and MSQ scores lower, in subgroups with higher HIT-6 (HIT-High) versus subgroups with lower HIT-6 (HIT-Low). Within both HIT-High and HIT-Low subgroups, those with higher MIBS-4 had higher MIDAS and lower MSQ. IMPAC grade, ASC-12 score, and WPAI-M absenteeism were higher in the High Interictal Burden subgroup versus the High Ictal Burden subgroup. Concerns between headaches were more frequent, and costs higher, in subgroups with higher MIBS-4 (MIBS-High) versus subgroups with lower MIBS-4 (MIBS-Low). Acute treatment prescription analgesics were more commonly used in HIT-High versus HIT-Low subgroups, but triptans, lasmiditan, and preventive drugs were more common in the High Interictal Burden subgroup versus the High Ictal Burden subgroup. These results revealed that high interictal burden negatively affects multiple aspects of daily life in Japanese people with migraine independently of the impact of headaches.

INTRODUCTION:Despite the availability of effective treatments, some patients with migraine in Japan do not receive appropriate medical management and treatment for migraine, potentially due to the lack of effective patient-doctor communication. This analysis of the ObserVational survey of the Epidemiology, tReatment, and Care Of MigrainE (OVERCOME [Japan)] 2nd study described the current state and challenges of patient-doctor communication in migraine treatment in Japan. METHODS:This analysis included adults with migraine who consulted doctors for headaches/migraine and reported details of their first consultation: their experiences with doctors regarding migraine diagnosis and treatments, migraine-related topics, and treatment goals discussed, and challenges in communication. RESULTS:Among the 6762 included respondents, 55.1% (3729/6762) consulted a general practitioner (GP) first for headaches. Of the 3192 respondents diagnosed with migraine and reported the diagnosing doctor's specialty (as GP, specialist, or non-headache specialist), specialists (64.0%; 2044/3192), followed by GPs (31.4%; 1001/3192), mostly commonly diagnosed migraine. In the first consultation, doctors told 48.0% (3249/6762) of respondents they had migraine. In the past year, 3854 respondents discussed migraine-related topics with doctors; most commonly, the use and effectiveness of prescription drugs, and headache symptoms, severity, and frequency [48.9% (1885/3854) to 67.8% (2612/3854)]. Specialists most commonly discussed migraine-related topics with respondents, but non-headache specialists, i.e., obstetricians and gynecologists, most commonly discussed menstrual-related migraine. A total of 1978 respondents had migraine-related topics they wanted to but could not discuss with doctors in the past year. Among them, 32.9% (651/1978) of respondents did not discuss the topics because the doctor did not ask. Although 96.6% (3724/3854) of respondents had treatment goals in mind, 36.0% (1388/3854) never discussed it with doctors. CONCLUSION:Open and considerate patient-doctor communication and appropriate medical judgment are needed for timely and adequate medical management of migraine. Training doctors in effective communication techniques and considering a migraine diagnosis during consultations may be associated with better patient outcomes.

Background The objective of this analysis was to gain new insights into the patient characteristics and other factors associated with lasmiditan usage and clinical outcomes under conditions resembling the real-world setting. Methods This was a post hoc analysis of data from the 12-month, open-label extension (OLE) of the phase 3, double-blind, randomized, controlled CENTURION trial, which examined the efficacy and safety of lasmiditan as acute treatment across four migraine attacks. Patients completing the main study who treated ≥ 3 attacks could continue in the OLE. The initial lasmiditan dose was 100 mg, with dose adjustments to 50 mg or 200 mg allowed at the investigator’s discretion. Patient and clinical characteristics were summarized by dosing pattern and completion status. Safety was assessed based on adverse event (AE) frequency by number of doses. Results In total, 445 patients treated ≥ 1 migraine attacks with lasmiditan during the OLE, 321 of whom (72.1%) completed the study. Forty-seven percent of patients remained on the 100-mg initial dose during the OLE whereas 20.2% used both 100 mg and 50 mg, 30.6% used both 100 mg and 200 mg, and 6 (1.3%) used multiple dose levels. All dosing patterns were associated with clinical and patient-reported improvement; however, the 100-mg group had the highest proportion of patients reporting improvement in the Patient Global Impression of Change – Migraine Headache Condition (56.5% vs 33.4%–52.2%). In comparison, all three groups that made dose adjustments had higher rates of completion compared to the 100-mg group (72.1%–83.3% vs 68.9%). The frequency of AEs decreased with continued use of lasmiditan. Concomitant triptans and lasmiditan use did not increase AE frequency. Conclusions Based on high persistence and patient satisfaction rates, the 100-mg dose appears optimal for most patients. For those who adjusted dose levels, dose adjustments appeared beneficial to improve efficacy or tolerability, retaining patients on treatment. Collectively, the data suggest that patients who experienced efficacy continued to use lasmiditan regardless of the occurrence or frequency of AEs, and continued use appeared associated with fewer AEs. Trial registration European Union Drug Regulating Authorities Clinical Trials Database (EudraCT): 2018–001661-17; ClinicalTrials.gov: NCT03670810; registration date: September 12, 2018. Graphical Abstract

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.

The impact of migraine on patients’ lives, including challenges they face before getting access to appropriate medical management, is not well understood. The ObserVational survey of the Epidemiology, tReatment, and Care Of MigrainE [OVERCOME (Japan)] 2nd study was conducted to provide information regarding burden and experience with migraine throughout the life course. This cross-sectional, population-based, nationwide online survey was conducted in adults with or without migraine. The migraine group reported their headache features and experiences in medical management since headache onset. Migraine’s burden and impact were assessed with various PRO instruments. Migraine and non-migraine groups reported their experiences in life events and answered questions on self-esteem. Subgroup analyses by the number of monthly headache days (MHD) were performed. The migraine group (n = 19,590) was numerically younger [mean (SD) age 40.5 (13.1) years vs. 53.1 (17.8) years] and included more females (68.8

Introduction The impacts of migraine on daily life, including daily activities and fundamental health indicators (sleep and mental health), have not been described in detail for people with migraine in Japan. Methods The cross-sectional ObserVational survey of the Epidemiology, tReatment, and Care Of MigrainE (OVERCOME [Japan]) study was conducted between July and September 2020. Impacts of migraine on housework, family/social/leisure activities, driving, and sleep were assessed using questions from the Migraine Disability Assessment (MIDAS), Migraine-Specific Quality-of-Life Questionnaire, and Impact of Migraine on Partners and Adolescent Children scales and questions developed for OVERCOME (Japan). The Migraine Interictal Burden Scale (MIBS-4) evaluated burden on days without headaches. Depression and anxiety were assessed with the Patient Health Questionnaire (PHQ-8) and Generalized Anxiety Disorder (GAD-7) scales, respectively. Impacts on daily life were also described across MIDAS/MIBS-4 categories. Results Among 17,071 respondents with migraine, 24.8% required assistance with housework at least sometimes. Migraine interfered with relationships, leisure, and social activities at least sometimes for 31.8%, 41.6%, and 18.0% of respondents, respectively. Between headache days, 26.8% of respondents worried about planning social/leisure activities at least sometimes. Among respondents living with family ( N = 13,548), migraine also had impacts on participation in and enjoyment of family activities. Among respondents who drove ( N = 10,921), 43.9% reported that symptoms interfered with driving at least sometimes. Migraine interfered with sleep and mood at least sometimes for 52.7% and 70.7% of respondents, respectively. PHQ-8 and GAD-7 thresholds for clinical depression and anxiety were met by 28.6% and 22.0% of respondents, respectively. Impact of migraine on daily life increased with increasing severity of MIDAS/MIBS-4 categories. Conclusion The burden of migraine on daily activities, sleep, and mental health is substantial for people with migraine in Japan. In clinical practice, it is important to evaluate the impact of migraine on daily life in addition to migraine symptoms.

Migraine is a disease that is difficult to be recognized by those around the patients, even though it causes significant hindrances. In this study, we conducted an exploratory comparison of the perceptions on migraine among patients, family members living with them, and physicians treating migraine patients. Patients and family members shared a common understanding on the pain of migraine, and hoped to spend more/better time together as a family. However, although family members felt compassion for the patients, lack of understanding by and patients' concern for the surroundings led to feelings of resignation and endurance on the side of patients. Regarding physicians' medical care, our results suggested the importance to understand the wishes and obstacles of each patient and to propose treatment accordingly. In order to reduce the burden of migraine, it is necessary to create an environment and raise awareness that allows people around the patients to understand and support the pain and hopes that each patient feels.

This analysis of two Japanese clinical trials evaluated efficacy and safety after galcanezumab (GMB) discontinuation in patients with episodic migraine (EM) and chronic migraine (CM). Data were from a 6-month, randomized, double-blind, placebo [PBO]-controlled primary trial (patients with EM) and a 12-month open-label extension trial (patients with EM/CM). Patients received 6 months’ (primary) or 12/18 months’ (extension) treatment with GMB 120 mg (GMB120) plus 240-mg loading dose or 240 mg (GMB240) with 4 months’ post-treatment follow-up. Efficacy was assessed as number of monthly migraine headache days during post-treatment. Safety was assessed via post-treatment-emergent adverse events (PTEAEs). The analysis population included 186 patients from the primary trial (PBO N = 93; GMB120 N = 45; GMB240 N = 48), 220 patients with EM from the extension trial (PBO/GMB120 N = 57; PBO/GMB240 N = 55; GMB120/GMB120 N = 55; GMB240/GMB240 N = 53), and 55 patients with CM (GMB120 N = 28; GMB240 N = 27). In patients with EM receiving 6 months’ GMB120, mean standard deviation (SD) monthly migraine headache days increased from 5.69 (4.64) at treatment end to 6.24 (4.37) at end of follow-up but did not return to pre-treatment levels (8.80 [2.96]). In the extension trial, mean monthly migraine headache days in patients with EM receiving GMB120 were 4.13 (3.85) after 12 months and 4.45 (3.78) at end of follow-up, and 3.59 (3.48) after 18 months and 3.91 (3.57) at end of follow-up. Monthly migraine headache days in patients with CM (12 months’ GMB120) were 10.71 (4.61) at treatment end and 11.17 (5.64) at end of follow-up (pre-treatment 20.15 [4.65]). Similar results were seen for patients receiving GMB240. The most observed PTEAE after GMB discontinuation was nasopharyngitis. Galcanezumab exhibited post-treatment efficacy for up to 4 months in Japanese patients with EM and with CM. No unexpected safety signals were observed. ClinicalTrials.gov, NCT02959177 and NCT02959190.

Using the Japanese version of the Impact of Migraine on Partners and Adolescent Children (IMPAC) and Family Question prepared based on IMPAC, we investigated the impact of migraine on family members from the perspectives of both patients and their family members. Our results showed that migraine had an impact on the family members living with the patients in Japan as well, and the perception of migraine differed partially between patients and their family members. We also found that the Japanese version of the IMPAC showed a correlation with existing instruments to evaluate impact of migraine, indicating its validity. The application of this study's findings in clinical practice could help alleviate the disease burden of migraine on patients and their family members.

Background: Migraine is often comorbid with other disorders. People with migraine may be prescribed one or more concomitant medications. This post hoc analysis assessed the safety and efficacy of lasmiditan in Japanese people with migraine comorbidities or using concomitant medications.Patients and Methods: The MONONOFU study was a Phase 2, randomized, placebo-controlled, multicenter study of lasmiditan for acute migraine treatment in Japanese adults. Patients reported comorbidities (pre-existing or coexisting conditions) during screening. Concomitant medications (any drugs taken +/- 48 hours of the study drug) and treatment-emergent adverse events (TEAEs) were recorded in a paper diary. Study drug efficacy (pain freedom 2 hours after administration of study drug) was reported in an eDiary. Logistic regression models were used for subgroup analyses of safety (incidence of TEAEs) and efficacy (pain freedom at 2 hours post dose) of lasmiditan in relation to presence/absence of comorbidities, and safety in relation to concomitant medications. Results: Common comorbidities (occurring in >= 10% of any lasmiditan dose group) were seasonal allergies, allergic rhinitis, tension-type headache, cervicobrachial syndrome, dysmenorrhea, nasopharyngitis, musculoskeletal stiffness, chronic gastritis, constipation, and insomnia. There was no significant interaction of treatment with comorbidity for safety or efficacy. There was also no significant interaction between treatment and concomitant medication groups of special interest (acetaminophen/nonsteroidal anti-inflammatory drugs, triptans, antiemetics, central nervous system depressant medications, serotonergic medications, antiepileptics, antihypertensive medications, Chinese herbal medicines, and contraceptives) for incidence of TEAEs.Conclusion: In Japanese people with migraine, the safety of lasmiditan appeared to be independent of common comorbidities and concomitant medications; efficacy appeared to be independent of comorbid conditions.Clinical Trials Registration: NCT03962738 (ClinicalTrials.gov).

ABSTRACT Background MONONOFU, a multicenter, randomized, double-blind, placebo-controlled phase 2 study of Japanese patients with migraine, was pivotal for lasmiditan approval in Japan. However, treatment-emergent adverse events (TEAEs) were more common than in global studies. A detailed safety profile would assist patient management. Research design and methods Safety assessments in MONONOFU included specific terms reported, frequency, severity, time to onset, duration, TEAE management, common TEAE risk factors, and TEAE–efficacy associations. Results Of 846 participants, 691 were assessed for safety. The proportion of participants reporting ≥1 TEAE was 23.4% with placebo and 70.9% with lasmiditan; 87.3% of TEAEs with lasmiditan were mild. The most frequent TEAEs with lasmiditan, dizziness (39.4%) and somnolence (19.3%), started ≤1 hour postdose (median durations: 2.5 and 3.3 hours, respectively). Higher lasmiditan dose, but not patient factors including body size, was identified as a clinically meaningful predictor of dizziness and somnolence. There were no adverse consequences of neurological TEAEs, which did not appear to adversely affect lasmiditan efficacy. Conclusions In the MONONOFU study, TEAEs appeared typically mild, transient, and self-limiting. Lasmiditan may represent a useful and well-tolerated acute treatment option for smaller (body mass index <30 kg/m2) patients and Asian patients with migraine. GRAPHICAL ABSTRACT

BACKGROUND:Following the CENTURION phase 3 randomized controlled trial's four-month double-blind phase, this 12-month open-label extension collected data for up to one year about dose optimization, patterns of use, migraine-related disability, and quality of life during lasmiditan treatment.METHODS:Migraine patients ≥18 years completing the double-blind phase and treating ≥3 migraine attacks could continue into the 12-month open-label extension. The initial oral lasmiditan dose was 100 mg; the dose could subsequently be adjusted to 50 mg or 200 mg at the investigator's discretion.RESULTS:477 patients entered and 321 (72.1%) completed the extension; 445 (93.3%) treated ≥1 attack with lasmiditan. Of 11,327 attacks, 8654 (76.4%) were lasmiditan-treated (84.9% of these involved moderate or severe pain). By study end, 17.8%, 58.7%, and 23.4% of patients were taking lasmiditan 50, 100, and 200 mg, respectively. Mean improvements were observed in disability and quality of life. The most common treatment-emergent adverse event was dizziness (35.7% of patients, 9.5% of attacks).CONCLUSIONS:During this 12-month extension, lasmiditan was associated with a high rate of study completion, most attacks were treated with lasmiditan, and patients reported improvements in migraine-related disability and quality of life. No new safety findings were observed with longer exposure.Trial registration: ClinicalTrials.gov (NCT03670810); European Union Drug Regulating Authorities Clinical Trials Database (EUDRA CT: 2018-001661-17).

The efficacy and safety of galcanezumab as a preventive treatment in Japanese patients with episodic migraine was demonstrated in a phase 2, randomized, placebo-controlled trial (conducted December 2016–January 2019). This post hoc analysis assessed the consistency of galcanezumab efficacy through the monthly dosing interval. Patients with 4–14 migraine headache days/month were randomized (2:1:1, stratified by baseline migraine frequency) to subcutaneous placebo (n = 230), 120-mg galcanezumab (with 240-mg loading dose; n = 115) or 240-mg galcanezumab (n = 114) once monthly for 6 months. Outcomes included change from baseline in weekly migraine headache days, proportion of patients with migraine headache on each day, and proportion of patients with worsening migraine headache days during each month ([average of weeks 3–4] − [average of weeks 1–2] > 0). In the 120-mg (approved dose) galcanezumab group, mean change from baseline in weekly migraine headache days was consistent and significantly greater (p < 0.05) than placebo for weeks 1–4; efficacy was consistent when averaged across months 1–6 and in most individual months. Averaged across months 1–6, the proportion of patients with migraine headache was significantly lower with galcanezumab than placebo on every day in both dose groups and was not significantly different between days 2 and 28 with 120-mg galcanezumab (p = 0.161). Within each month, the proportion of patients with migraine headache was generally consistent from days 2–28. The proportion of patients with worsening during the dosing interval did not significantly exceed 50

Knowledge of patient outcomes and treatment effectiveness associated with acute migraine treatments in Japan is lacking. 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. 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. 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

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-HT1F 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.

Rapid onset and sustained efficacy are important for acute migraine treatment. Global phase 3 trials have demonstrated the early onset and sustained efficacy of the 5-HT1F receptor agonist lasmiditan. In this prespecified analysis of the MONONOFU study, we assessed the onset and sustained efficacy of lasmiditan in Japanese patients with migraine. MONONOFU was a multicenter, randomized, placebo-controlled, phase 2 study conducted in Japan (May 2019–June 2020). Eligible adults with migraine (N = 846; modified intent-to-treat population, N = 682) were randomized 7:3:7:6 to placebo, lasmiditan 50 mg, 100 mg, or 200 mg, taken orally within 4 h of moderate-to-severe migraine onset. Patients recorded headache severity and symptoms predose and 0.5–48 h postdose. Sustained and modified sustained pain freedom were defined as patients who were headache pain-free 2 h postdose and had no pain (sustained pain freedom) or had mild or no pain (modified sustained pain freedom) at 24 or 48 h without rescue/recurrence medications. Efficacy outcomes were analyzed by logistic regression. Patients also recorded the actual time of pain-free and of meaningful pain relief (Kaplan–Meier analysis). Compared with placebo, significantly more lasmiditan-treated (100 or 200 mg) patients were headache pain-free, had pain relief, were free of their most bothersome symptom, or had total migraine freedom (no headache or migraine-associated symptoms) within 30–60 min. Median time to pain-free was 9.26, 6.88, 2.75, and 2.30 h in placebo, 50-mg, 100-mg, and 200-mg lasmiditan groups, respectively. Significantly greater proportions of patients treated with 100 (19.7–29.5

BACKGROUND Serum neurofilament light chain (sNFL) is becoming an important biomarker of neuro-axonal injury. Though sNFL correlates with CSF NFL (cNFL), 40% to 60% of variance remains unexplained. We aimed to mathematically adjust sNFL to strengthen its clinical value. METHODS We measured NFL in a blinded fashion in 1138 matched CSF and serum samples from 571 patients. Multiple linear regression (MLR) models constructed in the training cohort were validated in an independent cohort. RESULTS An MLR model that included age, blood urea nitrogen, alkaline phosphatase, creatinine, and weight improved correlations of cNFL with sNFL (from R2 = 0.57 to 0.67). Covariate adjustment significantly improved the correlation of sNFL with the number of contrast-enhancing lesions (from R2 = 0.18 to 0.28; 36% improvement) in the validation cohort of patients with multiple sclerosis (MS). Unexpectedly, only sNFL, but not cNFL, weakly but significantly correlated with cross-sectional MS severity outcomes. Investigating 2 nonoverlapping hypotheses, we showed that patients with proportionally higher sNFL to cNFL had higher clinical and radiological evidence of spinal cord (SC) injury and probably released NFL from peripheral axons into blood, bypassing the CSF. CONCLUSION sNFL captures 2 sources of axonal injury, central and peripheral, the latter reflecting SC damage, which primarily drives disability progression in MS. TRIAL REGISTRATION ClinicalTrials.gov NCT00794352. FUNDING Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH (AI001242 and AI001243).

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. 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. 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. 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.