Upcoming Biologic Agents for the Treatment of Rheumatic Diseases
The development of biologic agents has provided rheumatologists with a variety of new and effective treatment options. The success of early biologics, especially etanercept and infliximab for the treatment of rheumatoid arthritis, has spurred research into novel targets for the management of systemic inflammatory and autoimmune diseases. In addition, existing biologics approved for use in other diseases, such as rituximab, are now under study for the treatment of new indications. This article reviews ongoing research on the treatment of rheumatic diseases with new and existing biologic agents.

The terms biologic therapies and biologics have emerged as descriptive terms for therapeutic agents with biologic properties, including monoclonal antibodies and soluble cytokine receptors. In the treatment of rheumatic diseases, the first two biologics approved for use were the tumor necrosis factor (TNF)-




inhibiting agents etanercept and infliximab, both developed for the treatment of rheumatoid arthritis (RA). New agents have followed, including anakinra, a recombinant form of the naturally occurring interleukin (IL)-1 receptor antagonist, and adalimumab, a monoclonal antibody against TNF-



. The TNF-



and IL-1 antagonists have been approved for use and marketed for RA, but recent studies have demonstrated efficacy in other diseases. In addition, the commercial and clinical success of these agents has strongly influenced manufacturers to develop a new generation of biologic agents that inhibit cytokine behavior, cellular activation, and inflammatory gene transcription by various means. Some of the new therapies in development are not antibodies, soluble receptors, or natural antagonists, but rather small molecules that specifically inhibit intracellular, cell-cell, and cell-matrix interactions intrinsic to inflammatory and immune processes. Therefore, the term biologic therapies may better be replaced with a more accurate term, such as biologic response modifier or targeted therapy, that differentiates these finely tuned immunomodulators and antiinflammatory agents from less specific immunosuppressive drugs, such as cytotoxic agents and corticosteroids.


This review briefly examines the development of targeted therapies for the treatment of rheumatic disease. Each section is devoted to agents in development that aim to disrupt the inflammatory or immune response in a specific fashion, starting with cytokine inhibitors. The most extensively published activity has been the study of existing TNF inhibiting agents for new indications and new research into B-cell-directed therapy.