Background Serum urate is a risk marker for both gout and cardiovascular disease, but trial data demonstrating that drugs which reduce gout also reduce cardiovascular event rates is scarce. It is also uncertain if any such effects are mediated through urate levels.
Objectives We examined the relationships between serum urate (SUA), canakinumab, and incidence rates for gout and cardiovascular events in the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS), a randomised double-blind placebo controlled trial of IL-1β inhibition.
Methods 10 061 patients with stable atherosclerosis (prior myocardial infarction) and hsCRP ≥2 mg/L were randomly allocated to placebo or to one of three doses of canakinumab (50 mg, 150 mg, or 300 mg), administered subcutaneously once every three month. Serum urate and hsCRP were tested at baseline and every 3 months for the first year and then annually. A physician diagnosed history of gout was ascertained at baseline and subsequent attacks were assessed during follow-up as part of the systematic adverse event reporting. The rates of gout and major adverse cardiovascular events (myocardial infarction, stroke, re-vascularisation, and cardiovascular death) were compared across different baseline SUA levels and by randomised treatment assignment.
Results The groups were well balanced with respect to baseline characteristics with a median follow-up of 3.7 years. Median age was 61 years, 74% were male, median BMI was 29.8kg/m2, and median SUA at baseline was 6.1 mg/dl (IQR: 5.2, 7.2). In the placebo group, rates for both gout and major adverse cardiovascular events increased across baseline SUA strata. Rates were 0.28, 1.36, and 5.94 per 100 person years for gout and 4.1, 5.3, and 5.6 for major adverse cardiovascular events per 100 person years for SUA levels of <6.9, 6.9–8.9, and ≥9.0 mg/dL, respectively. Random allocation to all dosages of canakinumab reduced rates of incident gout (see figure 1). This reduction in gout by canakinumab was observed at all baseline SUA levels (see table 1), and canakinumab had no effect on SUA levels over time but did reduce hsCRP.
Conclusions The CANTOS trial confirms that serum urate is a risk marker for both gout and cardiovascular events and demonstrates that IL-1β inhibition is effective in preventing both of these inter-related conditions. However, canakinumab had no effects on serum urate itself.
Reference  Ridker PM, Everett BM, Thuren T, et al. Antiinflammatory therapy with canakinumab for atherosclerotic disease. N Engl J Med2017;377:1119.
Disclosure of Interest D. Solomon Grant/research support from: Astra Zeneca, R. Glynn: None declared, J. MacFadyen: None declared, P. Libby: None declared, T. Thuren Employee of: Novartis, B. Everett: None declared, P. Ridker: None declared
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