Background Patients (pts) with visible tophi and/or polyarticular disease (T/PD) may be at greater risk of gout flares (GFs) when initiating uric acid-lowering therapy (ULT).
Objectives To determine the risk presented by T/PD for occurrence of GFs during initiation of ULT and to evaluate the efficacy of the IL-1 antagonist rilonacept for GF prevention in these pts using data from three Phase 3 clinical trials.
Methods PRE-SURGE 1, PRE-SURGE 2, and RE-SURGE were randomized, double-blind, placebo (PBO)-controlled trials evaluating safety and efficacy of weekly SC doses of rilonacept 80mg (R80) and 160mg (R160) for prevention of GFs during initiation of ULT. Treatment duration was 16 wks. GF rate ratios were calculated in the PBO group for each study by comparing pts with T/PD vs pts without T/PD. GFs per pt and proportion of pts with ≥1 GF were estimated for pts with baseline serum urate ≥445 μmol/L (7.5 mg/dL), >2 GFs in the past year, and initiating allopurinol in each of the treatment groups within each study and pooled from the 3 studies. GFs were defined as pt-reported acute articular pain typical of a gout attack that required anti-inflammatory treatment.
Results Pts with T/PD had significantly higher rates of GFs than those with monoarticular, non-tophaceous disease: GF rate ratios (95% confidence intervals) in PBO groups were 1.97 (1.02, 3.79), 3.69 (1.51, 9.02), and 1.93 (1.30, 2.86), in PRE-SURGE 1, PRE-SURGE 2, and RE-SURGE, respectively. Pooled data showed that for pts with T/PD, R80 resulted in a 69.5% reduction in mean number of GFs per pt vs PBO (from 1.81±2.52 [PB0] to 0.55±1.20 [R80]; P≤0.0001); the reduction with R160 was 67.7% (to 0.59±1.19; P≤0.0001). Reductions were generally similar to that observed in the total population. The proportions of pts with ≥1GF in the pooled T/PD population were 59.4%, 29.8%, and 30.7% for PBO, R80, and R160, respectively, almost a 50% reduction with rilonacept. For the total study population, the most commonly reported adverse event (AE), infections, was balanced among treatment groups; the most frequently reported treatment-related AE was injection site reaction.
Conclusions The presence of T/PD represents a risk factor for GFs in pts initiating ULT. Among patients with these risk factors, rilonacept demonstrated efficacy for GF prevention that was generally similar to that of the overall population.
Disclosure of Interest R. Evans Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., H. Schumacher Grant/Research support from: Regeneron Pharmaceuticals, Inc., Consultant for: Regeneron Pharmaceuticals, Inc., R. Wu Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., C. Barton Shareholder of: Regeneron Pharmaceuticals, Inc., Employee of: Regeneron Pharmaceuticals, Inc., R. Terkeltaub Grant/Research support from: Regeneron Pharmaceuticals, Inc., Consultant for: Regeneron Pharmaceuticals, Inc.
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