白细胞介素-1β 抑制剂对髋关节和膝关节置换术发生率的影响：一项随机、双盲、安慰剂对照试验的探索性分析。
Effects of Interleukin-1β Inhibition on Incident Hip and Knee Replacement : Exploratory Analyses From a Randomized, Double-Blind, Placebo-Controlled Trial.
机构信息
Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, and Basel, Switzerland, and Ludwig Maximilian University of Munich, Munich, Germany (M.S.).
Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, and National Institute for Health Research Leeds BiomedicalResearch Centre, Leeds, United Kingdom (P.G.C.).
出版信息
Ann Intern Med. 2020 Oct 6;173(7):509-515. doi: 10.7326/M20-0527. Epub 2020 Aug 4.
BACKGROUND
Osteoarthritis is a common inflammatory disorder with no disease-modifying therapies. Whether inhibition of interleukin-1β (IL-1β) can reduce the consequences of large joint osteoarthritis is unclear.
OBJECTIVE
To determine whether IL-1β inhibition with canakinumab reduces incident total hip or knee replacement (THR/TKR).
DESIGN
Exploratory analysis of a randomized trial. (ClinicalTrials.gov: NCT01327846).
SETTING
1091 clinical sites in 39 countries.
PARTICIPANTS
10 061 CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcomes Study) participants.
INTERVENTION
Random allocation to placebo or canakinumab (50, 150, or 300 mg) subcutaneously once every 3 months.
MEASUREMENTS
The primary and secondary outcomes were time to first incident THR/TKR and time to first occurrence of an osteoarthritis-related adverse event (AE). Data were obtained through blinded ascertainment of trial clinical and safety databases.
RESULTS
Median follow-up was 3.7 years. For the individual canakinumab dose groups, compared with placebo, hazard ratios (HRs) for incident THR/TKR during follow-up were 0.60 (95% CI, 0.38 to 0.95) for the 50-mg group, 0.53 (CI, 0.33 to 0.84) for the 150-mg group, and 0.60 (CI, 0.38 to 0.93) for the 300-mg group. Thus, in the pooled canakinumab groups, compared with the placebo group, incidence rates for THR/TKR were 0.31 and 0.54 events per 100 person-years (HR, 0.58 [CI, 0.42 to 0.80]; = 0.001), respectively. The HR for the secondary end point of osteoarthritis-related AEs was 0.73 (CI, 0.61 to 0.87). Similar findings were observed in analyses restricted to participants with a history of osteoarthritis.
LIMITATION
Because the parent trial was not designed to examine the efficacy of IL-1β inhibitors in osteoarthritis, information on structural joint outcomes was not collected.
CONCLUSION
Findings from this exploratory analysis of a randomized controlled trial support further investigation of IL-1β inhibition for treatment of large joint osteoarthritis.
PRIMARY FUNDING SOURCE
Novartis Pharmaceuticals.
背景
骨关节炎是一种常见的炎症性疾病，目前尚无针对该病的治疗方法。白细胞介素-1β（IL-1β）抑制剂是否能减轻大关节骨关节炎的后果尚不明确。
目的
评估 IL-1β 抑制剂卡那奴单抗（canakinumab）能否减少全髋关节或全膝关节置换术（THR/TKR）的发生。
设计
随机试验的探索性分析。（ClinicalTrials.gov：NCT01327846）。
地点
39 个国家的 1091 个临床地点。
参与者
CANTOS（卡那奴单抗抗炎性血栓结局研究）参与者 10061 例。
干预
皮下注射安慰剂或卡那奴单抗（50、150 或 300mg），每 3 个月 1 次，随机分组。
测量
主要和次要结局为首次发生 THR/TKR 的时间和首次发生与骨关节炎相关的不良事件（AE）的时间。数据通过盲法确定试验临床和安全性数据库获得。
结果
中位随访 3.7 年。对于各个卡那奴单抗剂量组，与安慰剂相比，随访期间发生 THR/TKR 的风险比（HR）分别为 50mg 组 0.60（95%CI，0.38 至 0.95）、150mg 组 0.53（CI，0.33 至 0.84）和 300mg 组 0.60（CI，0.38 至 0.93）。因此，在卡那奴单抗联合治疗组中，与安慰剂组相比，THR/TKR 的发生率分别为每 100 人年 0.31 和 0.54 例（HR，0.58 [CI，0.42 至 0.80]；=0.001）。与骨关节炎相关 AE 的次要终点 HR 为 0.73（CI，0.61 至 0.87）。在仅限于有骨关节炎病史的参与者的分析中也观察到了类似的发现。
局限性
由于主要试验并非专门设计来评估 IL-1β 抑制剂在骨关节炎中的疗效，因此未收集结构关节结局的相关信息。
结论
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 抑制剂治疗大关节骨关节炎。
主要资金来源
诺华制药公司。
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