Wikipedia

Tocilizumab

(Redirected from RoActemra)

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 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.[18]

Tocilizumab
Monoclonal antibody
TypeWhole antibody
SourceHumanized (from mouse)
TargetIL-6 receptor
Clinical data
Trade namesActemra, Roactemra
Biosimilarstocilizumab-aazg,[1][2] tocilizumab-bavi,[3][4] Tofidence,[3][4][5][6][7] Tyenne[1][8]
AHFS/Drugs.comMonograph
MedlinePlusa611004
License data
Pregnancy
category
Routes of
administration		Intravenous, subcutaneous
ATC code
Legal status
Legal status
Pharmacokinetic data
Elimination half-life8–14 days during steady state (dependent on concentration)
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC6428H9976N1720O2018S42
Molar mass144987.06 g·mol−1
 ☒NcheckY (what is this?)  (verify)

Tocilizumab was approved for medical use in the European Union in January 2009,[15] and in the United States in January 2010.[19][20]

Medical uses

edit

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.[13]

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.[15]

Rheumatoid arthritis

edit

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.[21][22] The drug slows down the progression of the disease and can improve physical function of patients.[23]

Systemic juvenile idiopathic arthritis

edit

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.[24] In 2011, the US Food and Drug Administration (FDA) approved tocilizumab for the treatment of active systemic juvenile idiopathic arthritis.[25]

Castleman's disease

edit

In Japan, tocilizumab is also approved for the treatment of Castleman's disease,[21][26] a rare benign tumor of B cells.

Giant cell arteritis

edit

In May 2017, the FDA approved tocilizumab for giant cell arteritis.[27]

Cytokine release syndrome

edit

On 30 August 2017, the FDA approved tocilizumab for cytokine release syndrome, a side effect of CAR-T cell therapies.[28]

COVID-19

edit

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).[29][14][30] The FDA approved tocilizumab for those indications in December 2022.[31]

Adverse effects

edit

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.[32] 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%).[33]

Interactions

edit

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).[33]

Mechanism of action

edit

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.[33][34] 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.[35]

History

edit

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.[36]

Data presented in 2008 showed the effectiveness of tocilizumab in combination therapy with methotrexate for rheumatoid arthritis treatment.[37] 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.[38]

In June 2005, tocilizumab was approved in Japan for Castleman's disease.[21] 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.[39] Tocilizumab was approved by Australia's Therapeutic Goods Administration on 27 May 2009[40] and was listed on the Pharmaceutical Benefits Scheme from August 2010.[41] In New Zealand, tocilizumab was approved for distribution in July 2009,[42] and Pharmac approved subsidising it with special authority restrictions in July 2013, for systemic juvenile idiopathic arthritis[43] and in July 2014, for rheumatoid arthritis.[44] 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.[citation needed]

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.[36]

Society and culture

edit
edit

Tocilizumab was approved for medical use in the European Union in January 2009,[15] and in the United States in January 2010.[19][20]

In September 2023, Tyenne became the first tocilizumab biosimilar approved for medical use in the European Union,[8][45] and in March 2024, became the first biosimilar with both intravenous and subcutaneous formulations to be approved in the United States.[46][47]

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).[6][48] The applicant for this medicinal product is Biogen Netherlands B.V.[6] Tofidence is a biosimilar medicinal product.[6] Tofidence was approved for medical use in the European Union in June 2024.[7]

COVID-19

edit

Tocilizumab was approved for the treatment of COVID‑19 in the European Union in December 2021,[15] and in the United States in December 2022.[31]

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.[49]

In December 2021, tocilizumab was granted a provisional approval by the Australian regulator, Therapeutic Goods Administration, for treatment of adults.[50]

Tocilizumab was granted an emergency use authorization (EUA) for the treatment of COVID‑19 in the United States in June 2021.[29][14][30] It was approved for the treatment of COVID‑19 in the European Union in December 2021,[15][51][52] and in the United States in December 2022.[31]

Research

edit

Tocilizumab is being studied for pulmonary arterial hypertension (PAH).[53] Tocilizumab is under evaluation in a multicenter clinical trial (ALL-IN) for the prevention of acute cellular rejection in status post heart transplant patients.[54]

COVID-19

edit

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.[55]

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.[56][unreliable source?][57]

Neuromyelitis optica

edit

Early case reports suggest tocilizumab might be effective in otherwise refractory neuromyelitis optica (NMO, Devic's disease).[58][59][60][61]

Graves' ophthalmopathy

edit

Two small studies found tocilizumab to be beneficial in endocrine ophthalmopathy (Graves' orbitopathy) that is refractory to corticosteroid treatment.[62][63]

References

edit
  1. ^ a b "Tyenne- tocilizumab-aazg injection, solution, concentrate". DailyMed. 6 March 2024. Archived from the original on 25 April 2024. Retrieved 25 April 2024.
  2. ^ "Tyenne- tocilizumab-aazg injection, solution". DailyMed. 22 May 2024. Retrieved 28 November 2024.
  3. ^ a b "Tofidence- tocilizumab injection". DailyMed. 27 March 2024. Retrieved 16 June 2024.
  4. ^ a b "FDA approves first biosimilar to Actemra to treat adult and pediatric arthritis". U.S. Food and Drug Administration (FDA) (Press release). 29 September 2023. Archived from the original on 25 February 2024. Retrieved 6 March 2024.
  5. ^ "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.
  6. ^ a b c d e "Tofidence EPAR". European Medicines Agency. 25 April 2024. Archived from the original on 30 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.
  7. ^ a b "Tofidence PI". Union Register of medicinal products. 21 June 2024. Retrieved 26 June 2024.
  8. ^ a b c "Tyenne EPAR". European Medicines Agency. 2 October 2023. Archived from the original on 5 October 2023. Retrieved 5 October 2023.
  9. ^ a b "Australian Product Information Actemra (tocilizumab)" (PDF). MedAdvisor International. 2 September 2022. Archived from the original on 1 October 2023. Retrieved 19 April 2023.
  10. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 October 2023.
  11. ^ "Prescription medicines and biologicals: TGA annual summary 2017". Therapeutic Goods Administration (TGA). 21 June 2022. Archived from the original on 31 March 2024. Retrieved 31 March 2024.
  12. ^ "Actemra". COVID-19 vaccines and treatments portal. 13 October 2022. Archived from the original on 5 December 2022. Retrieved 29 October 2022.
  13. ^ a b "Actemra- tocilizumab injection, solution, concentrate Actemra- tocilizumab injection, solution Actemra ACTPen- tocilizumab injection, solution". DailyMed. Archived from the original on 7 June 2021. Retrieved 24 June 2021.
  14. ^ a b c "Tocilizumab Emergency Use Authorization (EUA)" (PDF). U.S. Food and Drug Administration (FDA). June 2021. Archived from the original on 25 November 2021. Retrieved 31 July 2021.   This article incorporates text from this source, which is in the public domain.
  15. ^ a b c d e f "Roactemra EPAR". European Medicines Agency. 17 September 2018. Archived from the original on 18 December 2021. Retrieved 18 December 2021.
  16. ^ "Tyenne Product information". Union Register of medicinal products. 18 September 2023. Archived from the original on 1 October 2023. Retrieved 1 October 2023.
  17. ^ "COVID-19 medicines". European Medicines Agency (EMA). 14 October 2024. Retrieved 14 October 2024.
  18. ^ Markus Harwart (2008). "Die Entwicklung von Tocilizumab" [The development of tocilizumab] (in German). Krankenpflege-Journal. Archived from the original on 15 October 2018. Retrieved 30 April 2016.
  19. ^ a b "Drug Approval Package: Actemra (Tocilizumab) Injection BLA 125276". U.S. Food and Drug Administration (FDA). 9 March 2010. Archived from the original on 26 January 2022. Retrieved 1 October 2023.
  20. ^ a b "Drug Approval Package: Actemra (tocilizumab) Solution for Subcutaneous Injection NDA #125472". accessdata.fda.gov. 17 July 2014. Archived from the original on 23 January 2023. Retrieved 1 October 2023.
  21. ^ a b c "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.
  22. ^ "Assessment report for Roactemra" (PDF). European Medicines Agency. Archived (PDF) from the original on 19 January 2016. Retrieved 6 October 2011.
  23. ^ 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.
  24. ^ 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.
  25. ^ "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.
  26. ^ Matsuyama M, Suzuki T, Tsuboi H, Ito S, Mamura M, Goto D, et al. (2007). "Anti-interleukin-6 receptor antibody (tocilizumab) treatment of multicentric Castleman's disease". Internal Medicine. 46 (11): 771–774. doi:10.2169/internalmedicine.46.6262. PMID 17541233.
  27. ^ "FDA Approves Actemra (tocilizumab) Subcutaneous Injection for Giant Cell Arteritis". Drugs.com. Archived from the original on 9 August 2020. Retrieved 25 May 2017.
  28. ^ "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.
  29. ^ a b "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.   This article incorporates text from this source, which is in the public domain.
  30. ^ a b "Frequently Asked Questions on the Emergency Use Authorization for Actemra (tocilizumab) for Treatment of COVID-19" (PDF). U.S. Food and Drug Administration (FDA). July 2021. Archived from the original on 25 November 2021. Retrieved 31 July 2021.   This article incorporates text from this source, which is in the public domain.
  31. ^ a b c "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.
  32. ^ Genovese MC, McKay JD, Nasonov EL, Mysler EF, da Silva NA, Alecock E, et al. (October 2008). "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. doi:10.1002/art.23940. PMID 18821691.
  33. ^ a b c Dinnendahl, V, Fricke, U, eds. (2010). Arzneistoff-Profile (in German). Vol. 4 (23 ed.). Eschborn, Germany: Govi Pharmazeutischer Verlag. ISBN 978-3-7741-9846-3.
  34. ^ Jones G, Sebba A, Gu J, Lowenstein MB, Calvo A, Gomez-Reino JJ, et al. (January 2010). "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. doi:10.1136/ard.2008.105197. PMC 3747519. PMID 19297346.
  35. ^ Kallen KJ (November 2002). "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. doi:10.1016/s0167-4889(02)00325-7. PMID 12421676.
  36. ^ a b Markus Harwart (2008). "Die Entwicklung von Tocilizumab" [The development of tocilizumab] (in German). Krankenpflege-Journal. Archived from the original on 15 October 2018.
  37. ^ "Jab hope for rheumatoid arthritis". 27 October 2008. Archived from the original on 26 January 2021. Retrieved 27 October 2008 – via news.bbc.co.uk.
  38. ^ Oldfield V, Dhillon S, Plosker GL (2009). "Tocilizumab: a review of its use in the management of rheumatoid arthritis". Drugs. 69 (5): 609–632. doi:10.2165/00003495-200969050-00007. PMID 19368420. Archived from the original on 16 January 2013. Retrieved 17 March 2010.
  39. ^ "Roche: FDA Approves Actemra For Rheumatoid Arthritis". The Wall Street Journal. 11 January 2010. Archived from the original on 14 January 2010.
  40. ^ "Australian Drug Evaluation Committee 263rd meeting resolutions". Therapeutic Goods Administration (Tga). Therapeutic Goods Administration. 27 May 2009. Archived from the original on 20 August 2009.
  41. ^ "Anakinra (Kineret) to be deleted from the PBS". National Prescribing Service Limited. 1 August 2010. Archived from the original on 3 June 2012.
  42. ^ Richards M (20 July 2009). "Consent to the Distribution of New Medicines". New Zealand Gazette. 2009 (105): 2418. Archived from the original on 9 August 2020. Retrieved 9 June 2015.
  43. ^ "Approval of proposal involving pegfilgrastim and tocilizumab" (PDF). Pharmaceutical Management Agency. 24 May 2013. Retrieved 9 June 2015.
  44. ^ "Decision to widen access to tocilizumab (Actemra) for rheumatoid arthritis in patients who are unable to be treated with methotrexate" (PDF). Pharmaceutical Management Agency. 14 May 2014. Retrieved 9 June 2015.
  45. ^ "Tyenne Biosimilar: EC Approval". Fresenius Kabi (Press release). 19 September 2023. Archived from the original on 11 October 2023. Retrieved 6 March 2024.
  46. ^ "Archived copy" (PDF). Archived (PDF) from the original on 7 March 2024. Retrieved 7 March 2024.{{cite web}}: CS1 maint: archived copy as title (link)
  47. ^ "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.
  48. ^ "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.
  49. ^ "Hetero obtains DCGI approval to produce Roche's Covid-19 drug in India". Pharmaceutical Technology. 7 September 2021. Archived from the original on 25 November 2021. Retrieved 28 September 2021.
  50. ^ "TGA Provisional Approval of Roche Products Pty Ltd COVID-19 treatment, tocilizumab (ACTEMRA)". Therapeutic Goods Administration (TGA). 1 December 2021. Archived from the original on 2 December 2021. Retrieved 2 December 2021.
  51. ^ "EMA recommends approval for use of Roactemra in adults with severe COVID-19". European Medicines Agency. 6 December 2021. Archived from the original on 23 December 2022. Retrieved 23 December 2022.
  52. ^ "Roactemra". Union Register of medicinal products. 19 January 2009. Archived from the original on 23 December 2022. Retrieved 23 December 2022.
  53. ^ "Roche links with UK gov for ground-breaking PAH trial". PharmaTimes Media Ltd. 6 January 2016. Archived from the original on 6 March 2016. Retrieved 19 January 2016.
  54. ^ Clinical trial number NCT03644667 for "Tocilizumab in Cardiac Transplantation" at ClinicalTrials.gov
  55. ^ Tleyjeh IM, Kashour Z, Riaz M, Hassett L, Veiga VC, Kashour T (August 2021). "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. doi:10.1016/j.cmi.2021.04.019. PMC 8076756. PMID 33915284.
  56. ^ Mutua V, Henry BM, Csefalvay CV, Cheruiyot I, Vikse J, Lippi G, et al. (March 2022). "Tocilizumab in addition to standard of care in the management of COVID-19: a meta-analysis of RCTs". Acta Bio-Medica. 93 (1): e2022014. doi:10.23750/abm.v93i1.12208. PMC 8972884. PMID 35315395. Archived from the original on 22 April 2022. Retrieved 15 March 2022.
  57. ^ Rezaei Tolzali MM, Noori M, Shokri P, Rahmani S, Khanzadeh S, Nejadghaderi SA, et al. (November 2022). "Efficacy of tocilizumab in the treatment of COVID-19: An umbrella review". Reviews in Medical Virology. 32 (6): e2388. doi:10.1002/rmv.2388. PMC 9539231. PMID 36029180.
  58. ^ Komai T, Shoda H, Yamaguchi K, Sakurai K, Shibuya M, Kubo K, et al. (9 December 2013). "Neuromyelitis optica spectrum disorder complicated with Sjogren syndrome successfully treated with tocilizumab: A case report". Modern Rheumatology. 26 (2): 294–296. doi:10.3109/14397595.2013.861333. PMID 24313919. S2CID 21195912.
  59. ^ Kieseier BC, Stüve O, Dehmel T, Goebels N, Leussink VI, Mausberg AK, et al. (March 2013). "Disease amelioration with tocilizumab in a treatment-resistant patient with neuromyelitis optica: implication for cellular immune responses". JAMA Neurology. 70 (3): 390–393. doi:10.1001/jamaneurol.2013.668. PMID 23599943.
  60. ^ Ayzenberg I, Kleiter I, Schröder A, Hellwig K, Chan A, Yamamura T, et al. (March 2013). "Interleukin 6 receptor blockade in patients with neuromyelitis optica nonresponsive to anti-CD20 therapy". JAMA Neurology. 70 (3): 394–397. doi:10.1001/jamaneurol.2013.1246. PMID 23358868.
  61. ^ Araki M, Aranami T, Matsuoka T, Nakamura M, Miyake S, Yamamura T (July 2013). "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. doi:10.1007/s10165-012-0715-9. PMC 3713263. PMID 22782533.
  62. ^ Perez-Moreiras JV, Gomez-Reino JJ, Maneiro JR, Perez-Pampin E, Romo Lopez A, Rodríguez Alvarez FM, et al. (November 2018). "Efficacy of Tocilizumab in Patients With Moderate-to-Severe Corticosteroid-Resistant Graves Orbitopathy: A Randomized Clinical Trial". American Journal of Ophthalmology. 195: 181–190. doi:10.1016/j.ajo.2018.07.038. PMID 30081019. S2CID 51925569.
  63. ^ Sánchez-Bilbao L, Martínez-López D, Revenga M, López-Vázquez Á, Valls-Pascual E, Atienza-Mateo B, et al. (August 2020). "Anti-IL-6 Receptor Tocilizumab in Refractory Graves' Orbitopathy: National Multicenter Observational Study of 48 Patients". Journal of Clinical Medicine. 9 (9): 2816. doi:10.3390/jcm9092816. PMC 7563792. PMID 32878150.
edit
  • 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
Retrieved from "https://en.wikipedia.org/w/index.php?title=Tocilizumab&oldid=1259981835"