It is my pleasure to welcome readers to this supplement of Rheumatology dedicated to the management of gout. This peer-reviewed supplement is a compilation of papers covering all aspects of gout treatment. As such, it represents a state of the art of the management of both flares and hyperuricaemia documented by well-known experts in the field, whom I would like to thank warmly for their contributions. Despite its high prevalence, estimated at 2–4% in developed countries , gout has long been neglected by health-care providers, including rheumatologists. It has been pushed to the background far behind other inflammatory disorders, such as RA and spondyloarthritis. Why is gout less attractive than other inflammatory disorders? There are several reasons for this. Undoubtedly, gout has suffered from a stigmatization that arose from old caricatures from the 17th–18th centuries (the disease of kings…) , an armamentarium that consists of old drugs, and misconceptions about its self-inflicted nature, making it, mistakenly, an old-fashioned disease. Hopefully, things are changing. In the last decade, gout has been the subject of exciting clinical and fundamental research that has led to major discoveries in the field. Significant advances have been made in understanding its pathophysiology, including genetics, but also in new imaging . The discovery and assessment of new treatments, notably novel uricosurics, have of course participated in the renewed interest in this disease. Unfortunately, despite these major advances, gout is still poorly managed, and premature mortality among patients with gout has remained unimproved over the past 15 years, unlike RA during the same period . At first glance, this poor management is difficult to understand, because gout is one of the few diseases in rheumatology that can easily be cured, by lowering, over the very long term, serum uric acid concentrations to lower than 360 µM (6 mg/dl) or 300 µM (5 mg/dl), depending on the disease severity . The EULAR , the British Society for Rheumatology  and the ACR  have all produced recommendations for management of the disease that stress the need for a treat-to-target strategy, found effective in many conditions . Barriers to cure the disease have been identified , and in this setting, individualized patient education by physicians or nurses can dramatically improve adherence to urate-lowering treatment [10, 11] and thus patient care. The management of gout involves treating both the flares and the hyperuricaemia itself. Misuse of colchicine is frequent in routine practice . The drug should never be used at a high dose to treat flares because low doses are as effective and are better tolerated than high doses. This drug, which has a narrow therapeutic window, is mainly metabolized through two proteins (P-glycoprotein and CYP3A4), which explains the multiple drug-to-drug interactions that physicians should be aware of . Interestingly, colchicine has recently been shown to benefit coronary artery disease [14, 15], which is important given the high prevalence of cardiovascular disease in people with gout. In patients with contraindications or who cannot tolerate NSAIDs, CSs or colchicine, IL-1 blockers are an excellent therapeutic option. The discovery that monosodium urate crystals could elicit active IL1b secretion from monocyte-derived macrophages by activating the inflammasome was a major step forward in understanding monosodium urate crystal inflammation [16, 17]. According to the EULAR  and the recent British Society for Rheumatology  recommendations, urate-lowering therapy (ULT) should be discussed and offered to all patients with a diagnosis of gout. Among the ULT, xanthine oxidase inhibitors (XOIs; i.e. allopurinol and febuxostat) hold a central position in the long-term treatment of gout. Allopurinol is the recommended first-line ULT drug, and international societies encourage properly increasing its dosage, when feasible, up to 800–900 mg/day, to reach the predefined serum urate target of 360 µM (6 mg/dl) or 300 µM (5 mg/dl). A recent randomized controlled trial tested a dose-escalation strategy to achieve a target serum urate concentration, which was effective in most patients . The main concern with the use of allopurinol is tolerance and, in particular, the risk of allopurinol hypersensitivity syndrome, which is rare but can be life threatening. The risk is notably high in patients carrying the haplotype HLA-B*58:01, which is frequent in some ethnic populations, particularly East Asians. Screening for HLA-B*58:01 in high-risk groups is recommended, and a low allopurinol starting dose may reduce the risk . Patients with gout often have co-morbidities such as cardiovascular disease, renal failure and metabolic syndrome components . Randomized controlled trials have suggested that allopurinol could improve exercise capacity in patients with chronic stable angina and decrease blood pressure in adolescents but had no effect in patients with heart failure. The impact of XOIs on renal function in patients with chronic kidney disease is unclear . Approximately 90% of the daily urate load filtered by the kidneys is reabsorbed. This process is mediated by specific urate transporters, such as uric acid transporter 1, glucose transporter 9 and organic anion transporters 1, 3 and 4 . Genome-wide association study has highlighted the role of these renal urate transporters in the control of uricaemia  and brought renewed interest in the use of uricosurics, because impaired renal excretion is the main mechanism underlying the increase in the urate pool . New uricosurics, notably lesinurad, combined with XOIs, offer promise to help a greater number of patients achieve sufficient reduction in serum uric acid concentration [23, 24]. Novel uricosurics should play an important role in the management of gout because, for a substantial proportion of patients, XOIs alone do not give proper control. Significant advances have also been made in the field of imaging. In particular, dual energy CT and ultrasonography have opened exciting perspectives for assessing the response to treatment in gout . I hope readers will enjoy reading this supplement that covers all aspects of the management of gout, with a special focus on new uricosurics. It emphasizes the need to adopt a treat-to-target strategy, the importance of patient education and the growing role of imaging to assess treatment response. The readers will also find useful tips for better use of colchicine and allopurinol that should help physicians to improve the quality of gout care in their daily practice. Acknowledgements I would like to thank all my colleagues who contributed to this supplement and Emma Welsh for helpful support. Supplement: This supplement was supported by an unrestricted grant from Grunenthal. Funding: No specific funding was received from any bodies in the public, commercial or not-for-profit sectors to carry out the work described in this manuscript. Disclosure statement: P.R. received consulting or speaker fees from AstraZeneca, Grunenthal, Ipsen, Menarini and Savient. References 1 Kuo CF, Grainge MJ, Zhang W, Doherty M. Global epidemiology of gout: prevalence, incidence and risk factors. 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Effects of colchicine on risk of cardiovascular events and mortality among patients with gout: a cohort study using electronic medical records linked with Medicare claims. Ann Rheum Dis 2016; 75: 1674– 9. http://dx.doi.org/10.1136/annrheumdis-2015-207984 Google Scholar CrossRef Search ADS PubMed 15 Hemkens LG, Ewald H, Gloy VL et al. Colchicine for prevention of cardiovascular events. Cochrane Database Systematic Rev 2016; CD011047. 16 Cavalli G, Dinarello CA. Treating rheumatological diseases and co-morbidities with interleukin-1 blocking therapies. Rheumatology 2015; 54: 2134– 44. Google Scholar PubMed 17 Dumusc A, So A. Interleukin-1 as a therapeutic target in gout. Curr Opin Rheumatol 2015; 27: 156– 63. http://dx.doi.org/10.1097/BOR.0000000000000143 Google Scholar CrossRef Search ADS PubMed 18 Stamp LK, Chapman PT, Barclay ML et al. A randomised controlled trial of the efficacy and safety of allopurinol dose escalation to achieve target serum urate in people with gout. 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Lesinurad in combination with allopurinol: a randomised, double-blind, placebo-controlled study in patients with gout with inadequate response to standard of care (the multinational CLEAR 2 study). Ann Rheum Dis 2017; 76: 811– 20. http://dx.doi.org/10.1136/annrheumdis-2016-209213 Google Scholar CrossRef Search ADS PubMed 24 Dalbeth N, Jones G, Terkeltaub R et al. Lesinurad, a selective uric acid reabsorption inhibitor, in combination with febuxostat in patients with tophaceous gout: a phase III clinical trial. Arthritis Rheumatol 2017; 69: 1903– 13. http://dx.doi.org/10.1002/art.40159 Google Scholar CrossRef Search ADS PubMed 25 Omoumi P, Zufferey P, Malghem J, So A. Imaging in gout and other crystal-related arthropathies. Rheum Dis Clinics North Am 2016; 42: 621– 44. http://dx.doi.org/10.1016/j.rdc.2016.07.005 Google Scholar CrossRef Search ADS © The Author 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. 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Rheumatology – Oxford University Press
Published: Jan 1, 2018
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