Tocilizumab
IL-6 receptor | |
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Clinical data | |
Trade names | Actemra, RoActemra |
Biosimilars | tocilizumab-aazg,[1] tocilizumab-bavi,[2][3] Tofidence,[2][3][4] Tyenne[1][5] |
AHFS/Drugs.com | Monograph |
MedlinePlus | a611004 |
License data |
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Pregnancy category |
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subcutaneous | |
ATC code | |
Legal status | |
Legal status | |
steady state (dependent on concentration) | |
Identifiers | |
CAS Number | |
DrugBank | |
ChemSpider |
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UNII | |
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Chemical and physical data | |
Formula | C6428H9976N1720O2018S42 |
Molar mass | 144987.06 g·mol−1 |
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Tocilizumab, sold under the brand name Actemra among others, is an
Tocilizumab was approved for medical use in the European Union in January 2009,[11] and in the United States in January 2010.[14][15]
Medical uses
In the United States, tocilizumab is
In the European Union, tocilizumab is indicated for the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, juvenile idiopathic polyarthritis, giant cell arteritis, cytokine release syndrome, and COVID‑19.
Rheumatoid arthritis
Tocilizumab is used for the treatment of moderate to severe rheumatoid arthritis, applied in combination with
Systemic juvenile idiopathic arthritis
The treatment of
Castleman's disease
In Japan, tocilizumab is also approved for the treatment of
.Giant cell arteritis
In May 2017, the FDA approved tocilizumab for giant cell (temporal) arteritis.[22]
Cytokine release syndrome
On 30 August 2017, the FDA approved tocilizumab for
COVID-19
In June 2021, the U.S.
Adverse effects
The most common adverse effects observed in clinical trials were
Interactions
There are no certain interactions with other drugs. The blood plasma levels of simvastatin were reduced by 57% after a single dose of tocilizumab, but it is not known whether this is clinically relevant. A possible mechanism is that the elevated IL-6 levels of patients with rheumatoid arthritis suppress the biosynthesis of various cytochrome P450 enzymes, notably CYP1A2, CYP2C9, CYP2C19 and CYP3A4. Tocilizumab lowers IL-6 and thus normalises cytochrome levels, increasing the metabolization of simvastatin (and possibly other cytochrome metabolised drugs).[29]
Mechanism of action
Besides other functions, interleukin 6 (IL-6) is involved in the development of immunological and inflammatory reactions. Some autoimmune diseases like rheumatoid arthritis are associated with abnormally high IL-6 levels. Tocilizumab binds soluble as well as membrane bound interleukin-6 receptors, hindering IL-6 from exerting its pro-inflammatory effects.[29][30] It has been noted that the membrane bound form and soluble form of the IL-6 receptor may have different effects in the pathogenesis of rheumatoid arthritis with the soluble form being more implicated in disease progression.[31]
History
Interleukin 6 and its receptor were discovered and cloned at
Data presented in 2008 showed the effectiveness of tocilizumab in combination therapy with methotrexate for rheumatoid arthritis treatment.[33] In further studies, it was effective and generally well tolerated when administered either as monotherapy or in combination with conventional DMARDs in adult patients with moderate to severe rheumatoid arthritis.[34]
In June 2005, tocilizumab was approved in Japan for Castleman's disease.
Tocilizumab is marketed by Chugai in some countries, especially in Japan and other Asian countries, and jointly by Chugai and Roche (Hoffmann–La Roche's holding company) in others, for example Great Britain, France and Germany.[32]
Society and culture
Legal status
Tocilizumab was approved for medical use in the European Union in January 2009,[11] and in the United States in January 2010.[14][15]
The biosimilar Tyenne was approved for medical use in the European Union in September 2023,[5][41] and in the United States in March 2024.[42][43]
In April 2024, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Tofidence, intended for the treatment of rheumatoid arthritis (RA), systemic juvenile idiopathic arthritis (sJIA), polyarticular juvenile idiopathic arthritis (pJIA) and coronavirus disease 2019 (COVID-19).[44] The applicant for this medicinal product is Biogen Netherlands B.V.[44] Tofidence is a biosimilar medicinal product.[44]
COVID-19
Tocilizumab was approved for the treatment of COVID‑19 in the European Union in December 2021,[11] and in the United States in December 2022.[27]
In September 2021, Indian pharmaceutical firm Hetero obtained emergency use approval from the country's health authority, Drugs Controller General of India (DCGI), to produce a generic version of tocilizumab to treat COVID‑19 in adults.[45]
In December 2021, tocilizumab was granted a provisional approval by the Australian regulator, Therapeutic Goods Administration, for treatment of adults.[46]
Tocilizumab was granted an
Research
Tocilizumab is being studied for
COVID-19
There is good evidence tocilizumab can help reduce the need for mechanical ventilation for people in hospital with COVID‑19, and some evidence it can help prevent secondary infections.[51]
A 2021 meta-analysis of randomized controlled trials found that, while tocilizumab does not show significant benefits on survival, it could play a role in preventing progression to intensive care and mechanical ventilation.[52][unreliable source?][53]
Neuromyelitis optica
Early case reports suggest tocilizumab might be effective in otherwise refractory
Graves' ophthalmopathy
Two small studies found tocilizumab to be beneficial in endocrine ophthalmopathy (Graves' orbitopathy) that is refractory to corticosteroid treatment.[58][59]
References
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- ^ a b c "Tofidence (tocilizumab-bavi) injection, for intravenous use" (PDF). Archived (PDF) from the original on 1 October 2023. Retrieved 1 October 2023.
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- ^ "FDA Approves Biogen's Tofidence (tocilizumab-bavi), a Biosimilar Referencing Actemra" (Press release). Biogen Inc. 29 September 2023. Archived from the original on 30 September 2023. Retrieved 1 October 2023 – via GlobeNewswire.
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- ^ Hoffmann–La Roche. 21 January 2009. Archived from the originalon 28 February 2009. Retrieved 5 January 2009.
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- ^ Fleischmann R, Burgos-Vargas R, Ambs P, Alecock E, Kremer J (October 2009). "LITHE: tocilizumab inhibits radiographic progression and improves physical function in rheumatoid arthritis (RA) patients (Pts) at 2 yrs with increasing clinical efficacy over time". Arthritis Rheum. 60 (10). ACR: S238-9. Archived from the original on 9 August 2020. Retrieved 1 August 2020.
- ^ De Benedetti F, Brunner H, Ruperto N, Calvo N, Cuttica I, Malattia R, et al. (2010). "Tocilizumab in Patients With Systemic Juvenile Idiopathic Arthritis: Efficacy Data From the Placebo-Controlled 12-Week Part of the Phase 3 TENDER Trial" (PDF). Arthritis & Rheumatism. 62 (Supplement 10): 1434. Archived (PDF) from the original on 31 December 2019. Retrieved 1 August 2020.
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- ^ "FDA approves tisagenlecleucel for B-cell ALL and tocilizumab for cytokine release syndrome". U.S. Food and Drug Administration (FDA). 30 August 2017. Archived from the original on 29 August 2021. Retrieved 5 September 2017.
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{{cite web}}
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- ^ a b c "Tofidence EPAR". European Medicines Agency. 25 April 2024. Retrieved 27 April 2024. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
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External links
- Clinical trial number NCT00109408 for "A Study to Assess the Safety and Efficacy of Tocilizumab in Patients With Active Rheumatoid Arthritis" at ClinicalTrials.gov
- Clinical trial number NCT00106535 for "A Study to Assess the Effect of Tocilizumab + Methotrexate on Prevention of Structural Joint Damage in Patients With Moderate to Severe Active Rheumatoid Arthritis (RA)" at ClinicalTrials.gov
- Clinical trial number NCT00106548 for "A Study to Assess the Effect of Tocilizumab + Methotrexate on Signs and Symptoms in Patients With Moderate to Severe Active Rheumatoid Arthritis" at ClinicalTrials.gov
- Clinical trial number NCT00106574 for "A Study to Assess the Effect of Tocilizumab + DMARD Therapy on Signs and Symptoms in Patients With Moderate to Severe Active Rheumatoid Arthritis" at ClinicalTrials.gov
- Clinical trial number NCT00106522 for "A Study to Assess the Effect of Tocilizumab + Methotrexate on Signs and Symptoms in Patients With Moderate to Severe Active Rheumatoid Arthritis Currently on Methotrexate Therapy" at ClinicalTrials.gov
- Clinical trial number NCT01331837 for "A Study of Tocilizumab in Comparison to Etanercept in Participants With Rheumatoid Arthritis and Cardiovascular Disease Risk Factors" at ClinicalTrials.gov
- Clinical trial number NCT00988221 for "A Study of Tocilizumab in Patients With Active Polyarticular Juvenile Idiopathic Arthritis" at ClinicalTrials.gov
- Clinical trial number NCT00642460 for "A Study of RoActemra/Actemra (Tocilizumab) in Patients With Active Systemic Juvenile Idiopathic Arthritis (JIA)" at ClinicalTrials.gov