Ustekinumab, sold under the brand name Stelara is a

monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies ca ...

medication developed by

Janssen Pharmaceuticals Janssen Pharmaceuticals is a pharmaceutical company headquartered in Beerse, Belgium, and wholly-owned by Johnson & Johnson. It was founded in 1953 by Paul Janssen. In 1961, Janssen Pharmaceuticals was purchased by New Jersey-based American c ...

, for the treatment of

Crohn's disease Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea (which may be bloody if inflammation is severe), fever, abdominal distension ...

ulcerative colitis Ulcerative colitis (UC) is a long-term condition that results in inflammation and ulcers of the colon and rectum. The primary symptoms of active disease are abdominal pain and diarrhea mixed with blood (hematochezia). Weight loss, fever, and a ...

plaque psoriasis Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by skin plaque, raised areas of abnormal skin. These areas are erythema, red, pink, or purple, Xeroderma, dry, itchy, and scaly. Psoriasis varies in severity from small ...

and

psoriatic arthritis Psoriatic arthritis is a long-term inflammatory arthritis that occurs in people affected by the autoimmune disease psoriasis. The classic feature of psoriatic arthritis is swelling of entire fingers and toes with a sausage-like appearance. Thi ...

, targeting both IL-12 and IL-23. Ustekinumab 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. It was found not effective for

multiple sclerosis Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This d ...

. It is administered either by intravenous infusion or subcutaneous injection. The antibody targets a subunit of human

interleukin 12 Interleukin 12 (IL-12) is an interleukin that is naturally produced by dendritic cells, macrophages, neutrophils, and human B- lymphoblastoid cells ( NC-37) in response to antigenic stimulation. IL-12 belongs to the family of interleukin-12. I ...

and

interleukin 23 Interleukin 23 (IL-23) is a heterodimeric cytokine composed of an IL-12B (IL-12p40) subunit (which is shared with IL-12) and an IL-23A (IL-23p19) subunit. IL-23 is part of the IL-12 family of cytokines. The functional receptor for IL-23 (the ...

, which are naturally occurring proteins that regulate the immune system and immune-mediated inflammatory disorders.

Medical uses

Ustekinumab is used to treat

psoriasis Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by raised areas of abnormal skin. These areas are red, pink, or purple, dry, itchy, and scaly. Psoriasis varies in severity from small, localized patches to complete ...

. This includes

when it affects the skin. It is indicated for the treatment of adult and adolescent patients (12 years and older) with moderate to severe

(Ps) who are candidates for

phototherapy Light therapy, also called phototherapy or bright light therapy is intentional daily exposure to direct sunlight or similar-intensity artificial light in order to treat medical disorders, especially seasonal affective disorder (SAD) and circadi ...

or systemic therapy, and adults with active psoriatic arthritis (PsA) alone or in combination with

methotrexate Methotrexate (MTX), formerly known as amethopterin, is a chemotherapy agent and immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancies. Types of cancers it is used for include breast cancer, leuke ...

. 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 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); 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

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 Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in ...

and an increased risk of certain types of

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

. As with some other immunosuppressant drugs like

ciclosporin Ciclosporin, also spelled cyclosporine and cyclosporin, is a calcineurin inhibitor, used as an immunosuppressant medication. It is a natural product. It is taken orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's disease, ...

, the brain swelling of

posterior reversible encephalopathy syndrome Posterior reversible encephalopathy syndrome (PRES), also known as reversible posterior leukoencephalopathy syndrome (RPLS), is a rare condition in which parts of the brain are affected by swelling, usually as a result of an underlying cause. Some ...

is a risk. The pharmaceutical company also reports serious

allergic reaction Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derma ...

as a possible side effect. More common side effects are

upper respiratory infection An upper respiratory tract infection (URTI) is an illness caused by an acute infection, which involves the upper respiratory tract, including the human nose, nose, Paranasal sinus, sinuses, pharynx, larynx or trachea. This commonly includes nasal ...

headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...

, and

tiredness Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...

. 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 Inflammation (from la, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and is a protective response involving immune cells, blood vessels, and molecu ...

through the suppression of certain

cytokines Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...

. Specifically, it blocks

interleukin Interleukins (ILs) are a group of cytokines (secreted proteins and signal molecules) that are expressed and secreted by white blood cells (leukocytes) as well as some other body cells. The human genome encodes more than 50 interleukins and related ...

IL-12 and IL-23 which help activate certain

T-cells A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell rec ...

. It binds to the

p-40 The Curtiss P-40 Warhawk is an American single-engined, single-seat, all-metal fighter and ground-attack aircraft that first flew in 1938. The P-40 design was a modification of the previous Curtiss P-36 Hawk which reduced development time an ...

subunit of both IL-12 and IL-23 so that they subsequently cannot bind to their receptors.

History

, there were five NIH-listed research studies involving CNTO 1275 on a multinational basis, including three Phase II and two 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 A biologics license application (BLA) is defined by the U.S. Food and Drug Administration (FDA) as follows: The biologics license application is a request for permission to introduce, or deliver for introduction, a biologic product into inters ...

(BLA) with the US Food and Drug Administration (FDA) was filed by Centocor and

Janssen-Cilag Johnson & Johnson (J&J) is an American multinational corporation founded in 1886 that develops medical devices, pharmaceuticals, and consumer packaged goods. Its common stock is a component of the Dow Jones Industrial Average and the company i ...

International (collaborator) submitted a Marketing Authorization Application (MAA) to the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...

(EMA). On November 21, 2008, the

Committee for Medicinal Products for Human Use The Committee for Medicinal Products for Human Use (CHMP), formerly known as Committee for Proprietary Medicinal Products (CPMP), is the European Medicines Agency's committee responsible for elaborating the agency's opinions on all issues regarding ...

(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.

Approvals

Since 2009, ustekinumab is approved in Canada, the European Union, and the United States to treat moderate to severe

. On September 24, 2013, the US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

(FDA) approved the use of ustekinumab for the treatment of

. 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. 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, for the treatment of Crohn's disease. Since September 2017, ustekinumab is available on the AU Pharmaceutical Benefits Scheme for the treatment of severe Crohn's disease in adults. In 2019, the European Commission approved 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.

References

External links

* {{Portal bar , Medicine Immunosuppressants Johnson & Johnson brands Janssen Biotech Monoclonal antibodies Disease-modifying antirheumatic drugs