Historically controlled comparison of glucocorticoids with or without tocilizumab versus supportive care only in patients with COVID-19-associated cytokine storm syndrome: results of the CHIC study
Historically controlled comparison of glucocorticoids with or without tocilizumab versus supportive care only in patients with COVID-19-associated cytokine storm syndrome: results of the CHIC study
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DOI：
10.1136/annrheumdis-2020-218479
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发表时间：
2020-09-01
影响因子：
27.4
通讯作者：
Landewe, Robert B. M.
中科院分区：
文献类型：
--
作者：
Ramiro, Sofia;Mostard, Remy L. M.;Landewe, Robert B. M.
目的前瞻性研究重度COVID-19相关细胞因子风暴综合征（CSS）患者与仅接受支持性治疗的历史对照组患者相比，糖皮质激素强化治疗加或不加托珠单抗是否能加速临床改善，降低死亡率并防止有创机械通气。方法从2020年4月1日起，COVID-19相关CSS患者，定义为快速呼吸恶化加上三种生物标志物中至少两种显著升高（C-反应蛋白>100 mg/L;铁蛋白>900 μ g/L; D-二聚体>1500 μ g/L），连续5天接受高剂量静脉内甲泼尼龙（第1天250 mg，第2-5天80 mg）。如果呼吸系统状况没有得到充分改善（43%），则在第2天或之后添加白细胞介素-6受体阻滞剂托珠单抗（8 mg/kg体重，单次输注）。从3月7日至3月31日期间入院的患者库（n=350）中回顾性抽样了COVID-19相关CSS（定义相同）的对照患者，并将其与接受治疗的患者在性别和年龄上一一匹配。主要结局为在严重流感性肺炎患者中进行的试验中，WHO认可的7项量表改善≥ 2个阶段或出院。结果基线时，治疗组（n=86）和对照组（n = 86）的所有COVID-19患者均出现CSS症状并面临急性呼吸衰竭。接受治疗的患者达到主要结局的可能性增加79%（HR：1.8; 95%CI 1.2 - 2.7）（提前7天），死亡率降低65%（HR：0.35; 95%CI 0.19 - 0.65），机械通气侵入性降低71%（HR：0.29; 95%CI 0.14 - 0.65）。治疗效果在混淆和敏感性分析中保持不变。结论在COVID-19相关CSS中，包括高剂量甲基强的松龙疗程，然后在需要时使用托珠单抗的策略可能会加速呼吸恢复，降低住院死亡率并减少有创机械通气的可能性。
Objectives To prospectively investigate in patients with severe COVID-19-associated cytokine storm syndrome (CSS) whether an intensive course of glucocorticoids with or without tocilizumab accelerates clinical improvement, reduces mortality and prevents invasive mechanical ventilation, in comparison with a historic control group of patients who received supportive care only.Methods From 1 April 2020, patients with COVID-19-associated CSS, defined as rapid respiratory deterioration plus at least two out of three biomarkers with important elevations (C-reactive protein >100 mg/L; ferritin >900 mu g/L; D-dimer >1500 mu g/L), received high-dose intravenous methylprednisolone for 5 consecutive days (250 mg on day 1 followed by 80 mg on days 2-5). If the respiratory condition had not improved sufficiently (in 43%), the interleukin-6 receptor blocker tocilizumab (8 mg/kg body weight, single infusion) was added on or after day 2. Control patients with COVID-19-associated CSS (same definition) were retrospectively sampled from the pool of patients (n=350) admitted between 7 March and 31 March, and matched one to one to treated patients on sex and age. The primary outcome was >= 2 stages of improvement on a 7-item WHO-endorsed scale for trials in patients with severe influenza pneumonia, or discharge from the hospital. Secondary outcomes were hospital mortality and mechanical ventilation.Results At baseline all patients with COVID-19 in the treatment group (n=86) and control group (n=86) had symptoms of CSS and faced acute respiratory failure. Treated patients had 79% higher likelihood on reaching the primary outcome (HR: 1.8; 95%CI 1.2 to 2.7) (7 days earlier), 65% less mortality (HR: 0.35; 95%CI 0.19 to 0.65) and 71% less invasive mechanical ventilation (HR: 0.29; 95%CI 0.14 to 0.65). Treatment effects remained constant in confounding and sensitivity analyses.Conclusions A strategy involving a course of high-dose methylprednisolone, followed by tocilizumab if needed, may accelerate respiratory recovery, lower hospital mortality and reduce the likelihood of invasive mechanical ventilation in COVID-19-associated CSS.