Focus on: biologics that affect therapeutic agents in dermatology

Tumor necrosis factor (TNF)-alpha is one of the oldest known cytokines in human physiology. It is involved in both normal and pathologic states. Virtually every cell and organ in the body are affected by TNF-alpha. Though TNF-alpha is usually involved in inflammation as a normal host defense response, when overproduced, it can become pathologic and affect almost every organ system. In this article, we address the role of TNF-alpha in diseases such as rheumatoid arthritis, Crohn's disease, psoriasis, and ankylosing spondylitis as well as the drugs used to modulate TNF-alpha. Specifically, we look at the structure, mechanism of action, and clinical use for etanercept, infliximab, and adalimumab. Historically, we also review the drug lenercept, another TNF-alpha modulator. These drugs offer alternative effective treatments to rheumatologic and dermatologic diseases without as many of the toxic side effects of some of the traditional therapies. The traditional agents target TNF-alpha in addition to several other modes of action (disease modifying anti-rheumatic drugs [DMARDS] such as cyclosporine and methotrexate) (Table 1). Though TNF-alpha immunomodulation seems to be a very effective, promising treatment in several TNF-alpha mediated disease processes, long-term studies need to be performed to assess the risk-benefit ratio of using these drugs over an extended period of time.