TocilizuMab

TocilizuMab (trade name: Actemra) is an antirheumatoid arthritis drug developed by Genentech, Inc.  It was first approved by the FDA on January 8, 2010, for the treatment of moderate to severe active rheumatoid arthritis.  On June 24, 2021, Actemra received Emergency Use Authorization from the FDA for the treatment of hospitalized adults and children with COVID-19, but not for outpatients with COVID-19.  At this time, it had not yet received formal approval.  By December 21, 2022, the FDA approved Actemra for the treatment of hospitalized adults with COVID-19.

Tocilizumab (Anti-Human IL6R, Humanized Antibody) is an anti-human interleukin-6 receptor (IL-6R) neutralizing antibody, prevents binding of IL-6 to the IL-6R, thereby inhibiting both classic and trans-signaling. Tocilizumab (Anti-Human IL6R, Humanized Antibody) can be used for the treatment of rheumatoid arthritis[1]. Tocilizumab is remarkablely effective for the study of severe COVID-19 (coronavirus disease)[4].

Interleukin inhibitor:
Treatment of rheumatoid arthritis in combination with methotrexate

Potentially hazardous interactions with other drugs
Live vaccines: avoid concomitant administration

IL-6

Tocilizumab undergoes biphasic elimination from the circulation. The total clearance of tocilizumab is concentration-dependent and is the sum of the linear and non-linear clearance. The concentration-dependent non-linear clearance plays a major role at low tocilizumab concentrations. Once the non-linear clearance pathway is saturated, at higher tocilizumab concentrations, clearance is mainly determined by the linear clearance.

[1] Garbers C, et al. Inhibition of classic signaling is a novel function of soluble glycoprotein 130 (sgp130), which is controlled by the ratio of interleukin 6 and soluble interleukin 6 receptor. J Biol Chem. 2011 Dec 16;286(50):42959-70. DOI:10.1074/jbc.M111.295758
[2] Mami Noda, et al. IL-6 Receptor Is a Possible Target against Growth of Metastasized Lung Tumor Cells in the Brain. Int J Mol Sci. 2013 Jan; 14(1): 515–526. DOI:10.3390/ijms14010515
[3] Shinriki S, et al. Humanized anti-interleukin-6 receptor antibody suppresses tumor angiogenesis and in vivogrowth of human oral squamous cell carcinoma. Clin Cancer Res. 2009 Sep 1;15(17):5426-34. DOI:10.1158/1078-0432.CCR-09-0287
[4] Chi Zhang, et al. Cytokine Release Syndrome in Severe COVID-19: Interleukin-6 Receptor Antagonist Tocilizumab May Be the Key to Reduce Mortality. Int J Antimicrob Agents. 2020 May;55(5):105954. DOI:10.1016/j.ijantimicag.2020.105954