The use of TNF-α blocking agents in rheumatoid arthritis: an update

Abstract

TNF-α has been found to play a pivotal role in the pathogenic mechanisms of rheumatoid arthritis (RA). Drugs targeting TNF-α have been developed to neutralise the deleterious effects of this inflammatory cytokine. There are, at present, three drugs available for the treatment of RA patients with active disease who are refractory to conventional treatments including methotrexate: 2 monoclonal antibodies, infliximab and adalimumab, and a fusion protein with p75 receptors, etanercept. These three agents have proved to be effective and safe in large placebo-controlled trials enrolling patients with established or early disease and showed effectiveness in controlling signs and symptoms of the disease, improving quality of life and in slowing and even arresting the progression of radiographic damage. With the long-term surveillance of these drugs were described serious adverse events, particularly infections such as tuberculosis, especially with infliximab. The risk for malignancies under TNF-α antagonists, especially lymphoma, remains controversial. Specific recommendations are given by international experts for selecting and monitoring RA patients with TNF-α antagonists. Other drugs targeting TNF-α such as PEGylated molecules (CDP870 or certolizumab) are in development. These new biological therapies blocking TNF-α undoubtedly constitute a considerable advancement in the management of RA, but careful evaluation at the initiation of the treatment and long-term surveillance of the patients receiving such drugs remains necessary.

Keywords::

• adalimumab
• etanercept
• infliximab
• methotrexate

Acknowledgements

The authors are indebted to Schering-Plough, Wyeth and Abbott laboratories for providing references to this article. Dr Éric Toussirot was invited by the Editorial board of Expert Opinion on Pharmacotherapy to write this review.