Effects of Interleukin-1β Inhibition on Incident Hip and Knee Replacement : Exploratory Analyses From a Randomized, Double-Blind, Placebo-Controlled Trial.
Effects of Interleukin-1β Inhibition on Incident Hip and Knee Replacement : Exploratory Analyses From a Randomized, Double-Blind, Placebo-Controlled Trial.
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DOI：
10.7326/m20-0527
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发表时间：
2020-10-06
影响因子：
39.2
通讯作者：
Ridker PM
中科院分区：
文献类型：
--
作者：
Schieker M;Conaghan PG;Mindeholm L;Praestgaard J;Solomon DH;Scotti C;Gram H;Thuren T;Roubenoff R;Ridker PM
骨关节炎(OA)是一种常见的炎症性疾病，目前尚无治疗方法。抑制白细胞介素1β(IL-1β)是否能减轻大关节骨关节炎的后果尚不清楚。目的：确定用Canakinumab抑制IL-1β是否能减少全髋关节或膝关节置换术的发生率。一项随机试验的探索性分析。39个国家和地区的1091个临床站点。10,061名参与者参加了Canakinumab抗炎性血栓形成结果研究。随机分配给安慰剂或Canakinumab(50 mg、150 mg或300 mg)，每3个月皮下注射一次。主要和次要结果是首次发生THR/TKR的时间和首次发生与骨性关节炎相关的不良事件的时间。数据是通过对试验、临床和安全数据库的盲法确定而获得的。中位随访期为3.7年。对于单独的Canakinumab剂量组，与安慰剂相比，50毫克组发生THR/TKR事件的风险比[HR]为0.60[95%可信区间0.38-0.95]；150毫克组为0.53[95%可信区间0.33-0.84]；300毫克组为0.60[95%可信区间0.38-0.93]。因此，与安慰剂组相比，在混合Canakinumab组中，Thr/TKR的发生率分别为每百人年0.31和0.54事件(HR0.58，[95%CI0.42-0.80]，p=0.001)。OA相关AEs次要终点的HR为0.73(95%CI为0.61~0.87)。在仅限于那些有骨性关节炎病史的人的分析中也观察到了类似的发现。由于亲本试验不是为了检查IL-1β抑制剂在骨性关节炎中的疗效而设计的，因此没有收集关于结构性关节结局的信息。这项随机对照试验的探索性分析结果支持进一步研究IL-1β抑制治疗大关节骨性关节炎。
Osteoarthritis (OA) is a common inflammatory disorder with no disease modifying therapies. Whether inhibition of interleukin-1β (IL-1β) can reduce the consequences of large joint OA is unclear. To determine whether IL-1β inhibition with canakinumab reduces incident total hip or knee replacement (THR/TKR). Exploratory analysis of a randomized trial. 1091 clinical sites in 39 countries. 10,061 participants in the Canakinumab Anti-inflammatory Thrombosis Outcomes Study. Random allocation to placebo or canakinumab (50mg, 150mg, or 300mg) subcutaneously once every 3 months. The primary and secondary outcomes were time to first incident THR/TKR and time to first occurrence of an OA related adverse event. Data were obtained through blinded ascertainment of trial clinical and safety databases. The median follow-up period was 3.7 years. For the individual canakinumab dose groups, compared to placebo, hazard ratios [HR] for incident THR/TKR during follow-up were 0.60 [95% CI 0.38–0.95] for the 50 mg group; 0.53 [95%CI 0.33–0.84] for the 150 mg group, and 0.60 [95%CI 0.38–0.93] for the 300 mg group. Thus, in the pooled canakinumab groups compared to the placebo group, incidence rates for THR/TKR were 0.31 and 0.54 events per 100-person years (HR 0.58, [95%CI 0.42–0.80], p=0.001). The HR for the secondary endpoint of OA related AEs was 0.73 (95% CI 0.61–0.87). Similar findings were observed in analyses restricted to those with a prior history of OA. As the parent trial was not designed to examine the efficacy of IL-1β inhibitors in OA, information on structural joint outcomes was not collected. Findings from this exploratory analysis of a randomized-controlled trial support further investigation of IL-1β inhibition for treatment of large joint OA.