Chronic Migraine Epidemiology and Outcomes - International (CaMEO-I) Study: Methods and multi-country baseline findings for diagnosis rates and care.

BACKGROUND: The Chronic Migraine Epidemiology and Outcomes-International study provides insight into people with migraine in multiple countries. METHODS: This cross-sectional, observational, web-based cohort study was conducted in Canada, France, Germany, Japan, United Kingdom, and United States. An initial Screening Module survey solicited general healthcare information from a representative sample and identified participants with migraine based on modified International Classification of Headache Disorders-3 criteria; those with migraine completed a detailed survey based on validated migraine-specific assessments. RESULTS: Among 90,613 people who correctly completed the screening surveys, 76,121 respondents did not meet the criteria for migraine, while 14,492 did. Among respondents with migraine, mean age ranged from 40 to 42 years. The median number of monthly headache days ranged from 2.33 to 3.33 across countries, while the proportion of respondents with moderate-to-severe disability (measured by Migraine Disability Assessment) ranged from 30% (Japan) to 52% (Germany). The proportion of respondents with ≥15 monthly headache days ranged from 5.4% (France) to 9.5% (Japan). Fewer than half of respondents with migraine in each country reported having received a migraine diagnosis. CONCLUSION: These results demonstrated high rates of migraine-related disability and underdiagnosis of migraine across six countries. This study will characterize country-level burden, treatment patterns, and geographical differences in care.

The relationship between headache-attributed disability and lost productivity: 3 Attack frequency is the dominating variable.

BACKGROUND: In an earlier paper, we examined the relationship between headache-attributed disability, measured as proportion of time in ictal state, and lost productivity. In a linear model, we found positive and significant associations with lost paid worktime, lost household worktime and total lost productivity (paid + household), but with high variance, which was increased when headache intensity was introduced as a factor. We speculated that analyses based on headache frequency alone as the independent variable, eliminating both the subjectivity of intensity estimates and the uncertainties of duration, might show stronger associations. METHODS: Focusing on migraine, we used individual participant data from 16 countries surveyed either in population-based studies or in the Eurolight project. These data included frequency (headache days/month), usual attack duration (hours), usual headache intensity ("not bad", "quite bad", "very bad") and lost productivity from paid and household work according to enquiries using the Headache-Attributed Lost Time (HALT) questionnaire. We used multiple linear regressions, calculating regression equations along with unstandardized and standardized regression coefficients. We made line and bar charts to visualize relationships. RESULTS: Both frequency and intensity were significant predictors of lost productivity in all multiple linear regressions, but duration was a non-significant predictor in several of the regressions. Predicted productivity in paid work decreased among males by 0.75-0.85 days/3 months for each increase of 1 headache day/month, and among females by 0.34-0.53 days/3 months. In household chores, decreases in productivity for each added day/month of headache were more similar (0.67-0.87 days/3 months among males, 0.83-0.89 days/3 months among females). Visualizations showed that the impact of duration varied little across the range of 2-24 h. The standardized regression coefficients demonstrated that frequency was a much better predictor of lost productivity than intensity or duration. CONCLUSION: In the relationship between migraine-attributed impairment (symptom burden) and lost productivity, frequency (migraine days/month) is the dominating variable - more important than headache intensity and far more important than episode duration. This has major implications for current practice in headache care and for health policy and health-resource investment. Preventative drugs, grossly underutilized in current practice, offer a high prospect of economic benefit (cost-saving), but new preventative drugs are needed with better efficacy and/or tolerability.

Migraine: epidemiology and systems of care.

Migraine is a neurovascular disorder that affects over 1 billion people worldwide. Its widespread prevalence, and associated disability, have a range of negative and substantial effects not only on those immediately affected but also on their families, colleagues, employers, and society. To reduce this global burden, concerted efforts are needed to implement and improve migraine care that is supported by informed health-care policies. In this Series paper, we summarise the data on migraine epidemiology, including estimates of its very considerable burden on the global economy. First, we present the challenges that continue to obstruct provision of adequate care worldwide. Second, we outline the advantages of integrated and coordinated systems of care, in which primary and specialist care complement and support each other; the use of comprehensive referral and linkage protocols should enable continuity of care between these systems levels. Finally, we describe challenges in low and middle-income countries, including countries with poor public health education, inadequate access to medication, and insufficient formal education and training of health-care professionals resulting in misdiagnosis, mismanagement, and wastage of resources.

Migraine-attributed burden, impact and disability, and migraine-impacted quality of life: Expert consensus on definitions from a Delphi process.

BACKGROUND: Migraine-attributed burden, impact, disability and migraine-impacted quality of life are important concepts in clinical management, clinical and epidemiological research, and health policy, requiring clear and agreed definitions. We aimed to formulate concise and precise definitions of these concepts by expert consensus. METHODS: We searched the terms migraine-attributed burden, impact, disability and migraine-impacted quality of life in Embase and Medline from 1974 and 1946 respectively. We followed a Delphi process to reach consensus on definitions. RESULTS: We found widespread conflation of concepts and inconsistent terminology within publications. Following three Delphi rounds, we defined migraine-attributed burden as "the summation of all negative consequences of the disease or its diagnosis"; migraine-attributed impact as "the effect of the disease, or its diagnosis, on a specified aspect of life, health or wellbeing"; migraine-attributed disability as "physical, cognitive and mental incapacities imposed by the disease"; and migraine-impacted quality of life as "the subjective assessment by a person with the disease of their general wellbeing, position and prospects in life". We complemented each definition with a detailed description. CONCLUSION: These definitions and descriptions should foster consistency and encourage more appropriate use of currently available quantifying instruments and aid the future development of others.

Establishing Stroke Services in the Republic of Georgia.

INTRODUCTION: This article summarizes the medical experience in establishing stroke units and systemic thrombolysis in Georgia, which, like many other post-Soviet countries, still faces problems in organizing stroke care even after 30 years of independence. PATIENTS AND METHODS: We created an example of treating acute stroke with systemic thrombolysis and introduced stroke units in several hospitals in the country, including standardization of the diagnostic and treatment process, consistent evaluation, and monthly feedback to the stroke unit staff. RESULTS: Systemic thrombolysis has become a clinical routine in some large hospitals and is meanwhile reimbursed by the state insurance. The data of consecutive 1,707 stroke patients in 4 major cities demonstrated significant time lost at the prehospital level, due to failure in identifying stroke symptoms, delay in notification, or transportation. The consequent quality reports resulted in a dramatic increase in adherence to the European and national guidelines. A mandatory dysphagia screening and subsequent treatment led to a decrease in pneumonia rates. DISCUSSION: We discuss our experience and suggestions on how to overcome clinical, financial, and ethical problems in establishing a stroke services in a developing country. CONCLUSION: The Georgian example might be useful for doctors in other post-Soviet countries or other parts of the world.

The Global Campaign turns 18: a brief review of its activities and achievements.

The Global Campaign against Headache, as a collaborative activity with the World Health Organization (WHO), was formally launched in Copenhagen in March 2004. In the month it turns 18, we review its activities and achievements, from initial determination of its strategic objectives, through partnerships and project management, knowledge acquisition and awareness generation, to evidence-based proposals for change justified by cost-effectiveness analysis.

European Headache Federation guideline on the use of monoclonal antibodies targeting the calcitonin gene related peptide pathway for migraine prevention - 2022 update.

BACKGROUND: A previous European Headache Federation (EHF) guideline addressed the use of monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway to prevent migraine. Since then, randomized controlled trials (RCTs) and real-world evidence have expanded the evidence and knowledge for those treatments. Therefore, the EHF panel decided to provide an updated guideline on the use of those treatments. METHODS: The guideline was developed following the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach. The working group identified relevant questions, performed a systematic review and an analysis of the literature, assessed the quality of the available evidence, and wrote recommendations. Where the GRADE approach was not applicable, expert opinion was provided. RESULTS: We found moderate to high quality of evidence to recommend eptinezumab, erenumab, fremanezumab, and galcanezumab in individuals with episodic and chronic migraine. For several important clinical questions, we found not enough evidence to provide evidence-based recommendations and guidance relied on experts' opinion. Nevertheless, we provided updated suggestions regarding the long-term management of those treatments and their place with respect to the other migraine preventatives. CONCLUSION: Monoclonal antibodies targeting the CGRP pathway are recommended for migraine prevention as they are effective and safe also in the long-term.

European Headache Federation (EHF) consensus on the definition of effective treatment of a migraine attack and of triptan failure.

BACKGROUND: Triptans are migraine-specific acute treatments. A well-accepted definition of triptan failure is needed in clinical practice and for research. The primary aim of the present Consensus was to provide a definition of triptan failure. To develop this definition, we deemed necessary to develop as first a consensus definition of effective treatment of an acute migraine attack and of triptan-responder. MAIN BODY: The Consensus process included a preliminary literature review, a Delphi round and a subsequent open discussion. According to the Consensus Panel, effective treatment of a migraine attack is to be defined on patient well-being featured by a) improvement of headache, b) relief of non-pain symptoms and c) absence of adverse events. An attack is considered effectively treated if patient's well-being, as defined above, is restored within 2 hours and for at least 24 hours. An individual with migraine is considered as triptan-responder when the given triptan leads to effective acute attack treatment in at least three out of four migraine attacks. On the other hand, an individual with migraine is considered triptan non-responder in the presence of failure of a single triptan (not matching the definition of triptan-responder). The Consensus Panel defined an individual with migraine as triptan-resistant in the presence of failure of at least 2 triptans; triptan refractory, in the presence of failure to at least 3 triptans, including subcutaneous formulation; triptan ineligibile in the presence of an acknowledged contraindication to triptan use, as specified in the summary of product characteristics. CONCLUSIONS: The novel definitions can be useful in clinical practice for the assessment of acute attack treatments patients with migraine. They may be helpful in identifying people not responding to triptans and in need for novel acute migraine treatments. The definitions will also be of help in standardizing research on migraine acute care.

Prevalence and risk factors of migraine and non-migraine headache in older people - results of the Heinz Nixdorf Recall study.

BACKGROUND: The prevalence of migraine and non-migraine headache declines with age. METHODS: Data from the third visit (2011-2015) of the population-based Heinz Nixdorf Recall study were analysed (n = 2038, 51% women, 65-86 years). Possible risk factors for headache activity (obesity, education, smoking, sports, alcohol, partnership status, living alone, having children, sleep quality, depression, hypertension, diabetes mellitus, stroke, coronary heart disease, medication), and headache symptoms were assessed. We estimated the lifetime prevalence and the prevalence of current active headache of migraine with and without aura, and non-migraine headache. The associations between possible risk factors and headache activity (active vs. inactive) were estimated by age and sex-adjusted odds ratios and 95% confidence intervals (OR [95% CI]) using multiple logistic regression. RESULTS: The lifetime prevalence of migraine was 28.6% (n = 584). One hundred and ninety-two (9.4%) had still-active migraine, 168 (3.5%) had migraine with aura, and 416 (5.9%) had migraine without aura. One hundred and sixty-eight (8.2%) had "episodic infrequent migraine, 0-8 headache days/month", 10 (0.5%) had "episodic frequent migraine, 9-14 headache days/month", and five (0.2%) had "chronic migraine, ≥15 headache days/month". Overall, 10 (0.5%) had "chronic headache, any headache on ≥15 days/month". Female gender and younger age were the most important associated migraine risk factors. Depression (1.62 [1.06; 2.47]) and poor sleep (1.06 [1.00; 1.12]) were associated with migraine and headache activity in general. Antihypertensives were associated with headache remission (0.80 [0.64; 1.00]). Additionally, undertaking less sports (0.72 [0.51; 1.03]) was associated with higher migraine activity. CONCLUSIONS: Headaches and migraines are not rare in the older population. They are related to mood and sleep disturbance, and migraine even to less physical activity. Antihypertensives are related to headache remission.

Social Impact of Prophylactic Migraine Treatments in Germany: A State-Transition and Open Cohort Approach.

OBJECTIVES: Migraine is a highly prevalent neurological disorder. The most characteristic symptom of migraine is moderate to severe recurrent headache along with other neurological symptoms. In this study, we modeled the potential reduction in migraine days and corresponding avoided productivity losses if erenumab was prescribed to the patient population indicated for prophylactic migraine treatment (≥ 4 monthly migraine days [MMDs]) in Germany from 2020 to the end of 2027. METHODS: We simulated the incremental benefits of erenumab against the standard of care. Response rates, transition probabilities, discontinuation rates, and productivity estimates were derived from the erenumab clinical trial program. Patients had a probability of residing in 1 of 7 states, given the MMDs in addition to the probability of death. Based on accrued MMDs in every cycle, days of absenteeism and presenteeism for paid and unpaid work were derived. Paid work was monetized according to gross value added using the human capital approach, whereas unpaid work was valuated according to the proxy good method. In addition, downstream macroeconomic effects were captured using value-added multipliers. Direct medical costs were concomitantly calculated. RESULTS: Our results show that prescribing erenumab for the indicated population in Germany could lead to a reduction of 166 million migraine days annually and reduce productivity losses in the range of €27 billion. This includes €13.1 billion from direct productivity and €13.5 billion from economic value chain effects. CONCLUSIONS: This study highlights the macroeconomic effects of a systematic introduction of novel inhibitors of the calcitonin gene-related peptide pathway for migraine in Germany.

The relationship between headache-attributed disability and lost productivity: 2. Empirical evidence from population-based studies in nine disparate countries.

BACKGROUND: Headache disorders are disabling, with major consequences for productivity, yet the literature is silent on the relationship between headache-attributed disability and lost productivity, often erroneously regarding the two as synonymous. We evaluated the relationship empirically, having earlier found that investment in structured headache services would be cost saving, not merely cost-effective, if reductions in headache-attributed disability led to > 20% pro rata recovery of lost productivity. METHODS: We used individual participant data from Global Campaign population-based studies conducted in China, Ethiopia, India, Nepal, Pakistan and Russia, and from Eurolight in Lithuania, Luxembourg and Spain. We assessed relationships in migraine and probable medication-overuse headache (pMOH), the most disabling common headache disorders. Available symptom data included headache frequency, usual duration and usual intensity. We used frequency and duration to estimate proportion of time in ictal state (pTIS). Disability, in the sense used by the Global Burden of Disease study, was measured as the product of pTIS and disability weight for the ictal state. Impairment was measured as pTIS * intensity. Lost productivity was measured as lost days (absence or < 50% productivity) from paid work and corresponding losses from household work over the preceding 3 months. We used Spearman correlation and linear regression analyses. RESULTS: For migraine, in a linear model, we found positive associations with lost paid worktime, significant (p < 0.05) in many countries and highly significant (p < 0.001) in some despite low values of R2 (0-0.16) due to high variance. With lost household worktime and total lost productivity (paid + household), associations were highly significant in almost all countries, although still with low R2 (0.04-0.22). Applying the regression equations for each country to the population mean migraine-attributed disability, we found pro rata recoveries of lost productivity in the range 16-56% (> 20% in all countries but Pakistan). Analysing impairment rather than disability increased variability. For pMOH, with smaller numbers, associations were generally weaker, occasionally negative and mostly not significant. CONCLUSION: Relief of disability through effective treatment of migraine is expected, in most countries, to recover > 20% pro rata of lost productivity, above the threshold for investment in structured headache services to be cost saving.

Burden and attitude to resistant and refractory migraine: a survey from the European Headache Federation with the endorsement of the European Migraine & Headache Alliance.

BACKGROUND: New treatments are currently offering new opportunities and challenges in clinical management and research in the migraine field. There is the need of homogenous criteria to identify candidates for treatment escalation as well as of reliable criteria to identify refractoriness to treatment. To overcome those issues, the European Headache Federation (EHF) issued a Consensus document to propose criteria to approach difficult-to-treat migraine patients in a standardized way. The Consensus proposed well-defined criteria for resistant migraine (i.e., patients who do not respond to some treatment but who have residual therapeutic opportunities) and refractory migraine (i.e., patients who still have debilitating migraine despite maximal treatment efforts). The aim of this study was to better understand the perceived impact of resistant and refractory migraine and the attitude of physicians involved in migraine care toward those conditions. METHODS: We conducted a web-questionnaire-based cross-sectional international study involving physicians with interest in headache care. RESULTS: There were 277 questionnaires available for analysis. A relevant proportion of participants reported that patients with resistant and refractory migraine were frequently seen in their clinical practice (49.5% for resistant and 28.9% for refractory migraine); percentages were higher when considering only those working in specialized headache centers (75% and 46% respectively). However, many physicians reported low or moderate confidence in managing resistant (8.1% and 43.3%, respectively) and refractory (20.7% and 48.4%, respectively) migraine patients; confidence in treating resistant and refractory migraine patients was different according to the level of care and to the number of patients visited per week. Patients with resistant and refractory migraine were infrequently referred to more specialized centers (12% and 19%, respectively); also in this case, figures were different according to the level of care. CONCLUSIONS: This report highlights the clinical relevance of difficult-to-treat migraine and the presence of unmet needs in this field. There is the need of more evidence regarding the management of those patients and clear guidance referring to the organization of care and available opportunities.

Structured headache services as the solution to the ill-health burden of headache: 1. Rationale and description

In countries where headache services exist at all, their focus is usually on specialist (tertiary) care. This is clinically and economically inappropriate: most headache disorders can effectively and more efficiently (and at lower cost) be treated in educationally supported primary care. At the same time, compartmentalizing divisions between primary, secondary and tertiary care in many health-care systems create multiple inefficiencies, confronting patients attempting to navigate these levels (the "patient journey") with perplexing obstacles.High demand for headache care, estimated here in a needs-assessment exercise, is the biggest of the challenges to reform. It is also the principal reason why reform is necessary.The structured headache services model presented here by experts from all world regions on behalf of the Global Campaign against Headache is the suggested health-care solution to headache. It develops and refines previous proposals, responding to the challenge of high demand by basing headache services in primary care, with two supporting arguments. First, only primary care can deliver headache services equitably to the large numbers of people needing it. Second, with educational supports, they can do so effectively to most of these people. The model calls for vertical integration between care levels (primary, secondary and tertiary), and protection of the more advanced levels for the minority of patients who need them. At the same time, it is amenable to horizontal integration with other care services. It is adaptable according to the broader national or regional health services in which headache services should be embedded.It is, according to evidence and argument presented, an efficient and cost-effective model, but these are claims to be tested in formal economic analyses.

The socioeconomic burden of migraine: An evaluation of productivity losses due to migraine headaches based on a population study in Germany.

BACKGROUND: This study estimates the socioeconomic impact of migraine headaches on paid and unpaid work productivity in the adult German population in 1 year. METHODS: We used data on headache frequency (days per month) from a longitudinal population-based study. Prevalence estimates of migraine were derived from the Global Burden of Disease Collaborative Network. Demography data were derived from official statistics in 2017. Aggregate headache days in 1 year were translated to losses in paid and unpaid productive hours based on estimates of presenteeism and absenteeism along with other socioeconomic parameters. Paid hours lost were distributed across the industry sectors. In this way, an age-, gender- and industry sector-specific monetary value was calculated for paid hours lost. Unpaid hours lost were valued by assigning the unpaid activities to their nearest market substitute. In a last step, value-added multipliers derived from input-output tables were used to calculate the economic value chain effects. RESULTS: A total of 15.5 million persons (20 years or older) suffer from migraine in Germany. Our analysis shows that 60% of those have three or fewer headache days per month, while patients suffering chronic migraine (15+ headache days per month) account for 5.4% of the adult migraine population. Females bear 65% of the total 836 million headache days per year. The socioeconomic losses due to migraine amount to €100.4 billion (€6493 on average per patient) in one year. CONCLUSION: In addition to time losses in paid work, migraine causes substantial socioeconomic losses to unpaid work activities due to its disproportionate prevalence among females. Economic value chain effects provide a novel perspective on losses beyond a patient's time loss. Overall, the elements of socioeconomic burden provide a strong rationale that innovative migraine therapies could be of high value to society.

The Many Faces of Medication-Overuse Headache in Clinical Practice.

The management of medication-overuse headache (MOH) is multifaceted and headache experts have different views on the optimal strategy to tackle this type of secondary headache. The purpose of this review is to provide an overview of the literature on the management of MOH, and to highlight important considerations in the clinical evaluation of the MOH patient. Managing MOH in clinical practice starts by evaluating the headache patient with medication overuse, determining the overused drug(s), assessing the impact of headaches on the patient and assessing comorbid conditions and disorders. Withdrawal of the overused medication is the cornerstone of treatment. An inpatient or outpatient setting is chosen based on the clinical profile of the patient. There is evidence for abrupt withdrawal combined with headache preventive treatment. Bridging therapy to bring relief to withdrawal headaches and/or symptoms should be offered. Education and motivational work through multidisciplinary assessment show benefits in sustaining withdrawal and preventing relapse. Although the reversal of chronic headache after cessation of overused acute medication has been noticed worldwide, different aspects of the management of MOH, such as complete or gradual withdrawal, or preventive treatment with or without withdrawal are still debated.

Administrative prevalence and incidence, characteristics and prescription patterns of patients with migraine in Germany: a retrospective claims data analysis.

BACKGROUND: Migraine is a frequent headache disorder with high disease burden. The aims of this study were to determine the administrative prevalence and incidence of migraine in Germany; and to elucidate disease characteristics, prescription patterns and the patient journey through the German healthcare system. METHODS: In this retrospective, observational study, adult patients with migraine (International Classification of Diseases, 10th revision, German modification G43) were identified in the anonymised German Company Sickness Fund database (CSFD) from 2008 through 2016. The administrative prevalence and incidence of migraine were calculated for the total CSFD study population and extrapolated to the German Statutory Health Insurance (SHI) population. Migraine subtypes, concurrent diagnoses, prescription patterns and visited healthcare professional groups were analysed. RESULTS: A total of 243,471 patients with migraine were identified in the CSFD (2008-2016); 78.0% were female and 45.3% were aged 35-54 years. The administrative prevalence of migraine, extrapolated to the SHI population, ranged between 2.89% in 2008 and 3.98% in 2016; administrative incidence ranged from 0.587% in 2009 to 0.267% in 2016, and varied between 0.399% and 0.442% during 2011 to 2015. Overall, 29.1% of patients received at least one prescription for any preventive medication listed in the German guideline. Only 7.9% received the same preventive medication for more than 1 year, with 82.9% of these patients discontinuing the medication before study end. Regarding acute medications, 74.2% of prescriptions were for analgesics/non-steroidal anti-inflammatory drugs and 21.2% were for triptans. General practitioners most commonly diagnosed and treated migraine in the CSFD population. Patients with prescriptions for two or more different preventive therapy classes had higher use of acute and emergency medications, and visited healthcare professionals and hospitals more frequently than patients with no prescriptions or prescriptions for only one preventive therapy class. CONCLUSIONS: The administrative prevalence of migraine in this claims database suggests many patients with migraine did not seek medical care. Of those who did, fewer than one-third received preventive medication, with most patients having been prescribed only one such medication and few having continued treatment beyond 1 year. These outcomes suggest there is scope for improvement in migraine management in Germany.

The impact of fremanezumab on medication overuse in patients with chronic migraine: subgroup analysis of the HALO CM study.

BACKGROUND: We evaluated the efficacy of fremanezumab, a fully humanized monoclonal antibody that selectively targets calcitonin gene-related peptide, in patients with chronic migraine (CM) with and without medication overuse (MO). METHODS: In a 12-week, phase 3 trial, patients with CM were randomized to fremanezumab quarterly (675 mg/placebo/placebo), monthly (675 mg/225 mg/225 mg), or placebo. Post hoc analyses assessed the impact of fremanezumab in patients with and without MO (monthly use of acute headache medication ≥15 days, migraine-specific acute medication ≥10 days, or combination medication ≥10 days) on efficacy outcomes, including headache days of at least moderate severity (HDs), and six-item Headache Impact Test (HIT-6) and Migraine-Specific Quality of Life (MSQoL) questionnaire scores. RESULTS: Of 1130 patients enrolled, 587 (51.9%) had baseline MO. Fremanezumab reduced placebo-adjusted least-squares mean (95% confidence interval) monthly HDs (- 2.2 [- 3.1 to - 1.2] and - 2.7 [- 3.7 to - 1.8]; P < 0.0001) in patients with MO and without MO (quarterly - 1.4 [- 2.3 to - 0.5], P = 0.0026; monthly - 1.4 [- 2.3 to - 0.6], P = 0.0017). Significantly more fremanezumab-treated patients had ≥ 50% reduction in HDs versus placebo, regardless of baseline MO (with: quarterly 70/201 [34.8%], monthly 78/198 [39.4%] vs placebo 26/188 [13.8%]; without: quarterly 71/174 [40.8%], monthly 75/177 [42.4%] vs placebo 41/183 [22.4%]). Fremanezumab improved HIT-6 and MSQoL scores. Significantly more fremanezumab-treated patients reverted to no MO (quarterly 111/201 [55.2%], monthly 120/198 [60.6%]) versus placebo (87/188 [46.3%]). CONCLUSIONS: Fremanezumab is effective for prevention of migraine in patients with CM, regardless of MO, and demonstrated a benefit over placebo in reducing MO. TRIAL REGISTRATION: ClinicalTrials.gov NCT02621931 (HALO CM), registered December 12, 2012.

European headache federation consensus on the definition of resistant and refractory migraine : Developed with the endorsement of the European Migraine & Headache Alliance (EMHA).

INTRODUCTION: Despite advances in the management of headache disorders, some patients with migraine do not experience adequate pain relief with acute and preventive treatments. It is the aim of the present document to provide a definition of those migraines which are difficult-to-treat, to create awareness of existence of this group of patients, to help Healthcare Authorities in understanding the implications, and to create a basis to develop a better pathophysiological understanding and to support further therapeutic advances. MAIN BODY: Definitions were established with a consensus process using the Delphi method. Patients with migraine with or without aura or with chronic migraine can be defined as having resistant migraine and refractory migraine according to previous preventative failures. Resistant migraine is defined by having failed at least 3 classes of migraine preventatives and suffer from at least 8 debilitating headache days per month for at least 3 consecutive months without improvement; definition can be based on review of medical charts. Refractory migraine is defined by having failed all of the available preventatives and suffer from at least 8 debilitating headache days per month for at least 6 consecutive months. Drug failure may include lack of efficacy or lack of tolerability. Debilitating headache is defined as headache causing serious impairment to conduct activities of daily living despite the use of pain-relief drugs with established efficacy at the recommended dose and taken early during the attack; failure of at least two different triptans is required. CONCLUSIONS: We hope, that the updated EHF definition will be able to solve the conflicts that have limited the use of definitions which have been put forward in the past. Only with a widely accepted definition, progresses in difficult-to-treat migraine can be achieved. This new definition has also the aim to increase the understanding of the impact of the migraine as a disease with all of its social, legal and healthcare implications. It is the hope of the EHF Expert Consensus Group that the proposed criteria will stimulate further clinical, scientific and social attention to patients who suffer from migraine which is difficult-to-treat.

Epidemiology of migraine in men: Results from the Chronic Migraine Epidemiology and Outcomes (CaMEO) Study.

OBJECTIVE: To assess migraine epidemiology in men by examining gender differences in disease presentation, comorbidities, and prognosis. PATIENTS AND METHODS: The Chronic Migraine Epidemiology and Outcomes (CaMEO) Study is a longitudinal survey of US adults with migraine identified by web questionnaire. Data were stratified by gender, collected between September 2012-November 2013, and included sociodemographics, headache features, Migraine Disability Assessment, Migraine Symptom Severity Score, Allodynia Symptom Checklist, and comorbidities. Discrete time hazard models addressed 1-year likelihood of transition from episodic to chronic migraine headache frequency. RESULTS: Of the 16,789 migraine respondents, 4294 were men (25.6%). Compared to women, men were slightly older at onset of their headaches (mean 24.1 vs. 22.3 years) and had fewer headache days/month (4.3 vs. 5.3 days), slightly less severe attacks (Migraine Symptom Severity Score, 21.6 vs. 22.6), reduced frequencies of grade IV Migraine Disability Assessment scores (15.7% vs. 24.1%), allodynia (32.6% vs. 49.7%), chronic migraine (6.5% vs. 9.6%, each p < 0.001), and common comorbidities. Men were less likely to report consulting a doctor for their headaches and receiving a migraine diagnosis if they consulted. Men and women with episodic migraine had similar crude 1-year risk of chronic migraine onset. Controlling for known risk factors (i.e. depression, headache frequency, allodynia), men had greater likelihood of chronic migraine onset at 6, 9, and 12 months (each p < 0.05). CONCLUSIONS: Findings confirmed gender differences. Men with migraine generally have less severe attacks and disability and are less likely to receive a diagnosis than women with migraine. Prognostic factors may be better understood for women than men.

Psychological, clinical, and therapeutic predictors of the outcome of detoxification in a large clinical population of medication-overuse headache: A six-month follow-up of the COMOESTAS Project.

AIM: To identify factors that may be predictors of the outcome of a detoxification treatment in medication-overuse headache. METHODS: Consecutive patients entering a detoxification program in six centres in Europe and Latin America were evaluated and followed up for 6 months. We evaluated anxious and depressive symptomatology (though patients with severe psychiatric comorbidity were excluded), quality of life, headache-related disability, headache characteristics, and prophylaxis upon discharge. RESULTS: Of the 492 patients who completed the six-month follow up, 407 ceased overuse following the detoxification (non overusers), another 23 ceased overuse following detoxification but relapsed during the follow-up. In the 407 non-overusers, headache acquired an episodic pattern in 287 subjects (responders). At the multivariate analyses, lower depression scores (odds ratio = 0.891; p = 0.001) predicted ceasing overuse. The primary headache diagnosis - migraine with respect to tension-type headache (odds ratio = 0.224; p = 0.001) or migraine plus tension-type headache (odds ratio = 0.467; p = 0.002) - and the preventive treatment with flunarizine (compared to no such treatment) (odds ratio = 0.891; p = 0.001) predicted being a responder. A longer duration of chronic headache (odds ratio = 1.053; p = 0.032) predicted relapse into overuse. Quality of life and disability were not associated with any of the outcomes. CONCLUSIONS: Though exploratory in nature, these findings point to specific factors that are associated with a positive outcome of medication-overuse headache management, while identifying others that may be associated with a negative outcome. Evaluation of the presence/absence of these factors may help to optimize the management of this challenging groups of chronic headache sufferers.