THE RELATIVE TOXICITY OF DISEASE-MODIFYING ANTIRHEUMATIC DRUGS

Objective. To compare the toxicities of commonly employed disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis (RA). Methods. Toxicity Index scores, computed from symptoms, laboratory abnormalities, and hospitalizations attributable to DMARD therapy, were assessed in 2,747 patients with RA receiving 3,053 courses of 6 DMARDs and 1,309 courses of prednisone over 7,278 patient-years. Results were adjusted for severity of illness and other covariates. Results. least toxic was hydroxychloroquine (mean +/- SEM score 1.38 +/- 0.15), followed by intramuscular gold (2.27 +/- 0.17) and the closely grouped D-penicillamine (3.38 +/- 0.36), methotrexate (3.82 +/- 0.35), and azathioprine (3.92 +/- 0.39). Auranofin (5.25 +/- 0.32) was most toxic, but this toxicity resulted from a high frequency of minor complications. Hospitalizations because of auranofin or hydroxychloroquine therapy were not noted. Prednisone (3.83 +/- 0.39) was of comparable toxicity, although it is likely that not all events of prednisone toxicity were captured. For reference, the toxicity of methotrexate and azathioprine was similar to that of the most toxic nonsteroidal antiinflammatory drugs (NSAIDs) (indomethacin 3.99, tolmetin sodium 3.96, and meclofenamate 3.86). Hydroxychloroquine showed less toxicity than the most commonly used prescription NSAIDs. Conclusion. There are substantial differences in toxicity among DMARDs and less important differences in toxicity between specific DMARDs and specific NSAIDs.