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 in Patients with Gouty Arthritis Experiencing an Acute Gout Attack.
Terkeltaub6, Robert, Schumacher5, H. Ralph, Curtis1, Craig, Patterson2, Neil, Evans3, Robert R., Wang4, Jian, King-Davis4, Shirletta
Compass Research, Orlando, FL
Private Practice, Oviedo, FL
Regeneron Pharmaceuticals, Inc., Tarrytown, NY
Regeneron Pharmaceuticals, Inc.
VA Medical Center, Philadelphia, PA
VA Medical Ctr, San Diego, CA
The role of IL-1b as a central mediator of acute gouty inflammation has been confirmed by animal models and gout prevention studies in patients initiating urate lowering therapy. Although IL-1 appears to trigger gout flares (GFs), available data on IL-1 inhibition in the treatment of GFs is limited to case reports and a single dose-ranging study.
To report initial findings from SURGE (Study of Rilonacept in Gout Exacerbations), a large phase 3, randomized, double-blind, double-dummy, active-controlled study of the IL-1b and IL-1a blocker rilonacept for the treatment of acute GFs, conducted at approximately 80 sites in North America.
Eligible patients with gout aged >=18 to <=70 y presenting within 48 hrs of onset of a GF with at least moderately severe pain, evidence of swelling and tenderness in the gouty index joint (most painful joint), and who had not initiated treatment for GF symptoms were randomized to 1 of 3 regimens: SC placebo (Pbo) at baseline (BL), plus oral indomethacin (IN) for at least 3 days (d) [50 mg TID × 3 d, then 25 mg TID × 9 d] (IN group); SC rilonacept 320 mg at BL, plus IN for at least 3 d (R+IN group); or SC rilonacept 320 mg at BL, plus oral Pbo for at least 3 d (R group). Patient assessment of pain intensity in the gouty index joint was recorded using a 5-point Likert scale (0= none; 4=extreme) at BL (pre-dose) and 4, 8, 12, 24, 48, and 72 h after administration of SC study drug, and then daily up to 12 d via electronic diary. The primary efficacy endpoint was change from BL pain score to the averaged values at 24, 48 and 72 h. Sequential testing of 2 primary endpoints was planned: R+IN vs IN group, followed by R vs IN group, with the second comparison contingent upon p<0.05 for the first. Secondary efficacy analyses included change from BL in pain scores at 24, 48 and 72 hours under the same conditions.
225 patients with an acute GF were randomized to treatment (IN n=76; R+IN n=74; R n=75). Baseline characteristics were similar among groups. IN resulted in a statistically significant (p<0.0001) within-group reported reduction from BL in pain intensity similar to that reported in previous studies of IN. Although a numerically greater reduction in pain intensity was observed with R+IN compared with IN alone (mean ± SD change R+IN -1.55±0.92 vs IN -1.40±0.96), the difference was not statistically significant (95% CI, -0.44 to 0.15; p=0.33). Therefore, comparison of the IN with the R group (mean change ± SD R -0.69± 0.97 from baseline) was not performed, per the analysis plan.
Treatment with rilonacept was generally well-tolerated, with 3 patients reporting serious adverse events in the R+IN group, none considered drug-related. Adverse events reported at an incidence of at least 5% in any group were headache and dizziness.
Under conditions in which the reduction of acute gout flare pain in the indomethacin alone group was similar to published reports, inhibition of IL-1 with rilonacept did not provide additional pain relief within 72 hours of flare onset. In comparison with prior studies, the results suggest that blockade of IL-1 for treatment of an early, established acute gout flare is less effective clinically than for acute gout flare prophylaxis.
To cite this abstract, please use the following information:
Terkeltaub, Robert, Schumacher, H. Ralph, Curtis, Craig, Patterson, Neil, Evans, Robert R., Wang, Jian, et al; Evaluation of Rilonacept in Patients with Gouty Arthritis Experiencing an Acute Gout Attack. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :153