Response to secukinumab on synovitis using Power Doppler ultrasound in psoriatic arthritis: 12-week results from a phase III study, ULTIMATE.

OBJECTIVES: To investigate the dynamics of response of synovitis to IL-17A inhibition with secukinumab in patients with active PsA using Power Doppler ultrasound. METHODS: The randomized, placebo-controlled, Phase III ULTIMATE study enrolled PsA patients with active ultrasound synovitis and clinical synovitis and enthesitis having an inadequate response to conventional DMARDs and naïve to biologic DMARDs. Patients were randomly assigned to receive either weekly subcutaneous secukinumab (300 or 150 mg according to the severity of psoriasis) or placebo followed by 4-weekly dosing thereafter. The primary outcome was the mean change in the ultrasound Global EULAR and OMERACT Synovitis Score (GLOESS) from baseline to week 12. Key secondary endpoints included ACR 20 and 50 responses. RESULTS: Of the 166 patients enrolled, 97% completed 12 weeks of treatment (secukinumab, 99%; placebo, 95%). The primary end point was met, and the adjusted mean change in GLOESS was higher with secukinumab than placebo [-9 (0.9) vs -6 (0.9), difference (95% CI): -3 (-6, -1); one-sided P=0.004] at week 12. The difference in GLOESS between secukinumab and placebo was significant as early as one week after initiation of treatment. All key secondary endpoints were met. No new or unexpected safety findings were reported. CONCLUSION: This unique ultrasound study shows that apart from improving the signs and symptoms of PsA, IL-17A inhibition with secukinumab leads to a rapid and significant reduction of synovitis in PsA patients. TRIAL REGISTRATION: ClinicalTrials.gov; NCT02662985.

Development of an environmental contextual factor item set relevant to global functioning and health in patients with axial spondyloarthritis.

OBJECTIVE: To describe the development of an Environmental contextual factors (EF) Item Set (EFIS) accompanying the disease specific Assessment of SpondyloArthritis international Society Health Index (ASAS HI). METHOD: First, a candidate item pool was developed by linking items from existing questionnaires to 13 EF previously selected for the International Classification of Functioning, Disability and Health (ICF) /ASAS Core Set. Second, using data from two international surveys, which contained the EF item pool as well as the items from the ASAS HI, the number of EF items was reduced based on the correlation between the item and the ASAS HI sum score combined with expert opinion. Third, the final English EFIS was translated into 15 languages and cross-culturally validated. RESULTS: The initial item pool contained 53 EF addressing four ICF EF chapters: products and technology (e1), support and relationship (e3), attitudes (e4) and health services (e5). Based on 1754 responses of axial spondyloarthritis patients in an international survey, 44 of 53 initial items were removed based on low correlations to the ASAS HI or redundancy combined with expert opinion. Nine items of the initial item pool (range correlation 0.21-0.49) form the final EFIS. The EFIS was translated into 15 languages and field tested in 24 countries. CONCLUSIONS: An EFIS is available complementing the ASAS HI and helps to interpret the ASAS HI results by gaining an understanding of the interaction between a health condition and contextual factors. The EFIS emphasizes the importance of support and relationships, as well as attitudes of the patient and health services in relation to self-reported health.

A Wearable System Based on Multiple Magnetic and Inertial Measurement Units for Spine Mobility Assessment: A Reliability Study for the Evaluation of Ankylosing Spondylitis.

Spinal mobility assessment is essential for the diagnostic of patients with ankylosing spondylitis. BASMI is a routine clinical evaluation of the spine; its measurements are made with goniometers and tape measures, implying systematic errors, subjectivity, and low sensitivity. Therefore, it is crucial to develop better mobility assessment methods. The design, implementation, and evaluation of a novel system for assessing the entire spine's motion are presented. It consists of 16 magnetic and inertial measurement units (MIMUs) communicated wirelessly with a computer. The system evaluates the patient's movements by implementing a sensor fusion of the triaxial gyroscope, accelerometer, and magnetometer signals using a Kalman filter. Fifteen healthy participants were assessed with the system through six movements involving the entire spine to calculate continuous kinematics and maximum range of motion (RoM). The intrarater reliability was computed over the observed RoM, showing excellent reliability levels (intraclass correlation >0.9) in five of the six movements. The results demonstrate the feasibility of the system for further clinical studies with patients. The system has the potential to improve the BASMI method. To the best of our knowledge, our system involves the highest number of sensors, thus providing more objective information than current similar systems.

Differential expression of TLR2 and TLR4 in α4ß7-positive leukocytes of patients with axial spondyloarthritis.

OBJECTIVES: Expression of α4ß7 integrin can identify gut-homing immune cells. This study aimed to determine the expression of Toll-like receptor 2 (TLR2) and TLR4 in α4ß7-positive leukocytes of patients with axial SpA (axSpA). METHODS: We analysed the frequencies of α4ß7-positive T cells, Tγδ cells and monocytes in 14 patients with axSpA and 14 healthy controls, together with the expression of TLR2 and TLR4 by flow cytometry. Also, the concentration of faecal calprotectin was measured in all patients and controls. RESULTS: We found significantly higher percentages of α4ß7-positive T (P = 0.026) and Tγδ cells (P = 0.0118) in the patients with axSpA than in controls; these cells showed differential expression of TLR2 and TLR4 when compared with α4ß7-negative cells. Such differences were not correlated with disease activity or faecal calprotectin concentration. CONCLUSION: There is an increase in circulating α4ß7-positive T and Tγδ cells in patients with axSpA. These cells differentially express TLR2 and TLR4.

Ixekizumab treatment of biologic-naïve patients with active psoriatic arthritis: 3-year results from a phase III clinical trial (SPIRIT-P1).

OBJECTIVE: The aim was to assess the safety and efficacy of up to 156 weeks of ixekizumab (an IL-17A antagonist) treatment in PsA patients. METHODS: In a phase III study, patients naïve to biologic treatment were randomized to placebo, adalimumab 40 mg every 2 weeks (ADA; active reference) or ixekizumab 80 mg every 2 weeks (IXEQ2W) or every 4 weeks (IXEQ4W) after an initial dose of 160 mg. At week 24 (week 16 for inadequate responders), ADA (after 8-week washout) and placebo patients were re-randomized to IXEQ2W or IXEQ4W. Outcomes were evaluated using a modified non-responder imputation [linear extrapolation for radiographic progression (modified total Sharp score = 0)] during extended treatment until week 156. RESULTS: Of 417 patients, 381 entered the extension, and 243 of 381 (63.8%) completed the 156-week study. Incidence rates of treatment-emergent and serious adverse events, respectively, were 38.0 and 5.2 with IXEQ2W (n = 189) and 38.1 and 8.0 with IXEQ4W (n = 197). One death occurred (IXEQ4W). With IXEQ2W and IXEQ4W, respectively, the response rates persisted to week 156 as measured by the ACR response ≥20% (62.5 and 69.8%), ≥50% (56.1 and 51.8%) and ≥70% (43.8 and 33.4%), psoriasis area and severity index (PASI) 75 (69.1 and 63.5%), PASI 90 (64.5 and 51.2%) and PASI 100 (60.5 and 43.6%). Inhibition of radiographic progression also persisted to week 156 in 61% of IXEQ2W and 71% of IXEQ4W patients. CONCLUSION: In this 156-week study of ixekizumab, the safety profile remained consistent with previous reports, and improvements in signs and symptoms of PsA were observed, including persistent low rates of radiographic progression. TRIAL REGISTRATION: ClinicalTrials.gov, http://clinicaltrials.gov, NCT01695239, EudraCT 2011-002326-49.

MRI lesions in the sacroiliac joints of patients with spondyloarthritis: an update of definitions and validation by the ASAS MRI working group.

OBJECTIVES: The Assessment of SpondyloArthritis international Society (ASAS) MRI working group (WG) was convened to generate a consensus update on standardised definitions for MRI lesions in the sacroiliac joint (SIJ) of patients with spondyloarthritis (SpA), and to conduct preliminary validation. METHODS: The literature pertaining to these MRI lesion definitions was discussed at three meetings of the group. 25 investigators (20 rheumatologists, 5 radiologists) determined which definitions should be retained or required revision, and which required a new definition. Lesion definitions were assessed in a multi-reader validation exercise using 278 MRI scans from the ASAS classification cohort by global assessment (lesion present/absent) and detailed scoring (inflammation and structural). Reliability of detection of lesions was analysed using kappa statistics and the intraclass correlation coefficient (ICC). RESULTS: No revisions were made to the current ASAS definition of a positive SIJ MRI or definitions for subchondral inflammation and sclerosis. The following definitions were revised: capsulitis, enthesitis, fat lesion and erosion. New definitions were developed for joint space enhancement, joint space fluid, fat metaplasia in an erosion cavity, ankylosis and bone bud. The most frequently detected structural lesion, erosion, was detected almost as reliably as subchondral inflammation (κappa/ICC:0.61/0.54 and 0.60/0.83) . Fat metaplasia in an erosion cavity and ankylosis were also reliably detected despite their low frequency (κappa/ICC:0.50/0.37 and 0.58/0.97). CONCLUSION: The ASAS-MRI WG concluded that several definitions required revision and some new definitions were necessary. Multi-reader validation demonstrated substantial reliability for the most frequently detected lesions and comparable reliability between active and structural lesions.

Stress proteins in the pathogenesis of spondyloarthritis.

Spondyloarthritis is an autoinflammatory rheumatic disease in which arthritis and osteoproliferation lead the patients who suffer from it to chronic disability. This disease is associated with the expression of class I MHC molecule HLA-B27, which tends to be misfolded in the endoplasmic reticulum and, therefore, expressed in aberrant forms. This phenomena lead to endoplasmic reticulum stress, which in time, evokes a whole response to cellular injury. Under these conditions, the molecules involved in restoring cell homeostasis play a key role. Such is the case of the "heat-shock proteins", which usually regulate protein folding, but also have important immunomodulatory functions, as well as some roles in tissue modeling. In this review, we attempt to summarize the involvement of cell stress and heat-shock proteins in the homeostatic disturbances and pathological conditions associated with this disease.

Measurement properties of the ASAS Health Index: results of a global study in patients with axial and peripheral spondyloarthritis.

OBJECTIVES: To evaluate construct validity, interpretability, reliability and responsiveness as well as determination of cut-off points for good and poor health within the original English version and the 18 translations of the disease-specific Assessment of Spondyloarthritis international Society Health Index (ASAS HI) in 23 countries worldwide in patients with spondyloarthritis (SpA). METHODS: A representative sample of patients with SpA fulfilling the ASAS classification criteria for axial (axSpA) or peripheral SpA was used. The construct validity of the ASAS HI was tested using Spearman correlation with several standard health outcomes for axSpA. Test-retest reliability was assessed by intraclass correlation coefficients (ICCs) in patients with stable disease (interval 4-7 days). In patients who required an escalation of therapy because of high disease activity, responsiveness was tested after 2-24weeks using standardised response mean (SRM). RESULTS: Among the 1548 patients, 64.9% were men, with a mean (SD) age 42.0 (13.4) years. Construct validity ranged from low (age: 0.10) to high (Bath AnkylosingSpondylitisFunctioning Index: 0.71). Internal consistency was high (Cronbach's α of 0.93). The reliability among 578 patients was good (ICC=0.87 (95% CI 0.84 to 0.89)). Responsiveness among 246 patients was moderate-large (SRM=-0.44 for non-steroidal anti-inflammatory drugs, -0.69 for conventional synthetic disease-modifying antirheumatic drug and -0.85 for tumour necrosis factor inhibitor). The smallest detectable change was 3.0. Values ≤5.0 have balanced specificity to distinguish good health as opposed to moderate health, and values ≥12.0 are specific to represent poor health as opposed to moderate health. CONCLUSIONS: The ASAS HI proved to be valid, reliable and responsive. It can be used to evaluate the impact of SpA and its treatment on functioning and health. Furthermore, comparison of disease impact between populations is possible.

Treating juvenile idiopathic arthritis to target: recommendations of an international task force.

Recent therapeutic advances in juvenile idiopathic arthritis (JIA) have made remission an achievable goal for most patients. Reaching this target leads to improved outcomes. The objective was to develop recommendations for treating JIA to target. A Steering Committee formulated a set of recommendations based on evidence derived from a systematic literature review. These were subsequently discussed, amended and voted on by an international Task Force of 30 paediatric rheumatologists in a consensus-based, Delphi-like procedure. Although the literature review did not reveal trials that compared a treat-to-target approach with another or no strategy, it provided indirect evidence regarding an optimised approach to therapy that facilitated development of recommendations. The group agreed on six overarching principles and eight recommendations. The main treatment target, which should be based on a shared decision with parents/patients, was defined as remission, with the alternative target of low disease activity. The frequency and timeline of follow-up evaluations to ensure achievement and maintenance of the target depend on JIA category and level of disease activity. Additional recommendations emphasise the importance of ensuring adequate growth and development and avoiding long-term systemic glucocorticoid administration to maintain the target. All items were agreed on by more than 80% of the members of the Task Force. A research agenda was formulated. The Task Force developed recommendations for treating JIA to target, being aware that the evidence is not strong and needs to be expanded by future research. These recommendations can inform various stakeholders about strategies to reach optimal outcomes for JIA.

The Paraguayan Spanish version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR).

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Paraguayan Spanish language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the 3 Likert assumptions, floor/ceiling effects, internal consistency, Cronbach's alpha, interscale correlations, and construct validity (convergent and discriminant validity). A total of 51 JIA patients (2% systemic, 27.4% oligoarticular, 37.2% RF negative polyarthritis, 33.4% other categories) and 100 healthy children, were enrolled. The JAMAR components discriminated well healthy subjects from JIA patients. Notably, there was no significant difference between healthy subjects and their affected peers in the school-related problem variable. All JAMAR components revealed good psychometric performances. In conclusion, the Paraguayan Spanish version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and clinical research.

The Mexican Spanish version of the Juvenile Arthritis Multidimensional Assessment Report (JAMAR).

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Mexican Spanish language. The reading comprehension of the questionnaire was tested in 10 JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the 3 Likert assumptions, floor/ceiling effects, internal consistency, Cronbach's alpha, interscale correlations, test-retest reliability, and construct validity (convergent and discriminant validity). A total of 100 JIA patients (16% systemic, 16% oligoarticular, 30% RF positive polyarthritis, 38% other categories) and 99 healthy children, were enrolled at the paediatric rheumatology department of the Hospital General de Mexico. The JAMAR components discriminated well healthy subjects from JIA patients. However, there was no significant difference between healthy subjects and their affected peers in school related problem variable. All JAMAR components revealed good psychometric performances. In conclusion, the Mexican Spanish version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and clinical research.

Prevalence of comorbidities and evaluation of their screening in spondyloarthritis: results of the international cross-sectional ASAS-COMOSPA study.

BACKGROUND: Increased risk of some comorbidities has been reported in spondyloarthritis (SpA). Recommendations for detection/management of some of these comorbidities have been proposed, and it is known that a gap exists between these and their implementation in practice. OBJECTIVE: To evaluate (1) the prevalence of comorbidities and risk factors in different countries worldwide, (2) the gap between available recommendations and daily practice for management of these comorbidities and (3) the prevalence of previously unknown risk factors detected as a result of the present initiative. METHODS: Cross-sectional international study with 22 participating countries (from four continents), including 3984 patients with SpA according to the rheumatologist. STATISTICAL ANALYSIS: The prevalence of comorbidities (cardiovascular, infection, cancer, osteoporosis and gastrointestinal) and risk factors; percentage of patients optimally monitored for comorbidities according to available recommendations and percentage of patients for whom a risk factor was detected due to this study. RESULTS: The most frequent comorbidities were osteoporosis (13%) and gastroduodenal ulcer (11%). The most frequent risk factors were hypertension (34%), smoking (29%) and hypercholesterolaemia (27%). Substantial intercountry variability was observed for screening of comorbidities (eg, for LDL cholesterol measurement: from 8% (Taiwan) to 98% (Germany)). Systematic evaluation (eg, blood pressure (BP), cholesterol) during this study unveiled previously unknown risk factors (eg, elevated BP (14%)), emphasising the suboptimal monitoring of comorbidities. CONCLUSIONS: A high prevalence of comorbidities in SpA has been shown. Rigorous application of systematic evaluation of comorbidities may permit earlier detection, which may ultimately result in an improved outcome of patients with SpA.

Defining active sacroiliitis on MRI for classification of axial spondyloarthritis: update by the ASAS MRI working group.

OBJECTIVES: To review and update the existing definition of a positive MRI for classification of axial spondyloarthritis (SpA). METHODS: The Assessment in SpondyloArthritis International Society (ASAS) MRI working group conducted a consensus exercise to review the definition of a positive MRI for inclusion in the ASAS classification criteria of axial SpA. Existing definitions and new data relevant to the MRI diagnosis and classification of sacroiliitis and spondylitis in axial SpA, published since the ASAS definition first appeared in print in 2009, were reviewed and discussed. The precise wording of the existing definition was examined in detail and the data and a draft proposal were presented to and voted on by the ASAS membership. RESULTS: The clear presence of bone marrow oedema on MRI in subchondral bone is still considered to be the defining observation that determines the presence of active sacroiliitis. Structural damage lesions seen on MRI may contribute to a decision by the observer that inflammatory lesions are genuinely due to SpA but are not required to meet the definition. The existing definition was clarified adding guidelines and images to assist in the application of the definition. CONCLUSION: The definition of a positive MRI for classification of axial SpA should continue to primarily depend on the imaging features of 'active sacroiliitis' until more data are available regarding MRI features of structural damage in the sacroiliac joint and MRI features in the spine and their utility when used for classification purposes.

Clinical efficacy and safety maintained up to 5 years in patients with rheumatoid arthritis treated with tocilizumab in a randomised trial.

OBJECTIVES: To report 5-year efficacy and safety in rheumatoid arthritis (RA) patients with active disease treated with tocilizumab. METHODS: LITHE was a 2-year, randomised, placebo-controlled study of tocilizumab in RA patients (ClinicalTrials.gov, NCT00106535), with an additional 3-year, open-label extension. Patients were randomly assigned to tocilizumab (4 or 8 mg/kg IV) or placebo every 4 weeks + methotrexate. They could receive rescue with tocilizumab from week 16; after week 52, patients could switch to open-label tocilizumab 8 mg/kg. Radiographs were analysed by randomized treatment using the Genant-modified Total Sharp Score (GmTSS). Patients with at least baseline, week 104 and post-week 104 radiographs were included. Clinical and safety data were pooled for all patients who received ≥1 dose of tocilizumab; results are presented from the first tocilizumab dose. RESULTS: 1,149 patients were included with 4,380 patient-years of exposure; 34% received 5 years of treatment. Mean 5-year change in GmTSS revealed greater inhibition of radiographic progression in tocilizumab patients than placebo patients (1.34 vs. 3.02), with the greatest annualised progression rate in year 1. Overall, 53% of tocilizumab and 35% of placebo patients experienced no progression (GmTSS ≤0). Clinical benefit was maintained - determined by ACR response, DAS28-ESR <2.6, EULAR good/moderate response and Boolean remission - as was physical function. The safety profile over 5 years was similar to that over 2 years. CONCLUSIONS: Over 5 years, tocilizumab + MTX inhibited radiographic progression and maintained improvements in signs and symptoms and physical function in MTX-inadequate responders with active disease; no new safety signals occurred.

Assessment of clinical efficacy and safety in a randomized double-blind study of etanercept and sulfasalazine in patients with ankylosing spondylitis from Eastern/Central Europe, Latin America, and Asia.

Despite the demonstrated efficacy of etanercept for the treatment of ankylosing spondylitis (AS), sulfasalazine is often prescribed, especially in countries with limited access to biologic agents. The objective of this subset analysis of the ASCEND trial was to compare the efficacy of etanercept and sulfasalazine in treating patients with AS from Asia, Eastern/Central Europe, and Latin America. A total of 287 patients, 190 receiving etanercept 50 mg once weekly and 97 receiving sulfasalazine 3 g daily, from eight countries were included in this subset analysis. Differences in disease activity and patient-reported outcomes assessing health-related quality-of-life (HRQoL) parameters in response to treatment were analyzed using the Cochran-Mantel-Haenszel test for categorical efficacy endpoints and analysis of covariance model for continuous variables. At week 16, a significantly greater proportion of patients receiving etanercept achieved ASAS20 (79.0 %) compared with patients receiving sulfasalazine (61.9 %; p = 0.002). At week 16, treatment with etanercept also resulted in significantly better responses than sulfasalazine for ASAS40 (64.7 vs. 35.1 %; p < 0.001), ASAS5/6 (48.1 vs. 26.3 %; p < 0.001), proportion of patients achieving 50 % response in Bath AS Disease Activity Index (65.8 vs. 42.3 %; p < 0.001), partial remission (35.3 vs. 17.5 %; p = 0.002), and all HRQoL parameters. Both treatments were well tolerated. Etanercept was significantly more effective than sulfasalazine in the treatment of patients with AS from Asia, Central/Eastern Europe, and Latin America.

Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis.

BACKGROUND: Systemic juvenile idiopathic arthritis (JIA) is the most severe subtype of JIA; treatment options are limited. Interleukin-6 plays a pathogenic role in systemic JIA. METHODS: We randomly assigned 112 children, 2 to 17 years of age, with active systemic JIA (duration of ≥6 months and inadequate responses to nonsteroidal antiinflammatory drugs and glucocorticoids) to the anti-interleukin-6 receptor antibody tocilizumab (at a dose of 8 mg per kilogram of body weight if the weight was ≥30 kg or 12 mg per kilogram if the weight was <30 kg) or placebo given intravenously every 2 weeks during the 12-week, double-blind phase. Patients meeting the predefined criteria for nonresponse were offered open-label tocilizumab. All patients could enter an open-label extension. RESULTS: At week 12, the primary end point (an absence of fever and an improvement of 30% or more on at least three of the six variables in the American College of Rheumatology [ACR] core set for JIA, with no more than one variable worsening by more than 30%) was met in significantly more patients in the tocilizumab group than in the placebo group (64 of 75 [85%] vs. 9 of 37 [24%], P<0.001). At week 52, 80% of the patients who received tocilizumab had at least 70% improvement with no fever, including 59% who had 90% improvement; in addition, 48% of the patients had no joints with active arthritis, and 52% had discontinued oral glucocorticoids. In the double-blind phase, 159 adverse events, including 60 infections (2 serious), occurred in the tocilizumab group, as compared with 38, including 15 infections, in the placebo group. In the double-blind and extension periods combined, 39 serious adverse events (0.25 per patient-year), including 18 serious infections (0.11 per patient-year), occurred in patients who received tocilizumab. Neutropenia developed in 19 patients (17 patients with grade 3 and 2 patients with grade 4), and 21 had aminotransferase levels that were more than 2.5 times the upper limit of the normal range. CONCLUSIONS: Tocilizumab was efficacious in severe, persistent systemic JIA. Adverse events were common and included infection, neutropenia, and increased aminotransferase levels. (Funded by Hoffmann-La Roche; ClinicalTrials.gov number, NCT00642460.).

Association of regional and cultural factors with the prevalence of rheumatoid arthritis in the Mexican population: a multilevel analysis.

BACKGROUND: The overall estimated prevalence of rheumatoid arthritis (RA) in Mexico is 1.6%, but there are major variations in different geographic areas of the country. OBJECTIVE: This study aimed to determine the impact of individual and regional variables on the geographic distribution of RA in Mexico. METHODS: This multilevel analysis used data from a cross-sectional study that investigated the prevalence of RA among 19,213 individuals older than 18 years throughout 5 geographic regions in Mexico. Logistic regression models were used to determine predictors of RA, including individual and regional variables as well as cultural factors. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were determined. RESULTS: The prevalence of RA varied from 0.77% to 2.8% across the 5 regions. Individual factors associated with RA were sex (OR, 2.32; 95% CI, 1.74-3.07), previous medical diagnosis of RA ( OR 3.3, 95%CI: 2919­5.1 [corrected]), disability (OR, 2.07; 95% CI, 1.48-2.93), and the 56- to 65-year age group (OR, 1.95; 95% CI, 1.08-3.74). The regional factor of speaking an indigenous language had an OR of 2.27 (95% CI, 1.13-4.55). CONCLUSIONS: Various individual and regional factors were associated with variations in the prevalence of RA in the Mexican population.

Efficacy and safety of open-label etanercept on extended oligoarticular juvenile idiopathic arthritis, enthesitis-related arthritis and psoriatic arthritis: part 1 (week 12) of the CLIPPER study.

OBJECTIVE: To investigate the efficacy and safety of etanercept (ETN) in paediatric subjects with extended oligoarticular juvenile idiopathic arthritis (eoJIA), enthesitis-related arthritis (ERA), or psoriatic arthritis (PsA). METHODS: CLIPPER is an ongoing, Phase 3b, open-label, multicentre study; the 12-week (Part 1) data are reported here. Subjects with eoJIA (2-17 years), ERA (12-17 years), or PsA (12-17 years) received ETN 0.8 mg/kg once weekly (maximum 50 mg). Primary endpoint was the percentage of subjects achieving JIA American College of Rheumatology (ACR) 30 criteria at week 12; secondary outcomes included JIA ACR 50/70/90 and inactive disease. RESULTS: 122/127 (96.1%) subjects completed the study (mean age 11.7 years). JIA ACR 30 (95% CI) was achieved by 88.6% (81.6% to 93.6%) of subjects overall; 89.7% (78.8% to 96.1%) with eoJIA, 83.3% (67.2% to 93.6%) with ERA and 93.1% (77.2% to 99.2%) with PsA. For eoJIA, ERA, or PsA categories, the ORs of ETN vs the historical placebo data were 26.2, 15.1 and 40.7, respectively. Overall JIA ACR 50, 70, 90 and inactive disease were achieved by 81.1, 61.5, 29.8 and 12.1%, respectively. Treatment-emergent adverse events (AEs), infections, and serious AEs, were reported in 45 (35.4%), 58 (45.7%), and 4 (3.1%), subjects, respectively. Serious AEs were one case each of abdominal pain, bronchopneumonia, gastroenteritis and pyelocystitis. One subject reported herpes zoster and another varicella. No differences in safety were observed across the JIA categories. CONCLUSIONS: ETN treatment for 12 weeks was effective and well tolerated in paediatric subjects with eoJIA, ERA and PsA, with no unexpected safety findings.

Treating spondyloarthritis, including ankylosing spondylitis and psoriatic arthritis, to target: recommendations of an international task force.

BACKGROUND: Therapeutic targets have been defined for diseases like diabetes, hypertension or rheumatoid arthritis and adhering to them has improved outcomes. Such targets are just emerging for spondyloarthritis (SpA). OBJECTIVE: To define the treatment target for SpA including ankylosing spondylitis and psoriatic arthritis (PsA) and develop recommendations for achieving the target, including a treat-to-target management strategy. METHODS: Based on results of a systematic literature review and expert opinion, a task force of expert physicians and patients developed recommendations which were broadly discussed and voted upon in a Delphi-like process. Level of evidence, grade and strength of the recommendations were derived by respective means. The commonalities between axial SpA, peripheral SpA and PsA were discussed in detail. RESULTS: Although the literature review did not reveal trials comparing a treat-to-target approach with another or no strategy, it provided indirect evidence regarding an optimised approach to therapy that facilitated the development of recommendations. The group agreed on 5 overarching principles and 11 recommendations; 9 of these recommendations related commonly to the whole spectrum of SpA and PsA, and only 2 were designed separately for axial SpA, peripheral SpA and PsA. The main treatment target, which should be based on a shared decision with the patient, was defined as remission, with the alternative target of low disease activity. Follow-up examinations at regular intervals that depend on the patient's status should safeguard the evolution of disease activity towards the targeted goal. Additional recommendations relate to extra-articular and extramusculoskeletal aspects and other important factors, such as comorbidity. While the level of evidence was generally quite low, the mean strength of recommendation was 9-10 (10: maximum agreement) for all recommendations. A research agenda was formulated. CONCLUSIONS: The task force defined the treatment target as remission or, alternatively, low disease activity, being aware that the evidence base is not strong and needs to be expanded by future research. These recommendations can inform the various stakeholders about expert opinion that aims for reaching optimal outcomes of SpA.

Multinational evidence-based recommendations for the diagnosis and management of gout: integrating systematic literature review and expert opinion of a broad panel of rheumatologists in the 3e initiative.

We aimed to develop evidence-based multinational recommendations for the diagnosis and management of gout. Using a formal voting process, a panel of 78 international rheumatologists developed 10 key clinical questions pertinent to the diagnosis and management of gout. Each question was investigated with a systematic literature review. Medline, Embase, Cochrane CENTRAL and abstracts from 2010-2011 European League Against Rheumatism and American College of Rheumatology meetings were searched in each review. Relevant studies were independently reviewed by two individuals for data extraction and synthesis and risk of bias assessment. Using this evidence, rheumatologists from 14 countries (Europe, South America and Australasia) developed national recommendations. After rounds of discussion and voting, multinational recommendations were formulated. Each recommendation was graded according to the level of evidence. Agreement and potential impact on clinical practice were assessed. Combining evidence and clinical expertise, 10 recommendations were produced. One recommendation referred to the diagnosis of gout, two referred to cardiovascular and renal comorbidities, six focused on different aspects of the management of gout (including drug treatment and monitoring), and the last recommendation referred to the management of asymptomatic hyperuricaemia. The level of agreement with the recommendations ranged from 8.1 to 9.2 (mean 8.7) on a 1-10 scale, with 10 representing full agreement. Ten recommendations on the diagnosis and management of gout were established. They are evidence-based and supported by a large panel of rheumatologists from 14 countries, enhancing their utility in clinical practice.