摘要：目的：應用別嘌醇降尿酸治療開(kāi)始時(shí)，評估IL-1受體拮抗劑利納西普預防痛風(fēng)急性發(fā)作療效和安全性，來(lái)自3期多中心臨床研究。方法：共納入248例來(lái)自南非、德國、亞洲的高尿酸血癥患者，這些患者在過(guò)去的1年內痛風(fēng)發(fā)作在2次或2次以上。按1:1:1隨機分為三組，在接受別嘌醇治療開(kāi)始后，分別給予注射利納西普80mg/周（R80組），利納西普160mg/周（R160組）及注射安慰劑/周（PBO組），共16周，觀(guān)察患者痛風(fēng)急性發(fā)作次數。結果：與安慰劑組相比，R80組痛風(fēng)急性發(fā)作減少71.3%，R160組痛風(fēng)急性發(fā)作減少72.6%?；颊咧饕獮槟行裕ò追N人占53.2%，亞洲人占33.1%，黑人占13.7%）。治療過(guò)程中，大多數患者完成了研究（87.8-92.9%）。在16周時(shí)，患者痛風(fēng)急性發(fā)作的平均次數，在R80組下降了71.3%（0.35），在R160組下降72.6%（0.34），而PBO組（1.23，P<0.0001）未急性發(fā)作的痛風(fēng)患者比例在R80組為74.4%，R160組79.5%，顯著(zhù)高于對照組（43.9%），P<0.0001。利納西普組患者發(fā)生多次痛風(fēng)急性發(fā)作的比例顯著(zhù)下降（P<0.001）。整體上講，不良事件發(fā)生率在安慰劑組(61.0%)和在利納西普組（65.1%）相似。注射部位出現局部反應是最常見(jiàn)的副作用（PBO組1.2%, R80組12.2%，R160組17.9%）,但通常輕微，且沒(méi)有因為注射部位反應導致退出。研究中，沒(méi)有藥物相關(guān)的嚴重副作用或死亡。結論：利納西普顯著(zhù)減少降尿酸藥物治療導致的痛風(fēng)急性發(fā)作，大于70%的患者未發(fā)生急性發(fā)作，并顯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). 2013 Jul;52(7):1285-92.
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