Ustekinumab

Ustekinumab
Monoclonal antibody
Type Whole antibody
Source Human
Target IL-12 and IL-23
Clinical data
Trade names Stelara
Synonyms CNTO 1275
AHFS/Drugs.com Monograph
MedlinePlus a611013
License data
Pregnancy
category
  • US: B (No risk in non-human studies)
    Routes of
    administration    		 subcutaneous injection, Infusion
    ATC code
    Legal status
    Legal status
    Pharmacokinetic data
    Metabolism unknown[1]
    Elimination half-life 15–32 days (average 3 weeks)[1]
    Identifiers
    CAS Number
    ChemSpider
    • none
    UNII
    KEGG
    ChEMBL
    Chemical and physical data
    Formula C6482H10004N1712O2016S46
    Molar mass 145.64 kg/mol
     ☒N☑Y (what is this?)   (verify)

    Ustekinumab,[2] sold under the brand name Stelara, is a human monoclonal antibody used to treat psoriasis.[3]

    It is manufactured in the Netherlands. It is directed against interleukin 12 and interleukin 23, naturally occurring proteins that regulate the immune system and immune-mediated inflammatory disorders.[4]

    Stelara is also FDA approved to treat Crohn's disease.[5] It was found not effective for multiple sclerosis.[6]

    Medical uses

    Ustekinumab is used to treat psoriasis. This includes psoriatic arthritis when it affects the skin.[3] It was also approved to treat Crohn's disease in September 2016.

    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.[7]

    Adverse effects

    According to information provided by Centocor, maker of one medication based on ustekinumab, their version of the drug 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.[8]

    Clinical trials have shown that subcutaneous ustekinumab was generally well tolerated. Most treatment-emergent adverse events were of mild severity.[9]

    Pregnancy

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

    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 U.S. Food and Drug Administration (FDA) was filed by Centocor and Janssen-Cilag International (collaborator) has submitted a Marketing Authorization Application (MAA) to the European Medicines Agency (EMEA).

    On November 21, 2008, the European Medicines Agency’s (EMEA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for ustekinumab for the treatment of moderate to severe plaque psoriasis in adult patients who failed to respond to other systemic therapies.[10]

    Approvals and indications

    Since 2009, Ustekinumab is approved in Canada, Europe and the United States to treat moderate to severe plaque psoriasis.[11] On September 24, 2013, the FDA approved the use of ustekinumab for the treatment of psoriatic arthritis.

    On December 12, 2008 the Canadian Health Authority approved the use of ustekinumab for the treatment of chronic moderate to severe plaque psoriasis in adult patients who are candidates for phototherapy or systemic therapy.[10]

    The FDA approved the drug on September 25, 2009 for the treatment of adult patients with moderate to severe plaque psoriasis.[12]

    The FDA approved the drug in September 2016 for the treatment of Crohn's disease.

    Clinical studies

    In September 2008, Centocor released result of a study comparing etanercept and ustekinumab. The etanercept group received subcutaneous injections of the drug twice weekly for 12-weeks while the ustekinumab group received 2 injections, one-month apart, of either 90 or 45 milligrams. At twelve weeks, psoriatic plaques were reduced by at least three-quarters in 68% of the low-dose ustekinumab group and 74% of the high-dose group. Both groups fared better than the etanercept group, 57% of whom saw such improvement. Dr. Alan Menter, chairman of psoriasis research at Baylor Research Institute said of the results, "now we have a drug that will be used less frequently ... with a significant increase in effectiveness. These results are as good as we've seen in psoriasis."[13]

    References

    1. 1 2 Summary of production characteristics Stelara, http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000958/WC500058513.pdf
    2. ↑ Cingoz, Oya (2009). "Ustekinumab". MAbs. 1 (3): 216–221. doi:10.4161/mabs.1.3.8593. PMC 2726595. PMID 20069753.
    3. 1 2 "Ustekinumab". The American Society of Health-System Pharmacists. Retrieved 8 January 2017.
    4. ↑ 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.
    5. ↑ FDA Approves STELARA® (Ustekinumab) for Treatment of Adults With Moderately to Severely Active Crohn's Disease. https://www.jnj.com/media-center/press-releases/fda-approves-stelara-ustekinumab-for-treatment-of-adults-with-moderately-to-severely-active-crohns-disease.
    6. ↑ 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.
    7. ↑ 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. PMC 2857612. PMID 20421912.
    8. ↑ "Important Safety Information". STELARA® (ustekinumab). Janssen Biotech.
    9. ↑ Weber J, Keam SJ (2009). "Ustekinumab". BioDrugs. 23 (1): 53–61. doi:10.2165/00063030-200923010-00006. PMID 19344192.
    10. 1 2 Centocor 12/19/08 Press Release, http://www.centocor.com/centocor/i/press_releases/FDA_ISSUES_COMPLETE_RESPONSE_LETTER_TO_CENTOCOR_FOR_USTEKINUMAB_BIOLOGIC_LICENSE_APPLICATION_
    11. ↑ Medarex to Receive Milestone Payment for Approval of STELARA(TM) (Ustekinumab) for the Treatment of Moderate to Severe Plaque Psoriasis
    12. ↑ Stelara approved for moderate to severe psoriasis. Sept 2009
    13. ↑ Johnson LL. "Study: Drug for serious psoriasis tops competition" The Associated Press. 18 Sept 2008. Archived September 27, 2008, at the Wayback Machine.
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