A roundtable meeting that comprised clinical, patient advocacy, and managed care experts discussed issues regarding the diagnosis and management of fibromyalgia. The panel agreed that earlier diagnosis and treatment, additional education for the medical community, and appropriate management by health plans, including patient access to US Food and Drug Administration-approved fibromyalgia medications, are needed. In addition, physicians, payers, and patient advocates must work to improve clinical, economic, and quality-of-life outcomes for fibromyalgia patients. Finally, treatment and diagnostic guidelines must be updated as advances in disease management are made (including approvals of 3 new pharmacologic agents), and development of a therapeutic category for "fibromyalgia" on payer formularies is needed. (Am J Manag Care. 2009;15:S197-S218)
On March 21, 2009, The American Journal of Managed Care (AJMC) held a roundtable of clinical, patient advocacy, and managed care experts to explore issues in the diagnosis and management of fibromyalgia. The attendees reached a consensus on the following issues:
1. The prevalence, patient burden, and economic burden associated with fibromyalgia merit earlier diagnosis and treatment, additional education for the medical community (particularly primary care physicians), and appropriate management by health plans, including patient access to US Food and Drug Administration (FDA)-approved fibromyalgia medications.
2. Physicians, payers, and patient advocates should work to satisfy 3 critical outcome domains for fibromyalgia patients: clinical-decreased symptoms and improved physical function; economic-lower fibromyalgia-related healthcare costs; and quality of life-continued involvement in employment, family, and social activities.
3. The current treatment and diagnostic guidelines for fibromyalgia attempted to identify treatment options for an often misunderstood disease state, but are not commonly used by physicians or payers as a treatment algorithm. The guidelines have limited utility to physicians and payers because they precede or do not consider recent FDA approvals of 3 pharmacologic agents for fibromyalgia; their recommendations for other treatments used for fibromyalgia are based on data mainly from uncontrolled, small, open-label trials of short duration; they lack a straightforward treatment algorithm (although an algorithm might be problematic given the idiosyncratic nature of the disease); and they need to be updated as advances in disease management are made.
4. The development of a therapeutic category for "fibromyalgia" on payer formularies would benefit patients, physicians, and payers as a step toward further legitimizing the disease state, raising awareness of fibromyalgia, educating physicians and patients on available FDA-approved treatments, enhancing patient access through improved and appropriate recognition of FDA-approved treatments, and improving understanding of disease-specific drug utilization by payers.
SECTION 1. FIBROMYALGIA: CLINICAL OVERVIEW AND ECONOMIC BURDEN
Figures 1A and 1B
Fibromyalgia (FM ) is a multisymptom condition characterized by chronic widespread pain (CWP) and usually accompanied by a multitude of additional symptoms.1-7 Most people with FM suffer from decreased physical function,2,3,8-10 which can lead to disability.6,11,12 Sleep disturbances, fatigue, and morning stiffness are present in more than 73% of FM patients.1 Many patients have headaches, cognitive impairment, decreased well-being, depressed mood, paresthesias, irritable bowel or bladder symptoms, anxiety, temporomandibular joint pain, restless legs, and/or hypersensitivity to noise, heat, and cold.1-7,13 Comorbidities, which are far more common in FM patients than controls, may include other neuropathic or gastrointestinal (GI ) disorders, migraine, respiratory or circulatory conditions, and mental and mood disorders ().4
The pain of FM is distinctive. Patients with FM have CWP for 3 months or longer in all 4 quadrants of the body, but not centered in the joints, as with rheumatoid arthritis.1,4,14,15 FM patients have a lower pain threshold than healthy control subjects9; generalized tenderness includes allodynia (pain from normally nonnoxious stimuli) and hyperalgesia (increased response to painful stimuli).6,16
Although they cannot detect pressure, electrical, or thermal stimuli at lower levels than controls, the stimulus level that causes pain is lower.9,14,17
This phenomenon is independent of psychological factors such as expectancy and hypervigilance.17 The pain of FM may even persist after stimuli cease.18
FM is more widespread than many are aware () and is believed to be underdiagnosed and undertreated. In the United States the prevalence is 2% to 4%2,4,19-21 with onset usually at 20 to 55 years,4 but prevalence increases with age.21 The female-to-male ratio is up to 9:1.4,21 FM is the second most common disorder treated by rheumatologists, after osteoarthritis.20 Managed care participants in the roundtable were surprised by the prevalence and said patients were difficult to track due to use of a broad range of diagnoses and varied drug utilization. Since prescription claims data do not consistently include International Classification of Diseases (ICD-9 or -10) diagnosis information (although the data can be included, it is not typically required by payers, thus not captured), pharmacy utilization data cannot be used with certainty to identify patients with FM, because many of the drugs and drug classes prescribed are also used for a variety of other medical conditions.
With its many and variable symptoms, some of which can occur in other disorders, FM can be difficult to identify. Recent laboratory, positron emission tomography,22 voxel-based morphometry,23 and functional magnetic resonance imaging (fMRI ) research has supported the legitimacy of FM as a genuine disorder.6,7,20 Nevertheless, legitimacy as a discrete entity is still not universally accepted,5,20,24,25 which can result in problems for patients afflicted with FM, from stigma to difficulty obtaining accurate diagnosis and treatment
Dr. Goldenberg (Rheumatology): I discuss this as a problem with pain volume control, that there is a decrease in threshold to various noxious stimuli. It's not just pain. It's all stimuli. So you hear these weird symptoms from people that smells, sounds, or bright lights bother them. If they have a CNS hypersensitivity or hyperirritability, it makes perfect sense.
The predominant theory of pathogenesis in FM is central sensitization due to dysregulation of pain pathways.10,12,18 Brain imaging has demonstrated this altered pain processing, with FM patients reporting pain at half the pressure required to register pain in controls.7,14,20 At the different pressures required to report similar pain, fMRI showed the same brain areas were involved in pain processing, indicating the FM patients and controls experienced the pain similarly while the stimuli were different.7 Although the exact etiology is unknown,3,5 genetics appears to play a major role in susceptibility.9 First-degree relatives of FM patients have 8 times the risk for FM as the general population.9 FM has been associated with polymorphisms in the serotonin transporter gene and the catecholamine-O-methyltransferase enzyme that inactivates catecholamines.9,20 These polymorphisms affect the metabolism or transport of the monoamine neurotransmitters serotonin and norepinephrine.9 Compared with controls, FM patients have been found to have lower levels of metabolites of serotonin and norepinephrine in their cerebrospinal fluid.7,9 Serotonin and norepinephrine are antinociceptive9; that is, they decrease the sensitivity of pain processing systems through the descending central nervous system (CNS) pain pathways.7,9 Low levels indicate dysregulation of pain impulses through decreased activity in descending antinociceptive pathways, resulting in hyperalgesia and allodynia.7,9 The low levels of serotonin and norepinephrine metabolites prevalent in FM subjects9 suggest that serotonin and norepinephrine reuptake inhibitors (SNRIs) might help realign altered pain processing in descending CNS pain pathways. Whereas SNRIs have had analgesic effects in animal models of hyperalgesia and allodynia, selective serotonin reuptake inhibitors (SSRIs) have not, which highlights the particular importance of norepinephrine in pain modulation.19 On the other hand, FM subjects are reported to have increased levels of pronociceptive transmitters substance P and glutamate that amplify pain impulses in the ascending pain pathway.7,9 Drugs such as anticonvulsants are thought to function by reducing the release of pronociceptive transmitters in the ascending pathway.
FM Causes Functional Impairment
FM is associated with functional disability. The chronic, impairing symptoms of FM can lead to loss of function, which negatively affects work and leisure activities,26 may increase over time, and reduces health-related quality of life (QOL).13,25 Up to 50% of patients can work only a limited number of days because of the disorder,26 and up to 55% receive disability or Social Security payments.13,26
Participation in family and social activities may decrease because of fatigue, pain, and/or mood symptoms, and inadequate restorative sleep increases the overall fatigue. Eventually, some FM patients become completely disabled and incapable of continuing employment (
FM is also associated with a significant cost burden on all involved, including patients and their families, employers, and payers. The condition imposes substantial direct medical costs27 and indirect costs of lost work productivity.27-29 Large US claims database analyses have demonstrated these high costs.4,30,31 In a US insurance database analysis of more than 60,000 FM patients and age- and sex-matched controls, FM patients had mean total healthcare costs approximately 3 times higher and median costs 5 times higher than controls ($9573 vs $3291 and $4247 vs $822, respectively, P <.001 for both comparisons) ().4 FM patients had 4 times as many doctors' office and emergency department visits as control patients.4 FM patients were almost 4 times as likely to receive pain-related prescription medications (including antidepressants) and also significantly more likely to receive non-pain-related medications.4 Almost half of the FM patients also had healthcare encounters for symptoms other than CWP, including headache, abdominal pain, chest pain, fatigue, and GI symptoms; psychiatric comorbid diagnoses were also significantly higher than in controls.4
Another claims database analysis of more than 15,000 privately insured US employees (FM , n = 8513; control, n = 7260) found that total annual medical, prescription drug, and indirect costs of FM patients were almost double those of controls ($10,199 vs $5274, P <.0001).30 Total direct costs (medical utilization plus prescription drugs) were 86% higher for employees with FM versus controls ($7286 vs $3915, P <.0001).30 Total costs for FM approached those of osteoarthritis ($10,199 vs $10,861, P = .3758), and indirect costs were significantly higher in FM than osteoarthritis ($2913 vs $2537, P <.0001).30 Compared with osteoarthritis, FM was associated with more claims for comorbidities such as psychiatric diagnoses, chronic fatigue syndrome, and most pain disorders.30
A single-employer US administrative claims database of 4699 employees with at least 1 FM claim found significantly higher total annual costs for FM claimants compared with typical beneficiaries ($5945 vs $2486, P <.001).31 Medical utilization and prescription drug costs were significantly higher in FM claimants (P <.001).31 Disability prevalence was twice as high among employees with FM (P <.001).31 Employees with FM who filed disability claims incurred $6669 in healthcare costs and $5654 in disability costs for total annual costs of $14,100 per employee.31 Each dollar spent by the employer on FM-specific claims was matched by $57 to $143 spent on other direct and indirect costs.31 The authors concluded that the employer burden was substantially increased by hidden costs of comorbidities and disability.31
Dr. Fouts (Family Medicine): I think I'm the type of person who needs to be educated. I'm the type of doctor who needs to be on the forefront of treating it. I would compare the situation with FM similar to depression 10 to 15 years ago where somebody went into their family doctor, and they just didn't want to talk about it. But if you did get them to talk about it, often their doctor didn't really want to take care of it. I think education will help overcome these situations.
Studies in Europe and Canada have shown similar high direct and indirect costs associated with FM.27,29 In addition, these types of claims database analyses do not include the costs of over-the-counter medications and uncovered alternative treatments, which could bring total costs even higher. The roundtable participants agreed that FM imposes high costs on the US healthcare system and speculated that the costs in the published studies likely underestimate reality.
Diagnosis of FM
The FM diagnosis can be difficult to diagnose and often is delayed. Although the leading theory of pathogenesis-central sensitization from dysregulated pain pathways-is supported by neurotransmitter, neurohormone, and sleep physiology irregularities, objective biomarkers of disease activity have not been validated.10 Because no objective laboratory test or marker exists, diagnosis is based on history and physical examination.13 FM should be diagnosed by its own clinical characteristics. Differential diagnosis is subtle, as FM can be difficult to distinguish from conditions with similar symptoms that may or may not be present as comorbidities.1,4,13,20
The roundtable participants observed that many patients self-diagnose FM and then initiate discussion of the diagnosis with their doctor.
They said that physician familiarity with the disorder has been improving in recent years, but the current state of FM recognition among primary care physicians (PCPs) is low and corresponds to that of depression about 10 to 15 years ago.
Nevertheless, it has been documented that PCPs are capable of diagnosing FM with similar accuracy to specialists.
A retrospective analysis of 646 consecutive rheumatology patients at an academic medical center in Israel found that of the 196 patients referred with an initial diagnosis of FM, 71% had that diagnosis confirmed by the consultant rheumatologist.32
The kappa statistic demonstrated a good level of agreement between the family practice physicians and rheumatologists (kappa = .70, P <.001).32
Sensitivity of the FM diagnosis by the family physicians was 87% and specificity was 88%.
The authors said PCPs in the area were well-informed about FM because of ongoing FM research at the medical center. They speculated that the strong results of the study may be related to this knowledge base among the generalists.32 The Israeli study
Participant Affiliations: From the Department of Pain Medicine, Associate Professor, Clinical Anesthesiology, Stony Brook School of Medicine, Stony Brook University Hospital, Stony Brook, NY (CWA); Outpatient Services, Monarch Healthcare, Irvine, CA (RB); Pharmacy Services, Health Plan of Nevada/Sierra Health & Life, Las Vegas, NV (RKB); Communications Department, American Pain Foundation, Smithsburg, MD (MAB); Forest Research Institute, Jersey City, NJ (RD, ID); Medical Director of Psychiatry and Addiction Medicine, Baptist Hospital and Middle Tennessee Medical Center, Nashville, TN (JWD); SelectHealth, Inc, Salt Lake City, UT (JDD); Musculoskeletal Medical Specialists, The Ohio State University College of Medicine and Public Health, Columbus, OH (JF); Family Medicine, Ashville, OH (DF); Johns Hopkins HealthCare, LLC, Glen Burnie, MD (HG); National Fibromyalgia Association, Anaheim, CA (RMG); Department of Rheumatology, Newton-Wellesley Hospital, and Professor of Medicine, Tufts University School of Medicine, Newton, MA (DLG); Adult and Psycho-Pharmacology Research, R/D Clinical Research, Inc, Lake Jackson, TX (RJ); Internal Medicine, Asheboro, NC (KL); and Navarro Pharma, LLC, Green Cove Springs, FL (RPN).
Funding Source: This supplement was supported by Forest Laboratories, Inc., New York, NY, and Cypress Bioscience, Inc., San Diego, CA, USA.
Participant Disclosures: The authors (CWA, RB, RKB, MAB, JWD, JDD, JF, DF, HG, RMG, DLG, RJ, KL, RPN) were members of the paid advisory board for Forest and received payment for involvement in the preparation of this manuscript; an employee of Forest Research Institute (RD, ID) and owner of Forest Laboratories stock (RD); consultant/paid advisory board member (DLG, RJ), received honoraria (DLG, RJ), and attended meetings/conferences (DLG, RJ) for Forest, Pfizer, and Lilly, and received lecture fees (DLG) from Pfizer; attended meetings/conferences for Lilly (RJ), and board member for Lilly, Forest, and Pfizer (RJ).
Participant Information: Concept and design (CWA, RB, RKB, RD, JWD, JF, DF, RJ, KL); acquisition of data (MAB, JWD, JDD, DLG); analysis and interpretation of data (RD, JWD, JDD, JF, DF, HG, DLG, KL); drafting of the manuscript (CWA, RB, RKB, MAB, JWD, HG, RMG, DLG, RJ, KL); critical revision of the manuscript for important intellectual content (CWA, RB, RKB, MAB, JWD, DF, RD, ID, JDD, JF, HG, RMG, DLG, RJ, KL, RPN); and helped supply resources for this supplement (RMG).
Address correspondence to: Robert P. Navarro, PharmD, Navarro Pharma, LLC, 411 Walnut St, #4641, Green Cove Springs, FL 32043. E-mail: Robert.email@example.com.
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