tocilizumab   Click here for help

GtoPdb Ligand ID: 6881

Synonyms: Actemra® | R-1569 | RG-1569 | RHPM-1 | RoActemra®
Approved drug Immunopharmacology Ligand
tocilizumab is an approved drug (Japan (2005), EMA (2009), FDA (2010))
Compound class: Antibody
Comment: Tocilizumab is an anti-IL-6 receptor mAb, with immunosuppressive action [12] that is approved for chronic autoimmune indications.
Annotated peptide sequences for this antibody are available from its IMGT/mAb-DB record.

SARS-CoV-2 and COVID-19: In early March 2020, China's National Health Commission issued guidance that allows use of tocilizumab to treat patients with serious COVID-19-induced lung damage. Tocilizumab is predicted to mitigate against the uncontrolled immune response that is triggered by SARS-CoV-2 infection [4,16] in some patients and which leads to potentially life-threatening damage to the lungs and other organs. Clinical trials are beginning to reveal outcomes (Oct 2020), but the level of benefit remains unclear [5-6,13-14] and requires further investigations. Differences between the studies (timing of treatment, severity of disease at initiation of treatment etc.) make it difficult to compare results and form a solid conclusion. In early January 2021, data was reported from a small cohort of severely ill, mechanically ventilated COVID-19 patients in the REMAP-CAP trial (NCT02735707) who received tocilizumab. The information released (data not yet peer-reviewed) suggested that tocilizumab (compared to standard care) significantly reduced mortality and that patients treated with this mAb were able to leave intensive care 7-10 days earlier than those who didn't receive the drug. This effect appears to be in addition to the clinical benefit conferred by dexamathasone. As a result of this latest report, the UK Department of Health and Social Care was set to issue updated guidance (on 8th Jan; link to gov.uk press release) which will encourage NHS trusts across the UK to immediately begin using existing stocks of tocilizumab in their treatment of critically ill COVID-19 patients in ICUs.

Biosimilars:
NameTrade nameCompanyClinical PhaseIndications
tocilizumab-bavi; BIIB800Tofidence BiogenApproved (2023)As per reference agent
QX003Sn/aQyuns Therapeutics1 [18]inflammatory/immune diseases
tocilizumab-aazg; MSB11456TyenneFresenius KabiApproved (2024)As per reference agent
LZM008n/a Livzon Mabpharm1 [3]inflammatory/immune diseases
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

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View more information in the IUPHAR Pharmacology Education Project: tocilizumab

References
1. Biran N, Ip A, Ahn J, Go RC, Wang S, Mathura S, Sinclaire BA, Bednarz U, Marafelias M, Hansen E et al.. (2020)
Tocilizumab among patients with COVID-19 in the intensive care unit: a multicentre observational study.
The Lancet, [Epub ahead of print]. DOI: 10.1016/S2665-9913(20)30277-0
2. Campochiaro C, Dagna L. (2020)
The conundrum of interleukin-6 blockade in COVID-19.
The Lancet, [Epub ahead of print]. DOI: 10.1016/S2665-9913(20)30287-3
3. Cao G, Wang J, He J, Hu Y, Yang H, Que L, Gu X, Yu J, Wu X, Wu J et al.. (2023)
LZM008, a proposed tocilizumab biosimilar: Pharmacokinetics, safety, and immunogenicity profiles compared with ACTEMRA® in Chinese healthy male subjects.
Front Pharmacol, 14: 1111893. [PMID:37081963]
4. Chen X, Zhao B, Qu Y, Chen Y, Xiong J, Feng Y, Men D, Huang Q, Liu Y, Yang B et al.. (2020)
Detectable Serum Severe Acute Respiratory Syndrome Coronavirus 2 Viral Load (RNAemia) Is Closely Correlated With Drastically Elevated Interleukin 6 Level in Critically Ill Patients With Coronavirus Disease 2019.
Clin Infect Dis, 71 (8): 1937-1942. [PMID:32301997]
5. Gupta S, Wang W, Hayek SS, Chan L, Mathews KS, Melamed ML, Brenner SK, Leonberg-Yoo A, Schenck EJ, Radbel J et al.. (2021)
Association Between Early Treatment With Tocilizumab and Mortality Among Critically Ill Patients With COVID-19.
JAMA Intern Med, 181 (1): 41-51. [PMID:33080002]
6. Hermine O, Mariette X, Tharaux PL, Resche-Rigon M, Porcher R, Ravaud P, CORIMUNO-19 Collaborative Group. (2021)
Effect of Tocilizumab vs Usual Care in Adults Hospitalized With COVID-19 and Moderate or Severe Pneumonia: A Randomized Clinical Trial.
JAMA Intern Med, 181 (1): 32-40. [PMID:33080017]
7. Maini RN, Taylor PC, Szechinski J, Pavelka K, Bröll J, Balint G, Emery P, Raemen F, Petersen J, Smolen J et al.. (2006)
Double-blind randomized controlled clinical trial of the interleukin-6 receptor antagonist, tocilizumab, in European patients with rheumatoid arthritis who had an incomplete response to methotrexate.
Arthritis Rheum, 54 (9): 2817-29. [PMID:16947782]
8. Matsuyama M, Suzuki T, Tsuboi H, Ito S, Mamura M, Goto D, Matsumoto I, Tsutsumi A, Sumida T. (2007)
Anti-interleukin-6 receptor antibody (tocilizumab) treatment of multicentric Castleman's disease.
Intern Med, 46 (11): 771-4. [PMID:17541233]
9. Mihara M, Kasutani K, Okazaki M, Nakamura A, Kawai S, Sugimoto M, Matsumoto Y, Ohsugi Y. (2005)
Tocilizumab inhibits signal transduction mediated by both mIL-6R and sIL-6R, but not by the receptors of other members of IL-6 cytokine family.
Int Immunopharmacol, 5 (12): 1731-40. [PMID:16102523]
10. Nishimoto N, Kishimoto T. (2008)
Humanized antihuman IL-6 receptor antibody, tocilizumab.
Handb Exp Pharmacol, (181): 151-60. [PMID:18071945]
11. Ohsugi Y, Kishimoto T. (2008)
The recombinant humanized anti-IL-6 receptor antibody tocilizumab, an innovative drug for the treatment of rheumatoid arthritis.
Expert Opin Biol Ther, 8 (5): 669-81. [PMID:18407769]
12. Paul-Pletzer K. (2006)
Tocilizumab: blockade of interleukin-6 signaling pathway as a therapeutic strategy for inflammatory disorders.
Drugs Today, 42 (9): 559-76. [PMID:17028666]
13. Salvarani C, Dolci G, Massari M, Merlo DF, Cavuto S, Savoldi L, Bruzzi P, Boni F, Braglia L, Turrà C et al.. (2021)
Effect of Tocilizumab vs Standard Care on Clinical Worsening in Patients Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial.
JAMA Intern Med, 181 (1): 24-31. [PMID:33080005]
14. Stone JH, Frigault MJ, Serling-Boyd NJ, Fernandes AD, Harvey L, Foulkes AS, Horick NK, Healy BC, Shah R, Bensaci AM et al.. (2020)
Efficacy of Tocilizumab in Patients Hospitalized with Covid-19.
N Engl J Med, 383 (24): 2333-2344. [PMID:33085857]
15. Unizony S, Kermani TA. (2018)
IL-6 Blockade and its Therapeutic Success in Giant Cell Arteritis.
J Neuroophthalmol, 38 (4): 551-558. [PMID:30199509]
16. Wang W, Liu X, Wu S, Chen S, Li Y, Nong L, Lie P, Huang L, Cheng L, Lin Y et al.. (2020)
Definition and Risks of Cytokine Release Syndrome in 11 Critically Ill COVID-19 Patients With Pneumonia: Analysis of Disease Characteristics.
J Infect Dis, 222 (9): 1444-1451. [PMID:32601708]
17. Yokota S, Miyamae T, Imagawa T, Katakura S, Kurosawa R, Mori M. (2005)
Clinical study of tocilizumab in children with systemic-onset juvenile idiopathic arthritis.
Clin Rev Allergy Immunol, 28 (3): 231-8. [PMID:16129907]
18. Zhang H, Li X, Liu J, Li C, Wu M, Zhu X, Sun J, Fang M, Ding Y. (2021)
A randomized phase-I pharmacokinetic trial comparing the potential biosimilar tocilizumab (QX003S) with the reference product (Actemra®) in Chinese healthy subjects.
Ann Med, 53 (1): 375-383. [PMID:33629921]