■ACTT风险简介,它是从ACTT-1(适应性COVID-19治疗试验-1)开发的,表明住院患者COVID-19处于高危四分位数(以绝对淋巴细胞计数[ALC]低,高绝对中性粒细胞计数[ANC],和低血小板计数在基线)受益于治疗与抗病毒雷德西韦。尚不清楚哪些患者特征与免疫调节剂巴利替尼治疗的益处相关。
■将ACTT风险概况应用于ACTT-2队列,以按风险四分位数调查潜在的巴利替尼相关治疗效果。
■对ACTT-2进行随机分析,双盲,安慰剂对照试验。(ClinicalTrials.gov:NCT04401579)。
■在8个国家的67个试验地点。
■因COVID-19住院的成年人(n=999;85%的美国参与者)。
■Baricitinib+remdesivir与安慰剂+remdesivir。
■死亡率,进展为有创机械通气(IMV)或死亡,和恢复,全部在28天内;ALC,ANC,和血小板计数轨迹。
■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至0.86];P=0.020),降低IMV或死亡的进展(HR,0.57[CI,0.35至0.93];P=0.024),和提高回收率(HR,1.53[CI,1.16至2.02];P=0.002)与安慰剂+remdesivir相比。5天后,与对照参与者相比,接受baricitinib+remdesivir的参与者ALC显著增加,ANC显著减少,在高风险四分位数中观察到最大的影响。
■对当前SARS-CoV-2变体在循环之前收集的数据进行二次分析。
ACTT风险概况确定了住院患者的亚组,这些患者从baricitinib治疗中受益最大,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轨迹的变化表明免疫调节剂限制严重COVID-19的机制。
■国家过敏和传染病研究所。
UNASSIGNED: 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.
UNASSIGNED: To apply the ACTT risk profile to the ACTT-2 cohort to investigate potential baricitinib-related treatment effects by risk quartile.
UNASSIGNED: Post hoc analysis of ACTT-2, a randomized, double-blind, placebo-controlled
trial. (ClinicalTrials.gov: NCT04401579).
UNASSIGNED: Sixty-seven
trial sites in 8 countries.
UNASSIGNED: Adults hospitalized with COVID-19 (n = 999; 85% U.S. participants).
UNASSIGNED: Baricitinib+remdesivir versus placebo+remdesivir.
UNASSIGNED: Mortality, progression to invasive mechanical ventilation (IMV) or death, and recovery, all within 28 days; ALC, ANC, and platelet count trajectories.
UNASSIGNED: 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.
UNASSIGNED: Secondary analysis of data collected before circulation of current SARS-CoV-2 variants.
UNASSIGNED: 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.
UNASSIGNED: National Institute of Allergy and Infectious Diseases.