Cryopyrin-associated periodic syndromes (CAPS) are a subgroup of the hereditary periodic fever syndromes, which are rare autoinflammatory and inherited disorders, characterized by recurrent inflammation and varying degrees of severity. CAPS are thought to be driven by excessive production of interleukin-1β (IL-1β), through over-activation of the inflammasome by gain of function mutations in the gene encoding cryopyrin (NLRP3). This conclusion is supported by the remarkable efficacy of IL-1β blockade in these conditions. Rilonacept (Arcalyst(TM); Regeneron) is the first us Food and Drug Administration-approved treatment for familial cold autoinflammatory syndrome and Muckle-Wells syndrome and the first in a new line of drugs designed for longer-acting IL-1 blockade. Rilonacept has been associated with a decrease in disease activity, high-sensitivity C-reactive protein (hsCRP) and serum amyloid A (SAA) in the treatment of CAPS. The clinical safety and efficacy of rilonacept in CAPS and non-CAPS populations will be summarized in this review. Rilonacept is also beneficial for patients who tolerate injections poorly, due to an extended half-life over the unapproved CAPS treatment, anakinra, requiring weekly rather than daily self-administration. Other autoinflammatory disorders may also benefit from rilonacept treatment, with clinical trials in progress for systemic onset juvenile idiopathic arthritis, gout and familial mediterranean fever.
Keywords: IL-1 TRAP; autoinflammatory; cryopyrin-associated periodic syndromes; inflammasome; interleukin-1; rilonacept.