INTRODUCTION

Immunosuppressive drugs other than glucocorticoids are used in the treatment of various rheumatologic conditions to achieve one or more of the following goals:

• To induce or maintain a remission
• To reduce the frequency of flare or relapse
• To allow tapering of glucocorticoids while maintaining disease control

This topic review will provide an overview of the use of immunosuppressive drugs in various rheumatic diseases. Detailed discussions concerning the use of these drugs in specific rheumatic disorders are presented in the appropriate topic reviews.

MECHANISMS OF ACTION

The immunosuppressive drugs act by a variety of mechanisms. In general, the precise mechanisms responsible for most therapeutic benefits observed with these agents are understood only partially. Unlike biologic agents that selectively inhibit a proinflammatory cytokine and/or block its receptor, conventional immunosuppressive drugs interfere with combinations of critical pathways in the inflammatory cascade (table 1). Among the immunosuppressive drugs, several are “cytotoxic,” causing either cell death or impaired proliferation; such drugs include cyclophosphamide, chlorambucil, methotrexate, and azathioprine.

Other drugs suppress the immune system by inhibiting the proliferation or function of lymphocytes. This class includes drugs such as cyclosporine and tacrolimus, which specifically target calcineurin and thereby inhibit the production of interleukin (IL)-2 by activated T-lymphocytes [1]. Others prevent lymphocyte proliferation by inhibiting nucleotide synthesis. For example, mycophenolate mofetil blocks the synthesis of purines, and leflunomide inhibits pyrimidine synthesis [2,3].