评估卡那奴单抗在不同严重表型的 Cryopyrin 相关周期性综合征患者中的安全性和疗效的开放性、多中心、III 期研究的两年结果。

Two-year results from an open-label, multicentre, phase III study evaluating the safety and efficacy of canakinumab in patients with cryopyrin-associated periodic syndrome across different severity phenotypes.

机构信息

Division of Pediatric Rheumatology, Department of Pediatrics, University Hospital Tübingen, Germany.

出版信息

Ann Rheum Dis. 2011 Dec;70(12):2095-102. doi: 10.1136/ard.2011.152728. Epub 2011 Aug 21.

DOI:10.1136/ard.2011.152728

PMID:21859692

Abstract

OBJECTIVE

Longer-term effects of prolonged selective interleukin-1β blockade with canakinumab were evaluated in the largest cohort of cryopyrin-associated periodic syndrome (CAPS) patients studied to date.

METHODS

Adult and paediatric CAPS patients (n=166, including canakinumab-naive and pretreated patients from previous studies) received canakinumab subcutaneously 150 mg or 2 mg/kg (≤40 kg) every 8 weeks for up to 2 years. Response and relapse was assessed using scores for disease activity, skin rash and C-reactive protein (CRP) and/or serum amyloid A (SAA) levels.

RESULTS

Complete response was achieved in 85 of 109 canakinumab-naive patients (78%; 79/85 patients within 8 days, and five patients between days 10 and 21). Of 141 patients with an available relapse assessment, 90% did not relapse, their CRP/SAA levels normalised (<10 mg/l) by day 8, and remained in the normal range thereafter. Median treatment duration was 414 days (29-687 days). Upward adjustments of dose or frequency were needed in 24.1% patients; mostly children and those with severe CAPS. Predominant adverse events (AE) were infections (65.7%) of mostly mild-to-moderate severity. Serious AE reported in 18 patients (10.8%) were mainly infections and were responsive to standard treatment. The majority of patients (92%) reported having no injection-site reactions and only 8% patients reported mild-to-moderate reactions. Patients receiving vaccination (15%) showed normal immune response.

CONCLUSIONS

Subcutaneous canakinumab 150 mg every 8 weeks was well tolerated and provided substantial disease control in children and adults across all CAPS phenotypes. Higher canakinumab doses in younger patients and more severe CAPS disease were efficacious in achieving complete responses without evidence of increased AE.

TRIAL REGISTRATION NUMBER

NCT00685373 (clinicaltrials.gov).

摘要

目的

评估卡那单抗对白细胞介素-1β的长期抑制作用，这是迄今为止对最大一批 Cryopyrin 相关周期性综合征（CAPS）患者进行的研究。

方法

纳入 166 例成人和儿科 CAPS 患者（包括来自先前研究的卡那单抗初治和预处理患者），每 8 周接受 150mg 或 2mg/kg（≤40kg）的卡那单抗皮下注射，最长治疗 2 年。使用疾病活动评分、皮疹和 C 反应蛋白（CRP）和/或血清淀粉样蛋白 A（SAA）水平来评估应答和复发。

结果

109 例卡那单抗初治患者中，85 例（78%；85 例患者在 8 天内，5 例患者在 10-21 天内）达到完全缓解。在 141 例可评估复发的患者中，90%未复发，其 CRP/SAA 水平在第 8 天恢复正常（<10mg/l），此后一直保持在正常范围。中位治疗持续时间为 414 天（29-687 天）。24.1%的患者需要调整剂量或频率；主要是儿童和严重 CAPS 患者。主要不良事件（AE）为感染（65.7%），多为轻中度。18 例患者（10.8%）报告 18 例严重不良事件（AE），主要为感染，对标准治疗有反应。大多数患者（92%）报告无注射部位反应，仅 8%患者报告轻度至中度反应。接受疫苗接种的患者（15%）显示出正常的免疫反应。