According to a phase II clinical trial, the drug rilonacept, which inhibits the protein interleukin-1 (IL-1), substantially reduces acute gout flares that occur at the start of uric acid-reducing therapy and is noted to be generally well tolerated with no serious infections or serious adverse events occurring in relation to the treatment. The findings of the first placebo controlled study, in which IL-1 targeted therapy to prevent gout flares has been evaluated, are published in Arthritis & Rheumatism, a journal of the American College of Rheumatology (ACR).

Gout, a form of inflammatory arthritis caused by the crystallization of urates in soft tissues, often affects the feet and is extremely painful causing swelling. According to a recent study in Arthritis & Rheumatism, doctor-diagnosed gout has increased in the past twenty years and currently affects 8.3 million individuals in the U.S.

Earlier research demonstrates that even though gout attacks typically resolve spontaneously within several days, the urate crystals remain in the joint and can lead to recurrent attacks. If left untreated, they can cause permanent damage to the joints.

Leading researcher Dr. H. Ralph Schumacher, Jr., Professor of Medicine at the University of Pennsylvania School of Medicine stated:

“To reduce deposits of crystals in the joints, we advise patients to initiate treatment with medications that lower levels of uric acid in the blood.”

The researchers explain that the crystals are broken up in the early months of urate-lowering therapy. This can lead to gout attacks that are suggested to occur because of the release of crystals from softened deposits. These urate crystals interact with cells releasing interleukin-1 (IL-1) that can lead to multiple inflammations and acute flares of joint pain.

Earlier research has demonstrated that patients who experienced acute gout attacks due to uric acid-lowering therapy are less likely to continue treatment. Dr. Schumacher said:

“Well tolerated drugs that reduce the risk of gout flares when initiating uric-acid lowering therapy could make patients more likely to continue important long-term treatments that control gout.”

Rilonacept is marketed under the brand name ARCALYST® to treat another disease, and has been developed to neutralize the IL-1 protein before it produces signals that can trigger inflammation. Because of this, the researchers decided to examine rilonacept’s efficacy in preventing gout flares. They enlisted 83 patients aged 18 years or older with gout, who had a history of two or more gout flares in the previous year and who had elevated blood levels of uric acid from 27 study centers across the U.S. for a phase II clinical trial.

In the double blind trial, the researchers randomized the participants with 41 patients receiving a double dose (320mg) of rilonacept via subcutaneous injection followed by 160 mg weekly for a period of 16 weeks, whilst the control group of 42 participants received weekly placebo. To reduce uric acid levels, the researchers started all patients on 300mg per day of allopurinol.

The findings showed that participants in the rilonacept group had a substantially lower number of gout flares with only 6 incidents compared with 33 incidents in the placebo group. Furthermore, patients in the rilonacept group also displayed fewer flares as early as four weeks after treatment initiation.

At 12 weeks the researchers observed only 15% of gout flares in patients in the rilonacept group compared with 45% in the placebo group. Neither group experienced any deaths or serious adverse events, whilst common adverse events included infections in 15% in the rilonacept group and 26% in the placebo group.

Dr. Schumacher states:

“This trial provides well-controlled evidence that this IL-1 blocker is effective in preventing acute gout flares in this setting. Rilonacept appears safe and well tolerated and could increase patient adherence to long-term urate-lowering therapy.”

The researchers suggest further rilonacept trials for evaluation in patients with gout.

Written by Petra Rattue