[IL-1 antagonists]

Interleukin (IL)-1 plays an important role not only in the mediation of inflammation but also in the destruction of cartilage and bone. Together with TNF-alpha it is one of the most important cytokines in the pathogenesis of rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA). The first IL-1 antagonist to be approved for RA was Anakinra, an IL-1 receptor antagonist. Anakinra appears to be less effective for RA than TNF blockers. Hence, Anakinra is rarely used for the treatment of RA, but more for the treatment of IL-1-mediated diseases such as autoinflammatory syndromes, adult-onset Still's disease and systemic onset JIA. Two newer IL-1 antagonists have recently been approved for the treatment of CAPS (cryopyrin-associated periodic syndromes): Canakinumab, a fully human IL-1beta antibody, and rilonacept, a fusion protein consisting of the ligand-binding domain of the IL-1 receptor and the IL-1-receptor accessory protein, bound to human IgG1. For RA, there is only one proof-of-concept study to date with canakinumab. There are no prospective data for the treatment of patients with RA who did not respond to or tolerate TNF antagonists; in a retrospective analysis, only 8% of anti-TNF pretreated patients achieved an ACR 20 response.