Trigo-Rodríguez Marta, Cárcel Sheila, Navas Ana, Espíndola-Gómez Reinaldo, Garrido-Gracia José Carlos, Esteban Moreno María Ángeles, León-López Rafael, Pérez-Crespo Pedro María Martínez, Alonso Eduardo Aguilar, Vinuesa David, Romero-Palacios Alberto, Pérez-Camacho Inés, Gutiérrez-Gutiérrez Belén, Martínez-Marcos Francisco Javier, Fernández-Roldán Concepción, León Eva, Caño Alexandra Aceituno, Corzo-Delgado Juan E, Perez-Nadales Elena, Riazzo Cristina, de la Fuente Carmen, Jurado Aurora, Torre-Cisneros Julián, Merchante Nicolás
Unidad de Enfermedades Infecciosas y Microbiología, Hospital Universitario de Valme, Universidad de Sevilla, Instituto de Investigaciones Biomédicas de Sevilla, IBIS (Universidad de Sevilla, Junta de Andalucía, CSIC), Sevilla, Spain.
Unidad de Gestión Clínica de Cuidados Intensivos, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía, Universidad de Córdoba (UCO), Córdoba, Spain.
Open Forum Infect Dis. 2023 Mar 11;10(4):ofad133. doi: 10.1093/ofid/ofad133. eCollection 2023 Apr.
The Clinical Trial of Sarilumab in Adults With COVID-19 (SARICOR) showed that patients with coronavirus disease 2019 (COVID-19) pneumonia and increased levels of interleukin (IL)-6 might benefit from blockade of the IL-6 pathway. However, the benefit from this intervention might not be uniform. In this subanalysis, we sought to determine if other immunoactivation markers, besides IL-6, could identify which subgroup of patients benefit most from this intervention.
The SARICOR trial was a phase II, open-label, multicenter, controlled trial (July 2020-March 2021) in which patients were randomized to receive usual care (UC; control group), UC plus a single dose of sarilumab 200 mg (sarilumab-200 group), or UC plus a single dose of sarilumab 400 mg (sarilumab-400 group). Patients who had baseline serum samples for cytokine determination (IL-8, IL-10, monocyte chemoattractant protein-1, interferon-inducible protein [IP]-10) were included in this secondary analysis. Progression to acute respiratory distress syndrome (ARDS) according to cytokine levels and treatment received was evaluated.
One hundred one (88%) of 115 patients enrolled in the SARICOR trial had serum samples (control group: n = 33; sarilumab-200: n = 33; sarilumab-400: n = 35). Among all evaluated biomarkers, IP-10 showed the strongest association with treatment outcome. Patients with IP-10 ≥2500 pg/mL treated with sarilumab-400 had a lower probability of progression (13%) compared with the control group (58%; hazard ratio, 0.19; 95% CI, 0.04-0.90; = .04). Conversely, patients with IP-10 <2500 pg/mL did not show these differences.
IP-10 may predict progression to ARDS in patients with COVID-19 pneumonia and IL-6 levels >40 pg/mL. Importantly, IP-10 value <2500 pg/mL might discriminate those individuals who might not benefit from sarilumab therapy among those with high IL-6 levels.
成人新型冠状病毒肺炎（COVID-19）的萨瑞鲁单抗临床试验（SARICOR）表明，2019冠状病毒病（COVID-19）肺炎且白细胞介素（IL）-6水平升高的患者可能从IL-6通路阻断中获益。然而，这种干预的获益可能并不一致。在这项亚组分析中，我们试图确定除IL-6之外，是否有其他免疫激活标志物能够识别出最能从这种干预中获益的患者亚组。
SARICOR试验是一项II期、开放标签、多中心对照试验（2020年7月至2021年3月），患者被随机分配接受常规治疗（UC；对照组）、UC加单剂量200mg萨瑞鲁单抗（萨瑞鲁单抗200组）或UC加单剂量400mg萨瑞鲁单抗（萨瑞鲁单抗400组）。有基线血清样本用于细胞因子测定（IL-8、IL-10、单核细胞趋化蛋白-1、干扰素诱导蛋白[IP]-10）的患者纳入该二次分析。根据细胞因子水平和接受的治疗评估进展为急性呼吸窘迫综合征（ARDS）的情况。
SARICOR试验纳入的115例患者中有101例（88%）有血清样本（对照组：n = 33；萨瑞鲁单抗200组：n = 33；萨瑞鲁单抗400组：n = 35）。在所有评估的生物标志物中，IP-10与治疗结果的关联最强。IP-10≥2500 pg/mL且接受萨瑞鲁单抗400治疗的患者进展概率较低（13%），而对照组为58%（风险比，0.19；95%CI，0.04 - 0.90；P = 0.04）。相反，IP-10<2500 pg/mL的患者未显示出这些差异。
IP-10可能预测IL-6水平>40 pg/mL的COVID-19肺炎患者进展为ARDS的情况。重要的是，IP-10值<2500 pg/mL可能区分出在IL-6水平高的患者中那些可能无法从萨瑞鲁单抗治疗中获益的个体。
