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.AbbVieAustralian National Health and Medical Research Council (NHMRC)Hosp Gen Univ Elda, Dept Reumatol, Elda 03600, SpainHosp Gen Univ Alicante, Dept Reumatol, Alicante, SpainUniv Camilo Jose Cela, Fac Ciencias Salud, Madrid, SpainUniv British Columbia, Div Rheumatol, Vancouver, BC V5Z 1M9, CanadaRoyal Melbourne Hosp, Parkville, Vic 3050, AustraliaUniv Hosp Southampton NHS Fdn Trust, Southampton, Hants, EnglandNIHR Wellcome Trust Clin Res Facil, Southampton, Hants, EnglandCtr Hosp Univ Liege, Liege, BelgiumMaastricht Univ, Med Ctr, Dept Internal Med Rheumatol, Maastricht, NetherlandsAtrium Med Ctr, Heerlen, NetherlandsUniv Toronto, Div Rheumatol, Toronto, ON, CanadaRepatriat Gen Hosp, Rheumatol Res Unit, Adelaide, SA, AustraliaFlinders Univ S Australia, Adelaide, SA 5001, AustraliaMed Univ Vienna, Dept Internal Med 3, Div Rheumatol, Vienna, AustriaUniv Toronto, Dept Hlth Policy Management & Evaluat, Toronto, ON, CanadaMt Sinai Hosp, Univ Hlth Network, Toronto Gen Res Inst, Div Clin Decis Making & Hlth Care, Toronto, ON M5G 1X5, CanadaCabrini Hosp, Monash Dept Clin Epidemiol, Malvern, Vic, AustraliaMonash Univ, Dept Epidemiol & Prevent Med, Malvern, Vic, AustraliaUniv Amsterdam, Acad Med Ctr, Dept Clin Immunol & Rheumatol, NL-1105 AZ Amsterdam, NetherlandsUniv Med Ctr Utrecht, Dept Rheumatol & Clin Immunol, Utrecht, NetherlandsUniv Nova Lisboa, Fac Ciencias Med, CEDOC, P-1200 Lisbon, PortugalEPE Hosp Egas Moniz, CHLO, Dept Rheumatol, Lisbon, PortugalHosp Gen Mexico City, Rheumatol Unit, Mexico City, DF, MexicoKarolinska Univ Hosp, Dept Rheumatol, Stockholm, SwedenKarolinska Inst, Stockholm, SwedenGhent Univ Hosp, Dept Rheumatol, Ghent, BelgiumUniversidade Federal de São Paulo, Div Rheumatol, São Paulo, BrazilSt Georges Healthcare NHS Trust, Dept Rheumatol, London, EnglandState Hosp Stockerau, Ctr Rheumatol, Lower Austria, Stockerau, AustriaUniv Pavia, IRCCS Policlin S Matteo, Cattedra Reumatol, I-27100 Pavia, ItalyUniv Giessen, Kerckhoff Klin, Dept Rheumatol & Clin Immunol, Bad Nauheim, GermanyCopenhagen Univ Hosp, Ctr Rheumatol & Spine Dis, Copenhagen Ctr Arthrit Res, Glostrup, DenmarkMenzies Res Inst Tasmania, Hobart, Tas, AustraliaColumbia Univ, Med Ctr, New York, NY USALeiden Univ, Med Ctr, Leiden, NetherlandsUniversidade Federal de São Paulo, Div Rheumatol, São Paulo, BrazilWeb of Scienc

Rheumatoid arthritis - treatment: 180. Utility of Body Weight Classified Low-Dose Leflunomide in Japanese Rheumatoid Arthritis

Background: In Japan, more than 20 rheumatoid arthritis (RA) patients died of interstitial pneumonia (IP) caused by leflunomide (LEF) were reported, but many of them were considered as the victims of opportunistic infection currently. In this paper, efficacy and safety of low-dose LEF classified by body weight (BW) were studied. Methods: Fifty-nine RA patients were started to administrate LEF from July 2007 to July 2009. Among them, 25 patients were excluded because of the combination with tacrolimus, and medication modification within 3 months before LEF. Remaining 34 RA patients administered 20 to 50 mg/week of LEF were followed up for 1 year and enrolled in this study. Dose of LEF was classified by BW (50 mg/week for over 50 kg, 40 mg/week for 40 to 50 kg and 20 to 30 mg/week for under 40 kg). The average age and RA duration of enrolled patients were 55.5 years old and 10.2 years. Prednisolone (PSL), methotrexate (MTX) and etanercept were used in 23, 28 and 2 patients, respectively. In case of insufficient response or adverse effect, dosage change or discontinuance of LEF were considered. Failure was defined as dosages up of PSL and MTX, or dosages down or discontinuance of LEF. Last observation carried forward method was used for the evaluation of failed patients at 1 year. Results: At 1 year after LEF start, good/ moderate/ no response assessed by the European League Against Rheumatism (EULAR) response criteria using Disease Activity Score, including a 28-joint count (DAS28)-C reactive protein (CRP) were showed in 14/ 10/ 10 patients, respectively. The dosage changes of LEF at 1 year were dosage up: 10, same dosage: 5, dosage down: 8 and discontinuance: 11 patients. The survival rate of patients in this study was 23.5% (24 patients failed) but actual LEF continuous rate was 67.6% (11 patients discontinued) at 1 year. The major reason of failure was liver dysfunction, and pneumocystis pneumonia was occurred in 1 patient resulted in full recovery. One patient died of sepsis caused by decubitus ulcer infection. DAS28-CRP score was decreased from 3.9 to 2.7 significantly. Although CRP was decreased from 1.50 to 0.93 mg/dl, it wasn't significant. Matrix metalloproteinase (MMP)-3 was decreased from 220.0 to 174.2 ng/ml significantly. Glutamate pyruvate transaminase (GPT) was increased from 19 to 35 U/l and number of leukocyte was decreased from 7832 to 6271 significantly. DAS28-CRP, CRP, and MMP-3 were improved significantly with MTX, although they weren't without MTX. Increase of GPT and leukopenia were seen significantly with MTX, although they weren't without MTX. Conclusions: It was reported that the risks of IP caused by LEF in Japanese RA patients were past IP history, loading dose administration and low BW. Addition of low-dose LEF is a potent safe alternative for the patients showing unsatisfactory response to current medicines, but need to pay attention for liver function and infection caused by leukopenia, especially with MTX. Disclosure statement: The authors have declared no conflicts of interes

Spondylarthropathies (including psoriatic arthritis): 244. Validity of Colour Doppler and Spectral Doppler Ultrasound of Sacroilicac Joints Againts Physical Examination as Gold Standard

Background: Sacroiliac joints (SJ) involvement is a distinctive and charasteristic feature of Spondyloarthritis (SpA) and x-ray is the test routinely used to make a diagnosis. However, x-ray reveals late structural damage but cannot detect active inflammation. The objective of this study was to assess the validity of Doppler ultrasound in SJ. Methods: Prospective blinded and controlled study of SJ, in which three populations were compared. We studied 106 consecutive cases, who were divided into three groups: a) 53 patients diagnosed with SpA who had inflammatory lumbar and gluteal pain assessed by a rheumatologist; b) 26 patients diagnosed with SpA who didn't have SJ tenderness and had normal physical examination; c) control group of 27 subjects (healthy subjetcs or with mechanical lumbar pain). All patients included that were diagnosed with SpA met almost the European Spondyloarthropathy Study Group (ESSG) classification criteria. Physical examination of the SJ included: sacral sulcus tenderness, iliac gapping, iliac compression, midline sacral thrust test, Gaenslen's test, and Patrick s test were used as gold standard. Both SJ were examined with Doppler ultrasound (General Electric Logiq 9, Wauwatosa WI, USA) fitted with a 9-14 Mhz lineal probe. The ultrasonographer was blinded to clinical data. Doppler in SJ was assessed as positive when both Doppler colour and resistance index (RI) < 0.75 within the SJ area were present. Statistical analysis was performed estimating sensitivity and specificity against gold standard. The Kappa correlation coefficient was used for reliability study. Results: 106 cases (53 female, 55 male; mean age 36 10 years) were studied. There were no statistical differences between groups related to age or sex. Physical examination of SJ was positive in 38 patients (59 sacroiliac joints). US detected Doppler signal within SJ in 37 patients (58 SJ): 33 of them were symptomatic SpA (52 SJ), one of them were asymptomatic SpA (1 SJ) and one was a healthy control (1 SJ). The accuracy of US when compared to clinical data as gold standard at subject level in the overall group was: sensitivity of 68.6% and specificity of 85.7%, positive predictive value of 70.5% and negative predictive value of 84.5%. A positive likelihood ratio of 4.8, a negative likelihood ratio of 0.36 and a kappa coefficient of 0.55 were achieved. Conclusions: Doppler US of SJ seems to be a valid method to detect active SJ inflammation. Disclosure statement: The authors have declared no conflicts of interes

Diagnostic and Predictive Value of Acute-phase Reactants in Adult Undifferentiated Peripheral Inflammatory Arthritis: A Systematic Review

To review the available literature on the diagnostic and predictive value of acute-phase reactants in adult undifferentiated peripheral inflammatory arthritis (UPIA) as an evidence base for generating multinational clinical practice recommendations in the 3e Initiative in Rheumatology. A systematic literature search was carried out using Medline, Embase, the Cochrane Library, and abstracts presented at the 2007 and 2008 meetings of the American College of Rheumatology and European League Against Rheumatism, searching for prognostic and diagnostic markers of acute-phase reactants in adult UPIA. Articles that fulfilled predefined inclusion criteria were systematically reviewed, and the quality was appraised. Likelihood ratios (LR), sensitivity, and specificity for diagnostic and prognostic outcomes were calculated. A total of 18 publications out of 3699 identified references were included in the review. Only a small number of studies with significant heterogeneity, including different outcome measures and different cutoff values, were eligible for review, so pooling data was not possible. Overall, LR showed poor diagnostic and prognostic performance for most investigated acute-phase reactants. Available data showed some value for erythrocyte sedimentation rate in establishing a diagnosis in patients with undifferentiated arthritis; some prognostic and diagnostic value for C-reactive protein; some prognostic value for plasma viscosity in predicting persistence of arthritis; and some diagnostic value for sulfhydryl levels and matrix metalloproteinase-3 in establishing a diagnosis of rheumatoid arthritis. There is little published evidence concerning the diagnostic and predictive value of acute-phase reactants in patients with UPIA. Studies were heterogeneous, and "undifferentiated arthritis" was not well defined or was equivocally defined. The role of acute-phase reactants in diagnosing and predicting outcome in patients presenting with undifferentiated arthritis is limite

Diagnostic and Prognostic Value of Synovial Biopsy in Adult Undifferentiated Peripheral Inflammatory Arthritis: A Systematic Review

Our aim was to systematically review the literature on the diagnostic and prognostic value of synovial biopsy in undifferentiated peripheral inflammatory arthritis (UPIA) as an evidence base for generating clinical practice recommendations. The results lead to multinational recommendations in the 3e Initiative in Rheumatology. We performed a systematic literature review according to the PICO strategy (Patients, Intervention, Comparator, and Outcome). Using a designed search strategy we ran literature searches using Medline, Embase, the Cochrane Library, and abstracts presented at the 2007 and 2008 meetings of the American College of Rheumatology and European League Against Rheumatism. Articles fulfilling predefined inclusion criteria were reviewed, and quality appraisal was performed. Six publications from a total of 3265 diagnostic and 3271 prognostic studies were included, of which 2 were review articles. Data pooling was impossible because of significant clinical and statistical heterogeneity. Three themes of outcome were identified: anti-citrullinated peptide antibody (ACPA) staining in synovium, immunohistochemistry (CD22, CD38, CD68), and vascular patterns. Prognostic and diagnostic value was poor for these themes, although diagnostic trends favoring a particular diagnosis were identified. In contrast to serological ACPA testing, ACPA staining was shown not to be specific for diagnosis of rheumatoid arthritis (RA). Synovial CD22 and CD38 positivity seem to differentiate between RA and non-RA, while synovial CD38 and CD68 positivity can differentiate among RA, spondyloarthritis (SpA), and other diagnoses. Vascular patterns in undifferentiated arthritis are insufficiently specific to differentiate between SpA and RA. There is sparse evidence that synovial biopsy has diagnostic or prognostic value in patients with UPIA in clinical care. We urgently need systematic studies investigating the diagnostic and prognostic potential of synovial markers. A clear, broadly accepted, and unequivocal definition of undifferentiated arthritis is required as a starting poin

OMERACT Magnetic Resonance Imaging Initiative on Structural and Inflammatory Lesions in Ankylosing Spondylitis - Report of a Special Interest Group at OMERACT 10 on Sacroiliac Joint and Spine Lesions

The ASAS/OMERACT MRI group recently described and defined magnetic resonance imaging (MRI) findings in sacroiliac joints (SIJ) that are essential for the diagnosis of sacroiliitis in patients with axial spondyloarthritis, including ankylosing spondylitis (AS). At the Outcome Measures in Rheumatology Clinical Trials (OMERACT) 2010 meeting, a special interest group (SIG) was formed to design a research agenda for the definition and description of structural lesions in the SIJ and the spine in patients with established AS. During the SIG, a summary of the previous work of the group was presented to all participants, containing: (1) a description of the current definitions of structural SIJ changes; (2) available scoring methods for SIJ changes; (3) data from a previous pilot MRI exercise on chronic SIJ changes performed by members of the group; and (4) a proposal for a research agenda for OMERACT 11. The group agreed on the project's scientific merits and the need to evaluate all available scoring methods and to have clear definitions for all possible abnormalities that can be seen on MRI, prior to the start of the exercise. It was also agreed that the exercise should include scoring of both structural and inflammatory lesions, due to lack of agreement about the best scoring method for assessing both types of lesions in AS. Participants agreed that longitudinal MRI over a certain period are needed to learn about the time sequence of pathologic changes and to understand the course of the disease. Finally, participants asked the group to add the development of a scoring method for structural changes in the spine in a subsequent exercise. Further to these objectives, all experts who agreed to contribute in the exercise will collaborate to achieve consensus on definitions and to organize training in the different scoring systems prior to the start of the project, with the aim to finalize the multiple reader exercise by the end of 2011, in time for OMERACT 1

Damage and Progression on Radiographs in Individual Joints: Data from Pivotal Randomized Controlled Trials

Radiographic progression is usually assessed by Sharp-based methods (van der Heijde-modified Sharp score and the Genant-modified Sharp score). The aim of this study was to evaluate, in a range of randomized controlled trials (RCT), the presence of erosions and joint space narrowing (JSN) in all individual joints, as well as progression in these joints, and to determine if any redundancy exists due to infrequently involved joints. Four databases of rheumatoid arthritis RCT that were all scored according to van der Heijde's modification of the Sharp score were included in a descriptive analysis. Irrespective of different readers, different patient populations, and different disease durations per trial, similar patterns emerged. Both erosions and JSN occurred in all sites. Erosions occurred most frequently in the feet, preferentially in 5th metatarsophalangeal joint (MTP-5). JSN occurred most frequently in the wrist. Change from baseline in erosions and JSN followed the pattern of involvement at baseline, so that MTP-5, and to a lesser extent MTP-3 and MTP-4, preferentially showed progression in erosive damage. Joints in the wrist showed highest tendency to worsen over time with respect to JSN. These data indicate that both erosions and JSN must be assessed for damage, and that a more abbreviated joint count cannot be used for radiographic scorin

Responsiveness and discriminative capacity of the assessments in ankylosing spondylitis disease-controlling antirheumatic therapy core set and other outcome measures in a trial of etanercept in ankylosing spondylitis

To investigate the responsiveness and discriminative capacity, and the relationship between both, of instruments selected for the disease-controlling antirheumatic therapy (DC-ART) core set by the Assessments in Ankylosing Spondylitis Working Group (ASAS). Responsiveness and discriminative capacity of different measures reflecting disease activity and function, either included in the ASAS DC-ART core set or not, were evaluated in a randomized controlled clinical trial comparing etanercept with placebo in patients with ankylosing spondylitis. Guyatt's method was used as the primary analysis for responsiveness, and Student's t-test for discriminative capacity. At day 28 of therapy, almost all measures indicated moderate to large responsiveness in the etanercept group (Guyatt 0.60-3.11). Some scales of the Short Form 36 (general health, mental component summary, and role emotional), the modified Schober's test, and the Fatigue Severity Scale were not responsive. The results were similar if analyzed at day 112 of therapy. Peripheral joint counts, joint scores, and occiput-to-wall distance could not be evaluated due to a floor effect. In general, the relation between responsiveness and discriminative capacity was strong: Measures that demonstrated high responsiveness also showed high between-group t values. Measures included in the ASAS DC-ART core set, except modified Schober's test, have good responsiveness and good discriminatory capacity. Some measures could not be evaluated due to a floor effec