Migraine Epidemiology and burden - PowerPoint Presentation

1. MigraineEpidemiology and burden1

2. MigraineMigraine epidemiologyAn estimated 1.3 billion individuals across the globe were estimated to have migraine in 20171In the WHO Global Burden of Disease study, ‘headache disorders’ has consistently been the 2nd most prevalent disease in the world1Women are approximately 3 times more likely than men to have migraine2 Among people aged less than 50 years old, migraine is the most common cause of disabillity3Migraine is associated with high levels of disability and comorbidity, including an increased risk of insomnia, depression, and anxiety4WHO=World Health Organization1. GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Lancet 2018;392(10159):1789–1858; 2. Gasparini et al. Curr Genomics 2013;14(5):300–315; 3. Steiner et al. J Headache Pain 2018;19(1):17; 4. Buse et al. J Headache Pain 2020;21(1):23Migraine is a highly prevalent and burdensome condition2

3. Prevalence of migraineMigraine

4. MigraineMigraine and headache in the WHO GBD studyGBD=Global Burden of Disease; WHO=World Health Organization; YLD=years lived with disability1. GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Lancet 2018;392:1789–1858; 2. GBD 2016 Headache Collaborators. Lancet Neurol 2018;17(11):954–976The WHO GBD 2017 study estimated that 1.3 billion individuals across the globe have migraine1In a detailed, migraine-focused analysis of the GBD 2016 study, the global age-standardised prevalence of migraine was 14.4% (18.9% for women, and 9.8% for men)2In the same analysis, the global age-standardised prevalence of tension-type headache was 26.1% (30.8% for women, and 21.4% for men)2There appear to be variations in the geographical spread of migraine – the prevalence is highest in Italy and Nepal, and lowest in China, although there may be differences in methodology between countries2Between 1990 and 2016, the estimated years lived with disability (YLDs) associated with migraine increased from 29.8 million to 45.1 million – an increase of 51.2%24

5. MigrainePrevalence of migraine with and without auraUSA=United States of America1. Weatherall. Ther Adv Chronic Dis 2015;6(3):115–123; 2. Queiroz et al. Cephalalgia 2011;31(16):1652–1658; 3. Takeshima et al. Headache 2004;44:8–19; 4. Zivadinov et al. Headache 2001;41:805–812; 5. Lipton et al. Neurology 2002;58(6):885–894Migraine without aura is more common than migraine with aura1It can be broadly estimated that 20% of individuals with migraine usually (but not always) experience migraine attacks with aura;1 estimates range from 11.9–44.3%2-4Migraine without aura(80%)FemalesMalesMigraine with aura(1.9%)Migraine(17.2%)Migraine(6.0%)(80%) Migraine without auraA telephone survey in the USA randomly interviewed 4,376 individuals, 568 of whom with migraine:5The 1-year period prevalence of migraine55(20%) Migraine with aura

6. MigrainePrevalence of migraine by age and sex1. Finocchi & Strada. Neurol Sci 2014;35(Suppl 1):S207–213; 2. Victor et al. Cephalalgia 2010;30(9):1065–1072; 3. Lipton & Bigal. Headache 2005;45(Suppl 1):S3–S13; 4. GBD 2016 Headache Collaborators. Lancet Neurol 2018;17(11):954–976; 5. Weatherall. Ther Adv Chronic Dis 2015;6(3):115–123; 6. Buse et al. Headache 2013;53(8):1278–1299Prevalence of migraine1The prevalence of migraine generally increases with age up to approximately 30–40 years, at which point the prevalence peaks1-3Migraine is more common among women than among men1-6Migraine is the most common cause of recurrent headaches, and is said be experienced at some point by and 1 in 10 men, and 1 in 5 women56

7. MigraineFemale versus male prevalence of migraine1. Weatherall. Ther Adv Chronic Dis 2015;6(3):115–123; 2. Vetvik & MacGregor. Lancet Neurol 2017;16(1):76–87; 3. Ripa et al. Int J Womens Health 2015;7:773–782; 4. Martin et al. Headache 2016;56(2):292–305; 5. Pinkerman & Holroyd. Cephalalgia 2010;30:1187–1194Migraine affects women disproportionately more than it does men1,2Women tend to report longer duration of migraine attacks compared with men2Population studies have shown that migraine frequency and symptoms improve in women after menopause2,3 However, there are inconsistencies across studies about difference in pain intensity, and attack frequency2The sex difference in migraine prevalence and risk of migraine attacks is thought to be partly due to the role of female hormones:Migraine prevalence peaks around menstruation2,3Migraine prevalence is thought to increase during the menopause transition period4Female hormones are also thought to effect structural brain changes, increasing the risk of migraine, or decreasing a threshold below which migraine symptoms may emerge2Genetic differences between men and women may partly explain the increased migraine risk in women2151015-5-10-15Day of menstrual cycleEstrone-3-glucuronidePregnanediol-3-glucuronideIncidenceof migraineIncidence of migraine versus mean female hormone concentrations across the menstrual cycle2,57

8. MigraineMigraine as a global health crisis – the top cause of disability in the under 50s1GBD=Global Burden of Disease; USA=United States of America; WHO=World Health Organization1. Steiner et al. J Headache Pain 2018;19(1):17; 2. GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Lancet 2018;392:1789–1858; 3. IHME. http://ghdx.healthdata.org/gbd-results-tool. Accessed Jun 2020; 4. GBD 2016 Headache Collaborators. Lancet Neurol 2018;17(11):954–976; 5. GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Lancet 2017;390(10100):1211–1259The WHO GBD 2017 study estimated that 1.3 billion individuals were affected by migraine across the globe2Migraine has a detrimental effect on public health, and is a major contributor to disability throughout the world, both in high-income and low-income countries1,4During the most productive years of a person’s life (15–49 years old), migraine is the leading cause of years lived with disability for women, and the second highest for men1,5If future population-based studies – needed to fill the current gaps in knowledge – are standardised and of high quality, this would allow future iterations of disease burden surveys to show the relative importance of headache and migraine, and track improvements in care, and treatment1An estimated 68.5 million individuals were affected by migraine in the USA in 20172,3Among people aged <50 years old, migraine is the most common neurological disorder18

9. MigraineGlobal burden of migrainehttps://vizhub.healthdata.org/gbd-compare/ Global Burden of Disease Collaborative Network, Global Burden of Disease Study 2017 (GBD 2017) Results, Seattle, United States: Institute for Health Metrics and Evaluation (IHME), 2018, Available from http://ghdx.healthdata.org/gbd-results-tool9

10. Risk factors for the onset of migraineMigraine

11. MigraineGeneticsGWAS=genome-wide association studies; SNP=single nucleotide polymorphism1. Sutherland et al. J Headache Pain 2019;20(1):72;2. van den Maagdenberg et al. J Headache Pain 2019;20(1):5Migraine is clearly a multifaceted disorder, and whilst there are many risk factors, including demographic and socioeconomic factors, a person’s genetics is an important risk factor for developing migraine1There are several specific migraine-related disorders with known genetic causes; e.g., familial hemiplegic migraine, or Mendelian migraine with aura, both of which can be caused by mutations in genes encoding ion channels1Family and twin studies also suggest that migraine, and migraine with aura, are heritable traits –heritability estimates range from 30–60%1However, migraine and migraine with aura are thought to be polygenic disorders, meaning that the phenotype is the result of the contribution of several gene loci with individually small risks1GWAS have compared the genomes of hundreds of thousands of individuals with migraine versus those of control individuals1SNPs and gene loci identified in GWAS have highlighted some common themes, which include vascular function, metal ion homeostasis, and ion channel activitity111

12. MigraineLifestyle factors and migraine riskDMKG=German Migraine and Headache Society; HUNT=Nord-Trøndelag Health Surveys; OR=odds ratio; RR=risk ratio1. Winter et al. J Headache Pain 2011;12:147–155; 2. Hagen et al. Cephalalgia 2018;38(13):1919–1926The German DMKG study used data from 7,417 participants to analyse the effect of 4 lifestyle factors on headache and migraine risk:1The HUNT study evaluated the effect of these same lifestyle factors at baseline on the risk of headache 11 years later in 15,276 participants without headache at baseline:2Alcohol consumptionBody mass indexPhysical activitySmokingInconsistent resultsParticipants who exercised ≥2 hr/week had a decreased risk of tension-type headache (not significant)Inconsistent resultsAlcohol consumption tended to be associated with a decreased risk of experiencing migraine (not significant)Alcohol consumptionBody mass indexPhysical activitySmokingNo association was foundReduced migraine risk among those who engaged in 1–2 hr/week of hard exercise (OR: 0.71; 95% CI: 0.54, 0.94)Increased migraine risk among smokers(RR: 1.30; 95% CI: 1.11, 1.52)Reduced migraine risk among those who used alcohol ≥8 times/month(RR: 0.52; 95% CI: 0.32, 0.82)12

13. MigraineMigraine attack triggers1. Turner et al. Headache 2019;59(4):495–508; 2. Wöber et al. J Headache Pain 2006;7(4):188–195; 3. Pavlovic et al. Headache 2014;54(10):1670–1679; 4. Sarchielli. J Headache Pain 2006;7:172–173; 5. Hoffmann & Recober. Curr Pain Headache Rep 2013;17(10):370; 6. Lipton et al. Headache 2014;54(10):1661–1669; 7. Onderwater et al. Eur J Neurol 2019;26(4):588–595; 8. Hagen et al. Cephalalgia 2018;38(13):1919–1926EmotionalPhysicalDietaryEnvironmentalFor individual patients, keeping diaries can be invaluable for identifying potential trigger factors1However, it is methodologically difficult to distinguish some premonitory symptoms from trigger factors5,6Furthermore, separating risk factors from migraine triggers and premonitory symptoms is difficult:In the LUMINA study of 2,197 people with migraine, alcoholic beverages (most commonly red wine) were reported to be a migraine trigger by 35.6% of people7However, red wine consistently led to a migraine attack in only 8.8% of participants7In other longitudinal studies, alcohol consumption is associated with a decreased risk of developing migraine8Alcohol is frequently identified as a migraine trigger, but this is challenged by the low rate of migraine provocation observed in several studies8StressSleep deprivationFatigueWeatherOver eatingFastingCaffeineAlcoholSmokingNoiseSunlightOdoursHormonal changes in womenExcessive sleepRelaxation from stressMigraine attack triggers – some trigger factors relate to changes in those conditions1-413

14. The economic burden of migraineMigraine

15. MigraineThe economic burden of migraineUSA=United States of America1. Hawkins et al. Headache 2008;48(4):553–563; 2. Hawkins et al. J Occup Environ Med 2007;49(4):368–37415Direct costs of migraineExamples of direct costs include prescription medication, and hospitalisation1A study of 215,209 people with migraine found that migraine was associated with $2,571 greater costs per person per year:1People with migraine: $7,007Control individuals: $4,436Estimates of direct migraine costs across the whole of the USA were:1Outpatient care: $5.21 billionPrescriptions: $4.61 billionInpatient care: $0.73 billionEmergency department care: $0.52 billionIndirect costs of migraineExamples of indirect costs include lost productivity at work, and workplace absence2An analysis of 6,622 people with migraine found that migraine was associated with $2,834 greater indirect workplace costs per person per year:2People with migraine: $4,453 Control individuals: $1,619The indirect cost of migraine across the whole of the USA was estimated to be $12 billion2Increased knowledge, and access to appropriate migraine management, are likely to help in reducing the economic burden of migraine2

16. MigraineMean total annual costs per person with episodic or chronic migraineAdapted from: Bloudek et al. J Headache Pain 2012;13(5):361–378Episodic migraineUKSpainItalyGermanyFranceChronic migraineAnnual cost:€1,579.00Annual cost:€866.56Annual cost:€486.28Annual cost:€1,495.20Annual cost:€2,648.12Annual cost:€696.12Annual cost:€828.52Annual cost:€1,092.48HospitalisationHealthcare provider visitsProceduresMedicationAnnual cost:€3,718.44Annual cost:€2,669.8016

17. MigraineIndirect costs of migraine – lost productivity1. Messali et al. Headache 2016;56(2):306–322; 2. Burton et al. Mayo Clin Proc 2009;84(5):436–445Indirect productivity costs per person over the past 3 months1Employed full-timeEmployed part-timeEpisodic migraine (n=1,101)Chronic migraine (n=103)p<0.05Days (mean)Cost ($)Cost ($)Days (mean)Days (mean)p<0.001p<0.001p<0.05p<0.001A systematic literature review found that, of studies that reported pre- and post-attack productivity losses, patients treated with triptan therapy experienced less of a productivity loss than patients treated with therapy as usual, with a difference of approximately 0.5–2.0 days2The total indirect cost of chronic migraine was 3x greater than that of episodic migraine117

18. The burden of migraineMigraine

19. MigraineThe burden of migraine1. Agosti. Headache 2018;58(Suppl 1):17–32; 2. Raggi et al. J Headache Pain 2012;13(8):595–606; 3. Smitherman et al. Headache 2013;53(3):427–436; 4. Buse et al. Headache 2019;59(8):1286–1299; 5. Martelletti et al. J Headache Pain 2018;19(1):115Migraine is a burdensome condition, and has a substantial impact on activities of daily living, such as work and career, school life, social activities, and relationships1-5A systematic literature review of the burden of migraine identified several psychosocial difficulties relevant to patients with migraine:2Energy and drive – fatigue, reduced vitality, difficulties with sleepEmotional functioning – depressive symptoms, anxiety, stress, angerPain – general pain, and the sensation of painEmployment – reduced efficiency at work, restriction in time given to work, partial absenceGeneral physical and mental health – general mobility, carrying out daily routineSocial functioning – relationships with others, family relationships, leisure activities Global disability – global functioning, quality of life, self-efficacyMany of the psychosocial difficulties identified in the review (e.g., emotional functioning, and employment) appeared to respond well to migraine therapy, particularly preventive treatment219

20. MigraineMigraine and stigmaSSCI=Stigma Scale for Chronic Illness1. Parikh & Young. Curr Pain Headache Rep 2019;23(1):8; 2. Basoglu Koseahmet et al. Neurol Sci 2022;43(6):3831–3838; 3. Young et al. PLoS One 2013;8(1):e54074Stigma affects social attitudes towards people with migraine, which increases the burden of this already burdensome condition1As ‘invisible’ conditions, diseases such as migraine and epilepsy, which do not have obvious outwardly visible physical effects, can lead to enacted (external) stigmatization as well as internalized (self) stigmatization2,3One study interviewed 246 people with migraine and 62 patients with epilepsy about stigma:3People with chronic migraine had significantly higher scores on the SSCI than people episodic migraine or patients with epilepsy (p<0.001)Ability to work was the strongest predictor of stigma, as measured by the SSCIBecause people with chronic migraine were less able to work than people with episodic migraine, those with chronic migraine experienced a greater degree of stigmaEducation and advocacy are key to ‘rebranding’ migraine and reducing the stigma of this disease120

21. MigraineThe impact of migraine symptoms on individuals with migraineWHO=World Health Organization1. GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Lancet 2018;392(10159):1789–1858; 2. Mannix et al. Health Qual Life Outcomes 2016;14:143; 3. Palacios-Ceña et al. BMJ Open 2017;7(8):e017851The WHO Global Burden of Disease study has consistently ranked headache disorders in the top two of all causes of global years lost to disability1A detailed interview study of 32 patients with migraine demonstrated that migraine impacts physical functioning, social and leisure activities, and emotion – “I feel like I’m a burden to people when I have migraines”2In a qualitative interview study of 20 women with migraine, 5 key themes emerged:3The shame of suffering an ‘invisible’ conditionDistrust and skepticism of migraine treatmentsLooking for physicians’ supportLimiting the impact of migraine symptoms on daily lifeManaging family and work responsibilities21

22. MigraineMigraine-related impairment in the AMPP studyAMPP=American Migraine Prevalence and Prevention; USA=United States of America1. Lipton et al. Neurology 2007;68:343–349The AMPP survey of 77,879 households in the USA asked respondents in what way they are “usually affected by severe headaches”:1 No impairment: able to work/function normally Some impairment: working ability or activity impaired to some degree Severe impairment: working ability or activity severely impaired, or bed rest requiredThe results showed that migraine-related impairment was common:147.7% of respondents did no household work29.1% of respondents missed family or social activity25.3% of respondents missed at least 1 day of work/school 3. Severe impairment(53.7%)2. Some impairment(39.1%)1. No impairment(7.2%)Headache-related impairment during severe headache in the AMPP survey1Migraine is commonly associated with severe impairment or need for bed rest122

23. MigraineDisability weights associated with migraine and headache disordersAdapted from: Salomon et al. Lancet Glob Health 2015;3(11):e712–e723Perfect health: 0.000The continuum of disability weightsModerate low back pain: 0.054Severe anxiety disorder: 0.523Severe dementia: 0.449Crohn’s disease:0.231Patients with migraine experience a high level of disability – similar to that experienced by patients with severe dementia, and patients with heart attackMigraine: 0.441Tension-type headache:0.037Medication overuse headache: 0.223Heart attack:0.432Spinal cord lesion: 0.589Acute schizophrenia: 0.77823

24. MigraineThe additional burden of chronic migraineMIDAS=Migraine Disability Assessment; MSQ=Migraine-Specific Quality of Life Questionnaire; PHQ-4=Patient Health Questionnaire – 4 items1. Blumenfeld et al. Cephalalgia 2011;31(3):301–315MSQ quality of life subscale scores for patients with episodic compared with chronic migraine1p<0.001p<0.001p<0.001A survey compared 499 (6%) patients with chronic migraine and 8,227 (94%) patients with episodic migraine1Patients with chronic migraine, compared with patients with episodic migraine, reported:1Greater disability (MIDAS score) Higher levels of anxiety Mean anxiety and depression PHQ-4 score: chronic migraine 5.63 versus episodic migraine 3.76, p<0.001Higher levels of healthcare resource use Patients with chronic migraine were nearly twice as likely to have visited primary care in the past 3 monthsGreater levels of comorbidityPatients with chronic migraine reported significantly higher levels of pain (39.1% vs 18.4%), vascular disease events (8.2% vs 3.3%), and psychiatric disorders (46.3% vs 28.5%)Episodic migraineChronic migrainep<0.00124

25. MigraineThe effect of migraine on quality of lifeNHWS=National Health and Wellness Survey; PRO=patient-reported outcome; QoL=quality of life1. Vo et al. J Headache Pain 2018;19(1):82; Leonardi & Raggi. J Headache Pain 2019;20(1):41; 3. Malone et al. J Pain Res 2015;8:537–547A retrospective study used data from the 2016 NHWS survey of 80,600 people across Europe:1Various PROs were compared between people with migraine (n=218) and control individuals (n=208)Across the endpoints sampled, there was an incremental burden from migraine on QoL, productivity at work, and use of healthcare resources, which increased with the frequency of migraine and headache attacks – patients with chronic migraine showed the greatest levels of burdenA literature review of migraine burden found that, between 1990–2018, there was an increased focus on 6 main themes of migraine burden:2Overall impact of migraine disordersImpact of migraine on work or school activitiesPrevalence of migraine disordersThe cost of migraine disordersImpact of migraine on family lifeThe interictal burden of migraineNegative life effects reported by patients with migraine3Migraine has a negative effect on patients’ QoL1,3 – and the stress of chronic migraine may create a vicious cycle of stress, worsening comorbidities, and more migraines325

26. MigraineThe effect of preventive treatments on the burden of migraineMSQ=Migraine-Specific Quality of Life Questionnaire; SF-36=36-item Short Form survey1. Dahlöf et al. Health Qual Life Outcomes 2007;5:56; 2. Lipton et al. Neurology 2020;95(7):e878–e888This was an analysis of a double-blind study of antiepileptic preventive treatment versus placebo (n=372) for patients with migraine (n=384)1Patients were followed over 26 weeks of treatment1Patients with migraine who responded successfully to preventive treatment with an antiepileptic showed improvements over 6 months in ability to carry out daily activities, compared with non-responders, as measured by:1 MSQ score – significant improvements in all 3 domainsSF-36 scale – significant improvements were seen in all subscales (p<0.001) except ‘Role–emotional’010203040Mean change from baselineRole function – restrictionRole function – preventionEmotional functionp<0.001p<0.001p<0.001Effect of response to preventive migraine treatment on patient functioning (MSQ scores)1Responders(n=233–235)Non-responders (n=434–435)Effective preventive treatment of migraine may reduce the burden of disease, and improve patients’ overall functioning and quality of life1,226

27. CaMEO study respondents with migraine reported that headaches negatively affected many important areas of their lives and perceived that their lives would be better or a lot better without migraine…we recommend that healthcare professionals caring for individuals with migraine ensure that they have an understanding of the overall burden of disease on the individual and their familiesBuse et al. Headache 2019;59(8):1286–129927