AMSTERDAM — Canakinumab (Ilaris, Novartis) reduces gout flares in patients with atherosclerosis, although the drug has no effect on serum urate levels, according to a secondary analysis of data from the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) NCT01327846.
"This is important as a proof of concept. It gives us insight into the nonurate underpinnings of gout," said Daniel Solomon, MD, from Harvard Medical School and Brigham and Women's Hospital in Boston.
The monoclonal antibody, which blocks an inflammatory pathway mediated by interleukin (IL)-1β, was associated with "a reduction in gout attacks by 50% to 60%," Solomon reported here at the European League Against Rheumatism Congress 2018.
In the United States, canakinumab is approved for the treatment of active systemic juvenile idiopathic arthritis and for several rare autoinflammatory diseases. In Europe, however, it is approved for the treatment of flares in patients with gout who are unable to tolerate standard therapies, although not for the prevention of flares.
The 10,061 CANTOS participants in the randomized double-blind placebo controlled trial had stable atherosclerosis after a heart attack and a high-sensitivity C-reactive protein (hsCRP) level of at least 2 mg/L, indicating an elevated risk for cardiovascular disease.
For their analysis, Solomon and his colleagues assessed history of physician-diagnosed gout and serum urate levels.
Median age of the study participants was 61 years, median body mass index was 29.8 kg/m², median baseline serum urate level was 6.1 mg/dL, and 74% of the cohort was male.
Baseline characteristics were well balanced in the treatment groups. "The majority of men were 61 to 63 years old and overweight or obese," Solomon reported.
Patients were randomly assigned to one of three doses of canakinumab once every 3 months — 50 mg, 150 mg, or 300 mg — or placebo.
"This dosing interval was chosen for the CANTOS primary outcome; other dosing might also be effective," Solomon added.
Serum urate levels and hsCRP were tested at baseline and every 3 months for the first year, and annually thereafter. Median follow-up was 3.7 years.
The researchers looked at gout and cardiovascular events (myocardial infarction, stroke, revascularization, and cardiovascular death) in the different treatment groups and in three ranges of baseline serum urate.
The reduction in gout of 50% to 60% was seen at all doses of canakinumab.
In the placebo group, rates for gout and major adverse cardiovascular events increased in all three serum urate ranges.
Table. Event Rates by Serum Urate Levels (per 100 Person-Years)
|Event||<6.9 mg/dL||6.9–8.9 mg/dL||≥9.0 mg/dL|
|Major cardiovascular event||4.1||5.3||5.6|
Serum urate is a risk marker for both gout and cardiovascular disease, although levels were not affected by canakinumab over time, the researchers report.
However, there was a decrease in hsCRP, they note.
"At its current price, it is unlikely to gain wide acceptance as a preventive treatment for gout. However, this trial demonstrates the possibility that future IL-1-targeted therapies may be useful adjuncts to current preventive treatments for gout," Solomon said.
This analysis is interesting "because it studies a particular risk group," said Rachel Knevel, MD, PhD, from Leiden University Medical Centre in the Netherlands and Brigham and Women's Hospital and Harvard Medical School.
Patients with gout are at increased risk for cardiovascular events, but the association is understudied, she explained.
It would have been even more interesting if there had been a group that received standard preventive medicine, such as allopurinol. Given the list price of $200,000 per year, canakinumab needs to be proven safer or more effective than standard preventive therapies, Knevel said. Currently, that is unclear.
It is certainly interesting that the researchers found that the prevention of cardiovascular events is about more than just lowering uric acid, she added. However, Knevel said she would like to see a comparison of uric acid levels — baselines, end points, and differences — between those who have experienced gout or a cardiovascular event and those who have not.
Solomon reports a financial relationship with AstraZeneca. Knevel reports no relevant financial disclosures.
European League Against Rheumatism (EULAR) Congress 2018: Abstract OP0014. Presented June 13, 2018.
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Cite this: Canakinumab Halves Gout in Patients With Atherosclerosis - Medscape - Jun 22, 2018.