Rilonacept (interleukin-1 trap) for prevention of gout flares during initiation of uric acid-lowering therapy: results from a phase III randomized, double-blind, placebo-controlled, confirmatory efficacy study.

Abstract

OBJECTIVE:

To evaluate the efficacy and safety of the interleukin-1 inhibitor rilonacept (interleukin-1 Trap) for gout flare prevention during initiation of uric acid-lowering therapy (ULT).

METHODS:

In total, 241 adult patients with gout, ≥2 gout flares within the past year, and a serum urate level ≥7.5 mg/dl were initiated on allopurinol 300 mg daily and randomly allocated in a 1:1:1 ratio to receive 16 once-weekly subcutaneous injections of placebo, rilonacept 80 mg, or rilonacept 160 mg, with a double (loading) dose on day 1. Allopurinol was titrated to achieve a serum urate level of <6.0 mg/dl. The study was powered for the primary efficacy end point, the number of gout flares per patient through week 16.

RESULTS:

More patients in the rilonacept groups (80.0% in the rilonacept 80 mg group, 86.4% in the rilonacept 160 mg group) completed the study than in the placebo group (72.5%; P < 0.05 for the rilonacept 160 mg group versus the placebo group). Over 16 weeks, the mean number of gout flares per patient was significantly reduced by rilonacept treatment (placebo: 1.06, rilonacept 80 mg: 0.29 [P < 0.001], rilonacept 160 mg: 0.21 [P < 0.001]). Significantly lower proportions of patients reported ≥1 gout flares with rilonacept 80 mg (18.8%) and rilonacept 160 mg (16.3%) relative to placebo (46.8%; P < 0.001 for both). Except for injection site reactions (1.3% in the placebo group versus 8.8% in the rilonacept 80 mg group [P = 0.0635, post hoc analysis] and 19.8% in the rilonacept 160 mg group [P = 0.0001, post hoc analysis]), the incidence of adverse events was generally balanced among the treatment groups.

CONCLUSION:

Rilonacept markedly reduced the occurrence of gout flares associated with the initiation of ULT. The efficacy and safety profile suggests that rilonacept may have the potential to improve long-term disease control for some patients by improving adherence to ULT by reducing flares during the first months after ULT initiation.

• Authors: H Ralph Schumacher Jr, Robert R Evans, Kenneth G Saag, James Clower, William Jennings, Steven P Weinstein, George D Yancopoulos, Jian Wang, Robert Terkeltaub
• Journal: Arthritis care & research (Arthritis Care Res (Hoboken)) Vol. 64 Issue 10 Pg. 1462-70 (Oct 2012) ISSN: 2151-4658 [Electronic] United States
• PMID: 22549879 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 by the American College of Rheumatology.

Chemical References

• Gout Suppressants
• Placebos
• Recombinant Fusion Proteins
• Uric Acid
• Allopurinol
• rilonacept

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Allopurinol (therapeutic use)
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Gout (blood, drug therapy)
• Gout Suppressants (therapeutic use)
• Humans
• Male
• Middle Aged
• Placebos
• Recombinant Fusion Proteins (therapeutic use)
• Treatment Outcome
• Uric Acid (blood)