Janssen Pharmaceutica NV, Beerse, Belgium.
Janssen Research & Development, LLC, PA, Spring House, USA.
Sci Rep. 2024 Oct 3;14(1):22981. doi: 10.1038/s41598-024-74196-9.
We examined candidate biomarkers for efficacy outcomes in hospitalized COVID-19 patients who were treated with sirukumab, an IL-6 neutralizing antibody, in a randomized, double-blind, placebo-controlled, phase 2 trial. Between May 2020 and March 2021, 209 patients were randomized (sirukumab, n = 139; placebo, n = 70); 112 had critical COVID-19. Serum biomarkers were evaluated for the pharmacodynamic effect of sirukumab and for their potential prognostic and predictive effect on time to sustained clinical improvement up to Day 28, clinical improvement at Day 28, and mortality at Day 28. The absence of detectable IL-4 increase and smaller increases in CCL13 post-baseline were most significantly associated with better response to sirukumab (versus placebo) treatment for all clinical efficacy outcomes tested, especially in patients with critical COVID-19. These data suggest that patients with critical COVID-19 without detectable sirukumab-induced IL-4 levels are more likely to benefit from sirukumab treatment. ClinicalTrials.gov Identifier: NCT04380961.
我们在一项随机、双盲、安慰剂对照的 2 期临床试验中，研究了在住院的 COVID-19 患者中，使用 IL-6 中和抗体 sirukumab 治疗的疗效结局的候选生物标志物。在 2020 年 5 月至 2021 年 3 月期间，共随机分配了 209 名患者（sirukumab，n=139；安慰剂，n=70）；其中 112 名患者患有重症 COVID-19。评估了血清生物标志物对 sirukumab 的药效学作用，以及对持续临床改善至第 28 天、第 28 天临床改善和第 28 天死亡率的潜在预后和预测作用。与安慰剂相比，未检测到 IL-4 增加和基线后 CCL13 增加较小，与所有临床疗效结局的 sirukumab（与安慰剂）治疗反应最显著相关，尤其是在患有重症 COVID-19 的患者中。这些数据表明，在没有检测到 sirukumab 诱导的 IL-4 水平的重症 COVID-19 患者中，更有可能从 sirukumab 治疗中获益。ClinicalTrials.gov 标识符：NCT04380961。
