Rilonacept Inhibits Gout Flares in Patients on Allopurinol

June 6, 2011 (London, United Kingdom) — Rilonacept, an interleukin 1 (IL-1) inhibitor, prevented gout flares to a greater extent in patients receiving uric acid–lowering therapy (specifically, allopurinol) compared with those receiving allopurinol and placebo, according to phase 3 trial results presented here at the European League Against Rheumatism (EULAR) Congress 2011. These findings confirm results of previous phase 2 data.

"These data support the concept of IL-1 inhibition as a treatment approach to gout. Rilonacept prevents flares in patients at high risk of flares," stated lead author Robert Evans, PharmD, an employee of Regeneron Pharmaceuticals, Inc, Tarrytown, New York.

The safety profile was acceptable, and tolerable injection-site reactions were the most commonly reported treatment-emergent adverse events. Dr. Evans noted that another IL blocker, canakinumab, is also in phase 3 trials for gout, but studies of the 2 IL-1 inhibitors have different designs and are not easily comparable. (Both drugs are approved in the United States and Europe for cryopyrin-associated periodic syndrome, but not yet for gout.)

Although lowering uric acid to a target level of less than 6 mg/dL is an important part of gout management, in some patients the initiation of allopurinol can elicit gout flares, which may compromise adherence to treatment. Thus, the availability of a treatment that can prevent gout flares during uric acid–lowering therapy is desirable.

The Preventative Study Against Urate-Lowering Drug-Induced Gout Exacerbations 1 (PRE-SURGE 1) was a randomized, double-blind, placebo-controlled, phase 3 study of 241 patients from 64 study centers in North America. Patients were randomly assigned to 1 of 3 treatment groups — placebo (n = 79), rilonacept 80 mg (n = 80), or rilonacept 160 mg (n = 81) — for 16 weeks of treatment.

At baseline, groups were comparable for demographic and disease characteristics. Mean age was about 52 years, and about 90% were men. Body mass index was about 32 kg/m², and mean duration of gout was about 10 years. At baseline, patients had a mean of 4.5 flares per year.

Rilonacept significantly reduced the number of flares from baseline at 16 weeks compared with placebo (P < .0001). At week 16, the number of flares was 84 in the placebo group vs 23 in the 80-mg dose group and 17 in the 160-mg dose group. This represents a 73% reduction for the lower dose and an 80% reduction for the higher dose, Dr. Evans said. Rilonacept also significantly reduced the percentage of patients reporting gout flares through week 16 (P < .0005), from 46.9% with placebo to 18.8% with the lower rilonacept dose and 16.3% with the higher dose.

No significant difference was observed for the rate of infections: 22.8% for placebo, 18.8% for rilonacept 80 mg, and 17.3% for rilonacept 160 mg.

"These data support that IL-1 inhibition [with both rilonacept and canakinumab] is working, and this is particularly relevant for those patients with refractory gout," stated Georg Schett, MD, EULAR Scientific Committee Chair and Chief of Rheumatology at Erlangen-Nuremberg University in Germany.

The inflammasome (the protein complex or "machinery" that produces the cytokine IL-1) partly drives the inflammation in gout, Dr. Schett explained. "Gout crystals activate the inflammasome like a bomb, and IL-1 blockers neutralize the product of the inflammasome," he added.

"IL-1 inhibition adds to the treatment options for gout. Allopurinol, an inexpensive drug, will be used until the patient is not doing well. Then these newer options [rilonacept and canakinumab] provide potential approaches for refractory patients," he said.

Robert Evans is a shareholder and employee of Regeneron Pharmaceuticals, Inc. Dr. Schett has disclosed no relevant financial relationships.

European League Against Rheumatism (EULAR) Congress 2011: Abstract THU0007. Presented May 26, 2011.