Chemistry:Ustekinumab

From HandWiki
Short description: Biopharmaceutical drug
Ustekinumab
Monoclonal antibody
TypeWhole antibody
SourceHuman
TargetIL-12 and IL-23
Clinical data
Trade namesStelara
Other namesCNTO 1275
AHFS/Drugs.comMonograph
MedlinePlusa611013
License data
Pregnancy
category
Routes of
administration		Subcutaneous, intravenous
ATC code
Legal status
Legal status
Pharmacokinetic data
Metabolismunknown[2]
Elimination half-life15–32 days (average 3 weeks)[2]
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC6482H10004N1712O2016S46
Molar mass145648.06 g·mol−1
 ☒N☑Y (what is this?)  (verify)

Ustekinumab, sold under the brand name Stelara among others, is a monoclonal antibody medication developed by Janssen Pharmaceuticals, for the treatment of Crohn's disease, ulcerative colitis, plaque psoriasis and psoriatic arthritis,[8] targeting both IL-12 and IL-23.[9]

Ustekinumab is approved to treat Crohn's disease in the United States, Israel, Australia, and the European Union, and ulcerative colitis in the US, and in the EU to people who have not responded to more traditional treatments.[3][4][10][11] It was found not effective for multiple sclerosis.[12]

It is administered either by intravenous infusion or subcutaneous injection.[8] The antibody targets a subunit of human interleukin 12 and interleukin 23, which are naturally occurring proteins that regulate the immune system and immune-mediated inflammatory disorders.[13]

Medical uses

Ustekinumab is used to treat psoriasis.[3] This includes psoriatic arthritis when it affects the skin.[8][3] It is indicated for the treatment of adult and adolescent patients (12 years and older) with moderate to severe plaque psoriasis (Ps) who are candidates for phototherapy or systemic therapy, and adults with active psoriatic arthritis (PsA) alone or in combination with methotrexate.[3][14] It is also used to treat moderately to severely active Crohn's disease and moderately to severely active ulcerative colitis.[3]

In the European Union, ustekinumab is approved to treat moderate to severe plaque psoriasis in adults and children above the age of six years whose condition has not improved with, or who cannot use, other systemic (whole-body) psoriasis treatments, such as ciclosporin, methotrexate or PUVA (psoralen ultraviolet A);[4] active psoriatic arthritis in adults;[4] moderately to severely active Crohn's disease in adults;[4] and moderately to severely active ulcerative colitis in adults.[4]

Adverse effects

According to information provided by Centocor, maker of one medication based on ustekinumab, their version of ustekinumab is associated with several types of serious adverse effects. These include an increased risk of infection, such as by tuberculosis and an increased risk of certain types of cancer. As with some other immunosuppressant drugs like ciclosporin, the brain swelling of posterior reversible encephalopathy syndrome is a risk. The pharmaceutical company also reports serious allergic reaction as a possible side effect. More common side effects are upper respiratory infection, headache, and tiredness.[15]

Clinical trials have shown that subcutaneous ustekinumab was generally well tolerated. Most treatment-emergent adverse events were of mild severity.[16]

Pregnancy

It is unknown if the medication is safe during pregnancy or breastfeeding.[2]

Mechanism of action

Ustekinumab is designed to interfere with the triggering of the body's inflammatory response through the suppression of certain cytokines. Specifically, it blocks interleukin IL-12 and IL-23 which help activate certain T-cells. It binds to the p-40 subunit of both IL-12 and IL-23 so that they subsequently cannot bind to their receptors.[17]

History

On December 4, 2007, a Biologic License Application (BLA) with the US Food and Drug Administration (FDA) was filed by Centocor and Janssen-Cilag International (collaborator) submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA). On November 21, 2008, the Committee for Medicinal Products for Human Use (CHMP) of the EMA adopted a positive opinion for ustekinumab for the treatment of moderate to severe plaque psoriasis in adults who failed to respond to other systemic therapies.[4][18]

Society and culture

Legal status

Since 2009, ustekinumab is approved in Canada, the European Union, and the United States to treat moderate to severe plaque psoriasis.[19] On September 24, 2013, the US Food and Drug Administration (FDA) approved the use of ustekinumab for the treatment of psoriatic arthritis.[citation needed]

On December 12, 2008, Health Canada approved the use of ustekinumab for the treatment of chronic moderate to severe plaque psoriasis in adults who are candidates for phototherapy or systemic therapy.[20]

The FDA approved ustekinumab in September 2009, for the treatment of adults with moderate to severe plaque psoriasis.[21][22]

The FDA approved ustekinumab in September 2016, for the treatment of Crohn's disease.[23]

Since September 2017, ustekinumab is available on the AU Pharmaceutical Benefits Scheme for the treatment of severe Crohn's disease in adults.[24]

In 2019, the European Commission approved the use of ustekinumab for adults with moderately to severely active ulcerative colitis.[10][4]

In October 2019, the FDA approved the use of ustekinumab for adults with moderately to severely active ulcerative colitis.[25][26]

Biosimilars

In October 2023, Wezlana was approved for medical use in the United States.[7]

In November 2023, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Uzpruvo, intended for the treatment of plaque psoriasis, including pediatric plaque psoriasis,[27] psoriatic arthritis and Crohn's disease in adults.[27] The applicant for this medicinal product is STADA Arzneimittel AG.[27] Uzpruvo is a biosimilar medicinal product.[27] Uzpruvo was approved for medical use in the European Union in January 2024.[5][6]

References

  1. ↑ "Ustekinumab (Stelara) Use During Pregnancy". November 26, 2019. https://www.drugs.com/pregnancy/ustekinumab.html. 
  2. ↑ 2.0 2.1 2.2 2.3 "Stelara 45 mg solution for injection (vials) - Summary of Product Characteristics (SmPC)". February 27, 2020. https://www.medicines.org.uk/emc/product/4413/smpc. 
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 "Stelara- ustekinumab injection, solution Stelara- ustekinumab solution". March 24, 2020. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c77a9664-e3bb-4023-b400-127aa53bca2b. 
  4. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 "Stelara EPAR". September 17, 2018. https://www.ema.europa.eu/en/medicines/human/EPAR/stelara. 
  5. ↑ 5.0 5.1 5.2 "Uzpruvo EPAR". 9 November 2023. https://www.ema.europa.eu/en/medicines/human/EPAR/uzpruvo. 
  6. ↑ 6.0 6.1 "Uzpruvo Product information". 8 January 2024. https://ec.europa.eu/health/documents/community-register/html/h1784.htm. 
  7. ↑ 7.0 7.1 7.2 "FDA Approves Interchangeable Biosimilar for Multiple Inflammatory Diseases". U.S. Food and Drug Administration (Press release). 31 October 2023. Retrieved 13 November 2023. This article incorporates text from this source, which is in the public domain.
  8. ↑ 8.0 8.1 8.2 "Ustekinumab". The American Society of Health-System Pharmacists. https://www.drugs.com/monograph/ustekinumab.html. 
  9. ↑ "Ustekinumab". mAbs 1 (3): 216–221. 2009. doi:10.4161/mabs.1.3.8593. PMID 20069753. 
  10. ↑ 10.0 10.1 "EC approves expanded use of Stelara for moderately to severely active ulcerative colitis". https://www.healio.com/gastroenterology/inflammatory-bowel-disease/news/online/%7B1092e4c0-15b5-4ba2-871b-3a7930e27283%7D/ec-approves-expanded-use-of-stelara-for-moderately-to-severely-active-ulcerative-colitis. 
  11. ↑ "Ustekinumab (Stelara) PBS listed for severe Crohn's disease". NPS Medicinewise. October 26, 2017. https://www.nps.org.au/radar/articles/ustekinumab-stelara-pbs-listed-for-severe-crohns-disease. 
  12. ↑ "Repeated subcutaneous injections of IL12/23 p40 neutralising antibody, ustekinumab, in patients with relapsing-remitting multiple sclerosis: a phase II, double-blind, placebo-controlled, randomised, dose-ranging study". The Lancet. Neurology 7 (9): 796–804. September 2008. doi:10.1016/S1474-4422(08)70173-X. PMID 18703004. 
  13. ↑ "Modulation of CLA, IL-12R, CD40L, and IL-2Ralpha expression and inhibition of IL-12- and IL-23-induced cytokine secretion by CNTO 1275". Cellular Immunology 247 (1): 1–11. May 2007. doi:10.1016/j.cellimm.2007.06.006. PMID 17761156. 
  14. ↑ "The IL23/Th17 pathway as a therapeutic target in chronic inflammatory diseases". Inflammation & Allergy - Drug Targets 11 (2): 159–168. April 2012. doi:10.2174/187152812800392805. PMID 22280236. 
  15. ↑ "Important Safety Information". Stelara (ustekinumab). Janssen Biotech. May 22, 2019. http://www.stelarainfo.com/safety. 
  16. ↑ "Ustekinumab". BioDrugs 23 (1): 53–61. 2009. doi:10.2165/00063030-200923010-00006. PMID 19344192. 
  17. ↑ "Review of ustekinumab, an interleukin-12 and interleukin-23 inhibitor used for the treatment of plaque psoriasis". Therapeutics and Clinical Risk Management 6: 123–141. April 2010. doi:10.2147/tcrm.s5599. PMID 20421912. 
  18. ↑ "FDA Issues Complete Response Letter to Centocor for Ustekinumab Biologic License Application". Drugs.com (Press release). Centocor. September 25, 2009. Archived from the original on April 6, 2020. Retrieved April 6, 2020.
  19. ↑ "Medarex to Receive Milestone Payment for Approval of Stelara (Ustekinumab) for the Treatment of Moderate to Severe Plaque Psoriasis". http://news.idsk.com/viewer/story.php?CLIENT=INFOMAILER&NEWSID=prn121520081223240607. 
  20. ↑ "drugbank.ca". https://www.drugbank.ca/drugs/DB05679. 
  21. ↑ "Stelara approved for moderate to severe psoriasis. Sept 2009". September 26, 2009. http://www.empr.com/stelara-approved-for-moderate-to-severe-psoriasis/article/149760/. 
  22. ↑ "Drug Approval Package: Stelara (Ustekinumab) Injection NDA #125261". December 24, 1999. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/125261s000TOC.cfm. 
  23. ↑ "Stelara (ustekinumab) Injection NDA #761044". January 12, 2018. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/761044Orig1s000TOC.cfm. 
  24. ↑ "12 Sept 2017". https://www.pbs.gov.au/medicine/item/10767Q-10774C-11164N-11178H-11182M-9304Q-9305R. 
  25. ↑ "Janssen's Stelara Gets FDA Approval for Ulcerative Colitis". https://www.fdanews.com/articles/193283-janssens-stelara-gets-fda-approval-for-ulcerative-colitis. 
  26. ↑ "Stelara: FDA-Approved Drugs". https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=761044. 
  27. ↑ 27.0 27.1 27.2 27.3 "Uzpruvo: Pending EC decision". November 10, 2023. https://www.ema.europa.eu/en/medicines/human/summaries-opinion/uzpruvo. 



Retrieved from "https://handwiki.org/wiki/index.php?title=Chemistry:Ustekinumab&oldid=3329729"