Fibromyalgia: A Chronic Widespread Neurologic Pain Condition 11/14/2018 Fibromyalgia: A Chronic Widespread Neurologic Pain Condition Disease Overview, Diagnosis, and Management PBP00542 © 2009 Pfizer Inc. All rights reserved. Printed in USA/September 2009

Pathogenesis of Fibromyalgia 11/14/2018 11/14/2018 What is Fibromyalgia? Pathogenesis of Fibromyalgia Clinical Features and Diagnosis of Fibromyalgia Management of Fibromyalgia 2 2

Central Pain Amplification Abnormal Pain Processing by CNS 11/14/2018 FM Is a Chronic Pain Condition and Is Distinct from Other Types of Pain Ref 1.a Woolf C Pg 441 Figure 1 Nociceptive Pain Neuropathic Pain Inflammatory Pain Central Pain Amplification Ref 1.a Woolf C Pg 442 Figure 1 (ie, Burn) FM is a chronic pain condition and is distinct from other types of pain Nociceptive pain is a response to a painful stimulus, such as fire. This is typically short in duration and involves acute pain1 Neuropathic pain, such as herpes zoster or diabetic peripheral neuropathy, is typically a result of damage to the nerves. Patients commonly develop a lesion or underlying condition causing the symptom1 Inflammatory pain can present with redness and swelling. Conditions such as Rheumatoid Arthritis present with inflammatory pain1 In the spectrum of clinical pain syndromes, fibromyalgia lies in the realm of central pain amplification. This is when abnormal pain processing occurs in the Central Nervous System (CNS). Often, no obvious cause can be identified.1 Fibromyalgia pain is chronic in nature Reference: Woolf CJ. Pain: Moving from Symptom Control toward Mechanism-Specific Pharmacologic Management. Ann Intern Med. 2004;140:441-451. (ie, Herpes zoster) (ie, Rheumatoid arthritis) (ie, Fibromyalgia) Painful Stimuli Neuronal Damage Inflammation Abnormal Pain Processing by CNS Ref 1.c Woolf C Pg 443 Col 1 Par 4 Lin 8-13 Ref 1.a Woolf C Pg 442 Figure 1 ------------ Ref 1.b Pg 443 Col 1 Par 4 Lin 1-6 Acute Pain Chronic Pain Adapted from Woolf C. Ann Intern Med. 2004;140:441-451. 3

Fibromyalgia (FM): A Chronic Widespread Neurologic Pain Condition 11/14/2018 Fibromyalgia (FM): A Chronic Widespread Neurologic Pain Condition Ref 1.a Wolfe et al Pg 19 Col 1 Par 1 Lin 1-3 FM is a neurological condition associated with chronic widespread pain (CWP) and tenderness1 American College of Rheumatology (ACR) criteria for the diagnosis of FM2 Chronic widespread pain Pain for ≥3 months Pain above and below the waist Pain on left and right sides of body and axial skeleton Pain at ≥11 of 18 tender points when palpated with 4 kg of digital pressure Ref 2.a Wolfe et al Pg 160 Abst Par 2 Lin 1-6 --------------- Ref 2.b Pg 171 Table 8 Ref 2.d Wolfe et al Pg 169 Col 1 Par 1 Lin 1-4 Fibromyalgia (FM) is a chronic widespread neurologic pain condition1 To diagnose FM using the ACR Diagnostic criteria: The patient must have chronic, widespread pain for ≥3 months2 The pain is located in all 4 quadrants of the body – that is both above and below the waist and on left and right sides of the body2 The pain includes the axial skeleton2 The patient has pain in at least 11 of the 18 tender points when palpated with 4 kg of digital pressure2 The American College of Rheumatology (ACR) guidelines provide a sensitive (88.4%) and specific (81.1%) tool that can be used to differentiate FM from other rheumatologic conditions. Sensitivity, or the true positive rate, is the proportion of FM patients positive for the criterion. Specificity, or the true negative rate, is the proportion of controls negative for the criterion2 References: 1. Wolfe F, Ross K, Anderson J, Russell IJ, Hebert L. The prevalence and characteristics of fibromyalgia in the general population. Arthritis Rheum. 1995;38:19-28. 2. Wolfe F, Smythe HA, Yunus MB, et al. The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum. 1990;33:160-172. Ref 1.a Wolfe et al Pg 19 Col 1 Par 1 Lin 1-3 Diagram Showing 18 Tender Points ACR criteria are:2 Sensitive (88.4%) – measure of correctly diagnosed patients Specific (81.1%) – statistical probability of an accurate negative diagnosis Ref 2.a Wolfe et al Pg 160 Abst Par 2 Lin 1-6 --------------- Ref 2.b Pg 171 Table 8 1Wolfe F, et al. Arthritis Rheum. 1995;38(1):19-28. 2Wolfe F, et al. Arthritis Rheum. 1990;33:160-172. Ref 2.c Wolfe et al Pg 169 Col 1 Par 1 Lin 1-4 -------------- Ref 2.d Pg 168 Table 6

Epidemiology of FM FM Is One of the Most Common CWP Conditions1 11/14/2018 Epidemiology of FM Ref 1.a Wolfe et al Pg 19 Col 2 Par 1 Lin 1-2 Ref 1.b Wolfe et al Pg 19 Col 2 Par 1 Lin 1-2 FM Is One of the Most Common CWP Conditions1 Prevalence in United States is estimated to be 2%-5% of the adult population1 FM is highly underdiagnosed2 Only 1 in 5 is diagnosed Diagnosis takes an average of 5 years3 Impacts a wide range of patients2 Most patients are between 25 and 60 years of age Women more likely to be diagnosed than men Ref 2.a Weir et al Pg 125 Col 2 Par 3 Lin 16-18 --------------- Ref 3.a NPF Website Pg 1 Bullet 6 Ref 2.a Weir et al Pg 125 Col 2 Par 3 Lin 16-18 --------------- Ref 2.b Table 2 Ref 1.a Wolfe et al Pg 19 Col 2 Par 1 Lin 1-2 FM affects 2%-5% of the US adult population.1 Only 1 in every 5 patients suffering from FM is diagnosed and it takes an average of 5 years for the diagnosis to be made2,3 FM impacts a wide range of patients2 Most patients are between 25 and 60 years of age Women are more likely to be diagnosed with FM than men References: Wolfe F, Ross K, Anderson J, Russell IJ, Hebert L. The prevalence and characteristics of fibromyalgia in the general population. Arthritis Rheum. 1995;38(1):19-28. Weir PT, Harlan GA, Nkoy FL, et al. The incidence of fibromyalgia and its associated comorbidities: a population-based retrospective cohort study based on International Classification of Diseases, 9th Revision codes. J Clin Rheumatol. 2006;12(3):124-128. National Pain Foundation. Available at: http://nationalpainfoundation.org/articles/849/facts-and-statistics. Accessed July 21, 2009. Ref 2.a Weir et al Pg 125 Col 2 Par 3 Lin 16-18 --------------- Ref 3.a NPF Website Pg 1 Bullet 6 Ref 2.a Weir et al Pg 125 Col 2 Par 3 Lin 16-18 --------------- Ref 2.b Table 2 1Wolfe F, et al. Arthritis Rheum. 1995;38:19-28. 2Weir PT, et al. J Clin Rheumatol. 2006;12:124-128. 3National Pain Foundation. Available at: http://nationalpainfoundation.org/articles/849/facts-and-statistics. Accessed July 21, 2009.

Risk Factors for FM Genetic factors1 Environmental factors2 Gender3 11/14/2018 Ref 1.a Arnold et al Pg 947 Col 2 Par 2 Lin 6-10 -------------------- Ref 1.b Pg 948 Par 1 Lin 1-6 Risk Factors for FM Genetic factors1 Relatives of FM patients are at higher risk for FM First-degree relatives are significantly more likely to have FM (Odds ratio=8.5; p=0.0002) Environmental factors2 Physical trauma or injury Infections (Lyme disease, hepatitis C) Other stressors (e.g., work, family, life-changing events) Gender3 Women are diagnosed with FM approximately 7 times more often than men Ref 2.a Mease PJ Pg 8 Col 1 Par 5 Lin 1-7 Ref 3.a Arnold et al Pg 2975 Col 1 Par 1 Lin 6-7 Ref 1.a Arnold et al Pg 947 Col 2 Par 2 Lin 6-10 While the cause of fibromyalgia is not known, evidence suggests that genetic, environmental, and other factors may predispose individuals to developing FM.1 Arnold et al demonstrated that FM and reduced pain pressure thresholds may aggregate in families1 First-degree relatives are significantly more likely to have FM2 This was adjusted for the relative’s age, sex, relationship to proband, interview status, and correlation of observations within families2 Environmental factors such as physical trauma, infections (Lyme disease, hepatitis C, parvovirus, Epstein-Barr virus), and other stressors such as work, family, or life-changing events may trigger the onset of FM2 Gender is also a factor as women are diagnosed with FM approximately 7 times more often than men3 References: 1. Arnold LM, Hudson JI, Hess EV, et al. Family study of fibromyalgia. Arthritis Rheum. 2004;50(3):944-952. 2. Mease P. Fibromyalgia syndrome: review of clinical presentation, pathogenesis, outcome measures, and treatment. J Rheumatol. 2005;32(suppl 75):6-21. 3. Arnold LM, Lu Y, Crofford LJ, et al. A Double-Blind, Multicenter Trial Comparing Duloxetine With Placebo in the Treatment of Fibromyalgia Patients With or Without Major Depressive Disorder. Arthritis Rheum. 2004;50(9):2974-2984. Ref 2.a Mease PJ Pg 8 Col 1 Par 5 Lin 1-7 Ref 3.a Arnold et al Pg 2975 Col 1 Par 1 Lin 6-7 Ref 2.a Mease PJ Pg 8 Col 1 Par 5 Lin 1-7 1Arnold LM, et al. Arthritis Rheum. 2004;50(3):944-952. 2Mease PJ. J Rheumatol. 2005;32(suppl 75):6-21. 3Arnold LM, et al. Arthritis Rheum. 2004;50(9):2974-2984.