Migraine in the 21st Century: Lessons from Epidemiologic Studies

1. Migraine in the 21st Century: Lessons from Epidemiologic Studies Marcelo E. Bigal, M.D.; Ph.D. Global Director for Scientific Affairs ─Neuroscience Merck Research Laboratories Dept of Neurology, Albert Einstein College of Medicine

2. Overview • To review the epidemiology of migraine. Is migraine worth attention? • To review the burden of migraine on the individual, family and society. Is migraine worth recognition? • To estimate patterns of diagnosis and treatment for migraine, as well as barriers for care • To discuss the prognosis of migraine

3. Epidemiology Lesson 1 Migraine peaks with incidents in the teens and early twenties Accordingly, first migraine attacks often happen in childhood or puberty

4. 30 25 20     15     10    5   0 0 5 10 15 20 25 30 Migraine, Incidence  Female Male Incidents per 1000person-years Age at Onset Stewart et al: Am J Epidemiol 1991

5. Epidemiology Lesson 2 Migraine is Very Prevalent

6. Prevalence in adults worldwide:1-year prevalence Population or community-based surveys of >500 participants covering ages 25-60 y, using IHS or modified IHS criteria 15.5 11.6 Lyngberg 14.7 Hagen 13.2 22.3 10.0 Patel Dahlof Roh Rasmussen 10.2 14.7 8.4 23.2 11.7 Lampl O’Brien Sakai 13.3 Launer 9.6 Stewart 5.9 Schwartz Bank 14.3 Takeshima 14.0 12.2 Steiner 16.7 Stewart Lipton 7.7 Zivadinov 8.5 11.6 Wang 8.5 Kryst Lipton 9.0 13.5 Morillo 3.0 Alders Miranda 10.0 12.6 Tekle Haimanot 10.1 Morillo 9.3 Morillo 5.0 Deleu Morillo 16.3 Dent 8.2 Wiehe Morillo 5.3 Jaillard Mean: 11.2 Median: 10.2 7.3 5.0 Lavados Morillo Steiner TJ. Lifting the burden: The global campaign against headache. Lancet Neurol 2004;3(4):204-205.

7. Epidemiology Lesson 3 • In the US migraine affects over 12% of the adults • Migraine is the most common neurological disease in men (6%) • Migraine is 3 times more common in women (18%) P • Prelavence peaks in adulthood, coinciding with the peak of work productivity

8. Migraine is very common in US. Results of 3 large studies conducted 15 years apart Lipton RB, Bigal ME, Diamond M, Freitag F, Reed ML, Stewart WF. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology 2007;68(5):343-349.

9. Migraine is Most Common in Women and During Peak Productive Years Lipton RB, Stewart WF, Diamond S, Diamond ML, Reed M. Prevalence and burden of migraine in the United States: data from the American Migraine Study II. Headache 2001;41(7):646-657.

10. Epidemiology Lesson 4 The Burden of Migraine is Severe and Complex

11. Burdens of One Person’s Migraine lifestyle compromise patienthood pain and suffering personal financial costs anxiety co-morbidity employer& work colleagues family burden societal burden

12. The Several Burdens of Migraine The burden of migraine is severe and affects: • Burden on Individual: • Health-related quality of life • Disability • Interictal burden of migraine • Burden on the family: • Migraine affects relationships • Burden on society: • Costs

13. Burden on the Individual - Leading Causes of Years of Life Lost to Disability (YLDs) – WHO Report Steiner TJ. Lifting the burden: The global campaign against headache. Lancet Neurol 2004;3(4):204-205.

14. The Burden of Migraine is Not Restricted to the Attack – The Interictal Burden Symptom Burdens • During attacks • pain and suffering, leading to • reduced functional ability • Beyond the attack • fear of the next attack, leading to • avoidance behaviour and lifestyle compromise

15. 73% Less able to communicate 56% 60% Less involved with partner at home 20% From the sufferers’ perspective 56% Spend less time with partner 35% From their partners’ perspective 50% More likely to argue 29% 47% Be a better partnerwithout headaches 36% 0 20 40 60 80 100 % Sufferers affected The Family Impact of Migraine – Migraine Damages Relationships WithSufferer’s Partner USA and UK populations (245 migraine sufferers, 100 partners) Lipton et al. Cephalalgia 2003;23:429-440

16. EmergencyRoom, Other Rx Office Visits The Economic Burden of Migraine - Migraine is Costly to Society Annual Cost in the US $14.5 Billion Annually (1998) Missed Work 10% $7.9B 30% Direct Medical Cost $1.2B 60% $5.4B Reduced Productivity Hu H et al. Arch Intern Med. 1999;159:813-818.

17. Epidemiology Lesson 5: There Are Several Barriers Preventing Good Outcomes in Migraine Treatment

18. Improve Diagnosis Improve Treatment Motivate Patients to Seek Care Encourage Follow-Up Barriers to Successful Outcomes Lipton RB et al. Neurology. 1994.

19. Although Progresses Were Made, a Significant Proportion of Migraineurs are Unaware of Their Diagnosis Lipton RB, Bigal ME. Ten lessons on the epidemiology of migraine. Headache 2007;47 Suppl 1:S2-9.

20. Most People With Migraine Still Use OTC Medications 6 in 10 Sufferers Still Rely on OTCs Alone or No Medication to Manage Headache Pain Lipton RB et al. Headache. 2001;41:638-645.

21. Epidemiology Lesson 6: Comorbidities are Frequent in Migraine and Complicate Diagnosis and Treatment

22. Neurologic disorders Epilepsy Ischemic stroke Tourette’s Psychiatric disorders Depression Bipolar disease Anxiety/panic disorder Other disorders Raynaud’s Snoring/sleep apnea Asthma/allergy Noncephalic pain GI disorders Arthritis Low back pain Migraine is Comorbid With:

23. Comorbidities Increase With Increased Headache Frequency % OR=2.1 (1.7 – 2.5)* % % % OR=1.8 (1.5 – 2.2)* % OR=1.6 (1.1 – 2.4)* % % OR=1.7 (1.4 – 2.1)* % % OR=2.5 (2.1 – 3.02)* % * ORs and 95% confidence intervals adjusted for age, gender and SES (income)

24. Epidemiology Lesson 7 Although the Prognosis of Migraine is Variable, in a Subgroup Migraine Progresses Into Chronic Migraine

25. Evolution to symptom free over prolonged period of time Remission Relative clinical stability and no markers of progression Persistence • Clinical • - Evolution to chronic migraine • Functional • - Changes in the PAG • - Central sensitization • Anatomical • Lesions in the brain • Lesions outside the brain Progression Migraine Bigal ME, Lipton RB. The prognosis of migraine. Curr Opin Neurol 2008;21(3):301-308.

26. Baseline 1-year follow-up 23 (3%) New-onset CDH (180+ headache days/year) 49 (6%) Intermediate(105 to 179 headache days/year) 798Migraineurs 726 (91%) Stable controls(2 to 104 headache days/year) Scher AI et al. Pain. 2003;16:81-89. Evidence from Epidemiology

27. Risk Factors for Migraine Progression Not modifiable by health interventions FemaleSex Low Socioeconomic Status Head Trauma Modifiable by health interventions Attack Frequency Obesity Medication Overuse Caffeine Overuse Stressful life events Snoring Other Allodynia Other pain syndromes Pro-Inflammatory Status Pro-Thrombotic Status Bigal and Lipton, Headache 2006

28. Probability of Chronic Migraine as a Function of Barbiturate Exposure Bigal ME, Serrano D, Buse D, Scher A, Stewart WF, Lipton RB. Acute migraine medications and evolution from episodic to chronic migraine: a longitudinal population-based study. Headache 2008;48(8):1157-1168.

29. Probability of Chronic Migraine as a Function of Opioid Exposure Bigal ME, Serrano D, Buse D, Scher A, Stewart WF, Lipton RB. Acute migraine medications and evolution from episodic to chronic migraine: a longitudinal population-based study. Headache 2008;48(8):1157-1168.

30. Summary • Migraine is a frequent and disabling chronic disease with recurrent attacks • Migraine is common in men and 3 times more common in women • The burden of migraine is higher in the years of peak productivity • The burden of migraine affects the individual, family and society

31. Summary • Despite improvements, several barriers to good migraine outcomes still exist • Several disorders are comorbid to migraine. They complicate diagnosis and treatment • In a subgroup, migraine progresses. Risk factors for progression have been identified and should be screened and treated.