Societal and individual burden of illness among fibromyalgia patients in France: Association between disease severity and OMERACT core domains

Fibromyalgia (FM) is a chronic disorder characterized by persistent, widespread pain [1]. FM patients may also report fatigue, sleep disturbance, anxiety, and depression [2–4]. Although estimates vary, FM has been reported to affect up to 6% of the general European population [5–7]. However, one community study in France estimated the point prevalence of FM to be lower at 1.4%, which translates to ~680,000 patients [8].

Confirming a diagnosis of FM is often difficult because there is no specific diagnostic test to clearly validate the disorder. Indeed, FM is often diagnosed by ruling out other conditions, such as rheumatoid arthritis, lupus, and multiple sclerosis [9]. Various professional bodies have issued guidelines to assist diagnosis of FM such as screening tools [10] or diagnostic criteria, such as those recently issued by the American College of Rheumatology (ACR) [11]. FM management guidelines published by the American Pain Society (APS) [12] and the European League Against Rheumatism (EULAR) [13] reflect that generalized pain does not adequately characterize FM and a broader assessment of pain, function, and psychosocial aspects may aid in FM management. Recognizing the need for a core set of domains that more fully describe FM, the Outcome Measures in Rheumatology Clinical Trials (OMERACT) workgroup on FM was established to identify domains that should be captured in clinical trials for FM therapies [14]. These domains include pain, patient global health, fatigue, health-related quality of life (HRQoL), multidimensional function, sleep, depression, physical function, tenderness, dyscognition, and anxiety.

Due in-part to the chronic nature of the disease, FM patients are high consumers of healthcare services in Europe [15–18]. The lack of a definitive diagnostic test means that FM patients repeatedly present to physicians prior to receiving a confirmed diagnosis. Furthermore, once diagnosed patients often experience suboptimal pain and symptom management which may lead to frequent physician office visits [16]. A review of the literature shows that there are currently no studies that have included a comprehensive assessment of the burden of illness associated with FM in France. The objective of this study was to better understand the impact of FM on French patients by conducting an evaluation of their clinical and comorbid profile, and FM's impact on HRQoL, symptom domains (such as pain, sleep, depression), productivity, and cost to society.

This is the first study to assess core FM symptom dimensions identified by OMERACT, in a group of 88 patients with FM from France. We examined FM burden of illness by investigating patients' tender points, HRQoL, general health, pain, sleep/fatigue, depression, anxiety, physical function, productivity losses for FM patients, medication use, treatment satisfaction, as well as the costs to society. Consistent with other studies [4, 30–32], our study demonstrated that patients have substantial burden due to FM, and FM is associated with direct and indirect costs.

The results of this study show a significant burden of illness associated with FM. FM severity was associated with certain sleep problems, anxiety, and depression. Patients reported poor HRQoL, overall and in negative health impact in relation to measures of pain, function, sleep, anxiety, and depression. Just over half (55%) of patients had moderate pain based on the BPI-sf Pain Severity Index, and 22% severe pain, supporting that moderate-to-severe chronic pain is a dominant feature for patients with FM.

Although the generalizability of our observations from these FM patients to the wider FM population in France is ultimately unknown, our results are consistent with other larger studies that have examined the impact of FM. For example, a Dutch study involving a sample of 3664 patients and examining the impact of musculoskeletal diseases on HRQoL, reported that patients with FM (with or without other musculoskeletal diseases) scored lower on all subscales of the Short Form-36 (SF-36) and EQ-5D health status measures than study patients with other musculoskeletal diseases [33]. The domains most affected were vitality, role-physical, and bodily pain for the SF-36; and usual activities and pain/discomfort for the EQ-5D. In a study of chronic widespread pain among patients with and without FM in Sweden, the FM group scored significantly lower than the non-FM group on general HRQoL measures and specific measures for activities of daily living, depression, anxiety, and pain [34]. Collectively with our study, data highlight the high societal and patient burden that FM inflicts across Europe [35].

Patients in our study reported a significant impact of FM on sleep, with the most affected areas on the MOS Sleep Scale being sleep adequacy and sleep disturbance. These observations are consistent with other larger studies of European patients with FM, and FM patients from other countries [3, 36] For example, in a study of 600 health maintenance organization (HMO) members with FM [3], patients demonstrated poor sleep quality as measured by the Pittsburgh Sleep Quality Index (PSQI) where scores of ≥5 indicates poor sleep. More specifically, Bigatti et al. reported patients had PSQI score of 11.22 (± 3.96) at baseline, with only 4% of patients scoring < 5 [3].

FM had a negative impact on work productivity in the present study, with 44% of patients reporting some disruption in productivity, and the overall employed sample reporting an average of 35 days of missed work per year per patient. Thirty-five days of missed work due to FM accounts for approximately 13% of all working days in a calendar year. Other studies have likewise highlighted the higher number of work days missed for employed patients with FM vs. the general population, in Europe and the United States. For example, in a similar small study of patients with FM, chronic low back pain, and ankylosing spondylitis, Boonen et al. (2005) found that 63% of FM patients with a paid job reported an episode of sick leave, with mean length of sick leave was 34 days per working-patient-year [15]. In a larger study of administrative claims database including 31 large self-insured companies in the United States, White et al. (2005) reported that FM patients missed significantly more days of work in the past year compared with non-FM patients (29.8 vs. 10.4 days; P < 0.001) [4]. Similarly, a study of 1081 patients with FM from Spain reported 20.9 sick days per year, significantly more than the reference group of subjects without FM syndrome (8 days) [32].

Patients reported an average of one physician office visit per month in the present study. Physicians reported that 84% of patients were taking a prescription medication related to their FM symptoms, with the majority of patients taking other analgesics, primarily opioids, and non-steroidal anti-inflammatory drugs. Furthermore, patients did not perceive their prescription medications as completely effective and expressed some dissatisfaction with current pharmacological treatments. Our findings suggest that there is room for improvement in the current management and use of prescription medications for FM in France. These observations are relatively consistent with other larger studies of European populations of FM patients. For example, a study of 299 patients with FM from France and Germany reported that their FM treatment regimens were not the most advantageous [18]. Other European studies have also documented frequent physician office services among patients with FM. In a UK study using a large electronic medical records database containing data on GP visits, Hughes et al. (2006) reported that, among 2,260 UK patients newly diagnosed with FM, there were 25 office visits, and 11 prescriptions per patient in the year prior to diagnosis, and levels of HRU generally increased following diagnosis [16]. Using a large electronic database recording GP encounters in Germany, Berger et al. (2008) also demonstrated significant HRU for FM patients. Among 4,983 FM patients, 67% were on at least one pain-related medication and 74% had four or more GP office visits over 1 year. Additionally, FM patients averaged approximately three-times as many outpatient office visits (19.6 vs. 5.2; P < 0.001) than patients without FM [17]. Similarly, a claims analysis from Spain documented an average of 13.5 GP office visits per year and the use of an annual average of 3.7 medications for 1081 FM patients [32]. Taken with the data presented in the current study, despite diagnosis and treatment, FM patients display considerable HRU across Europe, indicating an unmet need for FM patients in these studies.

Higher HRU rates resulted in higher total direct medical costs on a per-patient basis. The major drivers of direct medical costs to the payer were physician office visits and prescription medications. The largest contribution to FM costs in our study was related to lost productivity due to absenteeism and disability, accounting for approximately 88% of total costs. These results are supported by the published literature. Previous studies have demonstrated that employee disability and medical comorbidity associated with FM greatly increase the economic burden of the disease. White et al. (2008) reported that indirect costs, including actual employer payments for extended absence from work due to disability and imputed medically-related work-loss days and costs, accounted for approximately one-third of the total study costs, highlighting the significant burden imposed by FM to employers [4]. Robinson et al. (2003) also found that a substantial portion of total cost for FM was due to work disability; the prevalence of disability was twice as high among employees with FM when compared with the overall employee population [37].

The present study is the first to assess the impact of FM severity on key multiple FM dimensions. Eighty-one percent of the sample reported moderate (38%) or severe FM (43%) based on patients' FIQ total scores and the results of the study also show that, as FM severity increased, facets of patients' HRQoL, pain, elements of sleep, anxiety, and depression worsened significantly. In addition, there was a non-significant trend for patients' productivity and the total direct and indirect costs to society to increase as FM severity worsened.

This study had several limitations. Firstly, only practices that volunteered to participate were included in the study. It is possible that these sites may differ in unknown ways from others that routinely provide FM or general patient care. Additionally, these practices were predominantly GPs, and it is possible that FM patients presenting to GPs are not generalizable to the FM patient population in France as a whole. However, we note that GPs are the most accessible venue for FM patients to seek care, and a large proportion of patients were concurrently seeking care for their FM from other specialists. Data came from patients who were actively seeking care; the clinical/sociodemographic characteristics of FM patients who were not seeking care are not known, and our findings may not be generalizable to the wider FM patient population. It is possible that differences were not significant because the low number of patients in each severity cohort is underpowered to detect differences. Therefore these outcomes warrant further investigation in studies with larger sample sizes. Although each scale used in the present study has been independently validated to assess given symptoms in different patient populations, they have not all been validated in FM patients specifically. However, the scales picked are widely used in FM clinical trials to assess subjective outcomes, and some scales are recommended to healthcare providers for assessment of symptoms. Our costing algorithm made several assumptions that may have underestimated medication costs, including costing based on generic medications, determining costs using the largest package sizes available, and assuming lowest average dose where information from the CRF was incomplete. A less conservative costing methodology might have led to higher estimated costs associated with medications. While we captured out-of-pocket costs incurred by patients for non-prescription medications and services by allied healthcare professionals beyond the GP/hospital environment, these types of services and costs often recommended to FM patients, such as physiotherapists, exercise specialists, or psychotherapists, may have been underreported and increased the cost burden to patients or society as a result. Finally, the study was cross-sectional; therefore, while we can examine the association between FM and outcome measures, directionality cannot be established. Despite these limitations, given the lack of information on the burden of FM in patients from France; our study provides important insights into the impact of FM in this sample of patients with FM from France.

This study represents one of the first attempts to characterize the full patient experience of disease, function, HRQoL, and costs of patients with FM from France. Although the majority of patients were receiving medical attention and prescription medications for FM, patients still reported high levels of pain, anxiety, depression, sleep disturbance, diminished HRQoL, and substantial loss of productivity. Additionally, patients reported that prescription medications for their FM were not optimal in terms of perceived effectiveness and satisfaction. As FM severity increased, patients' health status and other key symptom domains worsened. Finally, the total direct and indirect costs to society increased as FM severity increased. These results highlight the significant disease burden as well as limitations of treatment options available.