摘要：目的：应用别嘌醇降尿酸治疗开始时，评估IL-1受体拮抗剂利纳西普预防痛风急性发作疗效和安全性，来自3期多中心临床研究。方法：共纳入248例来自南非、德国、亚洲的高尿酸血症患者，这些患者在过去的1年内痛风发作在2次或2次以上。按1:1:1随机分为三组，在接受别嘌醇治疗开始后，分别给予注射利纳西普80mg/周（R80组），利纳西普160mg/周（R160组）及注射安慰剂/周（PBO组），共16周，观察患者痛风急性发作次数。结果：与安慰剂组相比，R80组痛风急性发作减少71.3%，R160组痛风急性发作减少72.6%。患者主要为男性（白种人占53.2%，亚洲人占33.1%，黑人占13.7%）。治疗过程中，大多数患者完成了研究（87.8-92.9%）。在16周时，患者痛风急性发作的平均次数，在R80组下降了71.3%（0.35），在R160组下降72.6%（0.34），而PBO组（1.23，P<0.0001）未急性发作的痛风患者比例在R80组为74.4%，R160组79.5%，显著高于对照组（43.9%），P<0.0001。利纳西普组患者发生多次痛风急性发作的比例显著下降（P<0.001）。整体上讲，不良事件发生率在安慰剂组(61.0%)和在利纳西普组（65.1%）相似。注射部位出现局部反应是最常见的副作用（PBO组1.2%, R80组12.2%，R160组17.9%）,但通常轻微，且没有因为注射部位反应导致退出。研究中，没有药物相关的严重副作用或死亡。结论：利纳西普显著减少降尿酸药物治疗导致的痛风急性发作，大于70%的患者未发生急性发作，并显示了可接受的安全性和良好的耐受性。
附原文
Objectives: To evaluate the efficacy and safety of IL-1 inhibitor rilonacept (IL-1 Trap) for gout flare (GF) prevention during initiation of uric acid-lowering therapy (ULT) with allopurinol in a multiregional phase 3 clinical trial.Methods:Hyperuricaemic adults (n = 248) from South Africa, Germany and Asia with gout and two or more GFs within the past year were initiated on allopurinol and randomized 1:1:1 to once-weekly s.c. treatment with placebo (PBO),rilonacept 80 mg (R80) or rilonacept 160 mg (R160) for 16 weeks. The primary endpoint was the number of GFs per patient through week 16.Results: The population was predominantly male and racially diverse (white, 53.2%; Asian, 33.1%; black, 13.7%). Across treatments, most patients completed the study (87.8-92.9%). At 16 weeks the mean number of GFs per patient was reduced by 71.3% with R80 (0.35) and by 72.6% with R160 (0.34) relative to PBO (1.23; both P < 0.0001). The proportion of patients without GFs was higher with R80 (74.4%) and R160 (79.5%) than with PBO (43.9%; both P ≤ 0.0001), and the proportions of patients on rilonacept with multiple GFs were significantly lower (P < 0.001). Overall, the incidence of adverse events (AEs) was similar between PBO (61.0%) and rilonacept (65.1%).Injection site reactions, generally mild, were the most frequent AE with rilonacept (1.2% PBO, 12.2% R80 and 17.9% R160); none of these injection site reactions led to withdrawal. There were no study drug-related serious AEs or deaths.Conclution:Rilonacept significantly reduced the occurrence of GFs associated with initiation of ULT, with >70% of patients having no flares, and demonstrated an acceptable safety and tolerability profile.
---- 引自：Mitha E1, Schumacher HR, Fouche L. Rilonacept for gout flare prevention during initiation of uric acid-lowering therapy: results from the PRESURGE-2 international, phase 3, randomized, placebo-controlled trial. Rheumatology (Oxford). Jul;52(7):1285-92.
