OTEZLA
Otezla. Apremilast, sold under the brand name Otezla among others, is a medication for the treatment of certain types of psoriasis and psoriatic arthritis. It may also be useful for other immune system related inflammatory diseases. The drug acts as a selective inhibitor of the enzyme phosphodiesterase 4 (PDE4) and inhibits spontaneous production of TNF-alpha from human rheumatoid synovial cells. It is taken by mouth.
Apremilast, sold under the brand name Otezla among others, is a medication for the treatment of certain types of psoriasis and psoriatic arthritis. It may also be useful for other immune system related inflammatory diseases. The drug acts as a selective inhibitor of the enzyme phosphodiesterase 4 (PDE4) and inhibits spontaneous production of TNF-alpha from human rheumatoid synovial cells.[5] It is taken by mouth.
In the European Union, Apremilast alone or in combination with disease-modifying antirheumatic drugs (DMARDs), is indicated for the treatment of active psoriatic arthritis (PsA) in adults who have had an inadequate response or who have been intolerant to a prior DMARD therapy. It is also indicated for the treatment of moderate to severe chronic plaque psoriasis in adults who failed to respond to or who have a contraindication to, or are intolerant to other systemic therapy including cyclosporine, methotrexate or psoralen and ultraviolet-A light (PUVA). In the European Union, the drug is contraindicated during pregnancy because mice and monkeys receiving very high doses of apremilast have been observed to suffer miscarriages and other pregnancy problems. In the U.S., it may be used for pregnant women “if the potential benefit justifies the potential risk to the fetus”.
Apremilast is a small molecule inhibitor of PDE4, an enzyme that breaks down cyclic adenosine monophosphate (cAMP). In inflammatory cells, PDE4 is the dominant enzyme responsible for this reaction. The resulting increase in cAMP levels down-regulates expression of a number of pro-inflammatory factors like tumor necrosis factor alpha (TNFα), interleukin 17, interleukin 23, and many others, and up-regulates the anti-inflammatory interleukin 10. In ex vivo models of arthritis, IL-12/IL-23p40 was specifically identified as a downstream target of apremilast. The importance of these individual factors for the clinical effect of apremilast is not clear.
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