Disease-modifying antirheumatic drugs. Using their clinical pharmacological effects as a guide to their selection

Rheumatoid arthritis is a disease of unknown aetiology characterised by persistent joint swelling, functional disability and increased mortality. No curative therapy exists at present but some therapeutic agents, commonly referred to as disease-modifying drugs, offer the potential for suppression of the inflammatory activity and attenuation of the disease process. Since the precise mechanism of action of most disease modifying drugs is uncertain, the selection of a particular therapy must at present be based on the pharmacologic properties of each available agent, appropriately individualised for each clinical setting. The toxicity of disease-modifying agents often limits the dose and/or duration of therapy and makes careful monitoring mandatory. No consensus exists as to the order in which disease-modifying agents should be employed. Less toxic disease-modifying drugs such as auranofin, hydroxychloroquine, minocycline, and sulfasalazine are usually used in early and mild disease. Azathioprine, penicillamine (D-penicillamine), methotrexate and parenteral gold are usually considered to be more toxic and are most often used in the setting of progressive disease while the most toxic agents, such as chlorambucil and cyclophosphamide, are reserved for life-threatening manifestations such as vasculitis. Newer therapeutic approaches presently under study include the use of existing drugs in combination and novel biologic agents which selectively inhibit lymphocyte and cytokine activity. These strategies offer the hope of more efficacious and less toxic therapy in the future.