EULAR Evidence based recommendations for gout - part ii management: report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT)

W Zhang ^1*, M Doherty ¹, T Bardin ², E Pascual ³, V Barskova ⁴, P Conaghan ⁵, J Gerster ⁶, J Jacobs ⁷, B Leeb ⁸, F Liotè ⁹, G McCarthy ¹⁰, P Netter ¹¹, G Nuki ¹², F Perez-Ruiz ¹³, A Pignone ¹⁴, J Pimentão ¹⁵, L Punzi ¹⁶, E Roddy ¹, T Uhlig ¹⁷ and I Zimmermann-Gòrska ¹⁸

¹ Nottingham University, United Kingdom
² Hôpital Lariboisière, France
³ Hospital General Universitario de Alicante, Spain
⁴ Institute of Rheumatology RAMS, Russian Federation
⁵ University of Leeds, United Kingdom
⁶ Hôpital Nestlé, Switzerland
⁷ University Medical Center Utrecht, Netherlands
⁸ Lower Austrian Center for Rheumatology, Austria
⁹ Hôpital Lariboisiére, France
¹⁰ Mater Misericordiae University Hospital, Republic of Ireland
¹¹ Universite Henri Poincare, France
¹² University of Edinburgh, United Kingdom
¹³ Hospital de Cruces, Spain
¹⁴ University of Florence, Italy
¹⁵ Hospital Egas Moniz, Portugal
¹⁶ University of Padova, Italy
¹⁷ Diakonhjemmet Hospital, Norway
¹⁸ Poznan University of Medical Sciences, Poland

^* To whom correspondence should be addressed. E-mail: weiya.zhang{at}nottingham.ac.uk.

Accepted 8 May 2006

Abstract

Objectives: To develop evidence based recommendations for the management of gout.

Methods: The multidisciplinary guideline development group comprised 19 rheumatologists and one evidence based medicine expert representing 13 European countries. Key propositions regarding management were generated using a Delphi consensus approach. Research evidence was searched systematically for each proposition. Where possible, effect size (ES), number needed to treat (NNT), relative risk (RR), odds ratio and incremental cost-effectiveness ratio (ICER) were calculated. The quality of evidence was categorised according to the level of evidence. The strength of recommendation (SOR) was assessed using the EULAR visual analogue and ordinal scales.

Results: Twelve key propositions were generated after 3 Delphi rounds. Propositions included both non- pharmacological and pharmacological treatments and addressed symptomatic control of acute gout, urate lowering therapy (ULT) and prophylaxis of acute attacks. The SOR for each proposition varied according to the research evidence and expert opinion. It was recognised that optimal management requires both non- pharmacological and pharmacological treatment and needs to be tailored to the individual. The importance of patient education, modification of adverse lifestyle (weight loss if obese; reduced alcohol consumption, especially beer; low animal purine diet) and treatment of associated comorbidity and risk factors (eg hypertension, hyperlipidaemia, hyperglycaemia) were emphasised. Recommended drugs for acute attacks were oral NSAID (a convenient option in the absence of contraindications), oral colchicine (ES=0.87, 95%CI 0.25, 1.50) or joint aspiration and injection of corticosteroid. Because of the toxicity of high dose colchicine, especially diarrhoea (RR=8.38, 95%CI 1.14, 61.38), lower doses (eg 0.5mg three times daily) should be considered. ULT is indicated in patients with recurrent acute attacks, arthropathy, tophi or radiographic changes of gout. The aim of ULT is to promote crystal dissolution and prevent crystal formation - this is achieved by maintaining the serum uric acid below the saturation point for urate crystals (6 mg/dl or 360 µmol/l). Allopurinol was confirmed as effective long-term ULT (ES=1.39, 95%CI 0.78, 2.01) with a dose-dependent effect; it should be started at a low dose (eg 100mg daily) and increased by 100 mg every 2-4 weeks if required. If allopurinol toxicity occurs, options include other xanthine oxidase inhibitors, allopurinol desensitisation (only for mild rash, not severe toxicity) or a uricosuric. The uricosurics probenecid and sulphinpyrazone are contra-indicated in patients with urolithiasis or reduced renal function and are less effective than allopurinol. The uricosuric benzbromarone on a head to head comparison is more effective than allopurinol (ES=1.50, 95%CI 0.76, 2.24) and can be used in patients with mild-moderate renal insufficiency but carries a risk of hepatotoxicity. When gout associates with use of diuretics stop the diuretic if possible; in patients with hypertension or hyperlipidaemia consider use of losartan and fenofibrate respectively because of their modest uricosuric effects (fenofibrate ES=1.13, 9%%CI 0.18, 2.07). For prophylaxis against acute attacks either colchicine 0.5-1 mg daily (NNT=2, 95%CI 1, 6) and/or an NSAID (with gastroprotection if indicated) are recommended.

Conclusion: Twelve key recommendations for management of gout were developed using a combination of research-based evidence and expert consensus. The evidence was evaluated and the SOR provided for each proposition.

Keywords: EULAR, gout, guidelines, treatment

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EULAR evidence based recommendations for gout. Part I: Diagnosis. Report of a task force of the standing committee for international clinical studies including therapeutics (ESCISIT)

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