Interleukin-1 Receptor Blockade Is Associated With Reduced Mortality in Sepsis Patients With Features of Macrophage Activation Syndrome: Reanalysis of a Prior Phase III Trial.
Interleukin-1 Receptor Blockade Is Associated With Reduced Mortality in Sepsis Patients With Features of Macrophage Activation Syndrome: Reanalysis of a Prior Phase III Trial.
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DOI：
10.1097/ccm.0000000000001402
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发表时间：
2016-02
影响因子：
8.8
通讯作者：
Opal SM
中科院分区：
文献类型：
--
作者：
Shakoory B;Carcillo JA;Chatham WW;Amdur RL;Zhao H;Dinarello CA;Cron RQ;Opal SM
目的：探讨重组白介素1受体拮抗剂阿纳金纳(Anakinra)对巨噬细胞活化综合征(MAS)脓毒症患者28天存活率的改善作用。尽管败血症试验的结果不明确，但Anakinra在治疗MAS方面是有效的，MAS是一种类似于发热、弥散性血管内凝血(DIC)、肝胆功能障碍(HBD)、细胞减少和高铁素血症的疾病。因此，具有MAS特征的脓毒症患者可能受益于IL-1受体阻断。严重脓毒症的第三阶段随机白介素1受体拮抗剂试验中未确认数据的重新分析(Opal，et.艾尔急救室医疗中心。1997年7月；25：1115-24)。通过来自欧洲和北美11个国家的91个中心招聘多中心研究人员。脓毒症合并MODS和/或休克患者(原始研究)根据是否合并HBD和DIC作为MAS的特征进行重新分组(HBD/DIC组)。“非HBD/DIC”组包括仅有HBD、仅有DIC或两者都没有的患者。使用Anakinra或安慰剂进行治疗。28天死亡率。描述性统计、卡方检验、单因素方差分析、Logistic回归和Cox回归。从最初的研究队列中获得了763名成年人的数据，随机接受Anakinra或安慰剂。43名患者同时存在HBD/DIC(占总数的5.6%，年龄在18-75岁之间；47%为女性)。Anakinra和安慰剂治疗的非HBD/DIC患者的28天存活率相似(71.4%对70.8%，p=.88)。在COX回归分析中，Anakinra治疗与HBD/DIC患者28天存活率(65.4%Anakinra对35.3%安慰剂)的显著改善有关，治疗组的死亡比率为0.28(0.11-0.71，p=0.0071)。在这一亚组分析中，阻断IL-1受体与显著改善合并HBD/DIC的脓毒症患者的生存有关。应该进行一项前瞻性随机试验，利用MAS的特征进行死亡风险分层，以确认IL-1阻断的作用。
To determine the efficacy of anakinra (recombinant interleukin-1 receptor antagonist) in improving 28-day survival in sepsis patients with features of macrophage activation syndrome (MAS). Despite equivocal results in sepsis trials, anakinra is effective in treating MAS, a similar entity with fever, disseminated intravascular coagulation (DIC), hepatobiliary dysfunction (HBD), cytopenias, and hyperferritinemia. Hence, sepsis patients with MAS features may benefit from IL-1 receptor blockade. Re-analysis of de-identified data from the phase III randomized interleukin-1 receptor antagonist trial in severe sepsis (Opal, et. al. Crit Care Med. 1997 Jul;25:1115–24). Multi-center study recruiting through 91 centers from 11 countries in Europe and North America. Sepsis patients with MODS and/or shock (original study) were re-grouped based on presence or absence of concurrent HBD and DIC as features of MAS (HBD/DIC group). The “non-HBD/DIC” group included patients with only HBD, only DIC or neither. Treatment with anakinra or placebo. 28-day mortality. descriptive statistics, chi-square, ANOVA, logistic and Cox regression. Data were available for 763 adults from the original study cohort, randomized to receive either anakinra or placebo. Concurrent HBD/DIC was noted in 43 patients (5.6% of total, ages 18–75; 47% women). The 28-day survival was similar in both anakinra and placebo-treated non-HBD/DIC patients (71.4% vs. 70.8%, p=.88). Treatment with anakinra was associated with significant improvement in the 28-day survival rate in HBD/DIC patients (65.4% anakinra vs. 35.3% placebo), with HR for death 0.28 (0.11–0.71, p = 0.0071) for the treatment group in Cox regression. In this subgroup analysis, IL-1 receptor blockade was associated with significant improvement in survival of patients with sepsis and concurrent HBD/DIC. A prospective randomized trial using features of MAS for mortality risk stratification should be undertaken to confirm the role of IL-1 blockage.