Low-frequency Episodic Migraine Research Articles

Urine 5-Hydroxyindoleacetic Acid Negatively Correlates with Migraine Occurrence and Characteristics in the Interictal Phase of Episodic Migraine.

Although migraine belongs to the main causes of disability worldwide, the mechanisms of its pathogenesis are poorly known. As migraine diagnosis is based on the subjective assessment of symptoms, there is a need to establish objective auxiliary markers to support clinical diagnosis. Tryptophan (TRP) metabolism has been associated with the pathogenesis of neurological and psychiatric disorders. In the present work, we investigated an association between migraine and the urine concentration of TRP and its metabolites 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), kynurenic acid (KYNA) and quinolinic acid (QA) in 21 low-frequency episodic migraine patients and 32 controls. We chose the interictal phase as the episodic migraine patients were recruited from the outpatient clinic and had monthly migraine days as low as 1-2 in many cases. Migraine patients displayed lower urinary levels of 5-HIAA (p < 0.01) and KYNA (p < 0.05), but KYN and QA were enhanced, as compared with the controls (p < 0.05 and 0.001, respectively). Consequently, the patients were characterized by different values of the 5-HIAA/TRP, KYN/TRP, KYNA/KYN, and KYNA/QA ratios (p < 0.001 for all). Furthermore, urinary concentration of 5-HIAA was negatively correlated with Migraine Disability Assessment score and monthly migraine and monthly headache days. There was a negative correlation between Patient Health Questionnaire 9 scores assessing depression. In conclusion, the urinary 5-HIAA level may be further explored to assess its suitability as an easy-to-determine marker of migraine.

Impact of headache frequency and preventive treatment failure on quality of life, disability, and direct and indirect costs among individuals with episodic migraine in the United States.

To evaluate unmet needs among individuals with episodic migraine (EM) in the United States (US). Data are limited on the impact of headache frequency (HF) and preventive treatment failure (TF) on the burden of migraine in the US. A retrospective, cross-sectional analysis of 2019 National Health and Wellness Survey (NHWS) data was conducted from an opt-in online survey that identified respondents (aged ≥18 years) in the US with self-reported physician-diagnosed migraine. Participants were stratified by HF (low: 0-3 days/month; moderate-to-high: 4-14 days/month) and prior preventive TF (preventive naive; 0-1 TF; ≥2 TFs). Comparisons were conducted between preventive TF groups using multivariable regression models controlling for patient demographic and health characteristics. Among individuals with moderate-to-high frequency EM, the NHWS identified 397 with ≥2 TFs, 334 with 0-1 TF, and 356 as preventive naive. The 36-item Short-Form Health Survey (version 2) Physical Component Summary scores were significantly lower among those with ≥2 TFs, at a mean (standard error [SE]) of 41.4 [0.8] versus the preventive-naive 46.8 [0.9] and 0-1 TF 44.5 [0.9] groups; p < 0.001 for both). Migraine Disability Assessment Scale scores were significantly higher in the ≥2 TFs, at a mean (SE) of 37.7 (3.9) versus preventive-naive 26.8 (2.9) (p < 0.001) and 0-1 TF 30.1 (3.3) (p = 0.011) groups. The percentages of time that respondents experienced absenteeism (mean [SE] 21.6% [5.5%] vs. 13.4% [3.6%]; p = 0.022), presenteeism (mean [SE] 55.0% [8.3%] vs. 40.8% [6.5%]; p = 0.015), overall work impairment (mean [SE] 59.4% [5.6%] vs. 45.0% [4.4%]; p < 0.001), and activity impairment (mean [SE] 56.8% [1.0%] vs. 44.4% [0.9%]; p < 0.001) were significantly higher in the ≥2 TFs versus preventive-naive group. Emergency department visits (preventive-naive, p = 0.006; 0-1 TF, p = 0.008) and hospitalizations (p < 0.001 both) in the past 6 months were significantly higher in the ≥2 TFs group. Direct and indirect costs were significantly higher in the ≥2 TFs (mean [SE] $24,026 [3460]; $22,074 [20]) versus 0-1 TF ($10,897 [1636]; $17,965 [17]) and preventive-naive ($11,497 [1715]; $17,167 [17]) groups (p < 0.001 for all). Results were similar in the low-frequency EM group. In this NHWS analysis, individuals with more prior preventive TFs experienced significantly higher humanistic and economic burden regardless of HF.

Migraine chronification as an allostatic disorder: a proof-of-concept study

ObjectiveThe underpinning biologics of migraine chronification are not well understood. We aim to investigate the role of the cumulative burden of stress, namely the allostatic load, in migraine chronification.MethodsThis was a cross-sectional study. The allostatic load was measured with a composite multi-system score (BALI: Bologna Allostatic Load Index), evaluating 20 biomarkers representing four physiological systems: immune, metabolic, cardiovascular, and neuroendocrinological systems. BALI score was subdivided into high score and low score based on the distribution in controls. Migraine patients were included and subclassified into low-frequency episodic migraine group (low-EM group), high-frequency episodic migraine group (high-EM group), and chronic migraine group (CM group).ResultsThe distribution of BALI high-score increased in parallel with headache attacks monthly frequency: 16% in low-EM group (n = 10), 24% in high-EM group (n = 12), and 40% in CM group (n = 21) (p = 0.017). In a multivariable analysis, the odds ratio of having a high-score BALI in CM patients (vs. low-EM patients) was 2.78 (95% CI 1.07–7.22; p = 0.036). Individual BALI biomarkers values which were significantly different among migraine subgroups included systolic blood pressure (p = 0.018), diastolic blood pressure (p < 0.001), and heart rate (p = 0.019).ConclusionOur study substantiates this emerging concept of migraine chronification as an allostatic disorder.

Efficacy of Erenumab for Migraine Prevention in Japanese Patients with Episodic and Chronic Migraine: Results of a Post-Hoc Pooled Analysis.

Erenumab, a fully human monoclonal antibody against the calcitonin gene-related peptide receptor, is approved in Japan for the prevention of adult migraine. This post-hoc analysis evaluated the efficacy of erenumab in Japanese patients with low-frequency episodic migraine (LFEM) versus those with high-frequency episodic migraine (HFEM) and chronic migraine (CM). A pooled analysis of data from the 24-week double-blind treatment phases (DBTPs) of phase 2 and 3 studies evaluated the efficacy of once-monthly erenumab 70mg in Japanese patients. Patients were categorized into subgroups by monthly migraine days (MMD): LFEM and HFEM/CM. The main efficacy outcomes were change from baseline in MMD, acute migraine-specific medication treatment days (MSMD), and six-item Headache Impact Test (HIT-6™) scores. Patients with migraine (n=532) were included in the analysis (LFEM, n=215; HFEM, n=215; CM, n=102). Overall, mean age was 44years, 86.5% were female, and 63.3-88.2% had used or were taking migraine preventive treatment at baseline. Throughout the DBTP, the placebo-adjusted mean change from baseline in MMD, MSMD, and HIT-6 scores with erenumab was similar across LFEM and HFEM/CM subgroups. The proportion of patients achieving at least 50% or 75% reduction from baseline in MMD and MSMD was similar across migraine frequency groups. Reduction in MMD moderately correlated with improvement in HIT-6 scores in the LFEM and HFEM/CM groups. Furthermore, the proportion of patients converting from HFEM/CM to LFEM during the DBTP was higher in the erenumab group than in the placebo. In Japanese patients with different migraine frequencies, erenumab treatment resulted in significant improvements in MMD, MSMD, and headache impact. This pooled analysis of data from phase 2 and 3 studies increases confidence that erenumab is efficacious in patients with high MMD, which is associated with increased disability.

Real-world evidence on the economic implications of CGRP-mAbs as preventive treatment of migraine

BackgroundCalcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) are approved in Europe as preventive treatment of migraine in patients with at least four monthly migraine days. Migraine gives rise to direct healthcare expenditures, but most of the economic burden of migraine is socioeconomic. Evidence on the socioeconomic implications of CGRP-mAbs is, however, limited. There is an increasing interest in supplementing evidence from randomised controlled trials (RCTs) with real-world evidence (RWE) to aid clinical decision making and inform decision making for migraine management. The objective of this study was to generate RWE on the health economic and socioeconomic implications of administering CGRP-mAbs to patients with chronic migraine (CM) and episodic migraine (high-frequency episodic migraine (HFEM), and low-frequency episodic migraine (LFEM)).MethodsReal-world data (RWD) on Danish patients with CM, HFEM, and LFEM were collected via two Danish patient organisations and two informal patient networks and used in a tailored economic model. Treatment effects of CGRP-mAbs on health economic and socioeconomic outcomes were estimated using a sub-sample of patients with CM who receive CGRP-mAb treatment.ResultsA total of 362 patients (CM: 199 [55.0%], HFEM: 80 [22.1%], LFEM: 83 [22.9%]) were included in the health economic model (mean age 44.1 ± 11.5, 97.5% female, 16.3% received treatment with CGRP-mAbs), and 303 patients were included in the socioeconomic model (15.2% received treatment with CGRP-mAbs). Health economic savings from initiating CGRP-mAb treatment totalled €1,179 per patient with CM per year on average (HFEM: €264, LFEM: €175). Socioeconomic gains from initiating CGRP-mAb treatment totalled an average gross domestic product (GDP) gain of €13,329 per patient with CM per year (HFEM: €10,449, LFEM: €9,947).ConclusionOur results indicate that CGRP-mAbs have the potential to reduce both health economic expenditures and the socioeconomic burden of migraine. Health economic savings are used as a basis for health technology assessments (HTAs) of the cost-effectiveness of new treatments, which implies that important socioeconomic gains may not be given enough importance in decision making for migraine management.

Trigeminocervical pain sensitivity during the migraine cycle depends on headache frequency

ObjectiveThis experimental study aimed to assess pain sensitivity in low-frequency episodic migraine (LFEM), high-frequency episodic migraine (HFEM), and chronic migraine (CM) patients across the different phases of the migraine cycle.MethodIn this observational, experimental study, clinical characteristics (diary and time from the last/next headache attack), and quantitative sensory testing (QST) (wind-up pain ratio (WUR) and pressure pain threshold (PPT) from the trigeminal area and PPT from the cervical spine) was performed. LFEM, HFEM, and CM were assessed in each of the 4 migraine phases (HFEM and LFEM: interictal, preictal, ictal, and postictal; CM: interictal and ictal) and compared vs. each other’s (matched for the phase) and controls.ResultsA total of 56 controls, 105 LFEM, 74 HFEM, and 32 CM were included. No differences in QST parameters were observed between LFEM, HFEM, and CM in any of the phases.During the interictal phase and when comparing with controls the following were found: 1) LFEM had lower trigeminal PPT (p = 0.001) and 2) lower cervical PPT (p = 0.001). No differences were observed between HFEM or CM and healthy controls. During the ictal phase and when comparing with controls the following were found: HFEM and CM had 1) lower trigeminal PPTs (HFEM p = 0.001; CM = p < 0.001), 2) lower cervical PPT s (HFEM p = 0.007; CM p < 0.001), and 3) higher trigeminal WUR (HFEM p = 0.001, CM p = 0.006). No differences were observed between LFEM and healthy controls. During the preictal phase and when comparing with controls the following were found: 1) LFEM had lower cervical PPT (p = 0.007), 2) HFEM had lower trigeminal (p = 0.013) and 3) HFEM had lower cervical (p = .006) PPTs. During the postictal phase and when comparing with controls the following were found: 1) LFEM had lower cervical PPT (p = 0.003), 2) HFEM had lower trigeminal PPT (p = 0.005), and 3) and HFEM had lower cervical (p = 0.007) PPTs.ConclusionThis study suggested that HFEM patients have a sensory profile matching CM better than LFEM. When assessing pain sensitivity in migraine populations, the phase with respects to headache attacks is of utmost importance and can explain the inconsistency in pain sensitivity data reported in the literature.

Relationships between headache frequency, disability, and disability-related unemployment among adults with migraine.

BACKGROUND: Migraine is the second most common cause of disability worldwide. Understanding the relationship between migraine and employment status is critical for policymakers, as disability-related unemployment is associated with eligibility for private or governmental disability insurance payments and other associated support for those unable to work because of disability. OBJECTIVE: To assess the association between migraine frequency and selfreported employment status and overall disability in a US representative survey. METHODS: Using data from the 2019 National Health and Wellness Survey (NHWS) (Kantar Health), adults in the United States (aged 18-65 years) reporting at least 1 migraine day in the past 30 days were categorized by headache frequency: low-frequency episodic migraine (LFEM) (≤4 days/month), moderate-frequency EM (MFEM) (5-9 days/month), high-frequency EM (HFEM) (10-14 days/month), or chronic migraine (CM) (≥15 days/month). A control group of adults without migraine with similar baseline characteristics was identified by propensity score matching. Disability-related unemployment was defined as participants responding "short-term disability" or "long-term disability" to occupational status on the NHWS. The frequency of short- or long-term disability was then evaluated across headache frequency groups. In addition, participants were asked to assess migraine-related disability via the Migraine Disability questionnaire (MIDAS). RESULTS: A total of 1,962 respondents with LFEM, 987 with MFEM, 554 with HFEM, and 926 with CM were included in this analysis, along with 4,429 matched controls. Headache frequency was associated both with increased MIDAS score and with employment disability (P < 0.001); 12.3% (n = 114 of 926) of participants with CM reported employment disability, as did 4.4% (n = 86 of 1,962) of the LFEM group and 6.9% (n = 306 of 4,429) of matched controls. There was considerable discordance between the proportion of participants classified as disabled via MIDAS vs those reporting employment-related disability. CONCLUSIONS: More frequent migraine headaches are associated with a higher likelihood of self-reported short- and long-term employment disability and overall migraine-related disability, suggesting that health and economic policymakers must seek ways to maximize the employment opportunities for people living with migraine that may benefit from novel preventive treatments. DISCLOSURES: Robert E Shapiro is a research consultant for Eli Lilly and Lundbeck. Ashley A Martin and Martine C Maculaitis are employees of Cerner Enviza (formerly Kantar Health), which received payment from Lundbeck to conduct the research. Shiven Bhardwaj was an employee of Lundbeck at the time of study and manuscript development. Heather Thomson and Carlton Anderson are employees of Lundbeck. Steven M Kymes is an employee and stockholder of Lundbeck. Financial support for research conducted and manuscript preparation was provided by Lundbeck.

Shift in diagnostic classification of migraine after initiation of preventive treatment with eptinezumab: post hoc analysis of the PROMISE studies

BackgroundMonthly headache frequency directly correlates with personal/societal burden and impacts severity and preventive treatment decisions. This post hoc analysis identified shifts from higher to lower frequency headache categories over 6 months in patients with migraine participating in the PROMISE clinical trials receiving two eptinezumab doses.MethodsHeadache frequency at baseline and over study months 1–6 was categorized into 4 groups: chronic migraine (CM; ≥ 15 monthly headache days [MHDs]), high-frequency episodic migraine (HFEM; 10–14 MHDs), low-frequency episodic migraine (LFEM; 4–9 MHDs), and ≤ 3 MHDs. Outcomes included the percentage of patients within each MHD category, the percentage of patients improving by ≥ 1 MHD category, and the number of months with reduction of ≥ 1 MHD category. Data from patients who received approved eptinezumab doses (100 mg or 300 mg) or placebo were included.ResultsMean headache frequency at baseline in PROMISE-1 was 10 MHDs; most patients were classified as having HFEM (48.6%) or LFEM (43.9%). At Month 1, 62/221 (28.1%), 75/222 (33.8%), and 45/222 (20.3%) patients who received eptinezumab 100 mg, 300 mg, and placebo had ≤ 3 MHDs, with 97/221 (43.9%), 108/222 (48.6%), and 84/222 (37.8%), respectively, falling below the diagnostic EM threshold at Month 6. More than one-third (79/221 [35.7%], 83/222 [37.4%], and 68/222 [30.6%] of patients in the eptinezumab 100 mg, 300 mg, and placebo groups, respectively), had 6 months of reduction of ≥ 1 frequency category. At baseline in PROMISE-2, mean headache frequency was 20.5 MHDs. All patients (100%) in the eptinezumab 100 mg and placebo groups had CM, as did 99.4% of patients receiving eptinezumab 300 mg. At Month 1, 209/356 (58.7%), 216/350 (61.7%), and 167/366 (45.6%) patients treated with eptinezumab 100 mg, 300 mg, and placebo had ≤ 14 MHDs, with 240/356 (67.4%), 249/350 (71.1%), and 221/366 (60.4%), respectively, falling below CM threshold at Month 6. Additionally, 153/356 (43.0%), 169/350 (48.3%), and 116/366 (31.7%) patients in the eptinezumab 100 mg, 300 mg, and placebo groups, respectively, had 6 months of reduction of ≥ 1 frequency category.ConclusionIn the PROMISE studies, episodic and chronic migraine patients treated with eptinezumab were more likely to reduce their headache frequency versus placebo, which directly and in a sustained way improved their diagnostic category classification.Trial registrationClinicalTrials.gov Identifier: NCT02559895, NCT02974153.

Association of a Cyclical Migraine Phenotype With Disease Progression: A 1-Year Time Series Analysis.

Longitudinal studies assessing cyclic fluctuations of migraine attacks using time series analysis are scarce. Here, we analyze headache frequency fluctuations over a year in a cohort of patients with migraine, and we then evaluate how this behavior has an effect on clinical evolution. Monthly headache frequency was prospectively collected using an electronic diary. Prognosis after 1 year was calculated as the headache frequency change rate after 12 months (HCR-M12) as a dependent variable. Monthly headache time series was decomposed into all the possible sum of sinusoids through a fast Fourier transform (FFT) algorithm, and the frequencies with the highest power were used to define the patient's cyclic phenotype during 1 year (patient's number of cycles per year, c/y). Patients with a cyclic phenotype were those with >2 c/y. Finally, we studied how this cyclic phenotype was associated with HCR-M12 using generalized linear models (GLMs). A total of 142 patients were included (85.2% female; mean age 48.0 ± 9.7 years), 50.0% fulfilled the International Classification of Headache Disorders, third edition, criteria for chronic migraine (CM). After 1 year, a 50.7% (72/142) of patients changed their initial diagnosis, and progression (frequency worsening) was observed in 14.1% (10/71) of patients with episodic migraine (EM). After applying an FFT, 45.1% (64/142) of patients fitted into a cyclic phenotype. In GLM, statistically significant main effects associated with HCR-M12 were the use of preventive therapy (β [SE]: 74.1 [34.6]; p = 0.034) and cyclic phenotype (β [SE]: 158.33 [55.1]; p = 0.005). A post hoc analysis found that patients with EM with cyclic phenotype without adequate preventive therapy were statistically significantly associated with progression. Monthly headache frequency data can be fitted by sinusoidal models. Having a cyclic phenotype has an effect on clinical evolution and has been statistically significantly associated with migraine progression after 1 year. Particularly, patients with EM with cyclic phenotype tend to increase their headache frequency over time. Preventive treatment seems to play a fundamental role in modulating this cyclic behavior, especially in patients with low-frequency EM.

Conversion from chronic to episodic migraine in patients treated with galcanezumab in real life in Italy: the 12-month observational, longitudinal, cohort multicenter GARLIT experience.

ObjectiveTo investigate in real-life the conversion from chronic migraine (CM) to episodic migraine (EM), specifically to EM with High-Frequency (HFEM: 8–14 monthly migraine days, MMDs), Medium-Frequency (MFEM, 4–7 MMDs), and Low-Frequency EM (LFEM, 0–3 MMDs), and its persistence during 1 year of treatment with galcanezumab.MethodsConsecutive CM patients treated with galcanezumab completing 1 year of observation were enrolled. We collected data on MMDs, pain intensity (Numeric Rating Scale, NRS score), and monthly acute medication intake (MAMI) from baseline (V1) to the 12-month visit (V12).ResultsOf the 155 enrolled patients, 116 (around 75%) reverted to EM at every visit and 81 (52.3%) for the entire 1-year treatment. Patients with older onset age (p = 0.010) and fewer baseline MMDs (p = 0.005) reverted more frequently to EM. At V12, 83 participants (53.5%) presented MFEM or LFEM. Patients reverted to MFEM or LFEM for 7 months (25th 1, 75th 11). The medication overuse discontinuation rate at V12 was 82.8% and occurred for 11 months (25th 8, 75th 12). From baseline to V12, the MAMI decreased by 17 symptomatic drugs (p < 0.000001) while the NRS score reduced by almost 2 points (p < 0.000001). A consistent transition to EM for the entire treatment year was observed in 81 (52.3%) patients.DiscussionThe 1-year GARLIT experience suggests that more than half of CM patients treated with galcanezumab persistently reverted to EM in real life.Trial registrationClinicalTrials.gov NCT04803513.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00415-022-11226-4.

Diagnosis, consultation, treatment, and impact of migraine in the US: Results of the OVERCOME (US) study.

ObjectiveThe ObserVational survey of the Epidemiology, tReatment and Care of MigrainE (OVERCOME; United States) study is a multicohort, longitudinal web survey that assesses symptomatology, consulting, diagnosis, treatment, and impact of migraine in the United States.BackgroundRegularly updating population‐based views of migraine in the United States provides a method for assessing the quality of ongoing migraine care and identifying unmet needs.MethodsThe OVERCOME (US) 2018 migraine cohort involved: (I) creating a demographically representative sample of US adults using quota sampling (n = 97,478), (II) identifying people with active migraine in the past year via a validated migraine diagnostic questionnaire and/or self‐reported medical diagnosis of migraine (n = 24,272), and (III) assessing consultation, diagnosis, and treatment of migraine (n = 21,143). The current manuscript evaluated whether those with low frequency episodic migraine (LFEM; 0–3 monthly headache days) differed from other categories on outcomes of interest.ResultsAmong the migraine cohort (n = 21,143), 19,888 (94.1%) met our International Classification of Headache Disorders, 3rd edition‐based case definition of migraine and 12,905 (61.0%) self‐reported a medical diagnosis of migraine. Respondents’ mean (SD) age was 42.2 (15.0) years; 15,697 (74.2%) were women. Having at least moderate disability was common (n = 8965; 42.4%) and around half (n = 10,783; 51.0%) had consulted a medical professional for migraine care in the past year. Only 4792 (22.7%) of respondents were currently using a triptan. Overall, 8539 (40.4%) were eligible for migraine preventive medication and 3555 (16.8%) were currently using migraine preventive medication. Those with LFEM differed from moderate and high frequency episodic migraine and chronic migraine on nearly all measures of consulting, diagnosis, and treatment.ConclusionThe OVERCOME (US) 2018 cohort revealed slow but steady progress in diagnosis and preventive treatment of migraine. However, despite significant impact among the population, many with migraine have unmet needs related to consulting for migraine, migraine diagnosis, and getting potentially beneficial migraine treatment. Moreover, it demonstrated the heterogeneity and varying unmet needs within episodic migraine.

Task-switching abilities in episodic and chronic migraine.

Migraineurs show impaired cognitive functions interictally, mainly involving information processing speed, basic attention, and executive functions. We aimed to assess executive impairment in migraine patients with different attack frequencies through a task-switching protocol designed to assess different sub-processes of executive functioning. We enrolled 42 migraine patients and divided them into three groups based on the attack frequency: 13 subjects had episodic migraine with a low frequency (LFEM, 4-7 migraine days per month), 14 subjects had high-frequency episodic migraine (HFEM, 8-14days) and, finally, 15 subjects presented chronic migraine (≥ 15 headache days/month, CM); we compared them to 20 healthy control (HC), matched to both gender and education. Patients with high headache frequencies (CM and HFEM) showed worse performance than LFEM and HC controls, as indicated by poor accuracy, increased switch cost, and reaction times. Our study demonstrated a difference in task-switching abilities in patients with high frequency or chronic migraine compared with low-frequency episodic migraine and healthy controls. These difficulties in executive control processes could be related to altered functioning of the frontal cortex and its cortical and subcortical connections.

Erenumab for Migraine Prevention in a 1-Year Compassionate Use Program: Efficacy, Tolerability, and Differences Between Clinical Phenotypes.

During a 1-year compassionate use program, 156 patients with migraine self-administered a monthly dose of erenumab 140 mg with a subcutaneous autoinjector. Main inclusion criteria were: ≥ 4 migraine days/month and ≥two prior prophylactic treatment failures. The patients covered the migraine severity spectrum from episodic migraine (EM) (n = 80) to chronic migraine (CM) (n = 76). During the 3rd month of treatment, monthly headache days decreased by 45.7% in EM and 35.5% in CM. The 50% responder rate for reduction in monthly headache days was significantly higher in EM (55%) than in CM (43%) (p = 0.05). In both the migraine subgroups, the clinical improvement vs. baseline was already significant during the 1st month of treatment (p < 0.001). There were also significant reductions in mean headache severity, duration, and monthly days with acute drug intake. The 30% responder rate at 3 months was 60% in CM and 54.1% of patients reversed from CM to EM. The therapeutic effect was maintained at 12 months when 50% responder rates, considering discontinuation for lack of efficacy or adverse effects as 0% response, still were 51% in EM and 41% in CM. A total of 10 patients with EM (12.5%) and 23 patients with CM (30.3%) had discontinued treatment, considering the treatment as ineffective. At 3 months, 48% of patients reported non-serious adverse events among which the most frequent was constipation (20.5%); corresponding figures at 12 months were 30 and 15%. Discontinuation due to an adverse effect for the entire 12 month period was rare (3.8%). The lower efficacy in CM than in EM was mainly due to a very low 50% responder rate in patients with CM with continuous pain (13%) as compared to CM with pain-free periods (58%) (p < 0.001). Similarly, the 50% responder rate was lower in patients with ≥two prior prophylactic treatment failures (40.5%) compared to those with two failures (70%) (p < 0.05). There was no significant efficacy difference between low (4–7 migraine days/month, n = 22) and high frequency (8–14 days, n = 59) EM nor between patients with CM with (n = 50) or without (n = 26) acute medication overuse. Erenumab had no effect on the frequency of auras. Taken together, erenumab 140 mg monthly was highly effective for migraine prophylaxis over the whole severity spectrum of the disease, except in patients with continuous headaches. Its effect is significant after the first injection, quasi-maximal after the second injection, and does not wear off after 12 months. The most frequent adverse effect was constipation. These results are compared to those published for erenumab in the pivotal randomized placebo-controlled trials and to those reported in several recent real-world studies.

P.036 Burden of illness in patients with migraine in Canada: A patient survey and retrospective chart review

Background: There are limited Canadian data on the impact of migraine on quality of life, economic, and societal burden. Therefore, the aim of this study was to characterize the humanistic and economic burden of illness of migraine in Canada. Methods:Retrospective medical chart review and prospective patient survey were used to evaluate the clinical, social, and economic burden of migraine in patients who failed at least two prior prophylactic therapies.Results: 287 migraine patients were included. High- frequency episodic migraine (8 to 14 MMDs) and chronic migraine (15+ MMDs) made up the majority of the cohort (35.2% and 35.9%, respectively). 72.8% of the patients had underlying comorbidities 78% indicated that they experienced severe disability on their daily life due to their headaches. The total estimated annual cost of chronic migraine was $25,669 per patient while high-frequency episodic and low-frequency episodic migraine was associated with an annual cost of $24,885 and $15,651 per patient respectively. Conclusions: This study provides a recent and comprehensive assessment of the burden of illness associated with migraine in Canada and showed that migraine is associated with a substantial humanistic and economic burden for patients and healthcare systems.

Epidemiology, work and economic impact of migraine in a large hospital cohort: time to raise awareness and promote sustainability.

Migraine is not routinely assessed at work, making impossible to realize its impact and the potential benefit of migraine-related health strategies. We aimed to assess epidemiology, work and economic impact of migraine in a workplace cohort of a tertiary hospital. Cross-sectional analysis of a cohort of employees working in a Spanish tertiary hospital. Through a web questionnaire, we screened participants for migraine, collecting demographic data, work characteristics, work impairment due to headache (WPAI), treatments and healthcare resource utilization. We calculated direct and indirect costs for the hospital. Six hundred sixty-seven employees participated (8.8%). 71.2% (475/667) fulfilled criteria for migraine, being 76.8% (365/475) low-frequency episodic migraine (LFEM), 12.6% (60/475) high-frequency episodic migraine (HFEM) and 10.5% (50/475) chronic migraine (CM). Only 56.2% (267/475) were aware of suffering from migraine. Only 43.3% (26/60) of HFEM and 56.0% (28/50) of CM have been on preventive treatment in the last year. Migraine caused an overall economic loss for the hospital of 439,848.90 €/month, as a result of utilization of healthcare resources at the workplace (136,028.0 €/month) and indirect costs (absenteeism + presenteeism: 303,820.90 €/month). Specifically, only 110 participants (HFEM + CM) were responsible for half of indirect costs (165,017.2€/month). Although healthcare professionals have greater knowledge on health issues, migraine is underdiagnosed and undertreated, leading to a significant economic loss for the hospital. These results urge companies to assess migraine and promote stronger and migraine-specific health strategies at the workplace as a way to improve their own economic sustainability and the burden of migraine in their workforce.

Disability, burden, and symptoms related to sensitization in migraine patients associate with headache frequency.

This observational study aimed to assess the difference in disability, burden, and sensitization between migraine patients with low-frequency headache attack (1-8 headache days/month), high-frequency headache attack (9-14 headache days/months), and patients with chronic migraine (>14 headache days/months). Migraine patients with or without aura were divided into three groups according to headache frequency (low-frequency episodic migraine; high-frequency episodic migraine; chronic migraine). Questionnaires were used to assess the burden of headache, quality of life, phycological burden, and symptoms related to sensitization (estimated by the Central Sensitization Inventory). Differences among migraine groups were assessed using Chi-Quadro test, ANOVA, or Kruskal-Wallis as appropriate. 136 patients were included (68 low-frequency episodic migraine, 45 high-frequency episodic migraine, 23 chronic migraine). Patients with high frequency episodic migraine and chronic migraine differed from patients with low frequency episodic migraine showing a worse burden of headache (p=0.002; p=0.002), worse level of physical (p=0.001; p<0.001) and mental (p=0.002; p=0.001) quality of life, worse level of depression (p=0.008; p=0.003), and increase presence of symptoms related to sensitization (p<0.001; p=0.003). No differences were found in any variables between patients with high-frequency episodic migraine and patients with chronic migraine (p>0.05). Patients with high-frequency episodic migraine and chronic migraine could be considered in the same segment of the migraine population, with similar degrees of disability and sensitization related symptoms.

The Potentials of Uncariae Ramulus Cum Uncis for the Treatment of Migraine: Targeting CGRP in the Trigeminovascular System.

Migraine is a common chronic neurovascular disease characterized by headaches. Calcitonin gene-related peptide (CGRP) signaling in the trigeminovascular system plays a critical role in the development of migraine. The monoclonal antibodies against CGRP and its receptor have been used clinically for the prevention of migraine; however, they may not be a cost-effective option for patients with low-frequency episodic migraine. Thus, it is quite valuable to search for an alternative strategy to downregulate CGRP signaling. Uncariae Ramulus Cum Uncis (UR) has a long-term history for the treatment of cardiovascular and central nervous systems disorders in China and Eastern Asia. Several clinical studies showed that famous herbal formulas comprising UR were able to improve headaches in migraineurs. In addition, increasing in vivo studies further indicated that migraine-related changes, such as CGRP increase, inflammation, nitric oxide increase, and spontaneous behavior problems could be reduced by UR extraction and its active constituents. In this review, we summarize the pathophysiological factors affecting abnormal CGRP release in the trigeminovascular system during a migraine, and for the first time, analyze the effects of UR on these factors and evaluate the potentials of UR for the treatment of migraine.

PND65 Migraine Frequency and Its Association with Patient-Reported Disability Rates

Although migraine symptoms can interfere with many aspects of daily life, the relationship between disability burden and migraine frequency has not been fully characterized. We assessed the association between migraine frequency and patient-reported disability in a nationally representative survey. Using 2019 US National Health and Wellness Survey (Kantar Health) data, respondents (aged 18–65 years) reporting ≥1 migraine in the past 30 days were categorized by headache frequency: low frequency episodic migraine (LFEM, 0–4 days/month), moderate frequency episodic migraine (MFEM, 5–9 days/month), high frequency episodic migraine (HFEM, 10–14 days/month), or chronic migraine (≥15 days/month). A general population cohort (no migraine) with similar baseline characteristics was identified by propensity score matching. Outcomes across cohorts were compared using chi-square and analysis of variance tests. Data from 8858 respondents (LFEM, n=1962; MFEM, n=987; HFEM, n=554; chronic migraine, n=926; general population, n=4429) were analyzed. Full-time employment was reported by 54.9% with LFEM, 50.4% with MFEM, 45.5% with HFEM, 34.1% with chronic migraine, and 45.9% of the general population; short- or long-term disability was reported by 4.4% with LFEM, 6.4% with MFEM, 7.9% with HFEM,12.3% with chronic migraine, and 6.9% of the general population (P<0.001). Migraine frequency was associated with lower productivity at work (mean missed work days in the past 6 months among those employed [n=2964]: LFEM, 1.6; MFEM, 3.1; HFEM, 3.4; chronic migraine, 7.0; P<0.001) and at home (mean missed days of household activities in the past 6 months: LFEM, 3.6; MFEM, 6.7; HFEM, 10.5; chronic migraine, 19.8; P<0.001). Respondents with chronic migraine were less likely to be employed full-time and more likely to report being disabled, and miss work or household activities. There was a positive linear relationship between migraine frequency and patient-reported disability status, indicating that greater migraine frequency is associated with increased disability.

Shift from high-frequency to low-frequency episodic migraine in patients treated with Galcanezumab: results from two global randomized clinical trials

BackgroundPatients with episodic migraine (EM) with a higher-frequency of migraine headache days (HFEM: 8–14 migraine headache days/month) have a greater disease burden and a higher risk of progressing to chronic migraine (CM) with associated acute treatment overuse versus those with low-frequency EM (LFEM: 4–7 migraine headache days/month). In this post hoc analysis, we assessed the proportions of patients who shifted from HFEM to LFEM and to very low-frequency EM (VLFEM: 0–3 migraine headache days/month) status following treatment with galcanezumab versus placebo.MethodsEVOLVE-1 and EVOLVE-2 were double-blind, Phase 3 studies in patients with EM. Patients (18–65 years) were randomized (2:1:1) to subcutaneous monthly injections of placebo, galcanezumab 120 mg (240 mg loading dose) or 240 mg, for up to 6 months. Data were pooled and endpoints were change from baseline in number of migraine headache days/month and patients who shifted from HFEM to LFEM or VLFEM status. Impact of change in HFEM status on migraine headache days/month, quality of life and disability was also assessed.ResultsA total of 66% (1176/1773) patients from EVOLVE studies had HFEM status at baseline and were included in this analysis; placebo: 592, galcanezumab 120 mg: 294 and galcanezumab 240 mg: 290. At each month, both doses of galcanezumab resulted in a higher proportion of patients who shifted to 0–7 monthly headache days/month (VLFEM or LFEM status). Patients who shifted from HFEM at baseline to VLFEM status at Month 3, a relatively larger proportion of patients on galcanezumab 120 mg versus placebo remained at VLFEM status at Months 4–6; Months 4–5 for galcanezumab 240 mg versus placebo. Among the galcanezumab-treated patients who did-not-shift or shifted to LFEM or VLFEM status for ≥3 consecutive months until the end of the study, patients who shifted from HFEM to VLFEM status experienced the largest reduction in migraine headache days/month and the largest clinically meaningful improvements in daily functioning (MSQ-RFR) and disability (MIDAS).ConclusionsIn patients with HFEM, treatment with galcanezumab (120 mg and 240 mg) significantly reduced migraine headache days/month, maintained remission status at subsequent months until the end of the study, and improved patients’ quality of life versus placebo.Trial registrationClinicalTrials.gov Identifier: EVOLVE-1, NCT02614183; EVOLVE-2, NCT02614196.

The Burden of Illness of Migraine in Canada: New Insights on Humanistic and Economic Cost.

The aim of this study was to characterize the burden of illness of migraine in Canada. The primary objective was to estimate the annual direct medical resource use and associated costs in migraine patients who failed at least two prophylactic therapies for migraine. Adults with at least four migraine days per month and who had failed at least two prophylactic migraine therapies were included. Participation in a clinical trial within 12 months of enrollment was the sole exclusionary criterion. Patient demographic and clinical characteristics, migraine-related treatment and medical history, and direct medical resource utilization were collected through a retrospective medical chart review. Data on patient characteristics, lifestyle factors, treatments, medical resource utilization, out-of-pocket expenses, and indirect costs were collected through a cross-sectional patient survey. The patient survey also included validated patient-reported outcome instruments to assess migraine impact on quality of life and work productivity loss. In total, 287 migraine patients were included. The mean time since migraine diagnosis was 14.3 years and patients experienced a mean of 14.1 migraine days per month. The total estimated annual cost of chronic migraine (CM) was $25,669 per patient, while the annual total costs for high-frequency episodic and low-frequency episodic migraine (EM) were estimated to be $24,885 and $15,651, respectively. Migraine is associated with moderate to severe disability. This results in substantial economic burden, directly from healthcare costs such as prescription medications and indirectly through lost work productivity. We also observed that patients with high-frequency EM experience significant burden, similar to that observed for patients with CM.