1. EPIDEMIOLOGY

2. General

3. 5–20% of the General Population May Suffer from Neuropathic Pain Summary of Selected Prevalence Studies Adapted from: Bouhassira D et al. Pain 2008; 136(3):380-7; de Moraes Vieira EB et al. J Pain Symptom Manage 2012; 44(2):239-51; Elzahaf RA et al. Pain Pract 2013; 13(3):198-205; Harifi G et al. Pain Med 2013; 14(2):287-92; Ohayon MM, Stingl C. Psychiatr Res 2012; 46(4):444-50; Torrance N et al. J Pain 2006;7(4):281-9; Toth C et al. Pain Med 2009; 10(5):918-29;

4. Up to 20% of the General Population May Suffer from Neuropathic Pain Summary of Prevalence Studies Using Case Ascertainment Tool Adapted from: van Hecke O et al. Pain 2014; 155(4):654-62. DN4S-LANSS DN4, S-LANSS part A and additional questions Tool used

5. Neuropathic Pain is Prevalent Across a Range of Different Conditions HIV = human immunodeficiency virus 1. Sadosky A et al. Pain Pract 2008; 8(1):45-56; 2. Davis MP, Walsh D. Am J Hosp Palliat Care 2004; 21(2):137-42; 3. So YT et al. Arch Neurol 1988; 45(9):945-8; 4. Schifitto G et al. Neurology 2002; 58(12):1764-8; 5. Morgello S et al. Arch Neurol 2004; 61(4):546-51; 6. Stevens PE et al. Pain 1995; 61(1):61-8; 7. Smith WC et al. Pain 1999; 83(1):91-5; 8. Freynhagen R et al. Curr Med Res Opin 2006; 22(10):1911-20; 9. Andersen G et al. Pain 1995; 61(2):187-93; 10. Siddall PJ et al. Pain. 2003; 103(3):249-57; 11. Rae-Grant AD et al. Mult Scler 1999; 5(3):179-83. 11–26% 1 ~33% 2 35–53% 3–5 20–43% of mastectomy patients 6,7 Up to 37% 8 Diabetes Cancer HIV Post-surgical Postherpetic neuralgia Chronic low back pain 8% 9 75% 10 ~55% 11 Stroke Spinal cord injury Multiple sclerosis 7–27% of patients with herpes zoster 1 Condition % affected by peripheral neuropathic pain % affected by central neuropathic pain

6. Patients Suffering from Neuropathic Pain in Primary Care Represent Wide Variety of Etiologies Incidence of neuropathic back pain may be overestimated due to study definitions. UK = United Kingdom Adapted from: Hall GC et al. BMC Fam Pract 2013; 14:28.

7. Prevalence of Painful Diabetic Peripheral Neuropathy in Type 2 Diabetes 26% had painful diabetic peripheral neuropathy Associated with decreased quality of life 80% of patients report moderate to severe pain Davies M et al. Diabetes Care 2006; 29(7):1518-22.

8. Total 40–64 65+ Prevalence of Peripheral Neuropathy among Adults Aged 40 and Older Increases by Positive Diabetic Status and Age Source: National Health and Nutrition Examination Survey (NHANES). 1999–2004. Symptomatic persons reported numbness/loss of feeling or painful sensations/tingling in feet during the preceding 3 months; age-sex adjusted to the 2000 United States standard population. Pfizer Medical Division. The Burden of Pain Among Adults in the United States. Pfizer Inc.; New York, NY: 2008.

9. 20002030 Americas33,016,00066,812,000 Africa7,020,00018,324,000 Eastern Mediterranean15,188,00042,600,000 Europe33,332,00047,973,000 South-East Asia46,903,000119,541,000 Western Pacific35,771,00071,050,000 Worldwide171,000,000366,000,000 1.Sadosky A et al. Pain Pract 2008; 8(1):45-56; 2.World Health Organization. Country and Regional Data on Diabetes. Available at: http://www.who.int/diabetes/facts/world_figures/en/. Accessed: August 23, 2013.http://www.who.int/diabetes/facts/world_figures/en/ Estimated Prevalence of Diabetes 2 Up to 26% of People with Diabetes Develop Painful Diabetic Peripheral Neuropathy 1

10. Percentage Prevalence of Neuropathic Symptoms in 15,659 Diabetic Patients Characterized by Their Level of Clinical Neuropathy Patients with Severe Neuropathy Are More Likely to Experience Pain Related to Diabetic Peripheral Neuropathy NDS = neuropathy disability score Abbott CA et al. Diabetes Care 2011; 34(10):2220-4. Percentage Prevalence of Neuropathic Symptoms in 15,659 Diabetic Patients Characterized by Their Level of Clinical Neuropathy 70 60 50 40 30 20 10 0 % No neuropathy (NDS  2) n = 8033 Mild neuropathy (NDS 3–5) n = 4293 Moderate neuropathy (NDS 6–8) n = 2700 Severe neuropathy (NDS 9, 10) n = 633 No symptomsMild symptomsModerate symptoms Severe symptoms

11. Risk Factors for Painful Diabetic Neuropathy Include Gender, Ethnicity and Type 2 Diabetes OR = odds ratio; CI = confidence interval Abbott CA et al. Diabetes Care 2011; 34(10):2220-4.

12. A1C = glycosylated hemoglobin; BMI = body mass index; CI = confidence interval; OR = odds ratio Tesfaye S et al. N Engl J Med 2005; 352(4):341-50. Total cholesterol Triglycerides BMI Diabetes duration Change in A1C A1C Smoking Hypertension 1.57 1.38 1.48 1.36 1.40 1.27 1.21 1.15 Model 1: without cardiovascular disease and retinopathy OR (95% CI) n = 1101 with type 1 diabetes Follow-up: 7.3 ± 0.6 years Vascular Risk Factors and Diabetic Neuropathy

13. Incidence of Herpes Zoster and Postherpetic Neuralgia May Be Increasing Annual incidence of herpes zoster, annual incidence of postherpetic neuralgia, and percentage of patients with herpes zoster who developed postherpetic neuralgia in Harvard Vanguard Medical Associates, 1996-2008. Figure is adjusted for age and sex relative United States Census 2000. Klompas M et al. Mayo Clin Proc 2011; 86(12):1146-53. 4.0 Cases per 1000 patients 1996199820002002 Herpes zoster (incidence) 20062008 3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 50 40 30 20 10 0 Herpes zoster patients with postherpetic neuralgia (%) Postherpetic neuralgia (% of herpes zoster patients) Postherpetic neuralgia (incidence) 2004

14. Incidence of Herpes Zoster Increases with Age 1 RCGP = Royal College of General Practitioners; UK = United Kingdom; US = United States 1.Johnson R et al. Int J Infect Dis 2007; 11(Suppl 2):S43-8; 2.Sadosky A et al. Pain Pract 2008; 8(1):45-56. 7–27% of patients with herpes zoster (shingles) develop postherpetic neuralgia 2 Annual incidence (per 1000 person-years 120 100 80 60 40 20 0 01020304050607080 Age 7–27% of patients with herpes zoster (shingles) develop postherpetic neuralgia 2 Canada (Manitoba) – Law* UK – Hope - Simpson UK (RCGP) - Brisson Netherlands – de Melker US (Olmsted – Yawn** US (Medstat) – Insinga*

15. Age Is the Major Risk Factor for Developing Postherpetic Neuralgia Jih JS et al. Acta Derm Venereol 2009; 89(6):612-6. % of patients with herpes zoster developing postherpetic neuralgia 40.00 1-2021-2441-6061-80˃80 Age groups (years) 30.00 20.00 10.00 0.00 Male Female 2.6 3.6 3.8 5.0 7.1 6.9 15.4 13.5 31.5 21.9

16. Risk Factors for Postherpetic Neuralgia Include Diabetes, Lymphoma, Lupus and HIV Potential risk indicatorRR (95% CI)*p value Age ≥60 years2.344 (2.171–2.532)<0.001 Systemic lupus erythematosus2.268 (1.749–2.942)<0.001 Lymphoma/leukaemia1.735 (1.319–2.282)<0.001 Diabetes mellitus1.351 (1.246–1.467)<0.001 Female gender0.953 (0.886–1.025)0.2 Liver cancer0.864 (0.651–1.148)0.32 Breast cancer0.748 (0.526–1.063)0.11 HIV/AIDS0.475 (0.264–0.856)0.01 * Model adjusted for age and sex AIDS = acquired immunodeficiency syndrome; CI = confidence interval; HIV = human immunodeficiency virus; RR = relative risk Jih JS et al. Acta Derm Venereol 2009; 89(6):612-6.

17. Summary

18. Epidemiology: Summary Up to 20% of the population may suffer from neuropathic pain. 11–26% of people with diabetes develop painful diabetic peripheral neuropathy Risk factors include: Female gender South-East Asian ethnicity Type 2 (vs. type 1) diabetes 7–27% of people with herpes zoster develop postherpetic neuralgia Increasing age is the major risk factor for postherpetic neuralgia