> Now this is not the end. It is not even the beginning of the end. But it is, perhaps, the end of the beginning . > > —Winston Churchill The CANTOS trial (Canakinumab Anti-Inflammatory Thrombosis Outcome Study) provides intriguing support for the inflammatory hypothesis of atherosclerosis and cancer in man, demonstrating diverse clinical benefits of inhibiting IL (interleukin)-1β for cardiovascular events and lung cancer. Limited effects on cardiovascular mortality and safety concerns raised by a higher incidence of fatal infection warrant further studies to identify patient subgroups which profit most from anti-inflammatory therapy and a careful pursuit of alternative targets. Abundant evidence from experimental and clinical studies has lend strong support to the hypothesis that inflammation contributes to the pathogenesis of atherosclerotic disease in conjunction with or beyond elevated lipid levels; however, ultimate proof by selective anti-inflammatory treatment in a clinical trial remained elusive for decades. This has now changed with the results of the CANTOS, a double-blind trial involving high-risk patients with prior myocardial infarction (MI) and a residual inflammatory response (defined by hsCRP [high-sensitivity C-reactive protein] levels >2 mg/L despite intensive statin therapy), who were randomized to canakinumab (50, 150, or 300 mg every 3 months) or placebo.1 Canakinumab, a human monoclonal antibody targeting IL-1β as the master cytokine of innate immunity, dose dependently reduced hsCRP and IL-6 levels by ≤43% from baseline. At 150 mg (but not the other doses), canakinumab significantly lowered the risk for the primary (MI, stroke, cardiovascular death) and secondary end points (hazard ratio [HR], 0.85 and 0.83, respectively). Adversely, canakinumab was associated with leukopenia and a higher incidence of fatal infection. Whereas no significant difference in all-cause or cardiovascular mortality was observed, canakinumab strikingly reduced cancer mortality (exploratory results indicating HR 0.23, for lung cancer), supporting a role of inflammation in cancer progression. …

中文翻译：

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CANTOS试验验证了动脉粥样硬化的炎性发病机理

>现在，这还没有结束。这甚至还没开始结尾。但这也许是开始的结尾。>> —温斯顿·丘吉尔（Winston Churchill）CANTOS试验（Canakinumab抗炎性血栓形成结果研究）为人的动脉粥样硬化和癌症的炎症假设提供了有趣的支持，证明了抑制IL（白介素）-1β对心血管事件和肺癌的多种临床益处。致命感染的高发生率对心血管死亡率和安全性问题的影响有限，值得进一步研究，以鉴定从抗炎治疗和谨慎追求替代目标中受益最大的患者亚组。来自实验和临床研究的大量证据为以下假设提供了有力依据：炎症与脂质水平升高或升高有关，可导致动脉粥样硬化疾病的发病。然而，数十年来，在临床试验中通过选择性抗炎治疗的最终证据仍然难以捉摸。CANTOS的结果已改变了这一情况，这项双盲试验涉及具有先发性心肌梗塞（MI）和残余炎症反应（由hsCRP [高敏C反应蛋白]水平> 2 mg定义的高危患者） / L，尽管接受了他汀类药物的强化治疗），但仍被随机分配到canakinumab（每3个月50、150或300 mg）或安慰剂中。1Canakinumab，一种靶向IL-1β的人类单克隆抗体，作为先天免疫的主要细胞因子，剂量依赖性地使hsCRP和IL-6水平从基线水平降低≤43％。150毫克（但不是其他剂量）时，canakinumab显着降低了主要危险因素（MI，中风，心血管死亡）和次要危险因素（危险比[HR]分别为0.85和0.83）。不利的是，canakinumab与白细胞减少症和致命感染的发生率较高有关。尽管未观察到全因或心血管死亡率的显着差异，但canakinumab显着降低了癌症死亡率（探索性结果表明，对于肺癌，HR为0.23），支持了炎症在癌症进展中的作用。… 分别）。不利的是，canakinumab与白细胞减少症和致命感染的发生率较高有关。尽管未观察到全因或心血管病死亡率的显着差异，但canakinumab显着降低了癌症死亡率（探索性结果表明，对于肺癌，HR为0.23），支持了炎症在癌症进展中的作用。… 分别）。不利的是，canakinumab与白细胞减少症和致命感染的发生率较高有关。尽管未观察到全因或心血管死亡率的显着差异，但canakinumab显着降低了癌症死亡率（探索性结果表明，对于肺癌，HR为0.23），支持了炎症在癌症进展中的作用。…