IL-1 inhibitor reduces flare rate during gout treatment
MedWire News: The interleukin (IL)-1 inhibitor rilonacept significantly reduces the number of gout flares in patients given urate-lowering therapy (ULT), suggests research published in the journal Arthritis and Rheumatism.
"Rilonacept appears safe and well tolerated, and could increase patient adherence to long-term ULT," says Ralph Schumacher (University of Pennsylvania, Philadelphia, USA) in a press release.
Reduction of plasma uric acid helps remove urate crystals from joints but gout flares are common during ULT initiation and can lead to patients discontinuing treatment, increasing the risk for progressive joint disease.
Hypothesizing that blocking IL-1 production would combat inflammation and pain associated with gout, the team conducted a phase II trial with 83 adults, aged an average of 51 years, with a serum urate level of 9.1 mg/dL. The majority of patients were male and White, and patients had suffered gout for an average of 9.7 years.
In the double-blind trial, patients were randomly assigned to receive rilonacept (n=41) loading dose 320 mg, followed by 160 mg/week, or placebo (n=42) for 16 weeks. The patients were also given allopurinol 300 mg/day, titrated to achieve a serum urate level of less than 6 mg/dL.
At the 12-week checkpoint, 14.6% of rilonacept-treated patients and 45.2% of controls had experienced a flare, at a rate of 0.15 and 0.79 flares per patient, respectively. This represented a significant 81% decrease in flares, which began after 4 weeks of treatment and continued for 6 weeks after treatment ended.
Rilonacept-treated patients were significantly more likely to complete the treatment protocol than controls (98 vs 79%), and, when taking into account early withdrawal from the trial, rilonacept was associated with a significant reduction in serum urate level at 12 (5.6 vs 6.3 mg/dL) and 16 weeks (5.9 vs 6.4 mg/dL).
Rilonacept and placebo had similar adverse event rates, without any cases of serious infection or death, the researchers report.
"Further evaluation of rilonacept in this disease is warranted, for both prevention and treatment of acute flares," Schumacher et al conclude.
"Additional studies demonstrating the safety and efficacy of IL-1 blockade in gout will help determine its place in the therapeutic armamentarium."
By Lynda Williams