Rilonacept (arcalyst), an interleukin-1 trap for the treatment of cryopyrin-associated periodic syndromes.

Abstract

Cryopyrin-associated periodic syndromes (CAPS) comprise a group of rare inflammatory diseases that are inherited in an autosomal dominant pattern. Male and female offspring are affected equally with varying degrees of severity.1 CAPS comprise three syndromes: familial cold auto-inflammatory syndrome (FCAS), Muckle–Wells syndrome, and neonatal-onset multisystem inflammatory disease (NOMID), also referred to as chronic infantile neurological cutaneous articular syndrome (CINCA). The incidence of CAPS in the U.S. is estimated at 1 in 1,000,000 people, with a current prevalence of 300 to 500 individuals.2 Patients share common symptoms such as periodic fever, inflammation, and an urticaria-like skin rash. The diseases appear to represent a continuum, with FCAS the mildest and NOMID/CINCA the most severe.3,4 Clinical manifestations are listed in Table ​Table11.1,3–5 Table 1 Cryopyrin-Associated Periodic Syndromes Inflammation in CAPS is associated with autosomal-dominant mutations in the NLRP3 gene (also known as the CIAS1 gene) and resultant alterations in the protein cryopyrin, which it encodes. Cryopyrin regulates the activity of caspase-1, which is responsible for converting interleukin-1β (IL-1β) to its active form, resulting in the activation of the immune and inflammatory systems. Mutations in the NLRP3 gene lead to overproduction of IL-1β, resulting in the inflammatory symptoms associated with CAPS.2,6