Cryopyrin-associated periodic syndromes (CAPS) are rare monogenic autoinflammatory diseases, comprising a spectrum of phenotypes of varying severity. CAPS are associated with gain-of-function mutations in the NLRP3 inflammasome, a multiprotein complex critical for the activation of IL-1ß, and are characterized by episodes of fever, urticaria-like rash, musculoskeletal, ocular, and neurological symptoms. Areas covered: Accounting for the pivotal role of IL-1ß in the pathogenesis of CAPS, three therapeutic options, all blocking the action of IL-1ß, are currently approved: anakinra, a recombinant IL-1 receptor antagonist, the IL-1 trap rilonacept and canakinumab, a monoclonal anti-IL-1ß antibody. All agents reduce or even resolve clinical symptoms, biochemical activity markers and improve quality of life in CAPS. This review also covers pharmacokinetic, pharmacodynamic and safety aspects of the approved drugs and the potential utility of IL-1β blockers in a wide range of other conditions with an autoinflammatory component. Expert commentary: Due to the success story of current pharmaceutics, the therapeutic options in CAPS are not expected to expand in the near future. Prospective observational studies are needed to confirm long-term efficacy and sustained benefit. New IL-1ß blockers will likely address unmet clinical needs in other autoinflammatory conditions.
Keywords: Anakinra; Cryopyrin-associated periodic syndrome; Familial Cold Autoinflammatory Syndrome; Muckle-Wells Syndrome; NLRP3 inflammasome; Neonatal Onset Multisystem Inflammatory Disease; autoinflammatory; canakinumab; interleukin-1; rilonacept.