Rilonacept in cryopyrin-associated periodic syndromes: the beginning of longer-acting interleukin-1 antagonism

The remarkable effectiveness of interleukin (IL)-1 beta blockade in treating the cryopyrin-associated periodic syndromes ( CAPS), which present with unexplained fevers and severe localized inflammation, has provided strong evidence for a direct role of IL-1 beta in the pathogenesis of these diseases. Since 2003, patients with CAPS have been treated with anakinra, a recombinant nonglycosylated human IL-1 receptor antagonist. The short half-life of anakinra, however, necessitates daily injections; therefore, new IL-1 beta antagonists with longer half-lives, such as the fusion protein rilonacept (IL-1 Trap), have been developed. In an open-label pilot study of rilonacept, five patients with CAPS showed sustained responses and the agent was well tolerated, whilst a phase III clinical study in a large number of patients demonstrated the drug's safety and clinical efficacy. Rilonacept is the first therapy approved by the FDA for the treatment of CAPS and offers a new alternative to anakinra. Further trials are necessary to assess the long-term safety and efficacy of rilonacept.