Hein J.E.M. Janssens

2016 updated EULAR evidence-based recommendations for the management of gout

Background New drugs and new evidence concerning the use of established treatments have become available since the publication of the first European League Against Rheumatism (EULAR) recommendations for the management of gout, in 2006. This situation has prompted a systematic review and update of the 2006 recommendations. Methods The EULAR task force consisted of 15 rheumatologists, 1 radiologist, 2 general practitioners, 1 research fellow, 2 patients and 3 experts in epidemiology/methodology from 12 European countries. A systematic review of the literature concerning all aspects of gout treatments was performed. Subsequently, recommendations were formulated by use of a Delphi consensus approach. Results Three overarching principles and 11 key recommendations were generated. For the treatment of flare, colchicine, non-steroidal anti-inflammatory drugs (NSAIDs), oral or intra-articular steroids or a combination are recommended. In patients with frequent flare and contraindications to colchicine, NSAIDs and corticosteroids, an interleukin-1 blocker should be considered. In addition to education and a non-pharmacological management approach, urate-lowering therapy (ULT) should be considered from the first presentation of the disease, and serum uric acid (SUA) levels should be maintained at<6 mg/dL (360 µmol/L) and <5 mg/dL (300 µmol/L) in those with severe gout. Allopurinol is recommended as first-line ULT and its dosage should be adjusted according to renal function. If the SUA target cannot be achieved with allopurinol, then febuxostat, a uricosuric or combining a xanthine oxidase inhibitor with a uricosuric should be considered. For patients with refractory gout, pegloticase is recommended. Conclusions These recommendations aim to inform physicians and patients about the non-pharmacological and pharmacological treatments for gout and to provide the best strategies to achieve the predefined urate target to cure the disease.

Use of oral prednisolone or naproxen for the treatment of gout arthritis: a double-blind, randomised equivalence trial

BACKGROUND Non-steroidal anti-inflammatory drugs and colchicine used to treat gout arthritis have gastrointestinal, renal, and cardiovascular adverse effects. Systemic corticosteroids might be a beneficial alternative. We investigated equivalence of naproxen and prednisolone in primary care. METHODS We did a randomised clinical trial to test equivalence of prednisolone and naproxen for the treatment of monoarticular gout. Primary-care patients with gout confirmed by presence of monosodium urate crystals were eligible. 120 patients were randomly assigned with computer-generated randomisation to receive either prednisolone (35 mg once a day; n=60) or naproxen (500 mg twice a day; n=60), for 5 days. Treatment was masked for both patients and physicians. The primary outcome was pain measured on a 100 mm visual analogue scale and the a priori margin for equivalence set at 10%. Analyses were done per protocol and by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN14648181. FINDINGS Data were incomplete for one patient in each treatment group, so per-protocol analyses included 59 patients in each group. After 90 h the reduction in the pain score was 44.7 mm and 46.0 mm for prednisolone and naproxen, respectively (difference 1.3 mm; 95% CI -9.8 to 7.1), suggesting equivalence. The difference in the size of change in pain was 1.57 mm (95% CI -8.65 to 11.78). Adverse effects were similar between groups, minor, and resolved by 3 week follow-up. INTERPRETATION Oral prednisolone and naproxen are equally effective in the initial treatment of gout arthritis over 4 days.

A Diagnostic Rule for Acute Gouty Arthritis in Primary Care Without Joint Fluid Analysis

BACKGROUND Most cases of acute gouty arthritis are diagnosed in primary care and without joint fluid analysis in many instances. Our objectives were to estimate the validity of this diagnosis by family physicians and to develop a diagnostic rule. METHODS Patients with monoarthritis recruited in an open Dutch population with gout by family physician diagnosis were enrolled in a diagnostic study (March 24, 2004, through July 14, 2007). Validity variables were estimated using 2 x 2 tables, with the presence of synovial monosodium urate crystals as the reference test. For development of the diagnostic rule, clinical variables (including the presence of synovial monosodium urate crystals) were collected within 24 hours. Statistically significant variables and predefined variables were separately entered in multivariate logistic regression models to predict the presence of synovial monosodium urate crystals. Diagnostic performance of the models was tested by receiver operating characteristic curve analysis. The most appropriate model was transformed to a clinically useful diagnostic rule. RESULTS Three hundred twenty-eight patients were included in the study. The positive and negative predictive values of family physician diagnosis of gout were 0.64 and 0.87, respectively. The most appropriate model contained the following predefined variables: male sex, previous patient-reported arthritis attack, onset within 1 day, joint redness, first metatarsophalangeal joint (MTP1) involvement, hypertension or 1 or more cardiovascular diseases, and serum uric acid level exceeding 5.88 mg/dL (to convert serum uric acid level to micromoles per liter, multiply by 59.485). The area under the receiver operating characteristic curve for this model was 0.85 (95% confidence interval, 0.81-0.90). Performance did not change after transforming the regression coefficients to easy-to-use scores and was almost equal to that of the statistically optimal model (area under the receiver operating characteristic curve, 0.87; 95% confidence interval, 0.83-0.91). CONCLUSIONS The validity of family physician diagnosis of acute gouty arthritis was moderate in this study. An easy-to-use diagnostic rule without joint fluid analysis was developed for their use.

2015 Gout Classification Criteria: An American College of Rheumatology/European League Against Rheumatism Collaborative Initiative

Existing criteria for the classification of gout have suboptimal sensitivity and/or specificity, and were developed at a time when advanced imaging was not available. The current effort was undertaken to develop new classification criteria for gout.

Limited validity of the American College of Rheumatology criteria for classifying patients with gout in primary care

In order to classify gout without identification of monosodium urate (MSU) crystals, the American College of Rheumatology (ACR) formulated criteria in 1977.1 Of the 11 criteria, ≥6 have to be present to classify patients as having gout. The criteria were not developed with reference to MSU crystals, nor were they tested properly afterwards against this gold standard.1,–,3 However, as they are widely used and cited, testing their validity is critical to our ability to understand and treat gout.4 Many studies of gout include patients with ‘self-reported gout’, provided they fulfil the ACR criteria. Most self-reported diagnoses of gout will originate from a diagnosis made by a family physician as most patients presenting with acute gout are managed by them.2 5 This makes the primary care setting particularly relevant to test the ACR criteria. We designed a prospective study in a Dutch primary care population (∼200 000 subjects) to estimate the validity of the ACR criteria (patient recruitment 2004–6). We used identified MSU …

Gout, not induced by diuretics? A case-control study from primary care

Background: It is taken for granted that diuretics may induce gout, but there is a general lack of evidence on this topic. Objectives: To determine the incidence of gout in patients who use diuretics, taking into account concurrent hypertension and cardiovascular diseases. Methods: A case-control study was designed. From a primary care population all patients with a first gout registration (59 men, 11 women; mean (SD) age 55.1 (13.5)) were identified as cases. To relate the occurrence of gout to diuretic use a matched reference series of three controls for each case was compiled. Conditional logistic regression analyses were applied to estimate incidence rate ratios (IRRs) of gout, and 95% confidence intervals (CIs), in subjects with and without diuretic treatment, hypertension, and cardiovasculardiseases. Additional stratification analyses were made, particularly in the subjects not using diuretics. Results: The IRRs of gout in subjects with v those without diuretic treatment, hypertension, heart failure, and myocardial infarction were 2.8 (95% CI 1.2 to 6.6), 2.6 (95% CI 1.2 to 5.6), 20.9 (95% CI 2.5 to 173.8), and 1.9 (95% CI 0.7 to 4.7), respectively. After adjustment, the IRR of gout for diuretic use dropped to 0.6 (95% CI 0.2 to 2.0), while the IRRs of gout for hypertension, heart failure, and myocardial infarction were still >1. This was also the case for subjects with hypertension or myocardial infarction, who had not used diuretics. Conclusion: The results suggest that diuretics do not actually increase the risk of gout. Cardiovascular indications for treatment may have confounded previous inferences.

A Delphi Exercise to Identify Characteristic Features of Gout — Opinions from Patients and Physicians, the First Stage in Developing New Classification Criteria

Objective. To identify a comprehensive list of features that might discriminate between gout and other rheumatic musculoskeletal conditions, to be used subsequently for a case-control study to develop and test new classification criteria for gout. Methods. Two Delphi exercises were conducted using Web-based questionnaires: one with physicians from several countries who had an interest in gout and one with patients from New Zealand who had gout. Physicians rated a list of potentially discriminating features that were identified by literature review and expert opinion, and patients rated a list of features that they generated themselves. Agreement was defined by the RAND/UCLA disagreement index. Results. Forty-four experienced physicians and 9 patients responded to all iterations. For physicians, 71 items were identified by literature review and 15 more were suggested by physicians. The physician survey showed agreement for 26 discriminatory features and 15 as not discriminatory. The patients identified 46 features of gout, for which there was agreement on 25 items as being discriminatory and 7 items as not discriminatory. Conclusion. Patients and physicians agreed upon several key features of gout. Physicians emphasized objective findings, imaging, and patterns of symptoms, whereas patients emphasized severity, functional results, and idiographic perception of symptoms.

The validation of a diagnostic rule for gout without joint fluid analysis: a prospective study

OBJECTIVE The gold standard for diagnosing gout is the identification of MSU crystals in joint fluid. In secondary care, the facilities or expertise to analyse joint fluid are not always available and gout is diagnosed clinically. To improve the predictive value of the clinical diagnosis of gout in secondary care, a diagnostic rule developed in primary care could be helpful. The aim of this study was to validate this diagnostic rule in a secondary care population with the gold standard as reference test. METHODS Three hundred and ninety patients with monoarthritis were included. The variables of the diagnostic rule (male sex, previous arthritis attack, onset <1 day, joint redness, involvement of the first MTP joint, hypertension or one or more cardiovascular disease, and serum uric acid >5.88 mg/dl) were collected and scored. The affected joint was aspirated and joint fluid was analysed for the presence of MSU crystals. RESULTS In 219 patients (56%) MSU crystals were found. The positive predictive value of a score of ≥8 points was 0.87, the negative predictive value of a score of ≤4 points was 0.95. The area under the receiver operating characteristic curve for the diagnostic rule was 0.86 (95% CI 0.82, 0.89). The Hosmer-Lemeshow goodness-of-fit test showed that the difference between the expected and the observed probability was non-significant (P = 0.64), indicating good agreement. CONCLUSION An easy-to-use diagnostic rule for gout developed in primary care shows good performance in secondary care and improves the predictive value of the clinical diagnosis of gout when joint fluid analysis is not available.

SAT0532 Updated Eular Evidence-Based Recommendations for the Diagnosis of Gout

Background Gout has become the most common inflammatory arthritis but is still frequently misdiagnosed. New data on imaging and clinical diagnosis have become available since publication of the first EULAR recommendations for the diagnosis of gout in 2006. This has prompted a systematic review and update of the 2006 recommendations. Objectives To develop updated evidence-based recommendations for the diagnosis of gout Methods The 2014 EULAR task force comprised 15 rheumatologists, 1 radiologist, 2 GPs, 2 patients and 2 experts in methodology from 12 European countries. The expert group first voted to determine whether each of the 2006 recommendations for diagnosis should be retained, modified or deleted. MEDLINE, EMBASE and Cochrane Library reports were searched systematically to obtain research evidence from 2005 to 2013 on all aspects of the diagnosis of gout. Internal and external validity of the articles was assessed. The quality of evidence was categorised according to GRADE. The task force was presented with a synopsis of this literature review and generated a first draft of key recommendations after a two-day meeting. Final recommendations were agreed using a Delphi consensus approach. The level of agreement to each recommendation was assessed using EULAR numeral rating scales. Results A search for crystals in synovial fluid (SF) or tophus aspirates was recommended in every person with suspected gout, because demonstration of monosodium urate (MSU) crystals allows a definitive diagnosis of gout. SF should also be examined for crystals in any arthritis of unknown aetiology. There was consensus that a number of suggestive clinical features supported a clinical diagnosis of gout. These are: mono articular involvement of a foot or ankle joint (especially the first MTP); previous episodes of similar acute arthritis; rapid onset of severe pain and swelling (at its worst in <24 h); erythema; male gender; and associated cardiovascular diseases and hyperuricaemia. When crystal identification is not possible, it was recommended that any atypical presentation should be investigated by imaging, in particular with ultrasound to seek features suggestive of urate deposits (double contour sign and tophi). There was consensus a that a diagnosis of gout should not be based on the presence of hyperuricaemia alone. There was also a strong recommendation that all persons with gout should be systematically assessed for the presence of associated co-morbidities and risk factors for cardiovascular disease, as well as for risk factors for chronic hyperuricaemia. Conclusions Eight updated, evidence-based, expert consensus recommendations for the diagnosis of gout are proposed. Disclosure of Interest P. Richette Speakers bureau: Ménarini, Ipsen, Savient, Novartis, Astra-ZenecaM, E. Pascual Speakers bureau: Menarini, Savient, Novartis, Astra Zaneca, M. Doherty Speakers bureau: Menarini, Ardea and Novartis, V. Barskova: None declared, F. Becce: None declared, M. Coyfish: None declared, H. Janssens: None declared, T. Jansen Speakers bureau: Ménarini, F. Lioté Speakers bureau: Novartis, Ipsen, Menarini, SOBI, Mayolly-Spindler, Astra-Zeneca, Ardea, Savient, C. Mallen: None declared, G. Nuki Speakers bureau: Ipsen, Menarini, Novartis and Savient., F. Perez-Ruiz Speakers bureau: Astra-Zeneca, Menarini, Metabolex, Novartis, Pfizer, SOBI, J. Pimentão Speakers bureau: Ménarini, T. Piwell: None declared, L. Punzi Speakers bureau: Ménarini, A. So Speakers bureau: Novartis, SOBI, Astra-Zeneca and Menarini, A.-K. Tausche Speakers bureau: Menarini, Savient, Novartis, Sobi, Ardea Bioscience, T. Uhlig: None declared, J. Zavada Speakers bureau: Ménarini, Novartis, W. Zhang Speakers bureau: Savient, F. Tubach: None declared, T. Bardin Speakers bureau: Ménarini, Ipsen, Savient, Novartis, Astra-Zeneca, SOBI DOI 10.1136/annrheumdis-2014-eular.5546

Gout Is a Chronic Inflammatory Disease in Which High Levels of Interleukin-8 (CXCL8), Myeloid-Related Protein 8/Myeloid-Related Protein 14 Complex, and an Altered Proteome Are Associated With Diabetes Mellitus and Cardiovascular Disease.

The frequent association of gout with metabolic syndrome and cardiovascular disease (CVD) suggests that it has a systemic component. Our objective was to study whether circulating proinflammatory cytokines are associated with comorbidities in gout patients.