Fibromyalgia is a chronic illness with primary symptoms including widespread musculoskeletal pain, as well as stiffness, sleep disturbance, and fatigue. Headache, irritable bowel and bladder, anxiety, and depression are also commonly reported comorbidities [1-3]. Fibromyalgia generally presents in middle age [1] and most commonly affects women; estimates of fibromyalgia prevalence range from 0.66% in Denmark (females and males) [4] to 10.5% in Norway (females only) [5], with a recent study estimating prevalence to be 6.4% in the United States (US; females and males) [6]. Previous cross-sectional research has shown that fibromyalgia places a substantial burden on patients with respect to symptoms, loss of function and productivity, and decreased health-related quality of life [2, 7-13]. Fibromyalgia is also associated with burden on payers and employers with respect to healthcare resource use, lost productivity, and associated costs [2, 12-16].

Longitudinal research on outcomes of patients with fibromyalgia is limited; some previous studies have suggested that patients rarely achieve remission from fibromyalgia, although a portion may experience improvement or waxing and waning in symptoms over time [17-24]. One study on established fibromyalgia patients (median disease duration at first assessment was 7.8 years) found that functional disability worsened over the 7-year study period, while measures of pain, global severity, fatigue, sleep disturbance, anxiety, depression, and health status remained unchanged and patient satisfaction with health improved [24]. A study conducted in the US reported that two-thirds of the fibromyalgia sample indicated that their symptoms were a little to a lot better, 10% reported no change, and a quarter of the sample reported that they were a little to a lot worse at the 10-year interview than when they were first diagnosed [18]. A study conducted in Britain found that 26% of the fibromyalgia sample reported that symptoms were better, and 60% reported that symptoms were worse at a mean of 4 years after their initial diagnosis [20]. Previous studies have also reported that a portion (20%-44%) of diagnosed patients no longer met the study definition of fibromyalgia years after diagnosis [17, 22, 23].

Given the paucity of published US studies on outcomes among patients with fibromyalgia over time, as well as the variation in reported results, this study followed fibromyalgia patients for approximately 2 years to assess clinician and patient-reported outcomes over time.

This analysis was based on a multiyear observational cohort study with 2 assessments [25]. Patients with fibromyalgia who completed both Baseline and Follow-up assessments were included in this analysis (Fig. 1). Detailed study methods and findings from the Baseline assessment have been published previously [26]. Briefly, at Baseline, a sample of fibromyalgia patients was identified using a large opt-in online panel maintained by Toluna [27]. Patients were identified based on both their responses to a screening survey for CWP (bilateral pain, above/below waist lasting ≥ 1 week in the past 3 months), according to the 4 pain questions of the London Fibromyalgia Epidemiology Study Screening Questionnaire (LFESSQ-4; Table 1) [28], and a site visit for physician evaluation of fibromyalgia. During the site visit, physicians completed a tender point exam [29] and blood pressure cuff exam [30], and patients completed the EuroQol 5 dimensions (EQ-5D; Table 1) [31]. Physicians at the study sites had completed FM diagnostic training and reported treating at least 10 FM patients on average each month in their practice. Physicians relied on their clinical impression of the subject, following the assessment, to establish a FM diagnosis. Physicians or site coordinators entered the collected data into an online clinical case report form for each patient. All patients were aged 18 years or older and provided informed consent (in English or Spanish).

Following the site visit, patients completed an online questionnaire that incorporated several validated patient-reported outcome (PRO) instruments: Brief Pain Inventory-Short Form (BPI-SF) [32], modified (self-report) American College of Rheumatology (ACR 2010) Criteria [33], Fibromyalgia Impact Questionnaire-revised (FIQ-R) [34], Medical Outcomes Study Sleep Scale (MOS-SS) [35], 12-Item Short-Form Health Survey, version 2 (SF-12) [36], and Work Productivity and Activity Impairment (WPAI) Questionnaire [37]. Details about the items and content of each of these instruments can be found in Table 1. The questionnaire also included questions about comorbidities, clinical characteristics, symptoms (e.g., average pain over the past 7 days), productivity, healthcare resource use, and socioeconomic information. The collected healthcare resource use data included healthcare provider visits, emergency room visits, hospitalizations, prescription medications, physical treatments, nonprescription medications, and herbs, vitamins, or other pain supplements the patients were prescribed and/or used for their pain in the past 3 months.

Fig. (1). Study flow diagram. * Due to lack of valid e-mail address or Baseline site closure, 2 patients were not eligible to participate in Follow-up. † Patients who were unable to attend the site visit at Follow-up were invited to complete the online questionnaire only; however, given the patients’ fibromyalgia status/diagnosis was unknown at Follow-up, these patients were excluded from this analysis.

All fibromyalgia patients who completed the Baseline assessment were eligible to participate at Follow-up approximately 2 years later, with the exception of patients whose e-mail address was no longer available or patients whose study site was closed or did not participate at Follow-up (n=2). Eligible patients received an e-mail invitation to participate in the Follow-up assessments. If a response was not received after 5 attempts, patients were then called by study sites (3 call attempts, each on separate days at different times). Twenty geographically diverse sites participated (5 West, 5 Midwest, 5 South, 5 Northeast) at Baseline, and 17 (5 West, 4 Midwest, 4 South, 4 Northeast) of these sites also participated at Follow-up; 3 sites were unable to participate at Follow-up. Physicians who participated at both Baseline and Follow-up included 9 rheumatologists, 2 pain specialists, and 6 primary care physicians. At Follow-up, patients who provided consent were reassessed for fibromyalgia at the same study site and again completed the set of validated PRO measures administered at Baseline in the online patient questionnaire.* The EQ-5D and LFESSQ were completed on site and entered on the online case report form at Follow-up.

This observational study received Institutional Review Board approval from Quorum Review IRB, Seattle, Washington and Western Institutional Review Board, Olympia, Washington.

A total of 76 fibromyalgia patients completed the Baseline and Follow-up site visits for physician evaluation of fibromyalgia; 71 (93.4%) of those patients also completed the online patient questionnaire at Follow-up (Fig. 1). Demographic and clinical characteristics of the fibromyalgia group are presented in Table 2. The majority was female and non-Hispanic. The mean age at Baseline was 50.9 years and 53.2 years at Follow-up. Less than a third of patients were employed for pay at each assessment. The majority of patients was obese (body mass index [BMI] ≥ 30 kg/m²) [42] at both assessments. Mean time since fibromyalgia diagnosis at Baseline and Follow-up was 4.1 years and 6.2 years, respectively.

Comorbidities, such as arthritis, lower back pain, depression, high cholesterol, hypertension, headache/migraine, anxiety, and sleep apnea, were reported by ≥ 20% of patients at Follow-up. Among patients reporting comorbidities, the mean (standard deviation [SD]) number decreased from 5.1 (2.9) at Baseline to 4.8 (2.6) at Follow-up. There were no statistically significant differences in collected demographic and clinical characteristics observed over time.

TREATMENT PATTERNS

Table 3 presents healthcare resource use among the fibromyalgia patients at both assessments. Prescription medication use for pain in the previous 3 months was similar for both assessments: 59.2% and 62.0% of patients, respectively. Fig. (2) presents more detail on the use of prescription medications for pain by class at Baseline and Follow-up. The most commonly reported class of medication for pain in the sample at Follow-up was opioids, with 25.4% of patients reporting taking weak short-acting opioids, 8.5% taking strong short-acting opioids, and 7.0% taking long-acting and extended-release opioids. Opioid use was followed by selective serotonin reuptake inhibitors (SSRIs), tramadol, antiepileptics, and nonsteroidal anti-inflammatory drugs (NSAIDs) use (all >10%) at Follow-up. None of the differences in medication class use for pain were statistically significant; however the classes with the largest (at least a 5 percentage point) change in the rate of use were NSAIDs and muscle relaxants, both of which decreased.

Table 3. Healthcare resource use over the past 3 months.

Healthcare Resource Use, n (%)	Baseline (N=76)	Follow-up (N=71)	P value
HCP visit for pain	50 (65.8)	42 (59.2)	0.346
Emergency room visit for pain	4 (5.3)	3 (4.2)	1.000
Hospitalized for pain	3 (3.9)	2 (2.8)	1.000
Prescribed medication for pain	45 (59.2)	44 (62.0)	0.593
Nonprescription medications for pain	64 (84.2)	58 (81.7)	0.593
Herbs, vitamins, and other supplements for pain	25 (32.9)	16 (22.5)	0.127
Physical treatments for pain	22 (28.9)	27 (38.0)	0.088

Abbreviations: HCP, health care provider.

In addition to prescription medications for pain, most patients reported taking nonprescription medications for pain in the previous 3 months (Baseline: 84.2%; Follow-up: 81.7%). The proportion of patients reporting taking herbs, vitamins, or other pain supplements in the past 3 months dropped from 32.9% at the Baseline assessment to 22.5% at the Follow-up assessment. In contrast, there was an increase in the percentage of patients reporting physical treatments for pain over the past 3 months (Baseline: 28.9%; Follow-up: 38.0%). The mean (SD) number of health care provider visits over the past 3 months was 3.6 (5.4) and 2.9 (4.4) at Baseline and Follow-up, respectively, and there were few emergency room visits or hospitalizations at either assessment. No changes in pain-related healthcare resource use over time reached statistical significance.

Fig. (2). Medication Use for Pain Over the Past 3 Months by Class at Baseline and Follow-up. Abbreviations: misc., miscellaneous; NSAID, nonsteroidal anti-inflammatory drug; SNRI, serotonin-norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor. *No statistically significant differences over time were observed. †“Opioids” class includes weak short-acting, strong short-acting, and long-acting and extended-release opioids.

This prospective observational study used online data collection tools for PROs, combined with an in-person physician assessment, to evaluate changes in pain and clinical outcomes, sleep, pain interference with function, and health status among fibromyalgia patients over time.

The study sample was geographically diverse yet similar across baseline demographic and clinical characteristics to other fibromyalgia samples in the published literature [2, 6, 43, 44]. The study also included in-person evaluation at the same site at Baseline and Follow-up and administration of the same PRO measures at both time points, which allowed for an assessment of changes over time. The sample included fibromyalgia patients diagnosed, on average, 4.1 years before the Baseline visit. We observed no statistically significant differences among fibromyalgia patients between Baseline and Follow-up in terms of employment status, household income, health insurance, prescription coverage, BMI, and number of comorbidities.

Many patients in the sample received medical care and treatment for fibromyalgia, as reflected in the high levels of prescription and nonprescription pain medications, physical treatments, and visits to healthcare providers reported by patients. It is important to consider the frequently reported classes of prescription medications in this fibromyalgia sample in the context of Food and Drug Administration–approved medications for the treatment of fibromyalgia (pregabalin, duloxetine, milnacipran) and published treatment guidelines, which also include gabapentin, amitriptyline, SSRIs, SNRIs, and tramadol. Guidelines generally do not recommend opioids, especially strong opioids, for fibromyalgia [45-49]. However, in this study, opioids were the most widely utilized medication, and at Follow-up, increases in the percentage of patients prescribed weak short-acting opioids and long-acting and extended-release opioids were observed along with increases in the use of SSRIs. NSAIDs were also widely used at both time points.

Overall mean scores for general and disease-specific PROs reflect continued high levels of disease burden in this sample. For example, the SF-12 mental and physical component summary scores and EQ-5D at both time points were well below the US general population norms of 49.5, 49.7 [50], and 0.87 [51], respectively. Patients reported similar levels of pain (BPI-SF Pain Severity Index) and tender points, on average, at Baseline and Follow-up. Productivity impairment likewise remained high at both time points.

However, scores on several PROs suggest variability in terms of changes from Baseline to Follow-up. Patients reported improvement in fibromyalgia symptoms (modified ACR 2010 Criteria) and pain interference with function (BPI-SF Pain Interference Index), and these differences were statistically significant. Additionally, statistically significant improvements in sleep (MOS-SS Overall Sleep Problems) were observed. These results contrast with the findings of a previous 7-year US study of fibromyalgia patients in which functional disability worsened and pain, health status, fatigue, and sleep disturbance remained unchanged [24]. It is possible that patients in our sample over or underestimated their functional abilities over time. In future studies, longitudinal performance testing may be helpful to understand these phenomena better.

Our pain improvement subgroup analysis showed that a minority of patients (14.5%) experienced ≥2 point improvement in pain severity between the two time points. Physicians reported improvements in the number of tender points in these patients and the patients reported improvements in health status, sleep, and pain interference with function; whereas those who did not report this level of pain improvement, representing the majority of the sample, generally did not. Of note, Baseline scores for pain severity, pain interference with function, sleep, and health status were worse for the pain improvement subgroup than those who did not experience ≥2 point improvement in pain.

Taken together, these findings support the conclusions of previous research, which suggests that while fibromyalgia is a chronic illness, there may be waxing and waning of symptoms, as well as a portion of patients who experience improvements following diagnosis and treatment. In one previous study, 66% of fibromyalgia patients in rheumatology clinics reported their symptoms were a little to a lot better at the 10-year interview than when they were first diagnosed; those patient-reported improvements were correlated with younger age and shorter duration of fibromyalgia symptoms at diagnosis [18]. In a more recent study, 47% of outpatients with fibromyalgia reported moderate to marked improvement over 3 years [52]. Some published research suggests that outcomes are better for individuals in the community compared to individuals in rheumatology clinics [53, 54]. Improvements also may be related to treatment, both pharmacologic and nonpharmacologic.

Fibromyalgia patients continued to report high levels of disease burden, on average, in terms of pain and health status approximately 2 years after the Baseline assessment. There was variability among patients in clinician and patient-reported outcomes, with few significant differences observed over time. These data suggest some improvement over time in function and sleep, particularly among the minority of patients who reported greater improvement in pain.