ab21218

Molecular differences in anticytokine therapies

L.H. Calabrese

Section of Clinical Immunology, Department of Rheumatic & Immunologic Disease, The Cleveland Clinic Foundation, Cleveland, Ohio, USA.

ABSTRACT
Biologic agents that inhibit proinflammatory cytokines have made a profound impact on the treatment of rheumatoid arthritis (RA). Of the agents that are currently approved by the US Food and Drug Administration (FDA) for this indication, etanercept and infliximab neutralize tumor necrosis factor (TNF), and anakinra inhibits interleukin-1 (IL-1). Adalimumab, which was just recently approved by the FDA, is also a TNF inhibitor. Despite their common ability to inhibit cytokine bio-activity, the molecular structures and mechanisms of action of these biologic agents are significantly different. The TNF-binding moiety of etanercept is derived from soluble TNF receptor subunits. Infliximab is a chimeric (mouse-human) monoclonal antibody to TNF, while adalimumab is a fully human anti-TNF monoclonal antibody. Ana-kinra has yet another mechanism of ac-tion: it is an IL-1 receptor antagonist. The molecular characteristics of these agents may be relevant to clinical efficacy and safety. These agents are still relatively new: to date, the longest re-porting time is 5 years, for etanercept. Additional long-term data will be required to determine the relative benefits and drawbacks of different molecular characteristics in these anticytokine agents.

Key words
Antirheumatic agents, rheumatoid arthritis, soluble tumor necrosis factor receptor, tumor necrosis factor.

L.H. Calabrese, DO, Head, Section of Clinical Immunology, Department of Rheumatic & Immunologic Disease, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.
E-mail: calabrl@cesmtp.ccf.org