Arthritis treatment：关节炎的治疗.pptVIP

Image credit: /journal/the-internet-journal-of-rheumatology/volume-5-number-2/management-of-inadequate-response-to-tnf-antagonist-therapy-in-rheumatoid-arthritis-what-are-the-options.html#sthash.LcCZjZcm.dpbs * JAK Family Tyrosine kinase proteins Family includes: JAK1 JAK2 JAK3 TYK2 Plays an important role in mediating the intracellular signal transduction of cytokines * Acting in pairs, JAK proteins facilitate the phosphorylation of intracellular proteins Phosphorylation of the signal transducer and activator of transcription (STAT) leads to altered gene transcription STAT controls autoimmune and inflammatory responses 26 JAK Proteins * Tofacitinib Small, non-biologic DMARD with demonstrated efficacy in treating RA Interferes with the signalling pathways of JAK1 and JAK3 JAK3 associates with the ?-chain of common cytokine receptors These receptors are used by interleukins to regulate lymphocyte activation and production Inhibition leads to anti-inflammatory and immunosuppressive effects * Tofacitinib: Inhibiting JAK-Dependent STAT Pathways Summary Summary of RA Treatment RA is an auto-immune disease with upstream mechanisms of activated macrophages, activated B cells and activated T cells; resulting in downstream cytokine production and destruction signaling pathways. Activated macrophages secrete (downstream) inflammatory cytokines TNF-α, and IL-6 and IL-1. TNF-α inhibitors ? etanercept, infliximab, adalimumab IL-6 receptor antagonist ? tocilizumab IL-1 receptor antagonist ? anakinra Activated B cells contribute to inflammation and destruction by producing autoantibodies (RF) and cytokine IL-6 Bind to CD20 antigen on B Cell and depletes B cells ? rituximab Activated (CD4+) T cells activate macrophages and B cells Upstream regulation of T Cell activation pathway ? abatacept Downstream signaling pathways (RANK, MMPs) JAK inhibitors to down regulate inflammatory responses ? tofacitinib * References Actemra. E-Therapeutics [Internet]. Canadian Pharmacists Associa