Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany.
Expert Opin Biol Ther. 2010 Nov;10(11):1631-6. doi: 10.1517/14712598.2010.530653.
Autoinflammatory syndromes such as cryopyrin-associated periodic syndromes (CAPS) place a heavy burden on affected individuals as well as on their families due to significant morbidity and increased mortality. The inflammatory response in CAPS is caused by an overwhelming activation of the pro-inflammatory cytokine IL-1, which was identified as a promising treatment target.
This article focuses on the pathogenic background and different clinical manifestations in CAPS. Furthermore, the development program and characteristics of canakinumab, a recently approved fully human anti-IL-1β mAb for the treatment of CAPS, are described and compared to other available IL-1 blocking agents.
Canakinumab targets selectively human IL-1ß with high affinity and prevents the cytokine from interaction to its receptor and, thus, effectively blocks the inflammatory response in CAPS. In all studies performed, canakinumab showed a rapid improvement of symptoms of CAPS and a complete clinical response was achieved in most patients. Inflammatory markers such as C-reactive protein and serum amyloid-A protein were reduced to normal levels within few days. In comparison to other IL-1 blockers, canakinumab provides a longer plasma half-life and less injection site reactions.
Canakinumab offers the possibility of permanent disease control, almost symptom-free life, and hopefully less long-term morbidity and mortality in patients with CAPS.
自炎症性疾病,如 Cryopyrin 相关周期性综合征(CAPS),由于发病率高和死亡率增加,给患者及其家属带来了沉重的负担。CAPS 中的炎症反应是由过度激活促炎细胞因子 IL-1 引起的,IL-1 已被确定为一种有前途的治疗靶点。
本文综述了 CAPS 的发病机制背景和不同临床表现。此外,还描述了最近批准的用于治疗 CAPS 的全人源抗 IL-1β mAb 卡那单抗的开发项目和特点,并与其他可用的 IL-1 阻断剂进行了比较。
卡那单抗以高亲和力选择性靶向人 IL-1β,阻止细胞因子与其受体相互作用,从而有效阻断 CAPS 中的炎症反应。在所有进行的研究中,卡那单抗迅速改善了 CAPS 的症状,大多数患者达到了完全临床缓解。在几天内,炎症标志物如 C 反应蛋白和血清淀粉样蛋白 A 蛋白降至正常水平。与其他 IL-1 阻滞剂相比,卡那单抗提供了更长的血浆半衰期和更少的注射部位反应。
卡那单抗为 CAPS 患者提供了永久性疾病控制、几乎无症状的生活以及降低长期发病率和死亡率的可能性。