Do subjective components of disease activity contribute to heterogeneity in opioid prescriptions in inflammatory rheumatic diseases? Results from ESPOIR and DESIR cohorts.

OBJECTIVES: To determine whether subjective components of disease activity are associated with heterogeneity in opioid prescription in inflammatory rheumatic diseases (IRDs) after accounting for objective inflammatory markers. METHODS: Data from two prospective observational cohorts of early IRDs (ESPOIR for rheumatoid arthritis (RA) and DESIR for spondyloarthritis (SpA)) were included. Opioid prescription duration (converted to monthly binary opioid prescription), disease activity (Disease activity score 28 (DAS28) for RA; Axial spondyloarthritis disease activity score-C-reactive protein (ASDAS-CRP) for SpA) and its components were measured respectively at 13 and 9 occasions spanning 10- and 6-years of follow-up. Group-based trajectory modelling defined opioid-prescription trajectories and mixed-models characterised the evolution of disease activity and its subjective components by opioid-prescription trajectories. RESULTS: Four distinct opioid-prescription trajectories: no/low (60.5% and 54.3%), declining (14.7% and 15.8%), augmenting (11.9% and 10.7%), and persistent (12.9% and 19.1%) were identified in RA and SpA respectively (60% were prescribed opioids at least once). Those with regular opioid prescriptions (up to 30%) are often older, less educated, have higher BMI and worse disease. No/low trajectory was the reference for examining evolution of disease activity and subjective components (n=810 RA, n=679 SpA). In IRDs, consistently higher disease activity throughout follow-up were seen with persistent (DAS28(ß=0.4-0.8); ASDAS-CRP(ß=0.4-0.6)), and augmenting (DAS28(ß=0.2-0.5); ASDAS-CRP(ß=0.3-0.6)) trajectories and until 3- or 4-years of follow-up (DAS28(ß=0.3-0.4); ASDAS-CRP(ß=0.2-0.3)) with declining trajectory. Likewise, despite accounting for objective inflammation, subjective components had worse scores over follow-up in augmenting and persistent trajectory. CONCLUSIONS: Non-inflammatory pain mechanisms amplify subjective outcomes, thus, worsening composite measures like disease activity.

Evaluation of the agreement between the ACR 1990 fibromyalgia tender points and an enthesitis score in patients with axial spondyloarthritis.

OBJECTIVES: Coexistence of FM represents a challenge in the evaluation of enthesitis in patients with axial spondyloarthritis (axSpA) due to a possible overlap between the tender points (TP) due to enthesitis and those of FM. The objective was to assess the agreement between the MASES enthesitis score and the tender points of the ACR 1990 criteria in patients with axSpA. METHODS: This was a cross-sectional ancillary analysis of the Predict-SpA study (NCT03039088). Patients had a diagnosis of axSpA according to their rheumatologist and an indication to start a TNFα blocker. All patients were screened for FM according to the FiRST questionnaire. A physician was asked to assess 31 anatomically described sites in a random order without knowing to which instrument the site belonged (i.e. the 18 ACR 1990 TP and the 13 MASES sites). Agreement between the MASES and the ACR 1990 TPs by the intraclass correlation coefficient (ICC), also stratified by the presence/absence of concomitant FM according to the FiRST. RESULTS: Among the 526 patients, 53% were men and 202 (38%) had FM. Radiographic sacroiliitis and MRI sacroiliitis were present in 56% and 68% patients, respectively. Patients were mostly men (53.4%) with radiographic and MRI sacroiliitis in 56% and 68% patients, respectively. Mean number of ACR 1990 TP was 5.4 (s.d. 4.6) and mean MASES was 4.2 (s.d. 3.6). ICC between both scores was 0.7 [95% CI (0.6, 0.8)]. ICC between both scores was 0.6 [95% CI (0.3, 0.8)] and 0.7 [95% CI (0.6, 0.7)] for patients with and without FM, respectively. CONCLUSION: These results suggest a significant overlap between both scores in patients with axSpA, including in those without concomitant FM. TRIAL REGISTRATION: clinicaltrials.gov, https://clinicaltrials.gov, NCT03039088.

Disproportionate articular pain is a frequent phenomenon in rheumatoid arthritis and responds to treatment with sarilumab.

OBJECTIVES: In some patients with RA, joint pain is more severe than expected based on the amount of joint swelling [referred to as disproportionate articular pain (DP)]. We assessed DP prevalence and the effects of sarilumab, an IL-6 inhibitor, on DP. METHODS: Data from RA patients treated with placebo or 200 mg sarilumab in the phase 3 randomized controlled trials (RCTs) MOBILITY and TARGET, adalimumab 40 mg or sarilumab 200 mg in the phase 3 RCT MONARCH and sarilumab 200 mg in open-label extensions (OLEs) were used. DP was defined as an excess tender 28-joint count (TJC28) over swollen 28-joint count (SJC28) of ≥7 (TJC28 - SJC28 ≥ 7). Treatment response and disease activity were determined for patients with and without DP. RESULTS: Of 1531 sarilumab 200 mg patients from RCTs, 353 (23%) had baseline DP. On average, patients with DP had higher 28-joint DAS using CRP (DAS28-CRP) and pain scores than patients without DP, whereas CRP levels were similar. After 12 and 24 weeks, patients with baseline DP treated with sarilumab were more likely to be DP-free than those treated with placebo or adalimumab. In RCTs, more sarilumab-treated patients achieved low disease activity vs comparators, regardless of baseline DP status. In OLEs, patients were more likely to lose rather than gain DP status. CONCLUSION: About one-quarter of patients with RA experienced DP, which responded well to sarilumab. These data support the concept that other mechanisms (potentially mediated via IL-6) in addition to inflammation may contribute to DP in RA. TRIAL REGISTRATIONS: NCT01061736, NCT02332590, NCT01709578, NCT01146652.

Socio-demographic determinants in the evolution of pain in inflammatory rheumatic diseases: results from ESPOIR and DESIR cohorts.

OBJECTIVE: To determine whether socio-demographic factors are associated with heterogeneity in pain evolution in inflammatory rheumatic diseases (IRDs) after accounting for disease-specific characteristics in a system with universal health care. METHODS: This analysis included the data from two prospective observational cohorts of early IRDs (ESPOIR for early RA and DESIR for early SpA). Data on pain was measured, respectively, on 13 and 9 occasions spanning 10 and 6 years of follow-up using the Short-Form 36 bodily pain score for 810 participants of ESPOIR, and 679 participants of DESIR. Linear mixed models were used to characterize differences in pain evolution as a function of age (tertiles), sex, ethnicity, education, marital, and professional status, after accounting for disease-related, treatment, lifestyle, and health factors. RESULTS: While transitioning from early (disease duration ≤6 months for RA and ≤3 years for SpA) to long-standing disease, differences in pain evolution emerged as a function of age (P < 0.001), sex (P = 0.050), and ethnicity (P = 0.001) in RA, and as a function of age (P = 0.048) in SpA; younger age, males, and Caucasians exhibited lower pain in the latter phases of both diseases. Highly educated participants (RA, ß = -3.8, P = 0.007; SpA, ß = -6.0, P < 0.001) for both diseases, and Caucasians (ß = -5.6, P = 0.021) for SpA presented with low pain early in the disease, with no changes throughout disease course. CONCLUSION: Being older, female, non-Caucasian and having lower education was found to be associated with worse pain in early and/or long-standing IRDs, despite universally accessible health-care. Early identification of at-risk populations and implementation of multidisciplinary strategies may reduce patient-reported health outcome disparities. TRIAL REGISTRATION REGISTRATIONS: ESPOIR: ClinicalTrials.gov, www.clinicaltrials.gov, NCT03666091. DESIR: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01648907.

Lifestyle and chronic pain: double jeopardy?

Given the often disappointing results of pharmacotherapy, many patients with chronic pain seek to modify their lifestyle. Some lifestyle factors, such as the consumption of alcohol, tobacco, cannabis, or psychostimulants, are deleterious in this context, whereas others, such as physical activity and a balanced diet, are considered beneficial, but these require substantial effort on the part of patients. In all cases, it is important to analyse lifestyle factors in patients with chronic pain, without stigmatisation, as the co-existence of pain and inappropriate behaviour can be seen as double jeopardy in patients with pain.

Research Recommendations Following the Discovery of Pain Sensitizing IgG Autoantibodies in Fibromyalgia Syndrome.

BACKGROUND: Fibromyalgia syndrome (FMS) is the most common chronic widespread pain condition in rheumatology. Until recently, no clear pathophysiological mechanism for fibromyalgia had been established, resulting in management challenges. Recent research has indicated that serum immunoglobulin Gs (IgGs) may play a role in FMS. We undertook a research prioritisation exercise to identify the most pertinent research approaches that may lead to clinically implementable outputs. METHODS: Research priority setting was conducted in five phases: situation analysis; design; expert group consultation; interim recommendations; consultation and revision. A dialogue model was used, and an international multi-stakeholder expert group was invited. Clinical, patient, industry, funder, and scientific expertise was represented throughout. Recommendation-consensus was determined via a voluntary closed eSurvey. Reporting guideline for priority setting of health research were employed to support implementation and maximise impact. RESULTS: Arising from the expert group consultation (n = 29 participants), 39 interim recommendations were defined. A response rate of 81.5% was achieved in the consensus survey. Six recommendations were identified as high priority- and 15 as medium level priority. The recommendations range from aspects of fibromyalgia features that should be considered in future autoantibody research, to specific immunological investigations, suggestions for trial design in FMS, and therapeutic interventions that should be assessed in trials. CONCLUSIONS: By applying the principles of strategic priority setting we directed research towards that which is implementable, thereby expediating the benefit to the FMS patient population. These recommendations are intended for patients, international professionals and grant-giving bodies concerned with research into causes and management of patients with fibromyalgia syndrome.

Management of chronic low back pain and the impact on patients' personal and professional lives: Results from an international patient survey.

OBJECTIVE: The objective of this study was to investigate the impact of chronic low back pain (CLBP) on patients' personal and professional lives, and management strategies applied to treat CLBP. METHODS: A 60-question survey was developed, and respondents from 16 countries with a self-reported physician's diagnosis of CLBP were recruited via an online market research survey panel. Respondents were stratified as having mild, moderate, or severe pain. Target sample sizes per country and for pain severity were set. Data were weighted according to the known population and prevalence of CLBP in each country and the number of respondents from that country. RESULTS: Results from 9642 CLBP patients indicated that almost a quarter of patients with severe CLBP report a psychological comorbidity. Prescription pain medications were more commonly used by patients with severe CLBP (56%) than those with mild (20%) or moderate (34%) CLBP. Among those with severe CLBP who had been prescribed pain medication, 58% were prescribed opioids, with 1 in 4 patients using opioids for more than 5 years. Patients were primarily managed by general practitioners/primary care physicians, physiotherapists, neurologists, or orthopedic surgeons. CLBP negatively impacted patients' daily activities, social lives, and work productivity. CONCLUSION: Chronic low back pain has pronounced effects on patients' personal relationships, ability to work, and daily living. Almost 1 in four patients with severe CLBP reported a psychological comorbidity. Adherence to guidelines appears inconsistent, which is noteworthy as a substantial subgroup of patients with severe CLBP had been prescribed opioid medication for more than 5 years. Improved education is required to support healthcare professionals (HCPs) in identifying and understanding the complex biopsychosocial needs of CLBP patients to optimize pain management and to encourage referral of CLBP patients to physiotherapists and psychologists.

Burden of chronic low back pain: Association with pain severity and prescription medication use in five large European countries.

OBJECTIVE: This study assessed associations between severity of, and prescription medication use for, chronic low back pain (CLBP) and health-related quality of life, health status, work productivity, and healthcare resource utilization. METHODS: This cross-sectional study utilized SF-12, EQ-5D-5L, and work productivity and activity impairment (WPAI) questionnaires, and visits to healthcare providers among adults with self-reported CLBP participating in the National Health and Wellness Survey in Germany, France, UK, Italy, and Spain. Respondents were stratified into four groups according to pain severity (mild or moderate/severe) and prescription medication use (Rx-treated or Rx-untreated). Differences between groups were estimated using generalized linear models controlling for sociodemographics and health characteristics. RESULTS: Of 2086 respondents with CLBP, 683 had mild pain (276 Rx-untreated, 407 Rx-treated) and 1403 had moderate/severe pain (781 Rx-untreated, 622 Rx-treated). Respondents with moderate/severe pain had significantly worse health-related quality of life (SF-12v2 physical component summary), health status (EQ-5D-5L), and both absenteeism and presenteeism compared with those with mild pain, including Rx-untreated (moderate/severe pain Rx-untreated vs. mild pain Rx-untreated, p ≤ 0.05) and Rx-treated (moderate/severe pain Rx-treated vs. mild pain Rx-treated, p ≤ 0.05) groups. Significantly more visits to healthcare providers in the last 6 months were reported for moderate/severe pain compared with mild pain for Rx-treated (least squares mean 13.01 vs. 10.93, p = 0.012) but not Rx-untreated (8.72 vs. 7.61, p = 0.072) groups. Health-related quality of life (SF-12v2 physical component summary) and health status (EQ-5D-5L), as well as absenteeism and presenteeism, were significantly worse, and healthcare utilization was significantly higher, in the moderate/severe pain Rx-treated group compared with all other groups (all p ≤ 0.05). CONCLUSION: Greater severity of CLBP was associated with worse health-related quality of life, health status, and absenteeism and presenteeism, irrespective of prescription medication use. Greater severity of CLBP was associated with increased healthcare utilization in prescription medication users.

Are pain severity and current pharmacotherapies associated with quality of life, work productivity, and healthcare utilisation for people with osteoarthritis in five large European countries?

OBJECTIVES: Although the osteoarthritis (OA) burden is well-recognised, the benefit of currently available OA pharmacological therapy is not clear. This study aimed to assess whether the impact of OA pain on health-related quality of life (HRQoL), work, and healthcare resource utilisation (HRU) differed by both pain severity and prescription medication status. METHODS: This cross-sectional study used pooled data from the 2016/2017 European National Health and Wellness Survey. Respondents with self-reported physician-diagnosed OA and pain were included. Outcomes examined included HRQoL, health utility, health status, work productivity and activity impairment, and HRU. Groups derived from self-reported pain severity and prescription medication use were compared using chi-square tests, analysis of variance, and generalised linear models controlling for socio-demographics, health behaviours, and health status. RESULTS: Respondents with OA (n=2417) reported mild (40.4%, of which 44.9% prescription-treated) and moderate to severe pain (59.6%, of which 54.0% prescription-treated). HRQoL, health utility, health status, and work and activity impairment were substantially worse among the moderate/severe pain prescription-treated group compared to the rest (e.g. SF-12v2 physical component score [PCS] for moderate/severe pain prescription-treated=34.5 versus mild pain prescription-treated =39.3, moderate/severe pain prescription-untreated=40.6, and mild pain prescription-untreated=45.6; p<0.01). HRU such as the mean number of emergency room visits for >6 months was higher in the prescription-treated groups (0.51-0.52, 95% CI 0.437-0.71) than the prescription-untreated groups (0.30-0.34, 95% CI 0.21-0.46; p<0.05). CONCLUSIONS: Persons with moderate to severe OA pain treated with available prescription medications have poor health status and HRQoL and increased HRU compared to those not receiving prescription medications.

Diagnostic and therapeutic care pathway for fibromyalgia.

Early diagnosis and timely and appropriate treatments positively influence the history of fibromyalgia syndrome (FM), with favourable repercussions at clinical, psychological, social and economic levels. Notwithstanding, there are still significant problems with timeliness of diagnosis, access to pharmacological therapies - particularly to innovative ones - and appropriate and effective taking in charge of patients. All the aforementioned factors have a great impact on FM patients' quality of life. Indeed, even though the World Health Organisation recognised FM as a chronic condition in the International Classification of Diseases 10th edition (ICD-10), many countries still fail to recognise the syndrome, and this negatively influences the capability to appropriately protect and care for patients. This is the case in several European Countries. In Italy, a few Regions have started to put in place precise indications for people suffering from FM, aiming at the implementation of diagnostic-therapeutic pathways. The Diagnostic-Therapeutic Care Pathway (DTCP) provides an important tool to meet the needs of patients suffering from chronic diseases. They present the organisation of an integrated assistance network. This includes a seamless path for disease prevention, diagnosis and treatment, by means of cooperation among physicians and other healthcare professionals.

Fibromyalgia position paper.

Fibromyalgia syndrome is one of the most common causes of chronic widespread pain, but pain accompanies a wide range of ancillary symptoms. To date, its aetiopathogenesis remains elusive, and diagnosis is exquisitely clinical, due to the lack of biomarkers or specific laboratory alterations in fibromyalgia patients. This position paper has the purpose to summarise the current scientific knowledge and expert opinions about the main controversies regarding fibromyalgia syndrome, namely: (i) fibromyalgia definition and why it is still not recognised in many countries as a distinct clinical entity; (ii) fibromyalgia severity and how to evaluate treatment outcome; (iii) how to treat fibromyalgia and which is a correct approach to fibromyalgia patients.

Progressive Response to Repeat Application of Capsaicin 179 mg (8% w/w) Cutaneous Patch in Peripheral Neuropathic Pain: Comprehensive New Analysis and Clinical Implications.

OBJECTIVE: To investigate the efficacy of repeated application of capsaicin 179 mg cutaneous patch in nonresponders to the first application. DESIGN: Post hoc, as-treated analysis of two prospective trials (STRIDE and PACE) with 52-week follow-up. BLINDING: Open-label. SETTING: Multicenter clinical trial. SUBJECTS: STRIDE: nondiabetic neuropathic pain; PACE: painful diabetic peripheral neuropathy. METHODS: Patients were divided according to number of applications needed before attainment of a ≥30% reduction in average pain intensity (question 5 of the Brief Pain Inventory [BPI-Q5]). We assessed the change from baseline in average pain intensity (BPI-Q5), mean "interference with sleep" score, Patient Global Impression of Change, quality of life (QOL) via the EuroQol 5-dimension, and Self-Assessment of Treatment. RESULTS: In STRIDE and PACE, respectively, n = 306 and n = 313 received the capsaicin patch; n = 60 and n = 96 had a response after the first application, n = 33 and n = 68 after the second, and n = 11 and n = 43 after the third. Among patients without a ≥30% reduction in pain intensity at 3 months, in STRIDE and PACE, respectively, 23.3% and 28.1% achieved a ≥30% reduction at 6 months, increasing to 33.9% and 45.7% at 12 months. Similar results were obtained when a decrease of ≥50% was used as the responder definition. Progressive improvements in pain intensity in slower responders reached levels similar to those in early responders at month 12 and were accompanied by improvements in sleep, QOL, and patient satisfaction. CONCLUSIONS: Although some patients with peripheral neuropathic pain experience rapid improvements with a single treatment of capsaicin 179 mg patch, some may require two or three treatments before an initial response is observed. Similar benefits for pain, sleep, and QOL can be achieved in early and late responders.

Real-Life Management Pathways for Chronic Peripheral Neuropathic Pain at Tertiary Pain Clinics in France.

OBJECTIVE: Peripheral neuropathic pain (PNP) represents a major public health issue. Severe or refractory cases warrant tertiary multidisciplinary management, but little information is available about real-life care pathways. The primary objective of this cross-sectional, observational study was to investigate the pathways of patients with PNP consulting for the first time or followed for less than 1 year in French tertiary specialized pain clinics. METHODS: PNP was diagnosed with the NeuPSIG algorithm. Data collected included demographics, pain characteristics, and details of management before and after the study visit (e.g., drug and non-drug treatment, nature of medical visits), as well as time to referral to a pain clinic and time to a diagnosis of PNP. Factors associated with delayed referral or diagnosis were analyzed with multivariate analysis. RESULTS: A total of 404 patients with PNP (age 55.8 ± 15.6 years, 60.3% females, 78.3% retired or unemployed, pain duration 43.4 ± 68.9 months) were enrolled by 84 pain specialists. Pain affected mainly the lower limbs (53.5%) and was predominantly related to surgery or trauma (59.4%). Primary care management was characterized by a high proportion of conventional analgesics (60.7%). Time to referral to a pain clinic was 43.4 ± 68.9 months since pain onset and 20.1 ± 39.4 months since the diagnosis of PNP. Delayed referral to a pain clinic was independently predicted by the clinical specialty of the referring doctor and by male gender. CONCLUSIONS: This study highlights the need for accessible guidance for non-pain specialists to improve their diagnostic and management skills and for faster referral of patients with PNP to tertiary pain clinics.

Validity and Reliability of the Fibromyalgia Rapid Screening Tool Among Individuals with Chronic Daily Headache: A Clinic-Based Study.

BACKGROUND: Fibromyalgia is a common chronic pain disorder typically associated with headache disorders, particularly chronic daily headache. However, fibromyalgia is typically underdiagnosed and undertreated. The Fibromyalgia Rapid Screening Tool questionnaire is a brief, self-administered questionnaire composed of six "yes/no" questions for detecting fibromyalgia. The Fibromyalgia Rapid Screening Tool questionnaire has demonstrated high sensitivity and specificity among patients with chronic diffuse pain conditions. This study assessed the validity and reliability of the aforementioned questionnaire for detecting fibromyalgia among patients with chronic daily headache. METHODS: Consecutive first-visit headache patients with primary chronic daily headache (≥15 days/month for three or more months) at the outpatient clinics of four university hospitals were enrolled in this study from April 2015 to October 2015, and the validity and reliability of the Fibromyalgia Rapid Screening Tool questionnaire for determining fibromyalgia were evaluated. Fibromyalgia was diagnosed according to the American College of Rheumatology criteria of 2010. RESULTS: A total of 171 patients with primary chronic daily headache were recruited, and 100 (58.4%) were determined to have fibromyalgia. Receiver operating characteristic curve analysis revealed that a cutoff score of 5 (corresponding to the number of positive items) provided the highest rate of correct identification of patients (77.2%), with a sensitivity of 70.0% and specificity of 87.3%. The positive and negative predictive values were 88.6% and 67.4%, respectively. The Cronbach's alpha coefficient was 0.684. CONCLUSIONS: The Fibromyalgia Rapid Screening Tool is a valid and reliable instrument for identifying fibromyalgia among patients with chronic daily headache.

Evaluation of the performance of extreme patient-reported outcomes as surrogate markers for fibromyalgia in axial spondyloarthritis.

OBJECTIVES: The aim of the study is to evaluate the performance of extreme patient-reported outcomes (PRO) against definitions of fibromyalgia (FM) in patients with axial spondyloarthritis (axSpA). METHODS: Ancillary analysis of the Predict-SpA trial, an observational study of axSpA patients receiving TNF-α inhibitor, was performed. 'Extreme PRO' was defined as a score ≥ 8 on three out of the first five Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) questions (scored 0-10). FM was defined by the American College of Rheumatology (ACR) 1990 criteria and the Fibromyalgia Rapid Screening Test (FiRST). Performances of 'extreme PRO' for FM were evaluated by the sensitivity, specificity and positive likelihood ratio using the 1990 ACR criteria as gold standard. As secondary analysis, the FiRST was used as the external standard. RESULTS: The prevalence of 'extreme PRO' in this population was 28.8% at baseline and decreased to 9.9% at 12 weeks. 'Extreme PRO' had low sensitivity 12 weeks after TNF initiation (0.18, 95% confidence interval [CI] 0.10-0.27 vs 0.60, 95% CI 0.50-0.71, at baseline), but high specificity (0.92, 95% CI 0.89-0.94 vs 0.78, 95% 0.74-0.82, at baseline), using ACR 1990 criteria as gold standard. Performances when tested against FiRST at 12 weeks showed higher sensitivity (0.27, 95% CI 0.20-0.35) and specificity (0.96, 95% CI 0.94-0.98). CONCLUSION: The proposed extreme PRO definition showed great specificity for FM recognition in patients with axSpA, suggesting it could be used in observational studies when specific items for FM classification are not available.

Evaluation of the impact of concomitant fibromyalgia on TNF alpha blockers' effectiveness in axial spondyloarthritis: results of a prospective, multicentre study.

OBJECTIVE: To describe the prevalence of fibromyalgia (FM) in an axial spondyloarthritis (axSpA) population and to confirm that concomitant FM had a negative impact on tumour necrosis factor blockers' (TNFb) response. DESIGN: Prospective observational study with two visits 3 months apart. PATIENTS: Adult patients with AxSpa initiating a TNFb. STUDY GROUPS: FM was defined by the Fibromyalgia Rapid Screening Tool (FiRST) at baseline and also by a sustained positive FiRST (both visits) and by a fulfilment of the 1990 American College of Rheumatology criteria for FM. STATISTICAL ANALYSIS: Prevalence of FM; evaluation of the impact of a concomitant FM on TNFb response (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI 50) as primary endpoint), adjusted by factors known to have an impact on TNFb response. RESULTS: Among the 508 patients included in the main analysis, 192 (37.8%) were screened at baseline as FM. Percentage of success after 12 weeks of treatment was lower in the FM group for most of the effectiveness endpoints (eg, BASDAI 50: 45.3% vs 54.1% in the FM/not FM groups according to the FiRST), except for the C reactive protein change endpoints which were not different across groups. CONCLUSION: This study confirms that FM coexists in patients with axSpA and that its presence seems to have a negative impact on TNFb response, which seems more related to the self-reported instruments used in its evaluation, rather than a different treatment effect of the molecule in this subgroup of patients.

Patient phenotypes in fibromyalgia comorbid with systemic sclerosis or rheumatoid arthritis: influence of diagnostic and screening tests. Screening with the FiRST questionnaire, diagnosis with the ACR 1990 and revised ACR 2010 criteria.

OBJECTIVES: Fibromyalgia (FM) may occur with rheumatoid arthritis (RA) and systemic sclerosis (SSc), and debate remains about its diagnosis. We aimed to use three FM tools (a screening tool (FiRST), diagnostic criteria (ACR 1990 and revised 2010), to compare FM prevalence between RA and SSc patients, to describe the phenotypes of patients with comorbid FM, and to analyze links between FM and secondary Sjögren's syndrome (SS). METHODS: Consecutive adult patients with confirmed RA or SSc from four university hospitals were tested with the three FM tools. RESULTS: FiRST detected FM in 22.6% of the 172 RA patients, with confirmation in 22.1% (ACR1990) and 19.1% (ACR2010). ACR1990FM+ RA patients had more diffuse pain, whereas ACR2010FM+ RA patients had higher BMI and pain intensity, more diffuse pain, active disease, disability, and associated SS. FiRST detected FM in 27.8% of the 122 SSc patients, with confirmation in 30.3% (ACR1990) and 23.7% (ACR2010). ACR1990FM+ SSc patients had greater disability and pain intensity, and more diffuse pain, whereas ACR2010FM+ SSc patients had higher BMI, pain intensity, more disability and diffuse pain, and associated SS. Correlations between FM diagnostic and screening tool results were modest in both conditions. Secondary SS was associated with comorbid FM. CONCLUSIONS: The prevalence of FM is high in SSc and RA, whatever the FM diagnostic tool used. Secondary SS is associated with FM in both RA and SSc. The revised ACR 2010 FM criteria and FiRST screening tool reveal specific phenotypes potentially useful for improving disease management.

Validation of the Greek Version of the Fibromyalgia Rapid Screening Tool.

BACKGROUND AND AIM: The Fibromyalgia Rapid Screening Tool (FiRST) is a brief, simple, and straightforward self-administered questionnaire that was developed by Perrot et al. for the detection of fibromyalgia syndrome in patients with diffuse chronic pain. The aim of our study was to develop and validate the Greek version of FiRST. METHODS: The study was set up as a prospective observational study. The original French version of FiRST was adapted into Greek using forward and backward translation. Patients with chronic diffuse pain with a clinical diagnosis of fibromyalgia and osteoarthritis based on the criteria of the American College of Rheumatology were invited to participate to the study. RESULTS: Of the 101 patients who met our inclusion criteria, 42 were diagnosed with fibromyalgia and 59 with osteoarthritis. The 2 groups did not differ significantly regarding gender and pain characteristics (duration, intensity). Cronbach's alpha coefficient was 0.79. Receiver operating characteristic analysis showed an area under the curve of 89% (95% confidence interval = 83 to 95%; SE: 0.032, P < 0.001). At a cutoff score of ≥ 5, FiRST showed a sensitivity of 86%, a specificity of 83%, a positive predictive value of 78%, and a negative predictive value of 89%. The intraclass coefficient for the test-retest reliability was 0.96. CONCLUSION: The Greek version of FiRST is a valid screening tool for fibromyalgia in daily practice.

Capsaicin 8% patch repeat treatment plus standard of care (SOC) versus SOC alone in painful diabetic peripheral neuropathy: a randomised, 52-week, open-label, safety study.

BACKGROUND: This 52-week study evaluated the long-term safety and tolerability of capsaicin 8% w/w (179 mg) patch repeat treatment plus standard of care (SOC) versus SOC alone in painful diabetic peripheral neuropathy (PDPN). METHODS: Phase 3, multinational, open-label, randomised, controlled, 52-week safety study, conducted in Europe. Patients were randomised to capsaicin 8% patch repeat treatment (30 or 60 min; 1-7 treatments with ≥ 8-week intervals) to painful areas of the feet plus SOC, or SOC alone. The primary objective was the safety of capsaicin 8% patch repeat treatment (30 min and 60 min applications) plus SOC versus SOC alone over 52 weeks, assessed by changes in Norfolk Quality of Life-Diabetic Neuropathy (QOL-DN) total score from baseline to end of study (EOS). Secondary safety endpoints included Utah Early Neuropathy Scale (UENS) assessments and standardised testing of sensory perception and reflex function. RESULTS: Overall, 468 patients were randomised (30 min plus SOC, n = 156; 60 min plus SOC, n = 157; SOC alone, n = 155). By EoS, mean changes in Norfolk QOL-DN total score from baseline [estimated mean difference versus SOC alone; 90% CI for difference] were: 30 min plus SOC, -27.6% [-20.9; -31.7, -10.1]; 60 min plus SOC, -32.8% [-26.1; -36.8, -15.4]; SOC alone, -6.7%. Mean changes [difference versus SOC alone] in UENS total score by EoS versus baseline were: 30 min plus SOC, -2.1 [-0.9; -1.8, 0.1]; 60 min plus SOC, -3.0 [-1.7; -2.7, -0.8]; SOC alone, -1.2. No detrimental deterioration was observed in any of the Norfolk or UENS subscales by EoS with capsaicin. Also, no worsening in sensory perception testing of sharp, warm, cold and vibration stimuli was found with capsaicin by EoS. Capsaicin treatment was well tolerated and the most frequent treatment-emergent adverse events were application site pain (30 min, 28.2%; 60 min, 29.3%), burning sensation (30 min, 9.0%; 60 min, 9.6%) and application site erythema (30 min, 7.7%; 60 min, 8.9%). CONCLUSION: In patients with PDPN, capsaicin 8% patch repeat treatment plus SOC over 52 weeks was well tolerated with no negative functional or neurological effects compared with SOC alone. TRIAL REGISTRATION: ClinicalTrials.gov registration: NCT01478607 . Date of registration November 21, 2011; retrospectively registered.

The Discriminatory Ability of the Fibromyalgia Rapid Screening Tool (FiRST): An International Study in Spain and Four Latin American Countries.

OBJECTIVE: To assess the transcultural equivalency of the Spanish version of the Fibromyalgia Rapid Screening Tool (FiRST) and its discriminatory ability in different Latin American samples. DESIGN: Validation study. SETTING: Departments of Rheumatology in general hospitals and private centers; fibromyalgia unit in a university hospital. SUBJECTS: 350 chronic pain patients from Spain, Argentina, Mexico, Peru, and Ecuador. METHODS: The cultural relevance of the Spanish version of the FiRST was evaluated. The ability of the FiRST as a screening tool for fibromyalgia was assessed by logistic regression analysis. To determine the degree to which potential confounders, such as differences in demographics, pain, affective distress, catastrophizing, and disability, might affect the discriminatory ability, the tool was reassessed by hierarchical multivariate logistic regression. RESULTS: Slightly different versions of the FiRST were recommended for use in each Latin American subsample. The FiRST showed acceptable criterion validity and was able to discriminate between fibromyalgia and non-fibromyalgia patients even after controlling for the effect of potential confounders. However, low specificities were observed in samples from Spain and Mexico. CONCLUSIONS: The Spanish version of the FiRST may be used as a screening tool for fibromyalgia in several Latin American subsamples, even in those patients with high scores on potential confounders. In Spain and Mexico, the low specificity of the FiRST suggests, however, that it would be best used to support a suspected diagnosis of fibromyalgia, rather than to exclude the diagnosis.