Tocilizumab-Atlizumab Overview

Introduction of Tocilizumab

Tocilizumab, also known as atlizumab, is a recombinant humanized, anti-human monoclonal antibody (mAb) of the immunoglobulin G1κ subclass directed against soluble and membrane-bound interleukin-6 (IL-6) receptor (IL-6R) which plays an important role in immune response and is implicated in the pathogenesis of many diseases, such as autoimmune diseases, multiple myeloma and prostate cancer. It was developed by Hoffmann-La Roche and Chugai. It is marketed in the European Union (EU) under the trade name RoActemra and in the United States, Canada, Australia, and Japan as Actemra. Tocilizumab was first approved in 2005 as an orphan drug in Japan for the treatment of Castleman’s disease, a rare lymphoproliferative disease involving expansion of plasma cell numbers. Tocilizumab is now licensed in the EU for use alone or in combination with disease-modifying anti-rheumatic drugs (DMARDs) to treat adult patients with moderate to severely active rheumatoid arthritis (RA), children over 2 y of age with the systemic form of juvenile idiopathic arthritis (sJIA) or children over 2 y of age with the polyarticular form of juvenile idiopathic arthritis (pJIA). It has also been studied as a treatment of other conditions such as Crohn’s disease, systemic lupus erythematosus (SLE), Takayasu arteritis (TA), giant cell arteritis (GCA) polymyalgia rheumatica (PMR) and refractory adult-onset Still disease, but has not yet received licenses in these indications.

Mechanism of Action of Tocilizumab

IL-6 is a multifunctional cytokine that plays an important role in both acute and chronic inflammatory responses. Consequently, the dysregulated or persistent production of IL-6 can lead to the development of inflammatory disorders. Elevated levels of IL-6 in serum, synovial fluid, and various tissues have been correlated with disease activity in patients with rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA), Castleman’s disease, systemic sclerosis (SSc), giant cell arteritis (GCA), adult-onset Still’s disease (AOSD), familial Mediterranean fever (FMF), Schnitzler’s syndrome, polychondritis, and amyloidosis. Tocilizumab targets the IL-6 receptor subunit alpha (IL-6Rα), and its mechanism of action has been described in detail in previous reviews. Briefly, Tocilizumab targets both membrane-bound and soluble IL-6Rα, which prevents the binding of IL-6 to both the IL-6R and the signal transducer glycoprotein 130 complex and results in turn in inhibition of the downstream classic signaling and trans-signaling cascades involving the Janus-activated kinase-signal transducer and activator of transcription (JAK-STAT) pathway. Through this mechanism, Tocilizumab decreases the circulating levels of neutrophils, neutrophil infiltration into inflamed joints, circulation of myeloid dendritic cells, monocyte levels, serum macrophage migration inhibitory factor levels, and levels of T helper 17 (Th17) cells, while increasing regulatory T cells. Tocilizumab also induces regulatory B-cell expansion, decreases B-cell hyperactivity, and decreases the number of peripheral memory B cells.

Fig.1 Mechanism of action of tocilizumab

Clinical Projects of Tocilizumab*

Approved Drugs of Tocilizumab**

INN (trade name)	Therapeutic area	Dose	Strength	Route	Company	Marketing start	Market
Actemra	Rheumatoid Arthritis	Concentrate for solution	20 mg/mL	Intravenous infusion	Genentech	January 08, 2010
Actemra	Systemic Juvenile Idiopathic Arthritis (SJIA)	Concentrate for solution	20 mg/mL	Intravenous infusion	Genentech	April 15, 2011
Actemra	Polyarticular Juvenile Idiopathic Arthritis (PJIA)	Concentrate for solution	20 mg/mL	Intravenous infusion	Genentech	April 29, 2013
Actemra	Giant Cell Arteritis (GCA)	Concentrate for solution	20 mg/mL	Intravenous infusion	Genentech	May 22, 2017
Actemra	Cytokine Release Syndrome (CRS)	Concentrate for solution	20 mg/mL	Intravenous infusion	Genentech	August 30, 2017
Actemra	Rheumatoid Arthritis, Systemic Juvenile Idiopathic Arthritis (SJIA), Polyarticular Juvenile Idiopathic Arthritis (PJIA)	Solution for injection	162 mg/ 0.9 mL	Subcutaneous	Genentech	September 23, 2016
Actemra	Giant Cell Arteritis (GCA)	Solution for injection	162 mg/ 0.9 mL	Subcutaneous	Genentech	May 22, 2017
Actemra	Cytokine Release Syndrome (CRS	Solution for injection	162 mg/ 0.9 mL	Subcutaneous	Genentech	March 22, 2018
RoActemra	Arthritis, Rheumatoid; Arthritis, Juvenile Rheumatoid	Concentrate for solution	20 mg/mL	Intravenous infusion	Roche Registration GmbH	January 16, 2009
Actemra	Rheumatoid Arthritis, Systemic Juvenile Idiopathic Arthritis (SJIA), Polyarticular Juvenile Idiopathic Arthritis (PJIA)	Concentrate for solution	20 mg/mL	Intravenous infusion	Hoffmann-La Roche Limited	May 26, 2010
Actemra	Rheumatoid Arthritis, Giant Cell Arteritis (GCA)	Solution for injection	162 mg/ 0.9 mL	Subcutaneous	Hoffmann-La Roche Limited	May 30, 2014
Actemra	Rheumatoid Arthritis	Concentrate for solution	20 mg/mL	Intravenous infusion	Roche Products Pty Ltd	May 21, 2009
Actemra	Rheumatoid Arthritis	Concentrate for solution	20 mg/mL	Intravenous infusion	Chugai Pharmaceutical Co., Ltd.	April 16, 2008
Actemra	Rheumatoid Arthritis	Solution for injection	162 mg/ 0.9 mL	Subcutaneous	Roche Products Pty Ltd	January 21, 2016
Actemra	Rheumatoid Arthritis	Solution for injection	162 mg/ 0.9 mL	Subcutaneous	Chugai Pharmaceutical Co., Ltd.	April 16, 2008

What We Provide

Therapeutic Antibody

Tocilizumab/Atlizumab

We provide high-quality Tocilizumab/Atlizumab for use in WB, FC, IP, ELISA, Neut, FuncS, IF and most other immunological methods. For lab research use only, not for diagnostic, therapeutic or any in vivo human use.

* The table was excerpted from the following website
https://clinicaltrials.gov/ct2/results?cond=&term=Tocilizumab

** Information presented in the table were collected from the following websites:
https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=125472
https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=125276
http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000955/human_med_001042.jsp
https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=83535
https://health-products.canada.ca/dpd-bdpp/info.do?lang=en&code=90943
http://www.pmda.go.jp/PmdaSearch/iyakuDetail/GeneralList/6399421A1
http://www.pmda.go.jp/PmdaSearch/iyakuDetail/GeneralList/6399421G1
http://search.tga.gov.au/s/search.html?collection=tga-artg&profile=record&meta_i=149404
http://search.tga.gov.au/s/search.html?collection=tga-artg&profile=record&meta_i=234034

For research use only. Not intended for any clinical use.