Interleukin-1β inhibitors for the treatment of cryopyrin-associated periodic syndrome.

Cryopyrin-associated periodic syndrome (CAPS) comprises a group of rare, but severe, inherited autoinflammatory disorders associated with aberrant secretion of interleukin (IL)-1. These distinct conditions of autoinflammatory origin include Muckle-Wells syndrome, familial cold autoinflammatory syndrome, and neonatal-onset multisystem inflammatory disease (NOMID), which is also referred to as chronic infantile neurologic cutaneous and articular syndrome. Recently, this group of diseases has been associated with mutations in the NLRP3 gene that encodes for the protein cryopyrin, a component of the inflammasome complex that regulates the maturation and secretion of inflammatory cytokine IL-1β. Immune cells from patients with NOMID secrete higher levels of active IL-1β compared with monocytes from healthy subjects. Overproduction of IL-1 is believed to promote aberrant inflammatory response in CAPS patients. Evidence supporting the clinical value of IL-1β in CAPS has been provided from the complete response of patients after treatment with IL-1 blocking agents.