Old and new drugs used in rheumatoid arthritis: a historical perspective. Part 1: the older drugs

Am J Ther. Mar-Apr 2001;8(2):123-43. doi: 10.1097/00045391-200103000-00007.


Rheumatoid arthritis is the paradigmatic immune-mediated inflammatory arthropathy and may be of comparatively recent, New World origin. Apart from the symptom-relieving nonsteroidal anti-inflammatory drugs, whose natural congeners have been in use since antiquity for musculoskeletal pain and inflammation, only a dozen drugs or drug classes--the disease-modifying antirheumatic drugs--are currently in common use in rheumatoid arthritis. Development of these drugs has been a notable achievement of the 20th century. Some were developed serendipitously (glucocorticoids, antimalarials), some were the product of faulty reasoning (gold, D-penicillamine), and others were applied for plausible reasons but whose mechanism remains unproven (sulfasalazine, methotrexate, minocycline). A minority were originally applied on the basis of actions that remain germane to the pathophysiology of rheumatoid arthritis as currently understood (azathioprine, cyclosporine, leflunomide, infliximab, etanercept). Among the latter are the more recently introduced and effective agents. The practical use of these drugs is determined by efficacy-toxicity considerations, which have also driven the recent development of the cyclooxygenase-2-selective nonsteroidal anti-inflammatory drugs.

Publication types

  • Historical Article
  • Review

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / history
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Antimalarials / history
  • Antimalarials / therapeutic use
  • Antirheumatic Agents / history
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / history
  • Azathioprine / history
  • Azathioprine / therapeutic use
  • Glucocorticoids / history
  • Glucocorticoids / therapeutic use
  • Gold / history
  • Gold / therapeutic use
  • History, 20th Century
  • Humans
  • Methotrexate / history
  • Methotrexate / therapeutic use
  • Penicillamine / history
  • Penicillamine / therapeutic use
  • Sulfasalazine / history
  • Sulfasalazine / therapeutic use


  • Anti-Inflammatory Agents, Non-Steroidal
  • Antimalarials
  • Antirheumatic Agents
  • Glucocorticoids
  • Sulfasalazine
  • Gold
  • Penicillamine
  • Azathioprine
  • Methotrexate