Division of Pediatric Rheumatology, Department of Pediatrics, University Children's Hospital Tuebingen, Hoppe-Seyler-Strasse 1, 72076 Tübingen, Tuebingen, Germany.
Arthritis Res Ther. 2011 Feb 28;13(1):R34. doi: 10.1186/ar3266.
Cryopyrin-associated periodic syndrome (CAPS) represents a spectrum of three auto-inflammatory syndromes, familial cold auto-inflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), and neonatal-onset multisystem inflammatory disease/chronic infantile neurological cutaneous and articular syndrome (NOMID/CINCA) with etiology linked to mutations in the NLRP3 gene resulting in elevated interleukin-1β (IL-1β) release. CAPS is a rare hereditary auto-inflammatory disease, which may start early in childhood and requires a life-long treatment. Canakinumab, a fully human anti-IL-1β antibody, produces sustained selective inhibition of IL-1β. This study was conducted to assess the efficacy, safety, and pharmacokinetics of canakinumab in the treatment of pediatric CAPS patients.
Seven pediatric patients (five children and two adolescents) with CAPS were enrolled in a phase II, open-label study of canakinumab in patients with CAPS. Canakinumab was administered at a dose of 2 mg/kg subcutaneously (s.c.) (for patients with body weight ≤ 40 kg) or 150 mg s.c. (for patients with body weight > 40 kg) with re-dosing upon each relapse. The primary efficacy variable was time to relapse following achievement of a complete response (defined as a global assessment of no or minimal disease activity and no or minimal rash and values for serum C-reactive protein (CRP) and/or serum amyloid A (SAA) within the normal range, < 10 mg/L).
All patients achieved a complete response within seven days after the first dose of canakinumab and responses were reinduced on retreatment following relapse. Improvements in symptoms were evident within 24 hours after the first dose, according to physician assessments. The estimated median time to relapse was 49 days (95% CI 29 to 68) in children who received a dose of 2 mg/kg. Canakinumab was well tolerated. One serious adverse event, vertigo, was reported, but resolved during treatment.
Canakinumab, 2 mg/kg or 150 mg s.c., induced rapid and sustained clinical and biochemical responses in pediatric patients with CAPS.
ClinicalTrials.gov: NCT00487708.
冷吡啉相关周期性综合征 (CAPS) 代表了三种自身炎症综合征的谱，家族性冷自身炎症综合征 (FCAS)、Muckle-Wells 综合征 (MWS) 和新生儿发病多系统炎症性疾病/慢性婴儿神经皮肤关节综合征 (NOMID/CINCA)，其病因与 NLRP3 基因的突变有关，导致白细胞介素-1β (IL-1β) 释放增加。CAPS 是一种罕见的遗传性自身炎症性疾病，可能在儿童早期发病，需要终身治疗。Canakinumab，一种全人源抗 IL-1β 抗体，可产生持续的选择性 IL-1β 抑制。本研究旨在评估 canakinumab 在治疗儿科 CAPS 患者中的疗效、安全性和药代动力学。
7 名 CAPS 患儿（5 名儿童和 2 名青少年）参加了一项评估 canakinumab 治疗 CAPS 患者的 II 期、开放标签研究。Canakinumab 的剂量为 2mg/kg 皮下 (s.c.)（体重≤40kg 的患者）或 150mg s.c.（体重>40kg 的患者），每次复发时进行重新给药。主要疗效变量是从完全缓解到复发的时间（定义为全球评估无或轻度疾病活动和无或轻度皮疹，以及血清 C 反应蛋白 (CRP) 和/或血清淀粉样蛋白 A (SAA) 值在正常范围内，<10mg/L）。
所有患者在首次接受 canakinumab 治疗后 7 天内达到完全缓解，复发后再次治疗可重新诱导缓解。根据医生评估，症状改善在首次给药后 24 小时内即可显现。接受 2mg/kg 剂量的儿童估计中位复发时间为 49 天（95%CI 29 至 68）。Canakinumab 耐受性良好。报告了 1 例严重不良事件，即眩晕，但在治疗期间得到解决。
2mg/kg 或 150mg s.c. 的 canakinumab 可快速和持续诱导儿科 CAPS 患者的临床和生化反应。
ClinicalTrials.gov：NCT00487708。
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