Therapeutic ReviewsOld and New Drugs Used in Rheumatoid Arthritis: A Historical Perspective Part 2: The Newer Drugs and Drug StrategiesCase, John P. Author Information Division of Rheumatology, Cook County Hospital, and Section of Rheumatology, Rush Medical College, Chicago, IL. Address for correspondence: Section of Rheumatology, 1725 West Harrison Street, Suite 1017, Chicago, IL 60612, USA. American Journal of Therapeutics: May 2001 - Volume 8 - Issue 3 - p 163-179 Buy Abstract After a 20-year hiatus, drug development for rheumatoid arthritis resumed in the early 1980s with cyclosporine, continuing in the 1990s with minocycline, leflunomide, and the tumor necrosis factor-alpha antagonists, infliximab and etanercept. Unlike the older disease-modifying antirheumatic drugs (apart from the cytotoxics), the newer drugs were designed with strict reference to proven pathophysiology in rheumatoid arthritis and, apart from minocycline, the intended action of these agents is highly likely the explanation for the observed efficacy. The evidence for the evolution of more rational drug development in rheumatoid arthritis has not altered the fact that efficacy versus toxicity still remains the major determinant in the practical use of these agents, as well as in the use of other, experimental agents briefly discussed. Action, efficacy, and toxicity also determine the rational chronologic use of these drugs alone and, in particular, in combination. © 2001 Lippincott Williams & Wilkins, Inc.