Wikipedia:WikiProject Chemicals/Chembox validation/VerifiedDataSandbox and Tocilizumab: Difference between pages

{{Short description|Immunosuppressive drug}}

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| DailyMedID = Tocilizumab

| pregnancy_AU = C

| pregnancy_AU_comment = <ref name="Actemra PI" />

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| routes_of_administration = [[Intravenous infusion|Intravenous]], [[subcutaneous injection|subcutaneous]]

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| ATC_prefix = L04

| ATC_suffix = AC07

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| biosimilars = tocilizumab-aazg,<ref name="Tyenne FDA label" /> tocilizumab-bavi,<ref name="Tofidence FDA label">{{cite web |url=https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761354s000lbl.pdf |title=Tofidence (tocilizumab-bavi) injection, for intravenous use |access-date=1 October 2023 |archive-date=1 October 2023 |archive-url=https://web.archive.org/web/20231001233924/https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761354s000lbl.pdf |url-status=live }}</ref><ref name="FDA Tofidence PF">{{cite press release | title=FDA approves first biosimilar to Actemra to treat adult and pediatric arthritis | website=U.S. [[Food and Drug Administration]] (FDA) | date=29 September 2023 | url=https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-biosimilar-actemra-treat-adult-and-pediatric-arthritis | access-date=6 March 2024 | archive-date=25 February 2024 | archive-url=https://web.archive.org/web/20240225013429/https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-biosimilar-actemra-treat-adult-and-pediatric-arthritis | url-status=live }}</ref> Tofidence,<ref name="Tofidence FDA label" /><ref name="FDA Tofidence PF" /><ref>{{cite press release | title=FDA Approves Biogen's Tofidence (tocilizumab-bavi), a Biosimilar Referencing Actemra | publisher=Biogen Inc. | via=GlobeNewswire | date=29 September 2023 | url=https://www.globenewswire.com/news-release/2023/09/29/2752273/0/en/FDA-Approves-Biogen-s-TOFIDENCE-tocilizumab-bavi-a-Biosimilar-Referencing-ACTEMRA.html | access-date=1 October 2023 | archive-date=30 September 2023 | archive-url=https://web.archive.org/web/20230930035103/https://www.globenewswire.com/news-release/2023/09/29/2752273/0/en/FDA-Approves-Biogen-s-TOFIDENCE-tocilizumab-bavi-a-Biosimilar-Referencing-ACTEMRA.html | url-status=live }}</ref> Tyenne<ref name="Tyenne FDA label" /><ref name="Tyenne EPAR" />

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| legal_AU = S4

| legal_AU_comment = <ref name="Actemra PI">{{cite web |date=2 September 2022 |title=Australian Product Information Actemra (tocilizumab) |url=https://rss.medsinfo.com.au/ro/pi.cfm?product=ropactem11014 |format=PDF |access-date=19 April 2023 |website=MedAdvisor International |archive-date=1 October 2023 |archive-url=https://web.archive.org/web/20231001234004/https://rss.medsinfo.com.au/ro/pi.cfm?product=ropactem11014 |url-status=live }}</ref><ref>{{cite web | title=Prescription medicines and biologicals: TGA annual summary 2017 | website=Therapeutic Goods Administration (TGA) | date=21 June 2022 | url=https://www.tga.gov.au/resources/publication/publications/prescription-medicines-and-biologicals-tga-annual-summary-2017 | access-date=31 March 2024 | archive-date=31 March 2024 | archive-url=https://web.archive.org/web/20240331021323/https://www.tga.gov.au/resources/publication/publications/prescription-medicines-and-biologicals-tga-annual-summary-2017 | url-status=live }}</ref>

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| legal_CA = Rx-only

| legal_CA_comment = <ref>{{cite web | title=Actemra | website=COVID-19 vaccines and treatments portal | date=13 October 2022 | url=https://covid-vaccine.canada.ca/actemra/product-details | access-date=29 October 2022 | archive-date=5 December 2022 | archive-url=https://web.archive.org/web/20221205002007/https://covid-vaccine.canada.ca/actemra/product-details | url-status=live }}</ref>

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| legal_US = Rx-only

| legal_US_comment = <ref name="Actemra FDA label">{{cite web | title=Actemra- tocilizumab injection, solution, concentrate Actemra- tocilizumab injection, solution Actemra ACTPen- tocilizumab injection, solution | website=DailyMed | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2e5365ff-cb2a-4b16-b2c7-e35c6bf2de13 | access-date=24 June 2021 | archive-date=7 June 2021 | archive-url=https://web.archive.org/web/20210607171603/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=2e5365ff-cb2a-4b16-b2c7-e35c6bf2de13 | url-status=live }}</ref><ref name="Tofidence FDA label" /><ref name="Tyenne FDA label">{{cite web | title=Tyenne- tocilizumab-aazg injection, solution, concentrate | website=DailyMed | date=6 March 2024 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e400bbe6-43c5-4de6-82b9-cb44ce3cd906 | access-date=25 April 2024 | archive-date=25 April 2024 | archive-url=https://web.archive.org/web/20240425055902/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e400bbe6-43c5-4de6-82b9-cb44ce3cd906 | url-status=live }}</ref>

| legal_EU = Rx-only

| legal_EU_comment = <ref name="RoActemra EPAR"/><ref>{{cite web | title=Tyenne Product information | website=Union Register of medicinal products | date=18 September 2023 | url=https://ec.europa.eu/health/documents/community-register/html/h1754.htm | access-date=1 October 2023 | archive-date=1 October 2023 | archive-url=https://web.archive.org/web/20231001231152/https://ec.europa.eu/health/documents/community-register/html/h1754.htm | url-status=live }}</ref><ref name="Tyenne EPAR">{{cite web | title=Tyenne EPAR | website=European Medicines Agency | date=2 October 2023 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/tyenne | access-date=5 October 2023 | archive-date=5 October 2023 | archive-url=https://web.archive.org/web/20231005035054/https://www.ema.europa.eu/en/medicines/human/EPAR/tyenne | url-status=live }}</ref>

| legal_UN = <!-- N I, II, III, IV / P I, II, III, IV -->

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| CAS_number_Ref = {{cascite|changed|??}}

| CAS_number = 375823-41-9

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| DrugBank = DB06273

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| ChEMBL = 1237022

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<!-- Chemical data -->

| C=6428 | H=9976 | N=1720 | O=2018 | S=42

'''Tocilizumab''', sold under the brand name '''Actemra''' among others, is an [[immunosuppressive drug]], used for the treatment of [[rheumatoid arthritis]], [[systemic juvenile idiopathic arthritis]], a severe form of arthritis in children, and [[COVID-19|COVID{{nbhyph}}19]]. It is a [[humanized monoclonal antibody]] against the [[interleukin-6 receptor]] (IL-6R). [[Interleukin 6]] (IL-6) is a [[cytokine]] that 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]]. Tocilizumab was jointly developed by [[Osaka University]] and [[Chugai]], and was licensed in 2003 by [[Hoffmann-La Roche]].<ref name="2003KPJ">{{cite web|url=http://www.krankenpflege-journal.com/rheuma/768-die-entwicklung-von-tocilizumab-medizinischer-fortschritt-auf-basis-einer-erfolgreichen-kooperation-von-chugai-und-roche.html|language=de|title=Die Entwicklung von Tocilizumab|trans-title=The development of tocilizumab|author=Markus Harwart|year=2008|publisher=Krankenpflege-Journal|access-date=30 April 2016|archive-date=15 October 2018|archive-url=https://web.archive.org/web/20181015051035/http://www.krankenpflege-journal.com/rheuma/768-die-entwicklung-von-tocilizumab-medizinischer-fortschritt-auf-basis-einer-erfolgreichen-kooperation-von-chugai-und-roche.html|url-status=dead}}</ref>

Tocilizumab was approved for medical use in the European Union in January 2009,<ref name="RoActemra EPAR">{{cite web | title=RoActemra EPAR | website=European Medicines Agency | date=17 September 2018 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/roactemra | access-date=18 December 2021 | archive-date=18 December 2021 | archive-url=https://web.archive.org/web/20211218083546/https://www.ema.europa.eu/en/medicines/human/EPAR/roactemra | url-status=live }}</ref> and in the United States in January 2010.<ref name="Drug Approval Package: Actemra">{{cite web | title=Drug Approval Package: Actemra (Tocilizumab) Injection BLA 125276 | website=U.S. [[Food and Drug Administration]] (FDA) | date=9 March 2010 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/125276s000TOC.cfm | access-date=1 October 2023 | archive-date=26 January 2022 | archive-url=https://web.archive.org/web/20220126235316/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/125276s000TOC.cfm | url-status=live }}</ref><ref name="Drug Approval Package: Actemra 2">{{cite web | title=Drug Approval Package: Actemra (tocilizumab) Solution for Subcutaneous Injection NDA #125472 | website=accessdata.fda.gov | date=17 July 2014 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/125472Orig1s000TOC.cfm | access-date=1 October 2023 | archive-date=23 January 2023 | archive-url=https://web.archive.org/web/20230123142619/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/125472Orig1s000TOC.cfm | url-status=live }}</ref>

==Medical uses==

In the United States, tocilizumab is [[indicated]] for the treatment of rheumatoid arthritis, giant cell arteritis, systemic sclerosis-associated interstitial lung disease, polyarticular juvenile idiopathic arthritis, systemic juvenile idiopathic arthritis, cytokine release syndrome, and COVID{{nbhyph}}19.<ref name="Actemra FDA label" />

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{{nbhyph}}19.

===Rheumatoid arthritis===

Tocilizumab is used for the treatment of moderate to severe rheumatoid arthritis, applied in combination with [[methotrexate]], if other drugs like [[disease-modifying antirheumatic drug]]s (DMARDs) and [[TNF alpha blocker]]s have proven to be ineffective or were not tolerated. It can be used as a monotherapy for patients who do not tolerate methotrexate.<ref name="R090105">{{cite press release | title = RoActemra approved in Europe to treat patients suffering from Rheumatoid Arthritis | publisher = [[Hoffmann–La Roche]] | date = 21 January 2009 | url = http://www.roche.com/media/media_releases/med-cor-2009-01-21.htm | access-date = 5 January 2009 | url-status = dead | archive-url = https://web.archive.org/web/20090228170605/http://www.roche.com/media/media_releases/med-cor-2009-01-21.htm | archive-date = 28 February 2009 }}</ref><ref name="RoActemra">{{cite web|url=http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Assessment_Report_-_Variation/human/000955/WC500111086.pdf|title=Assessment report for RoActemra|publisher=European Medicines Agency|access-date=6 October 2011|archive-date=19 January 2016|archive-url=https://web.archive.org/web/20160119063056/http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Assessment_Report_-_Variation/human/000955/WC500111086.pdf|url-status=live}}</ref> The drug slows down the progression of the disease and can improve physical function of patients.<ref>{{cite journal | vauthors = Fleischmann R, Burgos-Vargas R, Ambs P, Alecock E, Kremer J | title = LITHE: tocilizumab inhibits radiographic progression and improves physical function in rheumatoid arthritis (RA) patients (Pts) at 2 yrs with increasing clinical efficacy over time. | journal = Arthritis Rheum. | date = October 2009 | volume = 60 | issue = 10 | pages = S238-9 |publisher=ACR |url=https://acr.confex.com/acr/2009/webprogram/Paper15221.html |access-date=1 August 2020|archive-date=9 August 2020 |archive-url= https://web.archive.org/web/20200809125820/https://acr.confex.com/acr/2009/webprogram/Paper15221.html|url-status=live}}</ref>

===Systemic juvenile idiopathic arthritis===

The treatment of [[systemic juvenile idiopathic arthritis]] (SJIA) is similar to rheumatoid arthritis treatment: tocilizumab is combined with methotrexate unless the latter is not tolerated. General safety and effectiveness is established for children of two years and older.<ref>{{cite journal|url=https://acrabstracts.org/wp-content/uploads/2018/06/2010_ACR_ARHP_Abstract_Supplement.pdf#page=604&zoom=auto,-67,314|title=Tocilizumab in Patients With Systemic Juvenile Idiopathic Arthritis: Efficacy Data From the Placebo-Controlled 12-Week Part of the Phase 3 TENDER Trial|journal=Arthritis & Rheumatism|year=2010|volume=62|issue=Supplement 10|page=1434| vauthors = De Benedetti F, Brunner H, Ruperto N, Calvo N, Cuttica I, Malattia R, Schneider R |access-date=1 August 2020|archive-date=31 December 2019|archive-url=https://web.archive.org/web/20191231153652/https://acrabstracts.org/wp-content/uploads/2018/06/2010_ACR_ARHP_Abstract_Supplement.pdf#page=604&zoom=auto,-67,314|url-status=live}}</ref> In 2011, the US [[Food and Drug Administration]] (FDA) approved tocilizumab for the treatment of active systemic juvenile idiopathic arthritis.<ref name="Genentech_actemra_2011">{{cite press release |url=http://www.gene.com/media/press-releases/13347/2011-04-15/fda-approves-actemra-tocilizumab-for-the |archive-url=https://web.archive.org/web/20181001232821/http://www.gene.com/media/press-releases/13347/2011-04-15/fda-approves-actemra-tocilizumab-for-the |archive-date=1 October 2018 |date=15 April 2011 |access-date=20 July 2015 |title=FDA Approves Actemra (tocilizumab) for the Treatment of Systemic Juvenile Idiopathic Arthritis (SJIA) |publisher=Genentech}}</ref>

===Castleman's disease===

In Japan, tocilizumab is also approved for the treatment of [[Castleman's disease]],<ref name ="R090105"/><ref name="pmid17541233">{{cite journal | vauthors = Matsuyama M, Suzuki T, Tsuboi H, Ito S, Mamura M, Goto D, Matsumoto I, Tsutsumi A, Sumida T | title = Anti-interleukin-6 receptor antibody (tocilizumab) treatment of multicentric Castleman's disease | journal = Internal Medicine | volume = 46 | issue = 11 | pages = 771–774 | year = 2007 | pmid = 17541233 | doi = 10.2169/internalmedicine.46.6262 | title-link = doi | doi-access = free }}</ref> a rare [[benign tumor]] of [[B cell]]s.

===Giant cell arteritis ===

In May 2017, the FDA approved tocilizumab for [[Giant cell arteritis|giant cell (temporal) arteritis]].<ref>{{cite web|url=https://www.drugs.com/newdrugs/fda-approves-actemra-tocilizumab-subcutaneous-giant-cell-arteritis-4535.html|title=FDA Approves Actemra (tocilizumab) Subcutaneous Injection for Giant Cell Arteritis|website=Drugs.com|access-date=25 May 2017|archive-date=9 August 2020|archive-url=https://web.archive.org/web/20200809205055/https://www.drugs.com/newdrugs/fda-approves-actemra-tocilizumab-subcutaneous-giant-cell-arteritis-4535.html|url-status=live}}</ref>

===Cytokine release syndrome===

On 30 August 2017, the FDA approved tocilizumab for [[cytokine release syndrome]], a side effect of [[Chimeric antigen receptor|CAR-T cell]] therapies.<ref>{{cite web|url=https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm574154.htm|title=FDA approves tisagenlecleucel for B-cell ALL and tocilizumab for cytokine release syndrome|date=30 August 2017|publisher=U.S. [[Food and Drug Administration]] (FDA)|access-date=5 September 2017|archive-date=29 August 2021|archive-url=https://web.archive.org/web/20210829090235/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tisagenlecleucel-b-cell-all-and-tocilizumab-cytokine-release-syndrome|url-status=live}}</ref>

=== COVID-19 ===

In June 2021, the U.S. [[Food and Drug Administration]] (FDA) issued an [[emergency use authorization]] (EUA) for tocilizumab for the treatment of COVID{{nbhyph}}19 in hospitalized people aged two years of age and older who are receiving systemic corticosteroids and require supplemental oxygen, non-invasive or invasive mechanical ventilation, or [[extracorporeal membrane oxygenation]] (ECMO).<ref name="FDA COVID PR" /><ref name="FDA EUA" /><ref name="FDA EUA FAQ" /> The FDA approved tocilizumab for those indications in December 2022.<ref name="Genentech PR">{{cite press release | title=FDA Approves Genentech's Actemra for the Treatment of COVID-19 in Hospitalized Adults | publisher=Genentech | via=Business Wire | date=21 December 2022 | url=https://www.businesswire.com/news/home/20221221005002/en/FDA-Approves-Genentech%E2%80%99s-Actemra-for-the-Treatment-of-COVID-19-in-Hospitalized-Adults | access-date=23 December 2022 | archive-date=23 December 2022 | archive-url=https://web.archive.org/web/20221223073244/https://www.businesswire.com/news/home/20221221005002/en/FDA-Approves-Genentech%E2%80%99s-Actemra-for-the-Treatment-of-COVID-19-in-Hospitalized-Adults | url-status=live }}</ref>

==Adverse effects==

The most common adverse effects observed in clinical trials were [[upper respiratory tract infection]]s (more than 10% of patients), [[nasopharyngitis]] (common cold), headache, and high blood pressure (at least 5%). The enzyme [[alanine transaminase]] was also elevated in at least 5% of patients, but in most cases without symptoms. Elevated total cholesterol levels were common.<ref>{{cite journal | vauthors = Genovese MC, McKay JD, Nasonov EL, Mysler EF, da Silva NA, Alecock E, Woodworth T, Gomez-Reino JJ | title = Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic drugs: the tocilizumab in combination with traditional disease-modifying antirheumatic drug therapy study | journal = Arthritis and Rheumatism | volume = 58 | issue = 10 | pages = 2968–2980 | date = October 2008 | pmid = 18821691 | doi = 10.1002/art.23940 | title-link = doi | doi-access = free }}</ref> Among the less common side effects were dizziness, various infections, as well as reactions of the skin and [[mucosae]] like mild rashes, [[gastritis]] and [[mouth ulcer]]. Rare but severe reactions were [[gastrointestinal perforation]]s (0.26% in six months) and [[anaphylaxis]] (0.2%).<ref name="Arzneistoff-Profile">{{cite book|title=Arzneistoff-Profile|editor=Dinnendahl, V |editor2=Fricke, U|publisher=Govi Pharmazeutischer Verlag|location=Eschborn, Germany|year=2010|edition=23|volume=4|isbn=978-3-7741-9846-3|language=de}}</ref>

== 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).<ref name="Arzneistoff-Profile" />

==Mechanism of action==

Besides other functions, [[interleukin 6]] (IL-6) is involved in the development of immunological and inflammatory reactions. Some [[autoimmune disease]]s 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.<ref name="Arzneistoff-Profile" /><ref>{{cite journal | vauthors = Jones G, Sebba A, Gu J, Lowenstein MB, Calvo A, Gomez-Reino JJ, Siri DA, Tomsic M, Alecock E, Woodworth T, Genovese MC | title = Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study | journal = Annals of the Rheumatic Diseases | volume = 69 | issue = 1 | pages = 88–96 | date = January 2010 | pmid = 19297346 | pmc = 3747519 | doi = 10.1136/ard.2008.105197 }}</ref> 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.<ref>{{cite journal | vauthors = Kallen KJ | title = The role of transsignalling via the agonistic soluble IL-6 receptor in human diseases | volume = 1592 | issue = 3 | pages = 323–343 | date = November 2002 | pmid = 12421676 | doi = 10.1016/s0167-4889(02)00325-7 | title-link = doi | journal = Biochimica et Biophysica Acta (BBA) - Molecular Cell Research | doi-access = free }}</ref>

==History==

Interleukin 6 and its receptor were discovered and cloned at [[Osaka University]], Japan, by [[Tadamitsu Kishimoto]] in the 1980s. In 1997, [[Chugai Pharmaceuticals]] began the clinical development of tocilizumab for the treatment of rheumatoid arthritis. Clinical studies for Castleman's disease and systemic juvenile idiopathic arthritis started in 2001 and 2002, respectively. Hoffmann–La Roche co-developed the drug due to a license agreement in 2003.<ref name="KPJ">{{cite web|url=http://www.krankenpflege-journal.com/rheuma/768-die-entwicklung-von-tocilizumab-medizinischer-fortschritt-auf-basis-einer-erfolgreichen-kooperation-von-chugai-und-roche.html |archive-url=https://web.archive.org/web/20181015051035/http://www.krankenpflege-journal.com/rheuma/768-die-entwicklung-von-tocilizumab-medizinischer-fortschritt-auf-basis-einer-erfolgreichen-kooperation-von-chugai-und-roche.html |archive-date=15 October 2018 |language=de|title=Die Entwicklung von Tocilizumab|trans-title=The development of tocilizumab|author=Markus Harwart|year=2008|publisher=Krankenpflege-Journal}}</ref>

Data presented in 2008 showed the effectiveness of tocilizumab in combination therapy with methotrexate for rheumatoid arthritis treatment.<ref>{{cite news|url=http://news.bbc.co.uk/2/hi/health/7692701.stm|title=Jab hope for rheumatoid arthritis|date=27 October 2008|via=news.bbc.co.uk|access-date=27 October 2008|archive-date=26 January 2021|archive-url=https://web.archive.org/web/20210126125411/http://news.bbc.co.uk/2/hi/health/7692701.stm|url-status=live}}</ref>

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.<ref name="tociliz">{{cite journal | vauthors = Oldfield V, Dhillon S, Plosker GL | title = Tocilizumab: a review of its use in the management of rheumatoid arthritis | journal = Drugs | volume = 69 | issue = 5 | pages = 609–632 | year = 2009 | pmid = 19368420 | doi = 10.2165/00003495-200969050-00007 | url = http://adisonline.com/drugs/abstract/2009/69050/Tocilizumab__A_Review_of_its_Use_in_the_Management.7.aspx | url-status = dead | access-date = 17 March 2010 | archive-url = https://archive.today/20130116072127/http://adisonline.com/drugs/abstract/2009/69050/Tocilizumab__A_Review_of_its_Use_in_the_Management.7.aspx | archive-date = 16 January 2013 }}</ref>

In June 2005, tocilizumab was approved in Japan for Castleman's disease.<ref name="R090105" /> In January 2009, the drug was approved by the [[European Medicines Agency]] (EMA) as ''RoActemra'' for the treatment of rheumatoid arthritis under the mentioned restrictions. On 11 January 2010, it was approved by the U.S. FDA as ''Actemra'' for the same purpose.<ref>{{cite news|url=https://online.wsj.com/article/BT-CO-20100111-701072.html?mod=WSJ_World_MIDDLEHeadlinesAsia |title=Roche: FDA Approves Actemra For Rheumatoid Arthritis |newspaper=The Wall Street Journal |date=11 January 2010 |url-status=dead |archive-url=https://web.archive.org/web/20100114015725/http://online.wsj.com/article/BT-CO-20100111-701072.html?mod=WSJ_World_MIDDLEHeadlinesAsia |archive-date=14 January 2010 }}</ref> Tocilizumab was approved by Australia's [[Therapeutic Goods Administration]] on 27 May 2009<ref name="TGA">{{cite web|url=http://www.tga.gov.au/docs/html/adec/adec0263.htm |archive-url=https://web.archive.org/web/20090820225127/http://www.tga.gov.au/docs/html/adec/adec0263.htm |archive-date=20 August 2009 |title=Australian Drug Evaluation Committee 263rd meeting resolutions|newspaper=Therapeutic Goods Administration (Tga) |publisher=Therapeutic Goods Administration|date=27 May 2009}}</ref> and was listed on the [[Pharmaceutical Benefits Scheme]] from August 2010.<ref name="PBS">{{cite web|url=http://www.nps.org.au/health_professionals/publications/nps_radar/2010/august_2010/brief_item_anakinra|title=Anakinra (Kineret) to be deleted from the PBS|publisher=National Prescribing Service Limited|date=1 August 2010|url-status=dead|archive-url=https://web.archive.org/web/20120603095255/http://www.nps.org.au/health_professionals/publications/nps_radar/2010/august_2010/brief_item_anakinra|archive-date=3 June 2012}}</ref> In New Zealand, tocilizumab was approved for distribution in July 2009,<ref>{{cite journal | vauthors = Richards M |date= 20 July 2009 |title= Consent to the Distribution of New Medicines |journal= [[New Zealand Gazette]] |volume= 2009 |issue= 105 |pages= 2418 |url= https://gazette.govt.nz/notice/id/2009-go6204 |access-date= 9 June 2015 |archive-date= 9 August 2020 |archive-url= https://web.archive.org/web/20200809100935/https://gazette.govt.nz/notice/id/2009-go6204 |url-status= live }}</ref> and [[Pharmaceutical Management Agency|Pharmac]] approved subsidising it with special authority restrictions in July 2013, for systemic juvenile idiopathic arthritis<ref>{{cite web |title= Approval of proposal involving pegfilgrastim and tocilizumab |date= 24 May 2013 |url= http://www.pharmac.health.nz/assets/notification-2013-05-24-pegfilgrastim-and-tocilizumab.pdf |publisher= Pharmaceutical Management Agency |access-date= 9 June 2015}}</ref> and in July 2014, for rheumatoid arthritis.<ref>{{cite web |title= Decision to widen access to tocilizumab (Actemra) for rheumatoid arthritis in patients who are unable to be treated with methotrexate |date= 14 May 2014 |url= http://www.pharmac.health.nz/assets/notification-2014-05-14-tocilizumab.pdf |publisher= Pharmaceutical Management Agency |access-date= 9 June 2015}}</ref> The FDA approved tocilizumab for the treatment of systemic juvenile idiopathic arthritis for children from two years of age in April 2011, and the EMA followed in August the same year.{{cn|date=March 2024}}

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.<ref name="KPJ" />

== Society and culture ==

=== Legal status ===

Tocilizumab was approved for medical use in the European Union in January 2009,<ref name="RoActemra EPAR" /> and in the United States in January 2010.<ref name="Drug Approval Package: Actemra" /><ref name="Drug Approval Package: Actemra 2" />

The biosimilar Tyenne was approved for medical use in the European Union in September 2023,<ref name="Tyenne EPAR" /><ref>{{cite press release | title=Tyenne Biosimilar: EC Approval | website=Fresenius Kabi | date=19 September 2023 | url=https://www.fresenius-kabi.com/news/european-commission-approval-tyenne-tocilizumab-biosimilar | access-date=6 March 2024 | archive-date=11 October 2023 | archive-url=https://web.archive.org/web/20231011182549/https://www.fresenius-kabi.com/news/european-commission-approval-tyenne-tocilizumab-biosimilar | url-status=live }}</ref> and in the United States in March 2024.<ref>{{Cite web |url=https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2024/761275Orig1s000ltr.pdf |title=Archived copy |access-date=7 March 2024 |archive-date=7 March 2024 |archive-url=https://web.archive.org/web/20240307003525/https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2024/761275Orig1s000ltr.pdf |url-status=live }}</ref><ref>{{cite press release | title=Tyenne marks the third biosimilar to receive FDA approval | website=Fresenius Kabi | date=7 March 2024 | url=https://www.fresenius-kabi.com/news/tyenne-first-iv-and-subcutaneous-tocilizumab-biosimilar-approved-by-fda | access-date=8 March 2024 | archive-date=7 March 2024 | archive-url=https://web.archive.org/web/20240307194514/https://www.fresenius-kabi.com/news/tyenne-first-iv-and-subcutaneous-tocilizumab-biosimilar-approved-by-fda | url-status=live }}</ref>

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).<ref name="Tofidence EPAR" /> The applicant for this medicinal product is Biogen Netherlands B.V.<ref name="Tofidence EPAR">{{cite web | title=Tofidence EPAR | website=[[European Medicines Agency]] | date=25 April 2024 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/truqap | access-date=27 April 2024 | archive-date=30 April 2024 | archive-url=https://web.archive.org/web/20240430024450/https://www.ema.europa.eu/en/medicines/human/EPAR/truqap | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.</ref> Tofidence is a biosimilar medicinal product.<ref name="Tofidence EPAR" />

==== COVID-19 ====

Tocilizumab was approved for the treatment of COVID{{nbhyph}}19 in the European Union in December 2021,<ref name="RoActemra EPAR" /> and in the United States in December 2022.<ref name="Genentech PR" />

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{{nbhyph}}19 in adults.<ref>{{cite web|url=https://www.pharmaceutical-technology.com/news/hetero-dcgi-roche-drug/|publisher=Pharmaceutical Technology|date=7 September 2021|access-date=28 September 2021|title=Hetero obtains DCGI approval to produce Roche's Covid-19 drug in India|archive-date=25 November 2021|archive-url=https://web.archive.org/web/20211125042832/https://www.pharmaceutical-technology.com/news/hetero-dcgi-roche-drug/|url-status=live}}</ref>

In December 2021, tocilizumab was granted a provisional approval by the Australian regulator, [[Therapeutic Goods Administration]], for treatment of adults.<ref>{{cite web |title=TGA Provisional Approval of Roche Products Pty Ltd COVID-19 treatment, tocilizumab (ACTEMRA) |url=https://www.tga.gov.au/media-release/tga-provisional-approval-roche-products-pty-ltd-covid-19-treatment-tocilizumab-actemra |website=Therapeutic Goods Administration (TGA) |access-date=2 December 2021 |date=1 December 2021 |archive-date=2 December 2021 |archive-url=https://web.archive.org/web/20211202000817/https://www.tga.gov.au/media-release/tga-provisional-approval-roche-products-pty-ltd-covid-19-treatment-tocilizumab-actemra |url-status=live }}</ref>

Tocilizumab was granted an [[emergency use authorization]] (EUA) for the treatment of [[COVID-19|COVID{{nbhyph}}19]] in the United States in June 2021.<ref name="FDA COVID PR">{{cite press release|title=Coronavirus (COVID-19) Update: FDA Authorizes Drug for Treatment of COVID-19|website=U.S. [[Food and Drug Administration]] (FDA)|date=24 June 2021|url=https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-drug-treatment-covid-19|access-date=24 June 2021|archive-date=24 June 2021|archive-url=https://web.archive.org/web/20210624230521/https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-drug-treatment-covid-19|url-status=live}} {{PD-notice}}</ref><ref name="FDA EUA">{{cite web|date=June 2021|title=Tocilizumab Emergency Use Authorization (EUA)|url=https://www.fda.gov/media/150319/download|url-status=live|archive-url=https://web.archive.org/web/20211125042744/https://www.fda.gov/media/150319/download|archive-date=25 November 2021|access-date=31 July 2021|website=U.S. [[Food and Drug Administration]] (FDA)|format=PDF}} {{PD-notice}}</ref><ref name="FDA EUA FAQ">{{cite web|date=July 2021|title=Frequently Asked Questions on the Emergency Use Authorization for Actemra (tocilizumab) for Treatment of COVID-19|url=https://www.fda.gov/media/150345/download|url-status=live|archive-url=https://web.archive.org/web/20211125042746/https://www.fda.gov/media/150345/download|archive-date=25 November 2021|access-date=31 July 2021|website=U.S. [[Food and Drug Administration]] (FDA)|format=PDF}} {{PD-notice}}</ref> It was approved for the treatment of COVID{{nbhyph}}19 in the European Union in December 2021,<ref name="RoActemra EPAR" /><ref>{{cite web | title=EMA recommends approval for use of RoActemra in adults with severe COVID-19 | website=European Medicines Agency | date=6 December 2021 | url=https://www.ema.europa.eu/en/news/ema-recommends-approval-use-roactemra-adults-severe-covid-19 | access-date=23 December 2022 | archive-date=23 December 2022 | archive-url=https://web.archive.org/web/20221223073244/https://www.ema.europa.eu/en/news/ema-recommends-approval-use-roactemra-adults-severe-covid-19 | url-status=live }}</ref><ref>{{cite web | title=RoActemra | website=Union Register of medicinal products | date=19 January 2009 | url=https://ec.europa.eu/health/documents/community-register/html/h492.htm | access-date=23 December 2022 | archive-date=23 December 2022 | archive-url=https://web.archive.org/web/20221223073244/https://ec.europa.eu/health/documents/community-register/html/h492.htm | url-status=live }}</ref> and in the United States in December 2022.<ref name="Genentech PR" />

==Research==

Tocilizumab is being studied for [[pulmonary arterial hypertension]] (PAH).<ref name="Roche-NIHR" >{{cite web|url=http://www.pharmatimes.com/Article/16-01-06/Roche_links_with_UK_gov_for_ground-breaking_PAH_trial.aspx|title=Roche links with UK gov for ground-breaking PAH trial|publisher=PharmaTimes Media Ltd|date=6 January 2016|access-date=19 January 2016|archive-date=6 March 2016|archive-url=https://web.archive.org/web/20160306063812/http://www.pharmatimes.com/Article/16-01-06/Roche_links_with_UK_gov_for_ground-breaking_PAH_trial.aspx|url-status=live}}</ref>

Tocilizumab is under evaluation in a multicenter clinical trial (ALL-IN) for the prevention of acute cellular rejection in status post heart transplant patients.<ref>{{ClinicalTrialsGov|NCT03644667|Tocilizumab in Cardiac Transplantation}}</ref>

=== COVID-19 ===

{{anchor|COVID-19 Research}}

There is good evidence tocilizumab can help reduce the need for mechanical ventilation for people in hospital with COVID{{nbhyph}}19, and some evidence it can help prevent secondary infections.<ref>{{cite journal | vauthors = Tleyjeh IM, Kashour Z, Riaz M, Hassett L, Veiga VC, Kashour T | title = Efficacy and safety of tocilizumab in COVID-19 patients: a living systematic review and meta-analysis, first update | journal = Clinical Microbiology and Infection | volume = 27 | issue = 8 | pages = 1076–1082 | date = August 2021 | pmid = 33915284 | pmc = 8076756 | doi = 10.1016/j.cmi.2021.04.019 }}</ref>

A 2021 [[meta-analysis]] of [[randomized controlled trial]]s found that, while tocilizumab does not show significant benefits on survival, it could play a role in preventing progression to [[Intensive care unit|intensive care]] and [[mechanical ventilation]].<ref>{{cite journal | vauthors = Mutua V, Henry BM, Csefalvay CV, Cheruiyot I, Vikse J, Lippi G, Bundi B, Mong'are N | title = Tocilizumab in addition to standard of care in the management of COVID-19: a meta-analysis of RCTs | journal = Acta Bio-Medica | volume = 93 | issue = 1 | pages = e2022014 | date = March 2022 | pmid = 35315395 | pmc = 8972884 | doi = 10.23750/abm.v93i1.12208 | url = https://mattioli1885journals.com/index.php/actabiomedica/article/view/12208 | access-date = 15 March 2022 | url-status = live | archive-url = https://web.archive.org/web/20220422053739/https://mattioli1885journals.com/index.php/actabiomedica/article/view/12208 | archive-date = 22 April 2022 }}</ref>{{Unreliable source?|date=November 2021|reason=Q3 in Scimago}}<ref>{{cite journal | vauthors = Rezaei Tolzali MM, Noori M, Shokri P, Rahmani S, Khanzadeh S, Nejadghaderi SA, Fazlollahi A, Sullman MJ, Singh K, Kolahi AA, Arshi S, Safiri S | title = Efficacy of tocilizumab in the treatment of COVID-19: An umbrella review | journal = Reviews in Medical Virology | volume = 32 | issue = 6 | pages = e2388 | date = November 2022 | pmid = 36029180 | pmc = 9539231 | doi = 10.1002/rmv.2388 }}</ref>

=== Neuromyelitis optica ===

Early case reports suggest tocilizumab might be effective in otherwise refractory [[neuromyelitis optica]] (NMO, Devic's disease).<ref>{{cite journal | vauthors = Komai T, Shoda H, Yamaguchi K, Sakurai K, Shibuya M, Kubo K, Takahashi T, Fujio K, Yamamoto K | title = Neuromyelitis optica spectrum disorder complicated with Sjogren syndrome successfully treated with tocilizumab: A case report | journal = Modern Rheumatology | volume = 26 | issue = 2 | pages = 294–296 | date = 9 December 2013 | pmid = 24313919 | doi = 10.3109/14397595.2013.861333 | s2cid = 21195912 }}</ref><ref>{{cite journal | vauthors = Kieseier BC, Stüve O, Dehmel T, Goebels N, Leussink VI, Mausberg AK, Ringelstein M, Turowski B, Aktas O, Antoch G, Hartung HP | title = Disease amelioration with tocilizumab in a treatment-resistant patient with neuromyelitis optica: implication for cellular immune responses | journal = JAMA Neurology | volume = 70 | issue = 3 | pages = 390–393 | date = March 2013 | pmid = 23599943 | doi = 10.1001/jamaneurol.2013.668 | title-link = doi | doi-access = free }}</ref><ref>{{cite journal | vauthors = Ayzenberg I, Kleiter I, Schröder A, Hellwig K, Chan A, Yamamura T, Gold R | title = Interleukin 6 receptor blockade in patients with neuromyelitis optica nonresponsive to anti-CD20 therapy | journal = JAMA Neurology | volume = 70 | issue = 3 | pages = 394–397 | date = March 2013 | pmid = 23358868 | doi = 10.1001/jamaneurol.2013.1246 | title-link = doi | doi-access = free }}</ref><ref>{{cite journal | vauthors = Araki M, Aranami T, Matsuoka T, Nakamura M, Miyake S, Yamamura T | title = Clinical improvement in a patient with neuromyelitis optica following therapy with the anti-IL-6 receptor monoclonal antibody tocilizumab | journal = Modern Rheumatology | volume = 23 | issue = 4 | pages = 827–831 | date = July 2013 | pmid = 22782533 | pmc = 3713263 | doi = 10.1007/s10165-012-0715-9 }}</ref>

=== Graves' ophthalmopathy ===

Two small studies found tocilizumab to be beneficial in [[endocrine ophthalmopathy]] ([[Graves' ophthalmopathy|Graves' orbitopathy]]) that is refractory to corticosteroid treatment.<ref>{{cite journal | vauthors = Perez-Moreiras JV, Gomez-Reino JJ, Maneiro JR, Perez-Pampin E, Romo Lopez A, Rodríguez Alvarez FM, Castillo Laguarta JM, Del Estad Cabello A, Gessa Sorroche M, España Gregori E, Sales-Sanz M | title = Efficacy of Tocilizumab in Patients With Moderate-to-Severe Corticosteroid-Resistant Graves Orbitopathy: A Randomized Clinical Trial | journal = American Journal of Ophthalmology | volume = 195 | pages = 181–190 | date = November 2018 | pmid = 30081019 | doi = 10.1016/j.ajo.2018.07.038 | s2cid = 51925569 }}</ref><ref>{{cite journal | vauthors = Sánchez-Bilbao L, Martínez-López D, Revenga M, López-Vázquez Á, Valls-Pascual E, Atienza-Mateo B, Valls-Espinosa B, Maiz-Alonso O, Blanco A, Torre-Salaberri I, Rodríguez-Méndez V, García-Aparicio Á, Veroz-González R, Jovaní V, Peiteado D, Sánchez-Orgaz M, Tomero E, Toyos-Sáenz de Miera FJ, Pinillos V, Aurrecoechea E, Mora Á, Conesa A, Fernández-Prada M, Troyano JA, Calvo-Río V, Demetrio-Pablo R, González-Mazón Í, Hernández JL, Castañeda S, González-Gay MÁ, Blanco R | title = Anti-IL-6 Receptor Tocilizumab in Refractory Graves' Orbitopathy: National Multicenter Observational Study of 48 Patients | journal = Journal of Clinical Medicine | volume = 9 | issue = 9 | page = 2816 | date = August 2020 | pmid = 32878150 | pmc = 7563792 | doi = 10.3390/jcm9092816 | title-link = doi | doi-access = free }}</ref>

== References ==

{{Reflist}}

== External links ==

* {{ClinicalTrialsGov|NCT00109408|A Study to Assess the Safety and Efficacy of Tocilizumab in Patients With Active Rheumatoid Arthritis}}

* {{ClinicalTrialsGov|NCT00106535|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)}}

* {{ClinicalTrialsGov|NCT00106548|A Study to Assess the Effect of Tocilizumab + Methotrexate on Signs and Symptoms in Patients With Moderate to Severe Active Rheumatoid Arthritis}}

* {{ClinicalTrialsGov|NCT00106574|A Study to Assess the Effect of Tocilizumab + DMARD Therapy on Signs and Symptoms in Patients With Moderate to Severe Active Rheumatoid Arthritis}}

* {{ClinicalTrialsGov|NCT00106522|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}}

* {{ClinicalTrialsGov|NCT01331837|A Study of Tocilizumab in Comparison to Etanercept in Participants With Rheumatoid Arthritis and Cardiovascular Disease Risk Factors}}

* {{ClinicalTrialsGov|NCT00988221|A Study of Tocilizumab in Patients With Active Polyarticular Juvenile Idiopathic Arthritis}}

* {{ClinicalTrialsGov|NCT00642460|A Study of RoActemra/Actemra (Tocilizumab) in Patients With Active Systemic Juvenile Idiopathic Arthritis (JIA)}}

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