The problem of choice: current biologic agents and future prospects in RA

The introduction of biologic agents to clinical practice has had a major bearing on the treatment of patients with chronic inflammatory diseases such as rheumatoid arthritis. These drugs have the potential to improve the outcome of disease and the quality of life for patients. However, clinical criteria alone are inadequate for determining which therapy is most appropriate for an individual patient. Furthermore, why a particular drug is effective in a particular patient, or indeed in any patient, but is ineffective for other individuals, is often unknown. In this Review, we provide an overview of biologic therapies currently available for patients with rheumatoid arthritis, and discuss why certain immunological regulators represent potential targets for intervention. Current agents can be clustered into three major types: cytokine blockers, lymphocyte-targeting agents, and small-molecule inhibitors of signal transduction pathways. We differentiate among the modes of action of each of these types of therapy and consider the challenges associated with their use in clinical practice.