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Update on gout: new therapeutic strategies and options

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A Correction to this article was published on 01 March 2011

Abstract

Gout, a disease recognized since antiquity, has increased in prevalence in recent years and the clinical profile of this disease has become increasingly complex, owing to large numbers of cases with iatrogenic factors, multiple comorbidities, advanced age, and hyperuricemia and arthritis refractory to treatment. In this Review, key advances in gout research made during the past decade are summarized. Revised strategies for safe and effective employment of dietary measures and pharmacologic treatments for active gouty arthritis, prevention of gout flares and urate lowering are also reviewed, with an emphasis on dosing of colchicine and allopurinol, and the evidence-based approach to systemic glucocorticosteroid treatment of acute gout. Also discussed are new and emerging treatments for gout and hyperuricemia, and the potential influence of dual energy CT imaging on treatment. In this context, the therapeutic role of febuxostat, and clinical development of pegylated uricase urate-lowering therapy and interleukin 1 antagonism for gouty inflammation are reviewed. Collectively, novel approaches will hopefully lead to improved management of hyperuricemia and gout, and also to improvements in patient-centered outcomes, even for those who have previously failed to respond to treatment.

Key Points

  • The prevalence of gout has approximately doubled in the past two decades, along with increases in its severity, treatment complexity and refractoriness

  • Major advances have been made in understanding the link between inherited susceptibility to gout and altered renal urate disposition

  • These advances have the potential to improve risk stratification for patients with incident gout and to optimize urate-lowering therapy via pharmacogenomics

  • Evolution in the evidence base for allopurinol, colchicine and oral glucocorticosteroid administration has validated improved and cost-effective treatment strategies for most patients

  • Febuxostat and biologic agents in development (interleukin 1 inhibitors and pegloticase) represent substantial therapeutic advances, particularly for severe, treatment-refractory gout, and patients with comorbidities or intolerance to other drugs

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Figure 1: Dual-energy CT imaging of tophi in patients with gout.
Figure 2: Pathways of uric acid metabolism and renal elimination, and primary therapeutic sites of actions of gout medications.
Figure 3: Mutations in renal urate transporters that are associated with gout.
Figure 4: Urate crystal uptake by phagocytes, NLRP3 inflammasome activation, and IL-1β secretion in promotion of gouty inflammation.
Figure 5: Proposed therapeutic algorithm for serum urate lowering in patients with gout.

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Acknowledgements

Dr. Terkeltaub is supported by the Research Service of the US Department of Veterans Affairs. Charles P. Vega, University of California, Irvine, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the MedscapeCME-accredited continuing medical education activity associated with this article.

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Dr. Terkeltaub has served as consultant for Altus, Ardea Biosciences, BioCryst Pharmaceuticals, EnzymeRx, Novartis, Pfizer, Regeneron, Savient Pharmaceuticals, Takeda and URL Pharma. Dr. Terkeltaub also is the past recipient of research grant support from Takeda.

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Terkeltaub, R. Update on gout: new therapeutic strategies and options. Nat Rev Rheumatol 6, 30–38 (2010). https://doi.org/10.1038/nrrheum.2009.236

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