Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Evaluation of Rilonacept for Prevention of Gout Flares during Initiation of Urate-Lowering Therapy: Results of a Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial.
Terkeltaub6, Robert, Schumacher5, H. Ralph, Saag4, Kenneth G., Clower7, James, Jennings1, William, Evans2, Robert R., Wang3, Jian
Radiant Research, San Antonio, TX
Regeneron Pharmaceuticals, Inc., Tarrytown, NY
Regeneron Pharmaceuticals, Inc.
University of Alabama-Birmingham, Birmingham, AL
VA Medical Center and UPenn, Philadelphia, PA
VA Medical Ctr, San Diego, CA
Westside Center for Clinical Research, Jacksonville, FL
The present study evaluated the efficacy and safety of rilonacept (IL-1 Trap) for the prevention of gout flares (GFs) during initiation of urate-lowering therapy (ULT) with allopurinol. While attaining target serum levels is critical to the long-term management of gout, ULT can elicit or prolong acute attacks during the initial months of therapy. This paradoxical finding may be attributable to remodeling of crystal deposits during dissolution.
This North American multicenter trial included adults with gout (ARA criteria), urate levels >=7.5 mg/dL, and self-reported history of >=2 GFs in the previous year. Eligible patients were initiated on allopurinol 300 mg daily (or lower dose in those with renal dysfunction, with subsequent titration to achieve urate <6 mg/dL) and randomized to receive treatment with weekly subcutaneous (SC) injections of placebo (Pbo; n=80), rilonacept 80 mg (R80; n=80), or rilonacept 160 mg (R160; n=81) (loading dose on Day 1). GFs were reported by the patient via interactive voice response diary and treated, as appropriate, with NSAIDs or oral glucocorticoids while continuing study treatments. Efficacy endpoints included the number of GFs, % of patients with 1 or more flares, and number of flare days. Safety and tolerability were also assessed.
Baseline characteristics were similar among treatment groups; 92.9% were male, the mean ± SD age was 52.3±12.6 years, and the number of flares reported in the prior year was 4.6 ± 3.3. Fewer patients on Pbo completed the 16-wk treatment period (72.5%) compared with those receiving active treatment (80.0% R80; 86.4% R160). Observed serum urate levels decreased similarly in all 3 groups. Through wk 16, the mean number of GFs per patient (primary endpoint) was significantly lower in both R groups relative to Pbo: 1.06 (84 flares) for Pbo; 0.29 (23 flares) for R80, and 0.21 (17 flares) for R160 (95% CI, 0.22 to 0.46; p<0.0001 vs Pbo). One or more flares were reported by 46.8% Pbo, 18.8% R80, and 16.3% of R160 patients (p<0.0001). The number of flare days per patient was significantly lower with rilonacept: 5.52, 2.36, and 0.98 for Pbo, R80, and R160, respectively (p<0.0001 vs Pbo). From day 1 to wk 16, the proportion of patients who experienced multiple flares was 31.6% Pbo (95% CI, 21.6 to 43.1) vs 5.0% R80 (95% CI, 1.4 to 12.3) vs 3.7% R160 (95% CI, 0.8 to 10.6; p<0.0001 for both comparisons), resulting in an 84% and 88% reduction in the respective R groups. The overall incidence of adverse events (AE) was similar between Pbo (60.8%) and rilonacept (63.4%). Injection site reactions were the most frequent AE with rilonacept (14.3% vs 1.3%). Other common AEs, reported by >=5% of patients, were respiratory infections, musculoskeletal system disorders, and headache, and rates were generally similar among the treatment groups. Three patients in each group experienced serious AEs; no rilonacept-related SAEs, deaths, or serious infectious AEs were reported.
This phase 3 trial confirmed that IL-1 blockade with rilonacept markedly reduced the occurrence of gout flares during initiation of urate lowering therapy. Rilonacept demonstrated an acceptable safety and tolerability profile.
To cite this abstract, please use the following information:
Terkeltaub, Robert, Schumacher, H. Ralph, Saag, Kenneth G., Clower, James, Jennings, William, Evans, Robert R., et al; Evaluation of Rilonacept for Prevention of Gout Flares during Initiation of Urate-Lowering Therapy: Results of a Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :152