Ustekinumab, sold under the brand name Stelara among others, is a monoclonal antibody medication used for the treatment of Crohn's disease, ulcerative colitis, plaque psoriasis and psoriatic arthritis, targeting both IL-12 and IL-23. It is administered either by intravenous infusion or subcutaneous injection. 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. Ustekinumab was developed by Centocor Ortho Biotech. Ustekinumab (an immunosuppressant interleukin inhibitor) is a fully human IgG1κ monoclonal antibody that binds to the shared p40 protein subunit of interleukin (IL) 12 and 23, thereby preventing them from binding to the IL-12Rβ1 receptor protein expressed on the surface of immune cells. By doing so, ustekinumab prevents the activation of the Th1 and Th17 cytokine pathways, which are central to the pathology of psoriasis, psoriatic arthritis, Crohn's disease and ulcerative colitis. Ustekinumab is approved to treat Crohn's disease in the United States, Israel, Australia, and the European Union; and ulcerative colitis in the United States, and in the European Union to people who have not responded to more traditional treatments. It was found not effective for multiple sclerosis. It is on the World Health Organization's List of Essential Medicines.
Medical uses Ustekinumab is used to treat psoriasis. This includes psoriatic arthritis when it affects the skin. 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. It is also used to treat moderately to severely active Crohn's disease and moderately to severely active ulcerative colitis. In the European Union, ustekinumab is authorized for the treatment of moderate to severe plaque psoriasis in people 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); active psoriatic arthritis in adults; moderately to severely active Crohn's disease in adults; and moderately to severely active ulcerative colitis in adults.
Adverse effects The most common side effects include upper respiratory tract infection, headache, fatigue, nausea, vomiting, nasopharyngitis, injection site erythema, vulvovaginal candidiasis/mycotic infection, bronchitis, pruritus, urinary tract infection, sinusitis, abdominal pain, fever, and diarrhea. Clinical trials have shown that subcutaneous ustekinumab was generally well tolerated. Most treatment-emergent adverse events were of mild severity.
Pregnancy It is unknown if the medication is safe during pregnancy or breastfeeding.
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.
History Ustekinumab is a human monoclonal antibody (mAb) discovered through the generation of hybridoma cultures from immunized human immunoglobulin (hu-Ig) transgenic (Tg) mice. In December 2007, a biologic license application with the US Food and Drug Administration (FDA) was filed by Centocor; and Janssen-Cilag International (collaborator) submitted a marketing authorization application to the European Medicines Agency (EMA). In November 2008, the Committee for Medicinal Products for Human Use of the EMA adopted a positive opinion, recommending to grant a marketing authorization for the medicinal product Stelara, 45 mg or 90 mg powder for solution for injection, intended for the treatment of moderate to severe plaque psoriasis in adults who have failed to respond to, or who have a contraindication to, or who are intolerant to other systemic therapies including cyclosporine, methotrexate and psoralen plus ultra- violet A light [PUVA]). The applicant for this medicinal product is Janssen-Cilag International NV.
Society and culture
Legal status Ustekinumab is approved in Canada, the European Union, and the United States to treat moderate to severe plaque psoriasis. In September 2013, the US Food and Drug Administration (FDA) approved the use of ustekinumab for the treatment of psoriatic arthritis. In December 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. Ustekinumab was authorized for medical use in the European Union in January 2009. The FDA approved ustekinumab in September 2009, for the treatment of adults with moderate to severe plaque psoriasis. The FDA approved ustekinumab in September 2016, to treat Crohn's disease. Since September 2017, ustekinumab has been available on the AU Pharmaceutical Benefits Scheme to treat severe Crohn's disease in adults. In 2019, the European Commission authorized the use of ustekinumab for adults with moderately to severely active ulcerative colitis. In October 2019, the FDA approved the use of ustekinumab for adults with moderately to severely active ulcerative colitis.
Biosimilars
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