Gout Attack Risk Lowered With Interleukin-1ß Blockade

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Inhibition of IL-1ß with canakinumab significantly decreased gout attack risk at all baseline serum uric acid (SUA) levels and without changing SUA levels.
Inhibition of IL-1ß with canakinumab significantly decreased gout attack risk at all baseline serum uric acid (SUA) levels and without changing SUA levels.

Inhibition of interleukin-1ß (IL-1ß) with canakinumab, a monoclonal antibody, is associated with a significantly decreased likelihood of gout attacks without any change in serum uric acid (SUA) levels, according to a new study. Canakinumab decreased gout attack risk at all baseline SUA levels.

The study, led by Daniel H. Solomon, MD, of Brigham and Women's Hospital in Boston, is a secondary analysis of CANTOS (Canakinumab Antiinflammatory Thrombosis Outcome Study), which showed that IL-1ß inhibition decreases the risk of cardiovascular events and lung cancer mortality. CANTOS participants reported both baseline and follow-up gout attacks and had serial SUA measurements. IL-1ß can initiate the inflammation of an acute gout attack and contribute to atherosclerosis, acute coronary syndromes, and certain inflammatory cancers, Dr Solomon and his colleagues noted.

In CANTOS, investigators randomly assigned 10,059 patients with a prior myocardial infarction and a high-sensitivity C-reactive protein level of at least 19.1 nmol/L to receive placebo or canakinumab (50, 150, or 300 mg) every 3 months. At each follow-up visit, patients were asked to report any and all adverse events, including gout attacks. The median follow-up was 3.7 years. Among patients with SUA levels of 404.5 µmol/L or lower, 404.6 to 535.3 µmol/L, and 535.4 µmol/L or higher, canakinumab treatment was associated with a 60%, 52%, and 55% decreased risk of gout attacks, respectively, compared with placebo, Dr Solomon's team reported online ahead of print in Annals of Internal Medicine. Compared with placebo, canakinumab did not affect SUA levels over time.

Dr Solomon and his collaborators said they believe their study is the first randomized controlled demonstration of gout prevention through IL-1ß inhibition.

“Although perhaps not surprising, this observation has considerable clinical relevance,” the authors commented. “Because the benefits were profound and were seen with the lowest canakinumab dosage (50 mg every 3 months), our data provide proof of concept that low-dose IL-1ß inhibition might prevent the incidence of gout attacks, particularly among patients in whom current therapies have failed.”

With regard to study limitations, Dr Solomon's team noted that CANTOS was not designed to study gout. “The current analyses are limited by the possibility of misclassification of gout attacks,” they pointed out. Follow-up reports of incident gout did not require a physician's diagnosis and may be less accurate, they stated.

Reference

Solomon DH, Glynn RJ, MacFadyen JG, et al. Relationship of interleukin 1ß  blockade with incidence gout and serum uric acid levels. Ann Intern Med. 2018; published online ahead of print.

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