Ustekinumab

Ustekinumab,[6] sold under the brand name Stelara®, is a monoclonal antibody medication developed by Janssen Pharmaceuticals, for the treatment of Crohn's disease, Ulcerative Colitis, Plaque Psoriasis and Psoriatic Arthritis treatment, targeting both IL-12 and IL-23.[7]

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
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only) [2]
  • US: ℞-only [3]
  • EU: Rx-only [4]
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Metabolismunknown[5]
Elimination half-life15–32 days (average 3 weeks)[5]
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC6482H10004N1712O2016S46
Molar mass145648.06 g·mol−1
 NY (what is this?)  (verify)

Stelara® is approved to treat Crohn's disease in the United States, Israel, Australia, and the European Union (EU), and ulcerative colitis in the US, and in the EU to patients who have not responded to more traditional treatments.[3][4][8][9] It was found not effective for multiple sclerosis.[10]

It is manufactured in the Netherlands. It is a subcutaneous human interleukin 12 and interleukin 23 antagonist. These are naturally occurring proteins that regulate the immune system and immune-mediated inflammatory disorders.[11]

Medical uses

Ustekinumab is used to treat psoriasis.[3] This includes psoriatic arthritis when it affects the skin.[7][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][12] 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.[13]

Clinical trials have shown that subcutaneous ustekinumab was generally well tolerated. Most treatment-emergent adverse events were of mild severity.[14]

Pregnancy

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

Mechanism of action

Ustekinumab (CNTO 1275) 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.[15]

History

As of January 2007, there were 5 NIH-listed research studies involving CNTO 1275 on a multinational basis, including 3 Phase II and 2 Phase III trials. Three studies were focused on patients with psoriasis, one on psoriatic arthritis, and one on multiple sclerosis.

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][16]

Approvals

Since 2009, ustekinumab is approved in Canada, the European Union, and the United States to treat moderate to severe plaque psoriasis.[17] On September 24, 2013, the US Food and Drug Administration (FDA) approved the use of ustekinumab for the treatment of psoriatic arthritis.

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.[18]

The FDA approved ustekinumab on September 25, 2009, for the treatment of adults with moderate to severe plaque psoriasis.[19][20]

The FDA approved ustekinumab in September 2016, for the treatment of Crohn's disease.[21]

Since September 2017, ustekinumab is available on the AU Pharmaceutical Benefits Scheme for the treatment of severe Crohn's disease in adults.[22]

In 2019, the European Commission approved the use of ustekinumab for adults with moderately to severely active ulcerative colitis.[8][4]

In October 2019, the FDA approved the use of ustekinumab for adults with moderately to severely active ulcerative colitis.[23][24]

References
  1. "Ustekinumab (Stelara) Use During Pregnancy". Drugs.com. 26 November 2019. Retrieved 6 April 2020.
  2. "Stelara 45 mg solution for injection (vials) - Summary of Product Characteristics (SmPC)". (emc). 27 February 2020. Retrieved 6 April 2020.
  3. "Stelara- ustekinumab injection, solution Stelara- ustekinumab solution". DailyMed. 24 March 2020. Retrieved 6 April 2020.
  4. "Stelara EPAR". European Medicines Agency (EMA). Retrieved 6 April 2020.
  5. Summary of production characteristics Stelara, http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000958/WC500058513.pdf
  6. Cingoz, Oya (2009). "Ustekinumab". mAbs. 1 (3): 216–221. doi:10.4161/mabs.1.3.8593. PMC 2726595. PMID 20069753.
  7. "Ustekinumab". The American Society of Health-System Pharmacists. Retrieved 8 January 2017.
  8. "EC approves expanded use of Stelara for moderately to severely active ulcerative colitis". Healio.com. Retrieved 26 September 2019.
  9. "Ustekinumab (Stelara) PBS listed for severe Crohn's disease". nps.org.au. Retrieved 4 October 2019.
  10. Segal BM, Constantinescu CS, Raychaudhuri A, Kim L, Fidelus-Gort R, Kasper LH (September 2008). "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". Lancet Neurol. 7 (9): 796–804. doi:10.1016/S1474-4422(08)70173-X. PMID 18703004. S2CID 20290673.
  11. Reddy M, Davis C, Wong J, Marsters P, Pendley C, Prabhakar U (May 2007). "Modulation of CLA, IL-12R, CD40L, and IL-2Ralpha expression and inhibition of IL-12- and IL-23-induced cytokine secretion by CNTO 1275". Cell. Immunol. 247 (1): 1–11. doi:10.1016/j.cellimm.2007.06.006. PMID 17761156.
  12. Toussirot E (April 2012). "The IL23/Th17 pathway as a therapeutic target in chronic inflammatory diseases". Inflamm Allergy Drug Targets. 11 (2): 159–68. doi:10.2174/187152812800392805. PMID 22280236.
  13. "Important Safety Information". Stelara (ustekinumab). Janssen Biotech.
  14. Weber J, Keam SJ (2009). "Ustekinumab". BioDrugs. 23 (1): 53–61. doi:10.2165/00063030-200923010-00006. PMID 19344192.
  15. Koutruba, N; Emer, J; Lebwohl, M (15 April 2010). "Review of ustekinumab, an interleukin-12 and interleukin-23 inhibitor used for the treatment of plaque psoriasis". Therapeutics and Clinical Risk Management. 6: 123–41. doi:10.2147/tcrm.s5599. PMC 2857612. PMID 20421912.
  16. "FDA Issues Complete Response Letter to Centocor for Ustekinumab Biologic License Application". Drugs.com (Press release). Centocor. 25 September 2009. Retrieved 6 April 2020.
  17. Medarex to Receive Milestone Payment for Approval of Stelara (Ustekinumab) for the Treatment of Moderate to Severe Plaque Psoriasis
  18. "drugbank.ca". Retrieved 4 October 2019.
  19. Stelara approved for moderate to severe psoriasis. Sept 2009
  20. "Drug Approval Package: Stelara (Ustekinumab) Injection NDA #125261". U.S. Food and Drug Administration (FDA). 24 December 1999. Retrieved 6 April 2020.
  21. "Stelara (ustekinumab) Injection NDA #761044". U.S. Food and Drug Administration (FDA). 12 January 2018. Retrieved 6 April 2020.
  22. 12 Sept 2017
  23. "Janssen's Stelara Gets FDA Approval for Ulcerative Colitis". FDA News. WCG. Retrieved October 31, 2019.
  24. "Stelara: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved 6 April 2020.
  • "Ustekinumab". Drug Information Portal. U.S. National Library of Medicine.
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