La Torre F, Caparello M C, Cimaz R
a Pediatric Rheumatology Regional Center, Department of Pediatrics , Antonio Perrino Hospital , Brindisi , Puglia , Italy.
b Pediatric Rheumatology Unit, Neurofarba Department , AOU Meyer, University of Florence , Florence , Italy.
Expert Rev Clin Immunol. 2017 Jun;13(6):513-523. doi: 10.1080/1744666X.2017.1324783.
TNF-receptor-associated periodic syndrome is an autoinflammatory disorder caused by mutations in TNF receptor superfamily 1A gene. The molecular pathogenesis of TRAPS remains unclear; it is known that a key role is played by mutations in TNFRSF1A that induce the hypersecretion of pro-inflammatory cytokines as well as IL-1β, resulting in uncontrolled inflammatory reactions. Furthermore, TNFRSF1A gene mutations result in intracellular stress ultimately leading to increased production of interleukin-1β, but the exact mechanism referred to in the connection between TNFRSF1A mutation and increased release of IL-1β, is still under study. This explains why IL-1 inhibition treatment can be effective in treating TRAPS patients. The purpose of this review is to discuss the safety and efficacy of canakinumab, a high-affinity human monoclonal anti IL-1β antibody. Areas covered: The data obtained from case reports, case series, Phase II study and a phase III randomized, double-blind, placebo controlled trial have been analyzed. Efficacy and safety profiles of canakinumab are discussed. Expert commentary: Was discussed an overview of treatment options in TRAPS patients. The understanding of pathogenesis of TNF-receptor-associated periodic syndrome led to realize why TRAPS patients respond to IL-1 inhibition. Canakinumab became approved for the treatment in TRAPS patients very recently.
肿瘤坏死因子受体相关周期性综合征是一种由肿瘤坏死因子受体超家族1A基因（TNF receptor superfamily 1A gene）突变引起的自身炎症性疾病。TRAPS的分子发病机制尚不清楚；已知TNFRSF1A中的突变起着关键作用，这些突变会诱导促炎细胞因子以及IL-1β的过度分泌，从而导致不受控制的炎症反应。此外，TNFRSF1A基因突变会导致细胞内应激，最终导致白细胞介素-1β的产生增加，但TNFRSF1A突变与IL-1β释放增加之间联系的确切机制仍在研究中。这就解释了为什么IL-1抑制治疗对治疗TRAPS患者有效。本综述的目的是讨论卡那单抗（一种高亲和力的人源单克隆抗IL-1β抗体）的安全性和有效性。涵盖领域：分析了从病例报告、病例系列、II期研究以及一项III期随机、双盲、安慰剂对照试验中获得的数据。讨论了卡那单抗的疗效和安全性概况。专家评论：讨论了TRAPS患者的治疗选择概述。对肿瘤坏死因子受体相关周期性综合征发病机制的理解，让人明白为什么TRAPS患者对IL-1抑制有反应。卡那单抗最近已被批准用于治疗TRAPS患者。
