Tocilizumab

Tocilizumab, as a humanised monoclonal antibody, can target both membrane-bound and soluble forms of the IL-6 receptor.^[1] Tocilizumab has been approved for treatment in patients with rheumatologic disorders and chimeric antigen receptor T cell-induced cytokine release syndrome.^[3]

In vitro efficacy test it shown that treatment with tocilizumab (1 or 10 μm) or SOMAmer (0.83 or 8.3 μm), SOMAmer suppressed the proliferation of U87MG and HepG2 cells to a greater extent than tocilizumab at similar molar concentrations.^[7]

In vivo efficacy test it indicated that treatment with 8 mg/kg tocilizumab using two consecutive intravenous infusions 12 h apart in 100 patients with COVID-19 and ARDS requiring ventilatory support in Brescia (Italy) has 20% mortality according to an optional third infusion based on clinical response.^[1] In vivo, tocilizumab 8 mg/kg?×?1 in mechanically ventilated patients, the results shown that receipt of tocilizumab was independently associated with improved survival.^[2] In vivo study for the treatment of rheumatoid arthritis, treatment with 4?mg/kg tocilizumab, the results exhibited that the average IL-6 level reached the peak at the second week after administration, and then decreased gradually.^[4] In a 61-year-old man with COVID-19, treatment with 324 mg Tocilizumab via subcutaneous with hydroxychloroquine can successfully manage the infection.^[6] In addition, the recommended dose of Tocilizumab is 4–8 mg/kg administered as a single 60- minute intravenous infusion every 4 weeks for treatment in moderate to severe active arthritis in adults, Giant cell arthritis, Polyarticular juvenile idiopathic arthritis and cytokine release syndrome in patients 2 years of age older with active disease.^[5]

References:
[1] Lan SH, et al. Tocilizumab for severe COVID-19: a systematic review and meta-analysis. Int J Antimicrob Agents. 2020 Sep;56(3):106103.
[2]Somers EC, et al. Tocilizumab for Treatment of Mechanically Ventilated Patients With COVID-19. Clin Infect Dis. 2021 Jul 15;73(2):e445-e454.
[3]Wei Q, et al. Tocilizumab treatment for COVID-19 patients: a systematic review and meta-analysis. Infect Dis Poverty. 2021 May 18;10(1):71.
[4]Smolen J.S, et al. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial.?Lancet.?2008;371(9617):987–997.
[5]Sebba A, et al. Tocilizumab: the first interleukin -6 receptor inhibitor.?Am J Health Syst Pharm.?2008;65(15):1413–1418. ?
[6]Fontana F, et al. Covid-19 pneumonia in a kidney transplant recipient successfully treated with Tocilizumab and Hydroxychloroquine.?Am. J. Transplant. American J. Transplant.?2020;20(7).
[7]Gupta S, et al. Chemically modified DNA aptamers bind interleukin-6 with high affinity and inhibit signaling by blocking its interaction with interleukin-6 receptor. J Biol Chem. 2014 Mar 21;289(12):8706-19.

Tocilizumab 作为一种人源化单克隆抗体，可以靶向 IL-6 受体的膜结合和可溶形式。^[1] Tocilizumab 已被批准用于治疗风湿病和嵌合体疾病患者抗原受体T细胞诱导的细胞因子释放综合征。^[3]

体外功效测试表明，在相似的摩尔浓度下，用托珠单抗（1 或 10 μm）或 SOMAmer（0.83 或 8.3 μm）处理时，SOMAmer 比托珠单抗更能抑制 U87MG 和 HepG2 细胞的增殖。<sup >[7]

体内疗效测试表明，在布雷西亚（意大利）需要通气支持的 100 名 COVID-19 和 ARDS 患者中，使用间隔 12 小时连续两次静脉输注 8 mg/kg tocilizumab 的死亡率为 20%，根据可选的根据临床反应进行第三次输注。^[1] 在机械通气患者体内，tocilizumab 8 mg/kg‰×‰1，结果显示接受 tocilizumab 与改善生存独立相关。^{[ 2]} 治疗类风湿性关节炎的体内研究，4〉mg/kg tocilizumab治疗，结果显示平均IL-6水平在给药后第二周达到峰值，然后逐渐下降。< sup>[4] 在一名患有 COVID-19 的 61 岁男性中，通过皮下注射 324 mg 托珠单抗和羟氯喹可以成功控制感染。^[6] 此外，托珠单抗的推荐剂量为 4-8 mg/kg，单次给药每 4 周静脉输注 60 分钟，用于治疗成人中度至重度活动性关节炎、巨细胞性关节炎、多关节幼年特发性关节炎和 2 岁以上活动性疾病患者的细胞因子释放综合征。^[5]