Interleukin-1 in Rheumatoid Arthritis: Its Inhibition by IL-1Ra and Anakinra

Abstract

Objective: To review the biology of interleukin-1 (IL-1) in the pathogenesis of rheumatoid arthritis (RA), as well as the biology of its natural inhibitor, IL receptor antagonist (IL-1Ra), and the clinical efficacy and safety of the recombinant form, anakinra. Data Sources: A MEDLINE search (1966–January 2007) of English-language articles was conducted using the key words anakinra, arthritis, clinical trial, interleukin-1 receptor antagonist, and Kineret. Study Selection and Data Extraction: Over 79 research articles and literature reviews were used to compile a discussion of the biology of IL-1 and IL-1Ra. Ten of these articles were selected to discuss the clinical safety and efficacy of anakinra. Data Synthesis: In RA, IL-1 primarily acts locally to mediate erosion of cartilage and bone. IL-1Ra serves to modulate its activity through competitive inhibition of cellular receptors. Administration of anakinra to animals with experimental arthritis reduced inflammation and joint damage. In clinical trials, anakinra was reasonably well tolerated; however, injection site reactions were frequent and there was a slight increased risk of serious infection. Alone or in combination with methotrexate, anakinra significantly reduced the symptoms and clinical signs of RA at the American College of Rheumatology 20% response level. However, no additive benefit was observed following coadministration with etanercept, a soluble tumor necrosis factor antagonist, and anakinra had no beneficial effect in patients that failed treatment with etanercept. Conclusions: Laboratory studies have indicated that IL-1 is primarily responsible for cartilage destruction and bone erosion in RA. The selective inhibition of IL-1 through administration of anakinra may offer symptomatic relief of RA in some patients.