Hal M Hoffman1. 1. University of California at San Diego, Division of Rheumatology and Allergy/Immunology, Mail Code 0635, 9500 Gilman Drive, La Jolla, CA 92093-0635, USA. hahoffman@ucsd.edu
Abstract
BACKGROUND: Cryopyrin-associated periodic syndromes (CAPS) encompass a group of rare inherited, autoinflammatory disorders that represent a spectrum of one disease with varying degrees of severity. Until recently, there was no effective treatment for CAPS, but identification of the genetic basis of CAPS highlighted the pathogenic role of IL-1beta. OBJECTIVES: Rilonacept is a recently FDA approved biologic therapy for CAPS with high affinity for IL-1beta. Limited pharmacological data has been reported to date. METHODS: A review of the phamacokinetics and pharmacodynamics data as well as the results of a pilot study and Phase III placebo-controlled trials of rilonacept in CAPS. Unpublished data on an open-label extension study in adult and pediatric subjects is also reviewed. RESULTS: Rilonacept produced rapid and profound improvements in symptoms and also reduced high-sesitivity C-reactive protein levels and normalized elevated serum amyloid A concentrations, an important risk factor for amyloidosis. The primary adverse events were injection- site reactions and upper respiratory tract infections. CONCLUSION: Rilonacept, the only IL-1 Trap, is the first of many novel IL-1-targeted therapies being developed. In a very short time it has changed the lives of CAPS patients.
BACKGROUND: Cryopyrin-associated periodic syndromes (CAPS) encompass a group of rare inherited, autoinflammatory disorders that represent a spectrum of one disease with varying degrees of severity. Until recently, there was no effective treatment for CAPS, but identification of the genetic basis of CAPS highlighted the pathogenic role of IL-1beta. OBJECTIVES: Rilonacept is a recently FDA approved biologic therapy for CAPS with high affinity for IL-1beta. Limited pharmacological data has been reported to date. METHODS: A review of the phamacokinetics and pharmacodynamics data as well as the results of a pilot study and Phase III placebo-controlled trials of rilonacept in CAPS. Unpublished data on an open-label extension study in adult and pediatric subjects is also reviewed. RESULTS: Rilonacept produced rapid and profound improvements in symptoms and also reduced high-sesitivity C-reactive protein levels and normalized elevated serum amyloid A concentrations, an important risk factor for amyloidosis. The primary adverse events were injection- site reactions and upper respiratory tract infections. CONCLUSION: Rilonacept, the only IL-1 Trap, is the first of many novel IL-1-targeted therapies being developed. In a very short time it has changed the lives of CAPS patients.