Rilonacept: A Novel Approach to Gout

Atlanta—Ongoing treatment with rilonacept reduced gout flares during urate-lowering therapy, according to a phase 3 study reported at the ACR meeting.

Lead author Robert Terkeltaub, MD, Veterans Affairs Medical Center in San Diego, California, said that these results are similar to results of a phase 2 study of rilonacept. “The results of the study suggest that rilonacept is a new way of preventing gout flares in people starting urate-lowering therapy,” he said. Rilonacept (also called interleukin-1 [IL-1] trap) is a dimeric fusion protein that is US Food and Drug Administration–approved for use in cryopyrin-associated periodic syndromes and is under review for the prevention of gout flares in patients who are initiating urate-lowering therapy. The drug is designed to attach to and neutralize IL-1 before it can bind to cell-surface receptors and generate signals that trigger inflammation.

Patients with gout attacks who have elevated serum levels of uric acid are prescribed uric acid–lowering medications to eliminate the uric acid crystals and prevent reformation. During uric acid–lowering therapy, the breakup of uric acid crystals previously deposited in the joints can trigger the release of IL-1, leading to acute flares of joint pain and inflammation. An antiinflammatory drug may be used to prevent flares, but often patients do not adhere to anti-inflammatory therapy due to tolerability issues.

The phase 3 trial randomized 241 patients 1:1:1 to receive weekly subcutaneous injections of placebo, rilonacept 80 mg, or rilonacept 160 mg for 16 weeks. All patients were treated daily with allopurinol 300 mg/day to lower uric acid levels. In the year prior to enrollment, patients reported an average of 4.6 flares. Gout flares were self-reported by patients via interactive voice response diary and were treated with nonsterodial anti-inflammatory drugs or glucocorticoid therapy while continuing study treatment.

Rilonacept reduced the number of gout flares per patient to 0.29 in the 80 mg-group and 0.21 in the 160-mg group compared with 1.06 in the placebo group (P<.0001 for both doses vs placebo). One or more flares occurred in 18.8% of the 80-mg group and 16.3% of the 160-mg group compared with 46.8% of placebo patients (P<.0001 for both doses vs placebo). The number of flare days was significantly reduced by rilonacept: 2.36 days per patient and 0.98 days per patient for the low and high doses of the drug, respectively, compared with 5.52 days for placebo (P<.0001 for both doses vs placebo). The incidence of multiple flares was 84% lower for patients treated with rilonacept 80 mg and 88% lower for those who received rilonacept 160 mg compared with placebo (P<.0001 for both doses vs placebo).

The overall incidence of adverse events was similar between groups: 63.4% for rilonacept and 60.8% for placebo. The most common adverse event was reaction at the injection site (14.3% for rilonacept vs 1.3% for placebo). Other adverse events reported in at least 5% of patients were respiratory infections, musculoskeletal system disorders, and headache, with similar rates for these effects among treatment groups. Serious adverse events were reported in 3 patients in each treatment group but were considered unrelated to study treatment.