A magic bullet for gout?

Do we need new treatments for gout? Hyperuricaemia, the metabolic condition underlying gouty inflammation, has attracted recent attention as new uratelowering treatments emerge on the horizon. For an acute attack of gout, the currently available drugs—non-steroidal anti-inflammatory drugs, colchicine and corticosteroids, seem to do a pretty good job for the majority of patients in relieving the acute symptoms of inflammation. However, recent data have highlighted the epidemiological shifts in the gouty population towards a more elderly group of patients who often present multiple medical problems. This as well as clinical practice have made us aware that our current treatments of acute gout are not ideal in all situations. They may cause significant side effects in patients with poor renal and cardiac function, and practical experience indicates that quite a number of patients with chronic gout end up receiving long-term steroids, with all the side effects that such treatment engenders. Furthermore, there are abundant reports pointing out that gout is poorly managed in routine clinical practice, suggesting that we are not using all the tools at our disposition adequately. Any new treatment for gout should therefore offer distinct advantages over existing ones to justify its introduction. With the discovery of the inflammasome as a major regulator of interleukin 1b (IL1b) processing and secretion in macrophages and dendritic cells, IL1 has once again returned to the spotlight as a mediator of acute inflammation. The identification of mutations in the NALP3 gene, a component of the inflammasome, in patients with a subset within the autoinflammatory syndromes (now called cryopyrin-associated periodic syndromes or CAPS) led to the idea of targeting IL1b in this disease. The results have been spectacular 2 and confirmed that IL1 inhibitors can have major clinical effects if the physiopathology of the disease involves excessive IL1 production. Martinon et al showed that monosodium urate (MSU) crystals can directly trigger the inflammasome to process IL1b, implying that acute gout may also be an IL1b-mediated disease. This concept has been strengthened by the findings of an open study on the effects of anakinra in gout and the articles by Torres and Terkeltaub in this issue of the journal (see articles on pages 1602 and 1613). 6 Torres showed convincingly in his animal studies that IL1 is a major trigger of joint inflammation. Using a new animal model of gout, where he injected MSU