KEVZARA is a fully human monoclonal antibody that inhibits IL-6 receptor signaling.1,2
KEVZARA targets and binds with high affinity to soluble and membrane-bound IL-6 receptors (sIL-6R and mIL-6R)2
By binding to these receptors, KEVZARA blocks inflammatory effects of IL-6 and inhibits IL-6-mediated signaling1,4
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Rheumatoid arthritis, or RA, is a systemic autoimmune disease characterized by persistent inflammation leading to joint damage and physical disability.1 Immune cells and pro-inflammatory cytokines, such as tumor necrosis factor alpha, or TNF-alpha, and interleukin-6, or IL-6, as well as intracellular signaling pathways, such as the Janus kinase and signal transducer and activator of transcription, or JAK/STAT, contribute to RA development and progression.2-4 TNF-alpha and IL-6 exert their inflammatory effects through activation of pro-inflammatory cytokine signaling pathways central to RA.3 When binding to its membrane bound receptor, TNF-alpha primarily activates the nuclear factor-kappa-light-chain-enhancer of activated b cells, or NF-kappa B, pathway.5 In contrast, IL-6 primarily activates the JAK/STAT pathway.6 Both TNF-alpha and IL-6 can activate the mitogen-activated protein kinase, or MAPK, signaling pathways.6,7 These signaling features help explain both the overlapping and distinct roles that TNF-alpha, IL-6, JAK/STAT, NF-kappa B, and MAPK pathways play in RA pathogenesis.3 Persistently elevated levels of IL-6 play a direct role in inflammation and autoimmunity in RA.8,9 IL-6 acts through a dual signaling mechanism involving both a soluble and a cell membrane bound receptor.2 The membrane-bound IL-6 receptor is expressed only on certain cells. The IL-6/IL-6 receptor complexes become activated when they associate with glycoprotein 130, a transmembrane receptor expressed ubiquitously on the surface of most cells.2,10 As a result, elevated levels of IL-6 have widespread effects throughout the body,10 modulating both adaptive and innate immune responses.2,11 IL-6 is one of the most abundant cytokines in the synovial fluid of inflamed joints in patients with RA and plays a central role in the inflammatory pathways that may lead to chronic inflammation, disease progression, joint destruction, and systemic manifestations, including anemia, fatigue, and pain.2,12 It is also important to note that systemic inflammation can be accompanied by activation of acute phase response, like C-reactive protein.2,13 The ability to modulate these effects may be important to control RA disease activity. KEVZARA is a human monoclonal antibody that inhibits IL-6 receptor signaling.14,15 KEVZARA targets and binds with high affinity to soluble and membrane-bound IL-6 receptors15,16 (copy that appears on screen in video as this sentence is being said: The clinical consequence of this affinity is unknown). Thus, KEVZARA helps disrupt the effects of elevated IL-6 levels in adult patients with moderately to severely active RA.14,15,17
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