The pathophysiology of pruritus is poorly understood, and the condition remains difficult to treat. Kiniksa’s mAb vixarelimab is a first-in-class fully human mAb that blocks OSMRβ. In the skin of patients with chronic pruritus, the cytokine OSM is highly expressed, as it is secreted by immune cells.
It signals through OSMRβ, but to generate itch sensations it must partner with interleukin-31 , made by T helper 2 cells. It is thought that pruritus is induced when IL-31 signals through the IL-31 receptor — which forms a heterodimer with OSMRβ — on keratinocytes and mast cells. These activated cells in turn mediate neuroimmune communications that transmit itch sensations to the central nervous system.
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