Relationship of Interleukin-1 Blockade With Incident Gout and Serum Uric Acid Levels

Abstract

TO THE EDITOR: I read Solomon and colleagues article (1) with interest. Gout is perceived as an acute disease that only requires treatment for acute attacks. However, long-term urate-lowering therapy that reduces serum uric acid levels to below the saturation threshold (404.5 mol/L) and long-term anti-inflammatory prophylaxis (especially while urate-lowering therapy is being initiated) are needed to combat this condition. Another article by Solomon and colleagues (2) discusses the use of interleukin-1 (Il-1) inhibition for prophylaxis of chronic gout. It focuses on Il-1, a proinflammatory cytokine that plays a key role in gouty inflammation and contributes to bone erosions and joint destruction. The article also discusses the importance of anti-inflammatory prophylaxis in the treatment of gout. This post hoc analysis evaluated rates of gout attacks in 10061 patients enrolled in CANTOS (Canakinumab Antiinflammatory Thrombosis Outcome Study) (3), which studied the effect of subcutaneous administration of the long-acting antiIl-1 monoclonal antibody canakinumab every 3 months on the secondary prevention of cardiovascular events in patients with a history of myocardial infarction. A total of 762 (8%) patients enrolled in CANTOS had a history of gout (2), suggesting an increased risk for this condition in patients with cardiovascular disease. Over 5 years of follow-up (2), the canakinumab group had a 52% lower risk for acute gout attacks than the placebo group. This finding is consistent with results from previous randomized controlled trials of canakinumab for gout prophylaxis. In 1 such trial (4), 432 patients who initiated urate-lowering therapy reported that a single dose of 50 to 300 mg of canakinumab or 4 weekly doses given over 16 weeks reduced the mean number of attacks per patient by 62% to 72%. These patients also had a 64% to 72% lower risk for at least 1 gout attack at 16 weeks than the group who received standard-of-care therapy (colchicine). In the 2 phase 3 randomized controlled trials and their extensions (5), a single dose of canakinumab during an acute attack provided rapid pain relief and prolonged prophylaxis and reduced the risk for a new attack by 62% versus triamcinolone acetate (P 0.0001). This post hoc study supports the need for gout prophylaxis to be an integral part of treatment of chronic gout. Interleukin-1 is a key mediator in inflammation associated with gout and cardiovascular disease. Canakinumab is the only Il-1 inhibitor that has regulatory approval (from the European Medicines Agency) to treat patients with frequent gout attacks that are refractory to standard treatments. As such, this agent reduces the risk for gout attacks and cardiovascular events. It is thus an appropriate therapeutic target for prophylaxis of chronic gout, especially in patients with cardiovascular disease.