Use of Canakinumab in the Cryopyrin-Associated Periodic Syndrome
Use of Canakinumab in the Cryopyrin-Associated Periodic Syndrome
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DOI：
10.1056/nejmoa0810787
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发表时间：
2009-06-04
影响因子：
158.5
通讯作者：
Hawkins, Philip N.
中科院分区：
文献类型：
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作者：
Lachmann, Helen J.;Kone-Paut, Isabelle;Hawkins, Philip N.
cryopyrin-associated periodic syndrome（CAPS）是一种罕见的遗传性炎症性疾病，与白细胞介素-1的过度产生有关。Canakinumab是一种人源抗白细胞介素-1 β单克隆抗体。METHODSWe进行了一项三部分，48周，双盲，安慰剂对照，随机退出研究canakinumab与CAPS患者。在第1部分中，35例患者接受了150 mg canakinumab皮下给药。对治疗有完全反应的患者进入第2部分，随机分配接受150 mg卡那单抗或安慰剂，每8周一次，持续24周。完成第2部分后或复发时（以先发生者为准），患者进入第3部分，并接受至少两次以上剂量的卡那奴单抗。我们使用疾病活动性评分和C反应蛋白（CRP）和血清淀粉样蛋白A（SAA）水平分析来评估治疗反应。在研究的第1部分，35名患者中有34名（97%）对canakinumab有完全反应。在这些患者中，31例进入第2部分，所有15例接受canakinumab的患者均保持缓解。16例接受安慰剂治疗的患者中有13例（81%）发生疾病发作（P
BACKGROUNDThe cryopyrin-associated periodic syndrome ( CAPS) is a rare inherited inflammatory disease associated with overproduction of interleukin-1. Canakinumab is a human anti-interleukin-1 beta monoclonal antibody.METHODSWe performed a three-part, 48-week, double-blind, placebo-controlled, randomized withdrawal study of canakinumab in patients with CAPS. In part 1, 35 patients received 150 mg of canakinumab subcutaneously. Those with a complete response to treatment entered part 2 and were randomly assigned to receive either 150 mg of canakinumab or placebo every 8 weeks for up to 24 weeks. After the completion of part 2 or at the time of relapse, whichever occurred first, patients proceeded to part 3 and received at least two more doses of canakinumab. We evaluated therapeutic responses using disease-activity scores and analysis of levels of C-reactive protein (CRP) and serum amyloid A protein (SAA).RESULTSIn part 1 of the study, 34 of the 35 patients (97%) had a complete response to canakinumab. Of these patients, 31 entered part 2, and all 15 patients receiving canakinumab remained in remission. Disease flares occurred in 13 of the 16 patients (81%) receiving placebo (P