巴托昔单抗、西尼利尤单抗或英夫利昔单抗治疗 COVID-19 肺炎住院成人：一项随机临床试验。

Abatacept, Cenicriviroc, or Infliximab for Treatment of Adults Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial.

机构信息

Washington University St Louis, St Louis, Missouri.

Duke University Health System, Durham, North Carolina.

出版信息

JAMA. 2023 Jul 25;330(4):328-339. doi: 10.1001/jama.2023.11043.

DOI:10.1001/jama.2023.11043

PMID:37428480

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10334296/

Abstract

IMPORTANCE

Immune dysregulation contributes to poorer outcomes in COVID-19.

OBJECTIVE

To investigate whether abatacept, cenicriviroc, or infliximab provides benefit when added to standard care for COVID-19 pneumonia.

DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-masked, placebo-controlled clinical trial using a master protocol to investigate immunomodulators added to standard care for treatment of participants hospitalized with COVID-19 pneumonia. The results of 3 substudies are reported from 95 hospitals at 85 clinical research sites in the US and Latin America. Hospitalized patients 18 years or older with confirmed SARS-CoV-2 infection within 14 days and evidence of pulmonary involvement underwent randomization between October 2020 and December 2021.

INTERVENTIONS

Single infusion of abatacept (10 mg/kg; maximum dose, 1000 mg) or infliximab (5 mg/kg) or a 28-day oral course of cenicriviroc (300-mg loading dose followed by 150 mg twice per day).

MAIN OUTCOMES AND MEASURES

The primary outcome was time to recovery by day 28 evaluated using an 8-point ordinal scale (higher scores indicate better health). Recovery was defined as the first day the participant scored at least 6 on the ordinal scale.

RESULTS

Of the 1971 participants randomized across the 3 substudies, the mean (SD) age was 54.8 (14.6) years and 1218 (61.8%) were men. The primary end point of time to recovery from COVID-19 pneumonia was not significantly different for abatacept (recovery rate ratio [RRR], 1.12 [95% CI, 0.98-1.28]; P = .09), cenicriviroc (RRR, 1.01 [95% CI, 0.86-1.18]; P = .94), or infliximab (RRR, 1.12 [95% CI, 0.99-1.28]; P = .08) compared with placebo. All-cause 28-day mortality was 11.0% for abatacept vs 15.1% for placebo (odds ratio [OR], 0.62 [95% CI, 0.41-0.94]), 13.8% for cenicriviroc vs 11.9% for placebo (OR, 1.18 [95% CI 0.72-1.94]), and 10.1% for infliximab vs 14.5% for placebo (OR, 0.59 [95% CI, 0.39-0.90]). Safety outcomes were comparable between active treatment and placebo, including secondary infections, in all 3 substudies.

CONCLUSIONS AND RELEVANCE

Time to recovery from COVID-19 pneumonia among hospitalized participants was not significantly different for abatacept, cenicriviroc, or infliximab vs placebo.

TRIAL REGISTRATION

ClinicalTrials.gov Identifier: NCT04593940.

摘要

重要性

免疫失调导致 COVID-19 患者预后较差。

目的

研究阿巴西普、西尼利罗克或英夫利昔单抗联合标准治疗对 COVID-19 肺炎的疗效。

设计、地点和参与者：采用主方案，对免疫调节剂联合标准治疗住院 COVID-19 肺炎患者的疗效进行随机、双盲、安慰剂对照临床试验。来自美国和拉丁美洲 85 个临床研究地点的 95 家医院的 3 项亚研究报告了结果。2020 年 10 月至 2021 年 12 月期间，纳入了 18 岁或以上、在 SARS-CoV-2 感染后 14 天内且有肺部受累证据的确诊 COVID-19 患者，并进行随机分组。

干预措施

单次输注阿巴西普（10mg/kg；最大剂量 1000mg）或英夫利昔单抗（5mg/kg）或西尼利罗克（300mg 负荷剂量，随后每日 2 次 150mg）口服 28 天。

主要结局和测量指标

主要结局是采用 8 分序贯量表评估的 28 天内恢复时间（得分越高表示健康状况越好）。恢复定义为参与者首次得分至少为 6 的那一天。

结果

在 3 项亚研究中，1971 名随机分组的参与者中，平均（SD）年龄为 54.8（14.6）岁，1218 名（61.8%）为男性。COVID-19 肺炎恢复的主要终点时间，阿巴西普（恢复率比值 [RRR]，1.12 [95% CI，0.98-1.28]；P=0.09）、西尼利罗克（RRR，1.01 [95% CI，0.86-1.18]；P=0.94）和英夫利昔单抗（RRR，1.12 [95% CI，0.99-1.28]；P=0.08）与安慰剂相比无显著差异。阿巴西普的 28 天全因死亡率为 11.0%，安慰剂组为 15.1%（比值比 [OR]，0.62 [95% CI，0.41-0.94]），西尼利罗克组为 13.8%，安慰剂组为 11.9%（OR，1.18 [95% CI 0.72-1.94]），英夫利昔单抗组为 10.1%，安慰剂组为 14.5%（OR，0.59 [95% CI，0.39-0.90]）。所有 3 项亚研究中，与安慰剂相比，活性治疗与安慰剂的安全性结局相当，包括继发性感染。