Chemistry:Tocilizumab

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Tocilizumab, sold under the brand name Actemra among others, is an immunosuppressive drug, used for the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis, polyarticular juvenile idiopathic arthritis, giant cell arteritis, cytokine release syndrome, COVID‑19, and systemic sclerosis-associated interstitial lung disease (SSc-ILD). It is a recombinant humanized monoclonal antibody of the immunoglobulin IgG1 subclass against the interleukin-6 receptor (IL-6R).[1] 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.[2]

Tocilizumab was approved for medical use in the European Union in January 2009,[3] and in the United States in January 2010.[4][5]

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‑19.[6]

In the European Union, tocilizumab is indicated for the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis, juvenile idiopathic polyarthritis, giant cell arteritis, cytokine release syndrome, and COVID‑19.[3]

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 drugs (DMARDs) and TNF alpha blockers have proven to be ineffective or were not tolerated. It can be used as a monotherapy for patients who do not tolerate methotrexate.[7][8] The drug slows down the progression of the disease and can improve physical function of patients.[9]

Systemic juvenile idiopathic arthritis

The treatment of systemic juvenile idiopathic arthritis 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.[10] In 2011, the US Food and Drug Administration (FDA) approved tocilizumab for the treatment of active systemic juvenile idiopathic arthritis.[11]

Castleman's disease

In Japan, tocilizumab is also approved for the treatment of Castleman's disease,[7][12] a rare benign tumor of B cells.

Giant cell arteritis

In May 2017, the FDA approved tocilizumab for giant cell arteritis.[13]

Cytokine release syndrome

On 30 August 2017, the FDA approved tocilizumab for cytokine release syndrome, a side effect of CAR-T cell therapies.[14]

COVID-19

As early as March 2020, at the height of the pandemic in Italy, Paolo Antonio Ascierto, an Italian oncologist, researched alongside his colleagues the use of the arthritis drug tocilizumab to treat severe COVID-19 pneumonia, seeing some results.[15] The results were recognized nationally and prompted national calls for treatment protocols surrounding the research.[16] Ascierto was heard in an official hearing at the Italian Chamber of Deputies, presenting data suggesting tocilizumab reduced COVID-19 mortality by approximately 22% in clinical use, underscoring its potential benefit.[17] Paolo was at the center of the development of multicenter evaluations of tocilizumab against COVID-19 pneumonia during the whole year, being essential to it.[17]

In 2021 his research of the usage of tocilizumab against COVID-19 was evaluated by the European Medicines Agency and the European Union, where Ascierto was called to as to support such thesis.[18]

In June 2021, the US Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for tocilizumab for the treatment of COVID‑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).[19][20][21] The FDA approved tocilizumab for those indications in December 2022.[22]

Adverse effects

The most common adverse effects observed in clinical trials were upper respiratory tract infections (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.[23] 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 perforations (0.26% in six months) and anaphylaxis (0.2%).[24]

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).[24]

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.[24][25] 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.[26]

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.[27]

Data presented in 2008 showed the effectiveness of tocilizumab in combination therapy with methotrexate for rheumatoid arthritis treatment.[28] 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.[29]

In June 2005, tocilizumab was approved in Japan for Castleman's disease.[7] 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.[30] Tocilizumab was approved by Australia's Therapeutic Goods Administration on 27 May 2009[31] and was listed on the Pharmaceutical Benefits Scheme from August 2010.[32] In New Zealand, tocilizumab was approved for distribution in July 2009,[33] and Pharmac approved subsidising it with special authority restrictions in July 2013, for systemic juvenile idiopathic arthritis[34] and in July 2014, for rheumatoid arthritis.Cite error: Closing </ref> missing for <ref> tag and in March 2024, became the first biosimilar with both intravenous and subcutaneous formulations to be approved in the United States.[35][36]

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).[37][38] The applicant for this medicinal product is Biogen Netherlands B.V.[37] Tofidence is a biosimilar medicinal product.[37] Tofidence was authorized for medical use in the European Union in June 2024.[39]

Tyenne was approved for medical use in Canada in October 2024.[40][41]

In December 2024, the CHMP adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Avtozma, intended for the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis, polyarticular juvenile idiopathic arthritis, giant cell arteritis, CAR-T cell-induced severe or life-threatening cytokine release syndrome and COVID-19.[1] The applicant for this medicinal product is Celltrion Healthcare Hungary Kft.[1] Avtozma is a biosimilar medicinal product.[1]

Tocilizumab-anoh (Avtozma) was approved for medical use in the United States in January 2025.[42][43][44]

Avtozma was approved for medical use in Canada in October 2025.[45]

COVID-19

Tocilizumab was approved for the treatment of COVID‑19 in the European Union in December 2021,[3] and in the United States in December 2022.[22]

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.[46]

In December 2021, tocilizumab was granted a provisional approval by the Australian regulator, Therapeutic Goods Administration, for treatment of adults.[47]

Tocilizumab was granted an emergency use authorization (EUA) for the treatment of COVID‑19 in the United States in June 2021.[19][20][21] It was approved for the treatment of COVID‑19 in the European Union in December 2021,[3][48][49] and in the United States in December 2022.[22]

Research

Tocilizumab is being studied for pulmonary arterial hypertension (PAH).[50] Tocilizumab is under evaluation in a multicenter clinical trial (ALL-IN) for the prevention of acute cellular rejection in status post heart transplant patients.[51]

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.[52]

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.[53] [54]

Neuromyelitis optica

Early case reports suggest tocilizumab might be effective in otherwise refractory neuromyelitis optica (NMO, Devic's disease).[55][56][57][58]

Graves' ophthalmopathy

Two small studies found tocilizumab to be beneficial in endocrine ophthalmopathy (Graves' orbitopathy) that is refractory to corticosteroid treatment.[59][60]

References

  1. ↑ 1.0 1.1 1.2 1.3 "Avtozma EPAR". 12 December 2024. https://www.ema.europa.eu/en/medicines/human/EPAR/avtozma.  Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  2. ↑ Markus Harwart (2008). "Die Entwicklung von Tocilizumab" (in de). Krankenpflege-Journal. http://www.krankenpflege-journal.com/rheuma/768-die-entwicklung-von-tocilizumab-medizinischer-fortschritt-auf-basis-einer-erfolgreichen-kooperation-von-chugai-und-roche.html. 
  3. ↑ 3.0 3.1 3.2 3.3 "Roactemra EPAR". 17 September 2018. https://www.ema.europa.eu/en/medicines/human/EPAR/roactemra. 
  4. ↑ "Drug Approval Package: Actemra (Tocilizumab) Injection BLA 125276". 9 March 2010. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/125276s000TOC.cfm. 
  5. ↑ "Drug Approval Package: Actemra (tocilizumab) Solution for Subcutaneous Injection NDA #125472". 17 July 2014. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/125472Orig1s000TOC.cfm. 
  6. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named Actemra FDA label
  7. ↑ 7.0 7.1 7.2 "Roactemra approved in Europe to treat patients suffering from Rheumatoid Arthritis" (Press release). Hoffmann–La Roche. 21 January 2009. Archived from the original on 28 February 2009. Retrieved 5 January 2009.
  8. ↑ "Assessment report for Roactemra". European Medicines Agency. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Assessment_Report_-_Variation/human/000955/WC500111086.pdf. 
  9. ↑ "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. (ACR) 60 (10): S238-9. October 2009. https://acr.confex.com/acr/2009/webprogram/Paper15221.html. Retrieved 1 August 2020. 
  10. ↑ "Tocilizumab in Patients With Systemic Juvenile Idiopathic Arthritis: Efficacy Data From the Placebo-Controlled 12-Week Part of the Phase 3 TENDER Trial". Arthritis & Rheumatism 62 (Supplement 10): 1434. 2010. https://acrabstracts.org/wp-content/uploads/2018/06/2010_ACR_ARHP_Abstract_Supplement.pdf#page=604&zoom=auto,-67,314. Retrieved 1 August 2020. 
  11. ↑ "FDA Approves Actemra (tocilizumab) for the Treatment of Systemic Juvenile Idiopathic Arthritis (SJIA)" (Press release). Genentech. 15 April 2011. Archived from the original on 1 October 2018. Retrieved 20 July 2015.
  12. ↑ "Anti-interleukin-6 receptor antibody (tocilizumab) treatment of multicentric Castleman's disease". Internal Medicine 46 (11): 771–774. 2007. doi:10.2169/internalmedicine.46.6262. PMID 17541233. 
  13. ↑ "FDA Approves Actemra (tocilizumab) Subcutaneous Injection for Giant Cell Arteritis". https://www.drugs.com/newdrugs/fda-approves-actemra-tocilizumab-subcutaneous-giant-cell-arteritis-4535.html. 
  14. ↑ "FDA approves tisagenlecleucel for B-cell ALL and tocilizumab for cytokine release syndrome". U.S. Food and Drug Administration (FDA). 30 August 2017. https://www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm574154.htm. 
  15. ↑ "Coronavirus. Al Pascale prosegue con successo la terapia con tocilizumab. Medici chiedono un protocollo nazionale per regolamentarne uso" (in it-IT). 20 November 2025. https://www.quotidianosanita.it/scienza-e-farmaci/coronavirus-al-pascale-prosegue-con-successo-la-terapia-con-tocilizumab-medici-chiedono-un-protocollo-nazionale-per-regolamentarne-uso/. 
  16. ↑ Scarano, Chiara Stella (18 March 2020). "Tocilizumab, semaforo verde dall’Aifa per la sperimentazione su larga scala" (in it-IT). https://www.sanitainformazione.it/tocilizumab-semaforo-verde-dallaifa-per-la-sperimentazione-su-larga-scala/. 
  17. ↑ 17.0 17.1 Scarl, Inferenze (12 May 2020). "Multicenter study on the efficacy and tolerability of tocilizumab in the treatment of patients with COVID-19 pneumonia" (in it-IT). https://repo.epiprev.it/index.php/2020/05/12/multicenter-study-on-the-efficacy-and-tolerability-of-tocilizumab-in-the-treatment-of-patients-with-covid-19-pneumonia/. 
  18. ↑ Lopes, Margherita (16 August 2021). "Covid, Ema valuta 'cura Ascierto' per forme severe" (in it-IT). https://www.fortuneita.com/2021/08/16/covid-ema-valuta-cura-ascierto-per-forme-severe/. 
  19. ↑ 19.0 19.1 "Coronavirus (COVID-19) Update: FDA Authorizes Drug for Treatment of COVID-19". U.S. Food and Drug Administration (FDA) (Press release). 24 June 2021. Archived from the original on 24 June 2021. Retrieved 24 June 2021. Public Domain This article incorporates text from this source, which is in the public domain.
  20. ↑ 20.0 20.1 "Tocilizumab Emergency Use Authorization (EUA)" (PDF). June 2021. https://www.fda.gov/media/150319/download.  Public Domain This article incorporates text from this source, which is in the public domain.
  21. ↑ 21.0 21.1 "Frequently Asked Questions on the Emergency Use Authorization for Actemra (tocilizumab) for Treatment of COVID-19" (PDF). July 2021. https://www.fda.gov/media/150345/download.  Public Domain This article incorporates text from this source, which is in the public domain.
  22. ↑ 22.0 22.1 22.2 "FDA Approves Genentech's Actemra for the Treatment of COVID-19 in Hospitalized Adults" (Press release). Genentech. 21 December 2022. Archived from the original on 23 December 2022. Retrieved 23 December 2022 – via Business Wire.
  23. ↑ "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". Arthritis and Rheumatism 58 (10): 2968–2980. October 2008. doi:10.1002/art.23940. PMID 18821691. 
  24. ↑ 24.0 24.1 24.2 Dinnendahl, V, ed (2010) (in de). Arzneistoff-Profile. 4 (23 ed.). Eschborn, Germany: Govi Pharmazeutischer Verlag. ISBN 978-3-7741-9846-3. 
  25. ↑ "Comparison of tocilizumab monotherapy versus methotrexate monotherapy in patients with moderate to severe rheumatoid arthritis: the AMBITION study". Annals of the Rheumatic Diseases 69 (1): 88–96. January 2010. doi:10.1136/ard.2008.105197. PMID 19297346. 
  26. ↑ "The role of transsignalling via the agonistic soluble IL-6 receptor in human diseases". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1592 (3): 323–343. November 2002. doi:10.1016/s0167-4889(02)00325-7. PMID 12421676. 
  27. ↑ Markus Harwart (2008). "Die Entwicklung von Tocilizumab" (in de). Krankenpflege-Journal. http://www.krankenpflege-journal.com/rheuma/768-die-entwicklung-von-tocilizumab-medizinischer-fortschritt-auf-basis-einer-erfolgreichen-kooperation-von-chugai-und-roche.html. 
  28. ↑ "Jab hope for rheumatoid arthritis". 27 October 2008. http://news.bbc.co.uk/2/hi/health/7692701.stm. 
  29. ↑ "Tocilizumab: a review of its use in the management of rheumatoid arthritis". Drugs 69 (5): 609–632. 2009. doi:10.2165/00003495-200969050-00007. PMID 19368420. http://adisonline.com/drugs/abstract/2009/69050/Tocilizumab__A_Review_of_its_Use_in_the_Management.7.aspx. Retrieved 17 March 2010. 
  30. ↑ "Roche: FDA Approves Actemra For Rheumatoid Arthritis". The Wall Street Journal. 11 January 2010. https://online.wsj.com/article/BT-CO-20100111-701072.html?mod=WSJ_World_MIDDLEHeadlinesAsia. 
  31. ↑ "Australian Drug Evaluation Committee 263rd meeting resolutions". Therapeutic Goods Administration. 27 May 2009. http://www.tga.gov.au/docs/html/adec/adec0263.htm. 
  32. ↑ "Anakinra (Kineret) to be deleted from the PBS". National Prescribing Service Limited. 1 August 2010. http://www.nps.org.au/health_professionals/publications/nps_radar/2010/august_2010/brief_item_anakinra. 
  33. ↑ "Consent to the Distribution of New Medicines". New Zealand Gazette 2009 (105): 2418. 20 July 2009. https://gazette.govt.nz/notice/id/2009-go6204. Retrieved 9 June 2015. 
  34. ↑ "Approval of proposal involving pegfilgrastim and tocilizumab". Pharmaceutical Management Agency. 24 May 2013. http://www.pharmac.health.nz/assets/notification-2013-05-24-pegfilgrastim-and-tocilizumab.pdf. 
  35. ↑ "Archived copy". https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2024/761275Orig1s000ltr.pdf. 
  36. ↑ "Tyenne marks the third biosimilar to receive FDA approval". Fresenius Kabi (Press release). 7 March 2024. Archived from the original on 7 March 2024. Retrieved 8 March 2024.
  37. ↑ 37.0 37.1 37.2 "Tofidence EPAR". 25 April 2024. https://www.ema.europa.eu/en/medicines/human/EPAR/tofidence.  Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  38. ↑ "Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 22-25 April 2024". European Medicines Agency (Press release). 26 April 2024. Retrieved 13 June 2024.
  39. ↑ "Tofidence PI". 21 June 2024. https://ec.europa.eu/health/documents/community-register/html/h1825.htm. 
  40. ↑ "Regulatory Decision Summary for Tyenne". 11 October 2024. https://dhpp.hpfb-dgpsa.ca/review-documents/resource/RDS1729607296633. 
  41. ↑ "Summary Basis of Decision for Tyenne". 1 September 2012. https://dhpp.hpfb-dgpsa.ca/review-documents/resource/SBD1739886817493. 
  42. ↑ "Drug Approval Package: Avtozma". https://www.accessdata.fda.gov/drugsatfda_docs/nda/2025/761420Orig1s000TOC.html. 
  43. ↑ "U.S. FDA approves Celltrion's Avtozma (tocilizumab-anoh), a biosimilar to Actemra" (Press release). Celltrion. 11 February 2025. Retrieved 24 January 2026 – via PR Newswire.
  44. ↑ "Celltrion launches Avtozma (tocilizumab-anoh) intravenous (IV) formulation in the United States" (Press release). Celltrion. 2 October 2025. Retrieved 24 January 2026 – via PR Newswire.
  45. ↑ "Summary Basis of Decision for Avtozma". 16 December 2025. https://dhpp.hpfb-dgpsa.ca/review-documents/resource/SBD1765981684341. 
  46. ↑ "Hetero obtains DCGI approval to produce Roche's Covid-19 drug in India". Pharmaceutical Technology. 7 September 2021. https://www.pharmaceutical-technology.com/news/hetero-dcgi-roche-drug/. 
  47. ↑ "TGA Provisional Approval of Roche Products Pty Ltd COVID-19 treatment, tocilizumab (ACTEMRA)". 1 December 2021. https://www.tga.gov.au/media-release/tga-provisional-approval-roche-products-pty-ltd-covid-19-treatment-tocilizumab-actemra. 
  48. ↑ "EMA recommends approval for use of Roactemra in adults with severe COVID-19". 6 December 2021. https://www.ema.europa.eu/en/news/ema-recommends-approval-use-roactemra-adults-severe-covid-19. 
  49. ↑ "Roactemra". 19 January 2009. https://ec.europa.eu/health/documents/community-register/html/h492.htm. 
  50. ↑ "Roche links with UK gov for ground-breaking PAH trial". PharmaTimes Media Ltd. 6 January 2016. http://www.pharmatimes.com/Article/16-01-06/Roche_links_with_UK_gov_for_ground-breaking_PAH_trial.aspx. 
  51. ↑ Clinical trial number NCT03644667 for "Tocilizumab in Cardiac Transplantation" at ClinicalTrials.gov
  52. ↑ "Efficacy and safety of tocilizumab in COVID-19 patients: a living systematic review and meta-analysis, first update". Clinical Microbiology and Infection 27 (8): 1076–1082. August 2021. doi:10.1016/j.cmi.2021.04.019. PMID 33915284. 
  53. ↑ "Tocilizumab in addition to standard of care in the management of COVID-19: a meta-analysis of RCTs". Acta Bio-Medica 93 (1): e2022014. March 2022. doi:10.23750/abm.v93i1.12208. PMID 35315395. PMC 8972884. https://mattioli1885journals.com/index.php/actabiomedica/article/view/12208. Retrieved 15 March 2022. 
  54. ↑ "Efficacy of tocilizumab in the treatment of COVID-19: An umbrella review". Reviews in Medical Virology 32 (6). November 2022. doi:10.1002/rmv.2388. PMID 36029180. 
  55. ↑ "Neuromyelitis optica spectrum disorder complicated with Sjogren syndrome successfully treated with tocilizumab: A case report". Modern Rheumatology 26 (2): 294–296. 9 December 2013. doi:10.3109/14397595.2013.861333. PMID 24313919. 
  56. ↑ "Disease amelioration with tocilizumab in a treatment-resistant patient with neuromyelitis optica: implication for cellular immune responses". JAMA Neurology 70 (3): 390–393. March 2013. doi:10.1001/jamaneurol.2013.668. PMID 23599943. 
  57. ↑ "Interleukin 6 receptor blockade in patients with neuromyelitis optica nonresponsive to anti-CD20 therapy". JAMA Neurology 70 (3): 394–397. March 2013. doi:10.1001/jamaneurol.2013.1246. PMID 23358868. 
  58. ↑ "Clinical improvement in a patient with neuromyelitis optica following therapy with the anti-IL-6 receptor monoclonal antibody tocilizumab". Modern Rheumatology 23 (4): 827–831. July 2013. doi:10.1007/s10165-012-0715-9. PMID 22782533. 
  59. ↑ "Efficacy of Tocilizumab in Patients With Moderate-to-Severe Corticosteroid-Resistant Graves Orbitopathy: A Randomized Clinical Trial". American Journal of Ophthalmology 195: 181–190. November 2018. doi:10.1016/j.ajo.2018.07.038. PMID 30081019. 
  60. ↑ "Anti-IL-6 Receptor Tocilizumab in Refractory Graves' Orbitopathy: National Multicenter Observational Study of 48 Patients". Journal of Clinical Medicine 9 (9): 2816. August 2020. doi:10.3390/jcm9092816. PMID 32878150. 
  • 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



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