Providence Little Company of Mary Medical Center, Torrance, CA, USA.
Dallas Regional Medical Center, Mesquite, TX, USA.
Clin Exp Immunol. 2023 Oct 13;213(3):265-275. doi: 10.1093/cei/uxad065.
MAS825, a bispecific IL-1β/IL-18 monoclonal antibody, could improve clinical outcomes in COVID-19 pneumonia by reducing inflammasome-mediated inflammation. Hospitalized non-ventilated patients with COVID-19 pneumonia (n = 138) were randomized (1:1) to receive MAS825 (10 mg/kg single i.v.) or placebo in addition to standard of care (SoC). The primary endpoint was the composite Acute Physiology and Chronic Health Evaluation II (APACHE II) score on Day 15 or on the day of discharge (whichever was earlier) with worst-case imputation for death. Other study endpoints included safety, C-reactive protein (CRP), SARS-CoV-2 presence, and inflammatory markers. On Day 15, the APACHE II score was 14.5 ± 1.87 and 13.5 ± 1.8 in the MAS825 and placebo groups, respectively (P = 0.33). MAS825 + SoC led to 33% relative reduction in intensive care unit (ICU) admissions, ~1 day reduction in ICU stay, reduction in mean duration of oxygen support (13.5 versus 14.3 days), and earlier clearance of virus on Day 15 versus placebo + SoC group. On Day 15, compared with placebo group, patients treated with MAS825 + SoC showed a 51% decrease in CRP levels, 42% lower IL-6 levels, 19% decrease in neutrophil levels, and 16% lower interferon-γ levels, indicative of IL-1β and IL-18 pathway engagement. MAS825 + SoC did not improve APACHE II score in hospitalized patients with severe COVID-19 pneumonia; however, it inhibited relevant clinical and inflammatory pathway biomarkers and resulted in faster virus clearance versus placebo + SoC. MAS825 used in conjunction with SoC was well tolerated. None of the adverse events (AEs) or serious AEs were treatment-related.
MAS825 是一种针对白细胞介素-1β（IL-1β）和白细胞介素-18（IL-18）的双特异性单克隆抗体，通过减少炎症小体介导的炎症，可改善 COVID-19 肺炎的临床结局。将 138 例住院非机械通气 COVID-19 肺炎患者（n=138）随机（1:1）分组，在标准治疗（SoC）基础上加用 MAS825（10 mg/kg 单次静脉注射）或安慰剂。主要终点为最差情况下死亡时的第 15 天或出院日（以较早者为准）的急性生理学与慢性健康评估 II（APACHE II）评分复合终点。其他研究终点包括安全性、C 反应蛋白（CRP）、SARS-CoV-2 存在情况和炎症标志物。第 15 天，MAS825 组和安慰剂组的 APACHE II 评分分别为 14.5±1.87 和 13.5±1.8（P=0.33）。与安慰剂+SoC 相比，MAS825+SoC 可使 ICU 入院率相对降低 33%，ICU 入住时间缩短约 1 天，平均氧疗时间缩短（13.5 天 vs 14.3 天），第 15 天病毒清除率高于安慰剂+SoC 组。第 15 天，与安慰剂组相比，MAS825+SoC 组的 CRP 水平降低 51%，IL-6 水平降低 42%，中性粒细胞水平降低 19%，干扰素-γ水平降低 16%，表明 IL-1β 和 IL-18 通路被激活。MAS825+SoC 并未改善住院 COVID-19 肺炎重症患者的 APACHE II 评分；然而，与安慰剂+SoC 相比，它抑制了相关的临床和炎症通路生物标志物，导致病毒清除速度更快。MAS825 联合 SoC 治疗耐受性良好，无治疗相关不良事件（AE）或严重不良事件（SAE）。
