Upadacitinib
生产企业：AbbVie Inc.
Upadacitinib is an oral Janus kinase (JAK)1-selective inhibitor used in the treatment of moderate to severe rheumatoid arthritis, active psoriatic arthritis, ankylosing spondylitis, and severe atopic dermatitis, including in patients who did not respond well to other therapies.
Upadacitinib is an oral Janus kinase (JAK)1-selective inhibitor used in the treatment of moderate to severe rheumatoid arthritis, active psoriatic arthritis, ankylosing spondylitis, and severe atopic dermatitis, including in patients who did not respond well to other therapies.
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that involves the interplay of several mediators, including the immune cells (mainly T- and B-lymphocytes) and pro-inflammatory cytokines, such as the tumour necrosis factor (TNF), transforming growth factor (TGF), and interleukin 6 (IL-6). The Janus Kinase (JAK) family plays an essential role in the normal physiological functions (such as erythropoiesis), but also the signalling of pro-inflammatory cytokines that are implicated in many immune-mediated diseases. The JAK family consists of four isoforms (JAK1, JAK2, JAK3, and Tyrosine Kinase 2) that each interacts with different cytokine receptors and uniquely associates with the intracellular domains of Type I/II cytokine receptors. JAK1 is primarily involved in the signalling transduction pathways of IL-6, IFN and the common γ -chain cytokines, including IL-2 and IL-15. IL-6 has been closely studied in particular, as it is a major cytokine involved in B- and T-cell differentiation and the acute phase response in inflammation. Upon interaction of cytokines with their cytokine receptors, the JAKs mediate the JAK-STAT signal transduction pathway in response to receptor activation. JAKs are tyrosine kinases that cause phosphorylation of several proteins, including cytokine receptors and JAKs themselves. Phosphorylation of JAKs promotes the phosphorylation and activation of the signalling molecules called STATs, leading to their nuclear translocation, binding to DNA promoters, and target gene transcription. JAK1-mediated signalling pathways ultimately promote pro-inflammatory events, such as increased proliferation and survival of immune cells, T cell differentiation, and macrophage activation. Upadacitinib is a selective JAK1 inhibitor that has a negligible effect on JAK3, leading to an improved drug safety profile. Upadacitinib blocks the cellular processes that contribute to the inflammatory conditions in rheumatoid arthritis. In human leukocytes cellular assays, upadacitinib inhibited JAK1/3-induced phosphorylation of STAT3/5 mediated by IL-6/7.
Upadacitinib is indicated for the treatment of moderately to severely active rheumatoid arthritis or active psoriatic arthritis in adult patients who have had an inadequate response or intolerance to one or more disease-modifying anti-rheumatic drugs (DMARDs), such as TNF blockers. In Europe, upadacitinib may be used as monotherapy or in combination with methotrexate for rheumatoid or psoriatic arthritis. Upadacitinib is indicated for use in patients 12 years of age and older with refractory, moderate-to-severe atopic dermatitis whose disease is inadequately controlled with other systemic therapies or when other therapies are inadvisable. Upadacitinib is indicated for the treatment of active ankylosing spondylitis or radiographic axial spondyloarthritis in adult patients who have an inadequate response to conventional therapy. It is also indicated to treat non-radiographic axial spondyloarthritis with objective signs of inflammation in adults who have had an inadequate response or intolerance to TNF blocker therapy. Upadacitinib is also indicated to treat moderately to severely active ulcerative colitis in adults who have had an inadequate response or intolerance to either conventional therapy or a biologic agent, such as to one or more TNF blockers. Upadacitinib is indicated to treat moderately to severely active Crohn’s disease in adults who have had an inadequate response or intolerance to one or more TNF blockers. Combining upadacitinib with other JAK inhibitors, biologic DMARDs, or other potent immunosuppressive agents is not recommended.
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