Secukinumab, sold under the brand name Cosentyx, is a human IgG1κ

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 ...

used for the treatment of

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 comple ...

ankylosing spondylitis Ankylosing spondylitis (AS) is a type of arthritis characterized by long-term inflammation of the joints of the spine typically where the spine joins the pelvis. Occasionally areas affected may include other joints such as the shoulders or hi ...

, 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. T ...

. It binds to the protein interleukin (IL)-17A and is marketed by

Novartis Novartis AG is a Swiss-American multinational pharmaceutical corporation based in Basel, Switzerland and Cambridge, Massachusetts, United States (global research).name="novartis.com">https://www.novartis.com/research-development/research-lo ...

Medical uses

Secukinumab is used to treat

, and

. It is given by

subcutaneous injection Subcutaneous administration is the insertion of medications beneath the skin either by injection or infusion. A subcutaneous injection is administered as a bolus into the subcutis, the layer of skin directly below the dermis and epidermis, c ...

and is sold in a pre-filled syringe or

autoinjector An autoinjector (or auto-injector) is a medical device designed to deliver a dose of a particular drug. The injectors were initially designed to overcome the hesitation associated with self-administration of the needle-based drug delivery devic ...

that can be used at home and as a lyophilized powder for use in hospitals and clinics. Secukinumab was not tested in pregnant women; animal studies did not show harm at relevant doses. The US

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...

advises that the drug should be used in pregnant women only if the risk to the fetus is justified by the potential benefit; 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 Eur ...

(EMA) advises that women should not become pregnant while taking it. Secukinumab should not be given to people with active infections since it suppresses the immune system. In the European Union, secukinumab is indicated for the treatment of: * moderate to severe plaque psoriasis in adults, children and adolescents from the age of six years who are candidates for systemic therapy. * active psoriatic arthritis in adults, alone or in combination with methotrexate (MTX), when the response to previous disease modifying anti rheumatic drug (DMARD) therapy has been inadequate. * active ankylosing spondylitis in adults who have responded inadequately to conventional therapy. * active non-radiographic axial spondyloarthritis with objective signs of inflammation as indicated by elevated C-reactive protein (CRP) and/or magnetic resonance imaging (MRI) evidence in adults who have responded inadequately to non steroidal anti inflammatory drugs (NSAIDs).

Adverse effects

Very common (greater than 10% of people experience them) adverse effects include upper respiratory tract infections. Common (between 1% and 10% of people experience them) include oral herpes, runny nose, and diarrhea. In clinical trials there were rare instances of hypersensitivity reactions, severe infections, and some cases of serious

inflammatory bowel disease Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine, Crohn's disease and ulcerative colitis being the principal types. Crohn's disease affects the small intestine and large intestine, as well ...

, some of which were new and some of which were exacerbations of existing conditions. Caution should be used when starting secukinumab in patients with inflammatory bowel disease, and patients being treated with secukinumab should be monitored for signs and symptoms of inflammatory bowel disease.

Pharmacology

Secukinumab inhibits a member of the

cytokine 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 au ...

family,

interleukin 17A Interleukin-17A is a protein that in humans is encoded by the ''IL17A'' gene. In rodents, IL-17A used to be referred to as CTLA8, after the similarity with a viral gene (). Function The protein encoded by this gene is a proinflammatory cytok ...

, which is produced mainly by inflammatory T helper 17 cells. IL17A is upregulated in serum of people with psoriasis and in the synovial fluid of people with psoriatic arthritis, and promotes inflammation when it binds to the interleukin-17 receptor which is expressed in various types of cells, including

keratinocytes Keratinocytes are the primary type of cell found in the epidermis, the outermost layer of the skin. In humans, they constitute 90% of epidermal skin cells. Basal cells in the basal layer (''stratum basale'') of the skin are sometimes referre ...

in skin. It is mostly eliminated by being taken up into cells via

endocytosis Endocytosis is a cellular process in which substances are brought into the cell. The material to be internalized is surrounded by an area of cell membrane, which then buds off inside the cell to form a vesicle containing the ingested material. ...

and being broken down inside them.

Chemistry

Secukinumab is a recombinant fully human IgG1/kappa monoclonal antibody and is manufactured in

Chinese hamster ovary cell Chinese hamster ovary (CHO) cells are an epithelial cell line derived from the ovary of the Chinese hamster, often used in biological and medical research and commercially in the production of recombinant therapeutic proteins. They have found wide ...

History

Secukinumab was discovered and developed by Novartis using developmental name AIN457, and the first publication was a Phase I trial published in 2010. In January 2015, secukinumab was approved in the United States and in the European Union to treat adults with moderate-to-severe plaque psoriasis. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged. It is the first IL17A inhibiting drug ever approved. In January 2016, the FDA approved it to treat adults with

, and

and in February 2018, a label update was approved to include the treatment for moderate-to-severe scalp psoriasis.

References

External links

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