Revised chronic widespread pain criteria: development from and integration with fibromyalgia criteria.

Background and aims Persons with chronic widespread pain (CWP) have poor medical outcomes and increased mortality. But there are no universally accepted criteria for CWP or of methods to assess it. The most common criteria come from the 1990 American College of Rheumatology (ACR) fibromyalgia (FM) criteria, but that method (WP1990) can identify CWP with as few as three pain sites, and in subjects with wide differences in illness severity. Recently, to correct WP1990 deficiencies, the 2016 fibromyalgia criteria provided a modified CWP definition (WP2016) by dividing the body into five regions of three pain sites each and requiring a minimum of four regions of pain. Although solving the geographic problem of pain distribution, the problem of just how many pain sites (pain diffuseness) are required remained a problem, as WP2016 required as few as four painful sites. To better characterize CWP, we compared four CWP definitions with respect to symmetry, extent of pain sites and association with clinical severity variables. Methods We characterized pain in 40,960 subjects, including pain at 19 individual sites and five pain regions, and calculated the widespread pain index (WPI) and polysymptomatic distress scales (PDS) from epidemiology, primary care and rheumatology databases. We developed and evaluated a new definition for CWP, (WP2019), defined as pain in four or five regions and a pain site score of at least seven of 15 sites. We also tested a definition based on the number of painful sites (WPI ≥ 7). Results In rheumatology patients, WP1990 and WPI ≥ 7 classified patients with <4 regions as WSP. CWP was noted in 51.3% by WP1990, 41.7% by WP2016, 37.6% of WPI ≥ 7 and 33.9% by WP2019. 2016 FM criteria was satisfied in WP1990 (51.1%), WP2016 (63.3%), WPI ≥ 7 (69.0%) and WP2019 (76.6%). WP2019 positive patients had more severe clinical symptoms compared with WP1990, WP2016 and WPI ≥ 7, and similar to but less than FM 2016 positive patients. In stepwise fashion, scores for functional disability, visual analog scale fatigue and pain, WPI, polysymptomatic distress score and Patient Health Questionnaire 15 (PHQ-15) worsened from WP1990 through WP2016, WPI ≥ 7 and WP2019. Conclusions WP2019 combines the high WPI scores of WPI ≥ 7 and the symmetry of WP2016, and is associated with the most abnormal clinical scores. The WP1990 does not appear to be an effective measure. We suggest that CWP can be better defined by combining 4-region pain and a total pain site score ≥7 (WP2019). This definition provides a simple, unambiguous measure that is suitable for clinical and research use as a standalone diagnosis that is integrated with fibromyalgia definitions. Implications Definitions of CWP in research and clinic care are arbitrary and have varied, and different definitions of CWP identify different sets of patients, making a universal interpretation of CWP uncertain. In addition, CWP is a mandatory component of some fibromyalgia criteria. Our study provides quantitative data on the differences between CWP definitions and their criteria, allowing better understanding of research results and a guide to the use of CWP in clinical care.

Validity and Reliability of Clinical Examination in the Diagnosis of Myofascial Pain Syndrome and Myofascial Trigger Points in Upper Quarter Muscles.

Objectives: To determine whether two independent examiners can agree on a diagnosis of myofascial pain syndrome (MPS). To evaluate interexaminer reliability in identifying myofascial trigger points in upper quarter muscles. To evaluate the reliability of clinical diagnostic criteria for the diagnosis of MPS. To evaluate the validity of clinical diagnostic criteria for the diagnosis of MPS. Design: Validity and reliability study. Setting: Provincial Hospital. Toledo, Spain. Participants: Twenty myofascial pain syndrome patients and 20 healthy, normal control subjects, enrolled by a trained and experienced examiner. Methods: Ten bilateral muscles from the upper quarter were evaluated by two experienced examiners. The second examiner was blinded to the diagnosis group. The MPS diagnosis required at least one muscle to have an active myofascial trigger point. Three to four days separated the two examinations. The primary outcome measure was the frequency with which the two examiners agreed on the classification of the subjects as patients or as healthy controls. The kappa statistic (K) was used to determine the level of agreement between both examinations, interpreted as very good (0.81-1.00), good (0.61-0.80), moderate (0.41-0.60), fair (0.21-0.40), or poor (≤0.20). Results: Interexaminer reliability for identifying subjects with MPS was very good (K = 1.0). Interexaminer reliability for identifying muscles leading to a diagnosis of MPS was also very good (K = 0.81). Sensitivity and specificity showed high values for most examination tests in all muscles, which confirms the validity of clinical diagnostic criteria in the diagnosis of MPS. Conclusions: Interrater reliability between two expert examiners identifying subjects with MPS involving upper quarter muscles exhibited substantial agreement. These results suggest that clinical criteria can be valid and reliable in the diagnosis of this condition.

The fibromyalgia family study: a genome-wide linkage scan study.

OBJECTIVE: Familial aggregation of fibromyalgia has been increasingly recognized. The goal of this study was to conduct a genome-wide linkage scan to identify susceptibility loci for fibromyalgia. METHODS: We genotyped members of 116 families from the Fibromyalgia Family Study and performed a model-free genome-wide linkage analysis of fibromyalgia with 341 microsatellite markers, using the Haseman-Elston regression approach. RESULTS: The estimated sibling recurrence risk ratio (λs ) for fibromyalgia was 13.6 (95% confidence interval 10.0-18.5), based on a reported population prevalence of 2%. Genome-wide suggestive evidence of linkage was observed at markers D17S2196 (empirical P [Pe ]=0.00030) and D17S1294 (Pe=0.00035) on chromosome 17p11.2-q11.2. CONCLUSION: The estimated sibling recurrence risk ratio (λs ) observed in this study suggests a strong genetic component of fibromyalgia. This is the first report of genome-wide suggestive linkage of fibromyalgia to the chromosome 17p11.2-q11.2 region. Further investigation of these multicase families from the Fibromyalgia Family Study is warranted to identify potential causal risk variants for fibromyalgia.

Elevated serum high-sensitivity C-reactive protein levels in fibromyalgia syndrome patients correlate with body mass index, interleukin-6, interleukin-8, erythrocyte sedimentation rate.

The levels of several inflammatory cytokines are abnormal in many patients with the fibromyalgia syndrome (FMS) and may play a role in its pathogenesis. The inflammatory marker C-reactive protein (CRP) is associated with the disease activity in patients with inflammatory rheumatic diseases, but its role in FMS is unknown. We undertook this study to determine whether high-sensitivity CRP (hsCRP) is elevated in FMS and whether its levels relate to key biologic or clinical measures. One hundred and five patients with FMS (1990 ACR criteria) and 61 healthy normal controls (HNC) at a ratio of 2:1 were recruited. The serum concentrations of hsCRP, interleukin-8 (IL-8), and interleukin-6 (IL-6) were assessed using enzyme-linked immunosorbent assays. The hsCRP levels were marginally higher in FMS than in HNC (p = 0.06) and its abnormality rate (>1.5 SD above the HNC mean) was significantly higher in FMS (25 %) compared with HNC (6.8 %) (p = 0.03). Serum IL-8 levels, IL-6 levels, and erythrocyte sedimentation rate (ESR) in FMS did not differ from those in HNC. Body mass index (BMI), ESR, IL-8, and IL-6 levels correlated with hsCRP levels in FMS. No associations were found between hsCRP and age, gender, ethnicity, or other clinical measures. Serum CRP levels were higher in FMS and significantly correlated with BMI, ESR, IL-8, and IL-6 levels, suggesting that inflammation may contribute to the symptoms in some FMS patients, particularly those who are obese. Weight loss and therapies directed against inflammation may be useful in the management of FMS patients with elevated hsCRP.

Evaluation of patient-rated stiffness associated with fibromyalgia: a post-hoc analysis of 4 pooled, randomized clinical trials of duloxetine.

BACKGROUND: Patients with fibromyalgia (FM) rate stiffness as one of the most troublesome symptoms of the disorder. However, there are few published studies that have focused on better understanding the nature of stiffness in FM. OBJECTIVES: The primary objectives of these analyses were to characterize the distribution of stiffness severity in patients at baseline, evaluate changes in stiffness after 12 weeks of treatment with duloxetine, and determine which outcomes were correlated with stiffness. METHODS: These were post-hoc analyses of 3-month data from 4 randomized, double-blind, placebo-controlled studies that assessed efficacy of duloxetine in adults with FM. Severity of stiffness was assessed by using the Fibromyalgia Impact Questionnaire (FIQ) on a scale from 0 (no stiffness) to 10 (most severe stiffness). The association between changes in stiffness and other measures was evaluated by using Pearson's correlation coefficient. The FIQ total score and items, the Brief Pain Inventory (BPI-modified short form), the Clinical Global Impression-Severity scale, the Multidimensional Fatigue Inventory, the 17-item Hamilton Depression Rating Scale, the Sheehan Disability Scale, the 36-item Short-Form Health Survey, and the EuroQoL Questionnaire-5 Dimensions were evaluated in the correlation analyses. Stepwise linear regression was used to identify the variables that were most highly predictive of the changes in FIQ stiffness. RESULTS: The analysis included 1332 patients (mean age, 50.2 years; 94.7% female; and 87.8% white). The mean (SD) baseline FIQ stiffness score was 7.7 (2.0), and this score correlated with baseline BPI pain score and FIQ function. Duloxetine significantly improved the FIQ stiffness score compared with placebo (P < 0.001) and provided a moderate effect size (0.23 for the 60-mg dose and 0.38 for the 120-mg dose). Changes in stiffness were best correlated (range, 0.52-0.75; all, P < 0.001) with changes in BPI/FIQ pain and interference scores, FIQ nonrefreshing sleep, FIQ anxiety, 36-item Short-Form Health Survey bodily pain, and Sheehan Disability Scale total score. Variables related to severity of pain, pain interfering with daily activities, and physical functioning were predictors of change in stiffness. CONCLUSIONS: Stiffness scores were high in this population with FM and best correlated at baseline with BPI pain score and FIQ function. Not unexpectedly, improvement in stiffness with duloxetine correlated with many of the other markers of FM severity, presumably a result of amelioration in FM comorbidities.

A brain-derived neurotrophic factor polymorphism Val66Met identifies fibromyalgia syndrome subgroup with higher body mass index and C-reactive protein.

A common single nucleotide polymorphism (SNP) in the gene of brain-derived neurotrophic factor (BDNF) results from a substitution at position 66 from valine (Val) to methionine (Met) and may predispose to human neuropsychiatric disorders. We proposed to determine whether these BDNF gene SNPs were associated with fibromyalgia syndrome (FMS) and/or any of its typical phenotypes. Patients with FMS (N = 95) and healthy normal controls (HNC, N = 58) were studied. Serum high-sensitivity C-reactive protein (hsCRP) levels were measured using an enzyme-linked immunosorbent assay (ELISA). The BDNF SNPs were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).The BDNF SNP distribution was 65 (68%) Val/Val, 28 (30%) Val/Met, and 2 (2%) Met/Met for FMS and 40 (69%), 17(29%), and 1 (2%) for HNC, respectively. The serum high-sensitivity C-reactive protein (hsCRP)and body mass index (BMI) in FMS were higher than in HNC. The FMS with BDNF Val66Val had significantly higher mean BMI (P = 0.0001) and hsCRP (P = 0.02) than did FMS carrying the Val66Met genotype. This pattern was not found in HNC. Phenotypic measures of subjective pain, pain threshold, depression, or insomnia did not relate to either of the BDNF SNPs in FMS. The relative distribution BDNF SNPs did not differ between FMS and HNC. The BDNF Val66Met polymorphism is not selective for FMS. The BDNF Val66Val SNP identifies a subgroup of FMS with elevated hsCRP and higher BMI. This is the first study to associate a BDNF polymorphism with a FMS subgroup phenotype.

Future perspectives in generalised musculoskeletal pain syndromes.

This article describes contemporary controversies regarding two categories of soft-tissue pain (STP)--chronic widespread pain and fibromyalgia syndrome. The tone is more editorial than review didactic. It draws upon history to explain current trends that project possible future implications. It begins with an orientation to classification of STP pain conditions and contrasts two ways to make the fibromyalgia diagnosis. Epidemiological data will be placed in perspective. The article ends with the voice of a non-physician patient advocate. STP classification divides relevant painful conditions into three subgroups, depending on the extent of body involvement (localised, regional and generalised). Fibromyalgia syndrome, in the generalised STP category, is distinguished from other types of chronic widespread pain by virtue of its greater severity. During the past 20 years, the diagnosis of fibromyalgia was based on a research classification (1990 American College of Rheumatology Research Classification Criteria (1990 ACR RCC)) that requires a history of chronic widespread pain and the examination finding of widespread mechanical allodynia. A new approach (2010 American College of Rheumatology Fibromyalgia Diagnostic Criteria (2010 ACR FDC)), validated for clinical use, still requires a history of chronic widespread pain, but the examination is replaced by a historical assessment of co-morbid symptom severity. The populations identified by the two criteria are similar but not identical. Misuse of the new criteria could expand fibromyalgia from 2 to 10% of the general population. Avoidance of the term 'fibromyalgia' could return it to the obscurity from whence it came, leaving a much larger problem in its stead.

Genetic polymorphisms of the beta2-adrenergic receptor relate to guanosine protein-coupled stimulator receptor dysfunction in fibromyalgia syndrome.

OBJECTIVE: To determine the genotype frequencies of ß(2)-adrenergic receptor (ß(2)AR) gene polymorphisms (Gly16Arg, Glu27Gln) in patients with fibromyalgia syndrome (FM) by comparison with unrelated healthy controls. We sought any clinical association with these polymorphisms and determined whether the polymorphisms would associate with a biologic guanosine protein-coupled stimulator receptor (Gs) dysfunction in FM. METHODS: Study subjects included 97 clinically characterized patients with FM and 59 controls. The ß(2)AR polymorphisms at codons 16 and 27 were determined using polymerase chain reaction-restriction fragment length polymorphism. The Gs functions of peripheral blood mononuclear cells (PBMC) were tested using isoproterenol (ISO) as the adrenergic Gs ligand and measuring intracellular cyclic adenosine monophosphate (cAMP) levels. RESULTS: The frequency of the ß(2)AR gene polymorphism Gly16Arg in FM (43.5%) was significantly lower than in controls (63.2%), suggesting that this genotype might have some effect on the risk of developing FM. The only clinical association in FM was with sleep dysfunction. Patients with FM who carried the ß(2)AR polymorphism Arg16Arg also exhibited significantly lower PBMC basal cAMP levels (p < 0.05) and lower ISO-stimulated cAMP levels (p < 0.05) than FM carrying Gly16Gly or Gly16Arg. CONCLUSION: This confirms a relationship between ß(2)AR polymorphism and FM. It is the first study to demonstrate ß(2)AR polymorphism-related differences in intracellular cAMP responses of FM PBMC after ß(2)AR stimulation in vitro. These findings may explain some of the differences in responsiveness of FM subgroups to the adrenergic agonist medications currently approved for FM treatment.

Estimation of minimum clinically important difference for pain in fibromyalgia.

OBJECTIVE: To estimate the minimum clinically important difference (MCID) for several pain measures obtained from the Brief Pain Inventory (BPI) for patients with fibromyalgia. METHODS: Data were pooled across 12-week treatment periods from 4 randomized, double-blind, placebo-controlled studies designed to evaluate the safety and efficacy of duloxetine for the treatment of fibromyalgia. Each study enrolled subjects with American College of Rheumatology--defined fibromyalgia who presented with moderate to severe pain. The MCIDs for the BPI average pain item score and the BPI severity score (the mean of the BPI pain scale values: right now, average, least, and worst) were estimated by anchoring against the Patient's Global Impressions of Improvement scale. RESULTS: The anchor-based MCIDs for the BPI average pain item and severity scores were 2.1 and 2.2 points, respectively. These MCIDs correspond to 32.3% and 34.2% reductions from baseline in scores. CONCLUSION: In these analyses, the MCIDs for several pain measures obtained from the BPI were similar (∼2 points) and corresponded to a 30-35% improvement from baseline to end point. These findings may be beneficial for use in designing clinical trials in which the BPI is used to evaluate improvements in pain severity.

Fibromyalgia criteria and severity scales for clinical and epidemiological studies: a modification of the ACR Preliminary Diagnostic Criteria for Fibromyalgia.

OBJECTIVE: To develop a fibromyalgia (FM) survey questionnaire for epidemiologic and clinical studies using a modification of the 2010 American College of Rheumatology Preliminary Diagnostic Criteria for Fibromyalgia (ACR 2010). We also created a new FM symptom scale to further characterize FM severity. METHODS: The ACR 2010 consists of 2 scales, the Widespread Pain Index (WPI) and the Symptom Severity (SS) scale. We modified these ACR 2010 criteria by eliminating the physician's estimate of the extent of somatic symptoms and substituting the sum of 3 specific self-reported symptoms. We also created a 0-31 FM Symptom scale (FS) by adding the WPI to the modified SS scale. We administered the questionnaire to 729 patients previously diagnosed with FM, 845 with osteoarthritis (OA) or with other noninflammatory rheumatic conditions, 439 with systemic lupus erythematosus (SLE), and 5210 with rheumatoid arthritis (RA). RESULTS: The modified ACR 2010 criteria were satisfied by 60% with a prior diagnosis of FM, 21.1% with RA, 16.8% with OA, and 36.7% with SLE. The criteria properly identified diagnostic groups based on FM severity variables. An FS score ≥ 13 best separated criteria+ and criteria- patients, classifying 93.0% correctly, with a sensitivity of 96.6% and a specificity of 91.8% in the study population. CONCLUSION: A modification to the ACR 2010 criteria will allow their use in epidemiologic and clinical studies without the requirement for an examiner. The criteria are simple to use and administer, but they are not to be used for self-diagnosis. The FS may have wide utility beyond the bounds of FM, including substitution for widespread pain in epidemiological studies.

The American College of Rheumatology preliminary diagnostic criteria for fibromyalgia and measurement of symptom severity.

OBJECTIVE: To develop simple, practical criteria for clinical diagnosis of fibromyalgia that are suitable for use in primary and specialty care and that do not require a tender point examination, and to provide a severity scale for characteristic fibromyalgia symptoms. METHODS: We performed a multicenter study of 829 previously diagnosed fibromyalgia patients and controls using physician physical and interview examinations, including a widespread pain index (WPI), a measure of the number of painful body regions. Random forest and recursive partitioning analyses were used to guide the development of a case definition of fibromyalgia, to develop criteria, and to construct a symptom severity (SS) scale. RESULTS: Approximately 25% of fibromyalgia patients did not satisfy the American College of Rheumatology (ACR) 1990 classification criteria at the time of the study. The most important diagnostic variables were WPI and categorical scales for cognitive symptoms, unrefreshed sleep, fatigue, and number of somatic symptoms. The categorical scales were summed to create an SS scale. We combined the SS scale and the WPI to recommend a new case definition of fibromyalgia: (WPI > or =7 AND SS > or =5) OR (WPI 3-6 AND SS > or =9). CONCLUSION: This simple clinical case definition of fibromyalgia correctly classifies 88.1% of cases classified by the ACR classification criteria, and does not require a physical or tender point examination. The SS scale enables assessment of fibromyalgia symptom severity in persons with current or previous fibromyalgia, and in those to whom the criteria have not been applied. It will be especially useful in the longitudinal evaluation of patients with marked symptom variability.

Long-term safety, tolerability, and efficacy of duloxetine in the treatment of fibromyalgia.

OBJECTIVES: To assess the long-term safety, tolerability, and efficacy of duloxetine in patients with fibromyalgia. METHODS: We report results from the 6-month extension phases of 2 randomized, double-blind, placebo-controlled clinical trials having 6-month placebo-controlled phases. In Study 1, all patients received duloxetine 120 mg/d after 28 weeks on placebo or duloxetine 60 or 120 mg/d. In Study 2, patients taking placebo were titrated to duloxetine 60 mg/d after 27 weeks on treatment, while duloxetine-treated patients remained on their dosages of 60 or 120 mg/d. Safety and tolerability were assessed via discontinuation rates, treatment-emergent adverse events (TEAEs), and changes in vital signs and laboratory measures. The primary efficacy measure was the Brief Pain Inventory average pain severity score. RESULTS: The percentage of patients entering and completing the extension phase was 56% (156/278) for Study 1 and 69% (140/204) for Study 2. Groups titrating from placebo to duloxetine showed the highest discontinuation rates due to an adverse event (Study 1, 25%; Study 2, 19%) and TEAE rates (Study 1, 82%; Study 2, 77%). The most common TEAEs were nausea and dry mouth. No significant within-group changes in blood pressure occurred in any group. Significant within-group mean increases in pulse (bpm) were observed in the placebo/duloxetine 120 mg group in Study 1 (3.7 [SD = 11.2], P

Neurophysiopathogenesis of fibromyalgia syndrome: a unified hypothesis.

The characteristic presenting complaint of patients with fibromyalgia syndrome (FMS) is chronic widespread allodynia. Research findings support the view that FMS is an understandable and treatable neuropathophysiologic disorder. The pain of FMS is often accompanied by one or more other manifestations, such as affective moods, cognitive insecurity, autonomic dysfunction, or irritable bowel or bladder. Growing evidence suggests that this is a familial disorder with many underlying genetic associations. New findings from brain imaging and polysomnography imply that FMS may be a disorder of premature neurologic aging. A conceptual model at the molecular level is proposed to explain many of the observed features of FMS. The model can also explain anticipated responses to FDA approved pharmacologic therapies.

The effects of pregabalin on sleep disturbance symptoms among individuals with fibromyalgia syndrome.

OBJECTIVES: Sleep disturbances are common in patients with fibromyalgia (FM). The objective of this analysis was to evaluate the effects of pregabalin on sleep in patients with FM. METHODS: Analyses were based on two randomized, double-blind, placebo-controlled trials of pregabalin (300mg, 450mg, and 600mg daily) in adult FM patients. Sleep outcomes included the Medical Outcomes Study (MOS) Sleep Scale and a daily diary assessment of sleep quality. Treatment effects were evaluated using analysis of covariance. Clinically important differences (CID) in the Sleep Quality Diary and MOS Sleep Disturbance scores were estimated using mixed-effects models of changes in scores as a function of patients' global impressions of change. Mediation modeling was used to quantify the direct treatment effects on sleep in contrast to indirect influence of the treatment on sleep via pain. RESULTS: A total of 748 and 745 patients were randomized in the respective studies. Patients were predominantly Caucasian females, average age 48-50 years, on average had FM for 9-10 years, and experienced moderate to severe baseline pain. Pregabalin significantly improved the Sleep Quality Diary (P<0.001), MOS Sleep Disturbance (P<0.01), MOS Quantity of Sleep (P<0.003), and MOS Sleep Problems Index scores (P<0.02) relative to placebo. Treatment effects for the 450mg and 600mg groups exceeded the estimated CID thresholds of 0.83 and 7.9 for the Sleep Quality Diary and MOS Sleep Disturbance scores, respectively. Mediation models indicated that 43-80% of the benefits on sleep (versus placebo) were direct effects of pregabalin, with the remainder resulting from an indirect effect of treatment via pain relief. CONCLUSIONS: These data demonstrate improvement in FM-related sleep dysfunction with pregabalin therapy. The majority of this benefit was a direct effect of pregabalin on the patients' insomnia, while the remainder occurred through the drug's analgesic activity.

Sodium oxybate relieves pain and improves function in fibromyalgia syndrome: a randomized, double-blind, placebo-controlled, multicenter clinical trial.

OBJECTIVE: To evaluate the safety and efficacy of sodium oxybate for management of the symptoms of fibromyalgia syndrome (FMS). METHODS: Patients with FMS (according to the American College of Rheumatology 1990 criteria) were randomized, after discontinuing their prestudy medications for FMS, to receive 4.5 gm or 6 gm of sodium oxybate or matching placebo once per night for 8 weeks. The primary outcome variable (POV) was a composite score for changes from baseline in 3 coprimary self-report measures: patient's pain rating (in daily electronic diaries) on a visual analog scale (PVAS), the Fibromyalgia Impact Questionnaire (FIQ) score, and the Patient Global Impression of Change (PGI-C). A beneficial response rate for the POV composite score was defined as >or=20% improvement in the PVAS and FIQ scores plus a rating of "much better" or "very much better" on the PGI-C. Secondary measures included subjective sleep outcomes (on the Jenkins Scale for Sleep) and quality-of-life measures. The analyses were based on an intent-to-treat (ITT) population. RESULTS: The ITT population included 188 patients with FMS, 78% of whom completed the trial. Significant benefit was observed with both dosages of sodium oxybate, according to changes in the POV and subjective sleep quality. Improvements in the PVAS score were significantly correlated with sleep outcomes. Sodium oxybate was well tolerated overall; dose-related nausea (

Biology and therapy of fibromyalgia. Evidence-based biomarkers for fibromyalgia syndrome.

Researchers studying fibromyalgia strive to identify objective, measurable biomarkers that may identify susceptible individuals, may facilitate diagnosis, or that parallel activity of the disease. Candidate objective measures range from sophisticated functional neuroimaging to office-ready measures of the pressure pain threshold. A systematic literature review was completed to assess highly investigated, objective measures used in fibromyalgia studies. To date, only experimental pain testing has been shown to coincide with improvements in clinical status in a longitudinal study. Concerted efforts to systematically evaluate additional objective measures in research trials will be vital for ongoing progress in outcome research and translation into clinical practice.

A 14-week, randomized, double-blinded, placebo-controlled monotherapy trial of pregabalin in patients with fibromyalgia.

UNLABELLED: The purpose of the study was to assess the efficacy and safety of pregabalin monotherapy in patients with fibromyalgia in a randomized, double-blinded, placebo-controlled trial. After 1 week of single-blinded administration of placebo, 750 patients meeting American College of Rheumatology criteria for fibromyalgia were randomly assigned to pregabalin (300 mg/d, 450 mg/d, 600 mg/d) or placebo, administered twice daily for 14 weeks. The primary outcome variable was comparison of end point mean pain scores, derived from daily diary ratings of pain intensity (0 to 10 scale), between each of the pregabalin groups and the placebo group. If positive, additional primary efficacy parameters included the Patient Global Impression of Change (PGIC) and the Fibromyalgia Impact Questionnaire (FIQ) total score. Compared with placebo-treated patients, mean changes in pain scores at the end point in pregabalin-treated patients were significantly greater (P < .001: 300 mg/d, -0.71; 450 mg/d, -0.98; 600 mg/d, -1.00). Compared with placebo, significantly more pregabalin-treated patients reported improvement on PGIC (P < .01 for all 3 pregabalin doses) and significant improvements in total FIQ score for the 450 mg/d (P = .004) and the 600 mg/d (P = .003) doses. Compared with placebo, all 3 doses of pregabalin were associated with significant improvement in sleep. The most commonly reported pregabalin-related adverse events were dizziness and somnolence, which tended to be dose-related. PERSPECTIVE: This randomized, placebo-controlled trial of 300, 450, and 600 mg/d of pregabalin monotherapy demonstrated that all 3 doses were efficacious for up to 14 weeks for the treatment of fibromyalgia and were well tolerated by most patients. These results provide evidence that pregabalin is an important treatment option for patients with fibromyalgia.

Identifying the clinical domains of fibromyalgia: contributions from clinician and patient Delphi exercises.

OBJECTIVE: In evaluating the effectiveness of fibromyalgia (FM) therapies, it is important to assess the impact of those therapies on the full array of domains considered important by both clinicians and patients. The objective of this research was to identify and prioritize the key clinically relevant and important domains impacted by FM that should be evaluated by outcome assessment instruments used in FM clinical trials, and to approach consensus among clinicians and patients on the priority of those domains to be assessed in clinical care and research. METHODS: Group consensus was achieved using the Delphi method, a structured process of consensus building via questionnaires together with systematic and controlled opinion feedback. The Delphi exercises involved 23 clinicians with expertise in FM and 100 patients with FM as defined by American College of Rheumatology criteria. RESULTS: The Delphi exercise revealed that the domains ranked most highly by patients were similar to the domain rankings by clinicians. Pain was consistently ranked highest by both panels. Fatigue, impact on sleep, health-related quality of life, comorbid depression, and cognitive difficulty were also ranked highly. Stiffness was ranked highly by patients but not clinicians. In contrast, side effects was important to clinicians but was not identified as important in the patient Delphi exercise. CONCLUSION: The clinician and patient Delphi exercises identified and ranked key domains that need to be assessed in FM research. Based on these results, a conceptual framework for measuring patient-reported outcomes is proposed.