Therapy for rheumatoid arthritis: combinations of disease-modifying drugs and new paradigms of treatment

Semin Arthritis Rheum. 1991 Oct;21(2 Suppl 1):21-34. doi: 10.1016/0049-0172(91)90048-5.


The last 10 years have witnessed a change in the way rheumatologists view rheumatoid arthritis (RA). It is no longer considered a slowly progressive disease limited to the joints, but rather an aggressive systemic disease that results in clinically significant morbidity early in its course and can contribute to excess mortality. Heightened awareness of the health impact of RA has spurred a search for effective therapy to be applied early in the course of disease for patients with moderate to severe RA. Combinations of disease-modifying antirheumatic drugs (DMARD) have become an increasingly popular alternative to sequential monotherapy. In this report, we review published series of patients with RA who have been treated with combinations of DMARDs, sometimes including chemotherapeutic agents, with some critical comment. Published paradigms of treatment are also reviewed and a new strategy is presented. The "step-down bridge" strategy allows early treatment with at least four DMARDs, but may place some patients with mild disease at an inappropriately high risk of adverse effects. The "sawtooth" strategy gives little guidance as to which DMARD(s) should be chosen for initial treatment. We describe a "graduated-step" strategy that provides numerical grading to match disease severity and disease activity with appropriate initial therapy and that facilitates therapeutic decisions throughout the course of treatment.

Publication types

  • Review

MeSH terms

  • Anti-Inflammatory Agents
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Arthritis, Rheumatoid / drug therapy*
  • Azathioprine / therapeutic use
  • Clinical Trials as Topic
  • Cyclophosphamide / therapeutic use
  • Drug Therapy, Combination
  • Humans
  • Hydroxychloroquine / therapeutic use
  • Methotrexate / therapeutic use
  • Penicillamine / therapeutic use


  • Anti-Inflammatory Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • Hydroxychloroquine
  • Cyclophosphamide
  • Penicillamine
  • Azathioprine
  • Methotrexate