Kyriazopoulou Evdoxia, Huet Thomas, Cavalli Giulio, Gori Andrea, Kyprianou Miltiades, Pickkers Peter, Eugen-Olsen Jesper, Clerici Mario, Veas Francisco, Chatellier Gilles, Kaplanski Gilles, Netea Mihai G, Pontali Emanuele, Gattorno Marco, Cauchois Raphael, Kooistra Emma, Kox Matthijs, Bandera Alessandra, Beaussier Hélène, Mangioni Davide, Dagna Lorenzo, van der Meer Jos W M, Giamarellos-Bourboulis Evangelos J, Hayem Gilles
4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
Rheumatology Department, Groupe Hospitalier Paris Saint-Joseph, Paris, France.
Lancet Rheumatol. 2021 Oct;3(10):e690-e697. doi: 10.1016/S2665-9913(21)00216-2. Epub 2021 Aug 9.
Anakinra might improve the prognosis of patients with moderate to severe COVID-19 (ie, patients requiring oxygen supplementation but not yet receiving organ support). We aimed to assess the effect of anakinra treatment on mortality in patients admitted to hospital with COVID-19.
For this systematic review and individual patient-level meta-analysis, a systematic literature search was done on Dec 28, 2020, in Medline (PubMed), Cochrane, medRxiv, bioRxiv, and the ClinicalTrials.gov databases for randomised trials, comparative studies, and observational studies of patients admitted to hospital with COVID-19, comparing administration of anakinra with standard of care, or placebo, or both. The search was repeated on Jan 22, 2021. Individual patient-level data were requested from investigators and corresponding authors of eligible studies; if individual patient-level data were not available, published data were extracted from the original reports. The primary endpoint was mortality after 28 days and the secondary endpoint was safety (eg, the risk of secondary infections). This study is registered on PROSPERO (CRD42020221491).
209 articles were identified, of which 178 full-text articles fulfilled screening criteria and were assessed. Aggregate data on 1185 patients from nine studies were analysed, and individual patient-level data on 895 patients were provided from six of these studies. Eight studies were observational and one was a randomised controlled trial. Most studies used historical controls. In the individual patient-level meta-analysis, after adjusting for age, comorbidities, baseline ratio of the arterial partial oxygen pressure divided by the fraction of inspired oxygen (PaO/FiO), C-reactive protein (CRP) concentrations, and lymphopenia, mortality was significantly lower in patients treated with anakinra (38 [11%] of 342) than in those receiving standard of care with or without placebo (137 [25%] of 553; adjusted odds ratio [OR] 0·32 [95% CI 0·20-0·51]). The mortality benefit was similar across subgroups regardless of comorbidities (ie, diabetes), ferritin concentrations, or the baseline PaO/FiO. In a subgroup analysis, anakinra was more effective in lowering mortality in patients with CRP concentrations higher than 100 mg/L (OR 0·28 [95% CI 0·17-0·47]). Anakinra showed a significant survival benefit when given without dexamethasone (OR 0·23 [95% CI 0·12-0·43]), but not with dexamethasone co-administration (0·72 [95% CI 0·37-1·41]). Anakinra was not associated with a significantly increased risk of secondary infections when compared with standard of care (OR 1·35 [95% CI 0·59-3·10]).
Anakinra could be a safe, anti-inflammatory treatment option to reduce the mortality risk in patients admitted to hospital with moderate to severe COVID-19 pneumonia, especially in the presence of signs of hyperinflammation such as CRP concentrations higher than 100 mg/L.
Sobi.
阿那白滞素可能改善中度至重度新型冠状病毒肺炎（COVID-19）患者的预后（即需要吸氧但尚未接受器官支持的患者）。我们旨在评估阿那白滞素治疗对COVID-19住院患者死亡率的影响。
对于这项系统评价和个体患者水平的荟萃分析，于2020年12月28日在Medline（PubMed）、Cochrane、medRxiv、bioRxiv和ClinicalTrials.gov数据库中进行系统文献检索，以查找关于COVID-19住院患者的随机试验、对照研究和观察性研究，比较阿那白滞素与标准治疗、安慰剂或两者的给药情况。于2021年1月22日重复检索。向符合条件研究的研究者和通讯作者索取个体患者水平的数据；如果无法获得个体患者水平的数据，则从原始报告中提取已发表的数据。主要终点为28天后的死亡率，次要终点为安全性（如继发感染风险）。本研究已在PROSPERO（CRD42020221491）注册。
共识别出209篇文章，其中178篇全文文章符合筛选标准并进行了评估。对9项研究中1185例患者的汇总数据进行了分析，其中6项研究提供了895例患者的个体患者水平数据。8项研究为观察性研究，1项为随机对照试验。大多数研究使用历史对照。在个体患者水平的荟萃分析中，在调整年龄、合并症、动脉血氧分压与吸入氧分数之比（PaO/FiO）基线值、C反应蛋白（CRP）浓度和淋巴细胞减少后，接受阿那白滞素治疗的患者死亡率（342例中的38例[11%]）显著低于接受标准治疗加或不加安慰剂的患者（553例中的137例[25%]；调整后的比值比[OR]为0·32[95%CI 为0·20 - 0·51]）。无论合并症（如糖尿病）、铁蛋白浓度或基线PaO/FiO如何，各亚组的死亡率获益相似。在亚组分析中，阿那白滞素在降低CRP浓度高于100 mg/L患者的死亡率方面更有效（OR为0·28[95%CI为0·17 - 0·47]）。在未联合地塞米松给药时，阿那白滞素显示出显著的生存获益（OR为0·23[95%CI为0·12 - 应。
阿那白滞素可能是一种安全的抗炎治疗选择，可降低中度至重度COVID-19肺炎住院患者的死亡风险，尤其是在存在如CRP浓度高于100 mg/L等炎症反应迹象的情况下。
Sobi。
