抑制白细胞介素(IL)-1代表了成人发作的斯蒂尔病(AOSD)的一种有希望的治疗选择。
通过多中心研究康纳单抗在AOSD和活动性关节受累患者中的疗效和安全性,双盲,随机化,安慰剂对照试验。
患有AOSD和活动性关节受累(关节压痛和肿胀计数≥4)的患者接受canakinumab(4mg/kg,每4周最大300毫克皮下)或安慰剂。主要终点是通过疾病活动性评分的变化(ΔDAS28>1.2)确定的在第12周具有临床相关疾病活动性降低的患者的比例。
报名时,canakinumab组患者患有高活性疾病,平均DAS28(ESR)为5.4,安慰剂组为5.3,分别。在意向治疗分析中,canakinumab组中的12名患者(67%)和安慰剂组中的7名患者(41%)符合主要结果标准(p=0.18)。在符合方案的分析中,显著高于美国风湿病学会(ACR)30%(61%vs20%,p=0.033),ACR50%(50%对6.7%,p=0.009)和ACR70%(28%对0%,p=0.049)与安慰剂组相比,在canakinumab组中观察到反应率。canakinumab组的两名患者经历了严重不良事件。
虽然研究提前终止,但未达到主要终点,canakinumab治疗改善了AOSD的几个结局指标.总体安全性发现与canakinumab的已知概况一致。因此,我们的数据支持在AOSD中使用canakinumab抑制IL-1的指示.
Inhibition of interleukin (IL)-1 represents a promising treatment option in adult-onset Still\'s disease (AOSD).
To investigate the efficacy and safety of canakinumab in patients with AOSD and active joint involvement by means of a multicentre, double-blind, randomised, placebo-controlled trial.
Patients with AOSD and active joint involvement (tender and swollen joint counts of ≥4 each) were treated with canakinumab (4 mg/kg, maximum 300 mg subcutaneous every 4 weeks) or placebo. The primary endpoint was the proportion of patients with a clinically relevant reduction in disease activity at week 12 as determined by the change in disease activity score (ΔDAS28>1.2).
At enrolment, patients had high active disease with a mean DAS28(ESR) of 5.4 in the canakinumab and 5.3 in the placebo group, respectively. In the intention-to-treat analysis, 12 patients (67%) in the canakinumab group and 7 patients (41%) in the placebo group fulfilled the primary outcome criterion (p=0.18). In the per-protocol analysis, significantly higher American College of Rheumatology (ACR) 30% (61% vs 20%, p=0.033), ACR 50% (50% vs 6.7%, p=0.009) and ACR 70% (28% vs 0%, p=0.049) response rates were observed in the canakinumab group compared with the placebo group. Two patients in the canakinumab group experienced a serious adverse event.
Although the study was terminated prematurely and the primary endpoint was not achieved, treatment with canakinumab led to an improvement of several outcome measures in AOSD. The overall safety findings were consistent with the known profile of canakinumab. Thus, our data support indication for IL-1 inhibition with canakinumab in AOSD.