本文由小咖机器人翻译整理

期刊来源：Ann Intern Med

原文链接：https://doi.org/10.7326/M23-2593

摘要内容如下：

背景

从ACTT-1（适应性COVID-19治疗试验-1）发展而来的ACTT风险概况表明，COVID-19住院患者在高风险四分位数（特征为低绝对淋巴细胞计数[ALC]、高绝对中性粒细胞计数[ANC]和基线低血小板计数）中从抗病毒药物Remdesivir治疗中获益最多。目前尚不清楚哪些患者特征与免疫调节剂Baricitinib治疗的获益相关。

客观

将ACTT风险概况应用于ACTT-2队列，通过风险四分位数研究潜在的baricitinib相关治疗效果。

设计

ACTT-2的事后分析，一项随机、双盲、安慰剂对照试验（ClinicalTrials.gov：NCT04401579）

设置

在8个国家设立了67个试验点。

参与者

因COVID-19住院的成人（n=999；85%的美国参与者）。

干预

Baricitinib+Remdesivir与安慰剂+Remdesivir比较。

测量

死亡率、进展至有创机械通气（IMV）或死亡以及恢复，均在28天内；ALC、ANC和血小板计数轨迹。

结果

在高风险四分位数中，baricitinib+Remdesivir与死亡风险降低相关（风险比[HR]，0.38[95%CI，0.16-0.86]；P=0.020），减少进展至IMV或死亡（HR，0.57[CI，0.35至0.93]；P=0.024），并提高了恢复率（HR，1.53[CI，1.16至2.02]；P=0.00 2）与安慰剂+瑞德西韦相比。5天后，与对照组参与者相比，接受baricitinib+Remdesivir治疗的参与者的ALC显著增加，ANC显著降低，在高风险四分位数中观察到的影响最大。

局限性

对当前SARS-CoV-2变异体传播前收集的数据进行二次分析。

结论

ACTT风险概况确定了从Baricitinib治疗中获益最多的住院患者亚组，并捕获了患者对免疫调节剂和抗病毒药物的治疗反应表型。ALC和ANC轨迹的变化提示免疫调节剂限制严重COVID-19的机制。

主要资金来源

国家过敏和传染病研究所。

英文原文如下：

Abstracts

BACKGROUND  The ACTT risk profile, which was developed from ACTT-1 (Adaptive COVID-19 Treatment Trial-1), demonstrated that hospitalized patients with COVID-19 in the high-risk quartile (characterized by low absolute lymphocyte count [ALC], high absolute neutrophil count [ANC], and low platelet count at baseline) benefited most from treatment with the antiviral remdesivir. It is unknown which patient characteristics are associated with benefit from treatment with the immunomodulator baricitinib.

OBJECTIVE  To apply the ACTT risk profile to the ACTT-2 cohort to investigate potential baricitinib-related treatment effects by risk quartile.

DESIGN  Post hoc analysis of ACTT-2, a randomized, double-blind, placebo-controlled trial. (ClinicalTrials.gov: NCT04401579).

SETTING  Sixty-seven trial sites in 8 countries.

PARTICIPANTS  Adults hospitalized with COVID-19 (n = 999; 85% U.S. participants).

INTERVENTION  Baricitinib+remdesivir versus placebo+remdesivir.

MEASUREMENTS  Mortality, progression to invasive mechanical ventilation (IMV) or death, and recovery, all within 28 days; ALC, ANC, and platelet count trajectories.

RESULTS  In the high-risk quartile, baricitinib+remdesivir was associated with reduced risk for death (hazard ratio [HR], 0.38 [95% CI, 0.16 to 0.86]; P = 0.020), decreased progression to IMV or death (HR, 0.57 [CI, 0.35 to 0.93]; P = 0.024), and improved recovery rate (HR, 1.53 [CI, 1.16 to 2.02]; P = 0.002) compared with placebo+remdesivir. After 5 days, participants receiving baricitinib+remdesivir had significantly larger increases in ALC and significantly larger decreases in ANC compared with control participants, with the largest effects observed in the high-risk quartile.

LIMITATION  Secondary analysis of data collected before circulation of current SARS-CoV-2 variants.

CONCLUSION  The ACTT risk profile identifies a subgroup of hospitalized patients who benefit most from baricitinib treatment and captures a patient phenotype of treatment response to an immunomodulator and an antiviral. Changes in ALC and ANC trajectory suggest a mechanism whereby an immunomodulator limits severe COVID-19.

PRIMARY FUNDING SOURCE  National Institute of Allergy and Infectious Diseases.

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