Gout

Gout attacks halved in atherosclerosis patients treated with canakinumab


Prof Dan Solomon

The anti-inflammatory biological therapy canakinumab (Ilaris) has been found to more than halve the rate of gout in atherosclerosis patients.

In a secondary analysis of data from the CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcomes Study), which examined the effectiveness of the canakinumab for the prevention of cardiovascular events, the effect on gout was seen regardless of baseline serum urate levels.

Canakinumab, a monoclonal antibody that blocks an inflammatory pathway mediated by interleukin-1β, is licensed to treat several rare auto-inflammatory disorders and is sometimes also used to treat gout flare ups in patients with contraindications to standard therapies.

CANTOS included 10,061 patients with stable atherosclerosis (prior myocardial infarction) and high sensitivity C-reactive protein (hsCRP) ≥2mg/L, which indicates an increased risk of CV disease. Patients were randomly assigned to receive placebo or one of three doses of canakinumab (50mg, 150mg, or 300mg) subcutaneously once every three months. Serum urate and hsCRP were tested every three months for the first year and then annually, and rates of gout attacks and major adverse CV events (heart attack, stroke, re-vascularisation, and CV death) were compared.

For this secondary analysis of CANTOS data presented at the Annual European Congress of Rheumatology (EULAR 2018), participants were divided into three groups based on their serum urate level at baseline; low (<0.41 mmol/L), medium (0.41 – 0.53 mmol/L), and high (≥0.54 mmol/L).

The analysis showed that canakinumab significantly reduced the rate of flares of gout compared to placebo, across all baseline serum urate groups. The hazard ratios (95% confidence interval) were 0.40, 0.48, and 0.45 for the low, medium and high baseline serum urate groups, respectively. Canakinumab had no effect on serum urate levels over time but did reduce hsCRP.

“Our results demonstrate a striking effect of canakinumab on reducing the risk of gout attacks in atherosclerosis patients,” said Professor Daniel Solomon, a rheumatologist & epidemiologist at Brigham and Women’s Hospital, and Professor of Medicine at Harvard Medical School

“Moreover, these data illustrate serum urate as a risk marker for both gout and cardiovascular events, though canakinumab has no effect on serum urate levels due to its mechanism of action.”

Asked whether canakinumab might become a feasible therapy for preventing gout, Professor Solomon noted that the drug is currently very expensive and is used sparingly mainly in orphan diseases. But he predicted that canakinumab’s price would fall as it became available for other conditions, and added that, “there are a number of IL-1 blocking agents, some of them small molecules, that are under development, so I think this is really important as proof of concept and it also gives some insights into mechanisms that are important underpinning gout as well as cardiovascular disease.”

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