ab_S18

Pharmacotherapeutic strategies for disease-modifying antirheumatic drug (DMARD) combinations to treat rheumatoid arthritis (RA)

T. Münster, D.E. Furst

Virginia Mason Research Center, Seattle, Washington, USA.

ABSTRACT
Objective
To provide a rational model for the use of disease-modifying antirheumatic drug (DMARD) combinations in the treatment of rheumatoid arthritis.

Methods
The DMARDs used today were examined for their mechanisms of action, kinetics, and toxicity, and collected into tabular formats for easier comparison. From these tables, matrices of potential positive or negative interfaces among combinations were constructed. Finally, these matrices were used to examine the usefulness of DMARD combinations by comparing them with published data.

Results
When clearly overlapping cells were found with respect to mechanisms of action, kinetics, or toxicity (e.g., methotrexate [MTX] plus azathioprine or MTX plus auranofin) predictions were good. When knowledge in these areas of kinetics and/or mechanisms of action were inadequate, predictions and results were not always consonant (e.g. MTX plus sulfasalazine; D-penicillamine plus hydroxychloroquine).

Conclusions
The approach demonstrated in this paper toward rational combination therapy is logical and can be successful, although its success is circumscribed by our knowledge about the drugs we use. The rational approach to combination therapy demonstrated in this article can: 1) help prevent the use of combinations unlikely to be effective; 2) can point toward directions for useful research; and 3) can even be used when physicians are faced with patients whose needs have exceeded our present scientific knowledge.

Key words
Rheumatoid arthritis, combination DMARD therapy, disease-modifying anti-rheumatic drugs, azathioprine, cyclosporine A, D-penicillamine, gold, hydroxychloroquine, leflunomide, methotrexate, minocycline, sulfasalazine.

Partially funded by the Rasmuson Center for Arthritis, Orthopedics and Musculoskeletal Diseases.

Please address correspondence and reprint requests to: Daniel E. Furst, MD, Director of Arthritis Clinical Research, Virginia Mason Research Center, 1100 9th Avenue R1 RHE, Box 900, Seattle, WA 98101, USA.