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期刊来源：Nat Med

原文链接：https://doi.org/10.1038/s41591-024-03043-1

摘要内容如下：

白细胞介素-6（IL-6）介导的炎症与心血管风险密切相关。在2B期剂量探索研究中，我们评估了靶向IL-6配体的单克隆抗体clazakizumab。患有心血管疾病和/或糖尿病的成人接受维持性透析，基线时高敏C反应蛋白（hs-CRP）≥2mgL-1，随机接受clazakizumab（2.5mg、5mg或10mg，每剂量组n=32）或安慰剂（n=31），每4周一次。主要终点是从基线到第12周hs-CRP的变化，以几何平均比率表示。在第12周，随机接受2.5mg、5mg或10mg clazakizumab治疗的患者的血清hs-CRP浓度相对于安慰剂分别显著降低了86%、90%和92%（均P<0.0001），达到了主要转归。关于次要终点，与安慰剂相比，clazakizumab治疗降低了血清纤维蛋白原、淀粉样蛋白A、分泌型磷脂酶A2和脂蛋白（a）浓度，并在12周时增加了平均血清白蛋白浓度。在2.5mg、5mg和10mg clazakizumab治疗组中，达到hs-CRP<2.0mgL-1的患者比例分别为79%、82%和79%，而安慰剂治疗组为0%。关于安全性，未观察到持续3级或4级血小板减少症或中性粒细胞减少症的病例。在安慰剂组、clazakizumab 2.5mg组和clazakizumab 5mg组中，严重感染的发生率相似，但在clazakizumab 10mg组中，严重感染的发生率更高。该试验的结果表明，在接受维持性透析的患者中，clazakizumab降低了与心血管事件相关的炎症生物标志物。ClinicalTrials.gov注册：NCT05485961。

英文原文如下：

Abstracts

Inflammation mediated by interleukin-6 (IL-6) is strongly associated with cardiovascular risk. Here we evaluated clazakizumab, a monoclonal antibody targeting the IL-6 ligand, in a phase 2b dose-finding study. Adults with cardiovascular disease and/or diabetes receiving maintenance dialysis with high-sensitivity C-reactive protein (hs-CRP) ≥ 2 mg l-1 at baseline were randomized to receive clazakizumab (2.5 mg, 5 mg or 10 mg, n = 32 per dose group) or placebo (n = 31) every 4 weeks. The primary endpoint was the change from baseline in hs-CRP to week 12, expressed as the geometric mean ratio. Clazakizumab treatment signficantly reduced serum hs-CRP concentrations at week 12 by 86%, 90% and 92% relative to placebo in patients randomized to 2.5 mg, 5 mg or 10 mg clazakizumab, respectively (all P < 0.0001), meeting the primary outcome. With regard to secondary endpoints, clazakizumab treatment reduced serum fibrinogen, amyloid A, secretory phospholipase A2, and lipoprotein(a) concentrations, as well as increased mean serum albumin concentrations at 12 weeks, relative to placebo. The proportion of patients who achieved hs-CRP < 2.0 mg l-1 was 79%, 82% and 79% in the 2.5 mg, 5 mg and 10 mg clazakizumab groups, respectively, compared with 0% of placebo-treated patients. With regard to safety, no cases of sustained grade 3 or 4 thrombocytopenia or neutropenia were observed. Serious infections were seen with similar frequency in the placebo, clazakizumab 2.5 mg and clazakizumab 5 mg groups, but were numerically more frequent in the clazakizumab 10 mg group. The results of this trial indicate that in patients receiving maintenance dialysis, clazakizumab reduced inflammatory biomarkers associated with cardiovascular events. ClinicalTrials.gov registration: NCT05485961 .

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