A REEVALUATION OF ASPIRIN THERAPY IN RHEUMATOID-ARTHRITIS

Background: Aspirin therapy has been largely superseded by prescriptio n nonsteroidal anti-inflammatory drug (NSAID) therapy in rheumatoid ar thritis, in part because of premarketing studies suggesting lesser tox ic effects for NSAIDs than for aspirin. This study evaluates these tox ic effects in a postmarketing population of patients with rheumatoid a rthritis. Methods: We studied 1521 consecutive courses of aspirin and 4860 courses of NSAIDs in patients with rheumatoid arthritis from eigh t Arthritis, Rheumatism, and Aging Medical Information System Post-mar keting Surveillance Centers. Toxicity index scores were generated from symptoms, laboratory abnormalities, and hospitalizations, weighted fo r variable severity and severity of side effect. Results: The toxicity index was only 1.37 (SE=0.10) for aspirin and 1.87 to 2.90 for select ed nonsalicylate NSAIDs. These differences were consistent across cent ers and remained after statistical adjustment for differing patient ch aracteristics. There was a different toxicity with different aspirin p reparations, with a score for plain aspirin of 1.36 (SE=0.23), for buf fered aspirin of 1.10 (0.20), and for enteric-coated aspirin preparati ons of 0.92 (0.14). Most important, there were strong dose effects, wi th a score of 0.73 (0.09) for 651 to 2600 mg daily, 1.08 (0.17) for 26 01 to 3900 mg, and 1.91 (0.38) for more than 3900 mg. The average aspi rin dose taken was only 2665 mg/d, approximately eight ''tablets,'' co mpared with 3600 to 4800 mg/d used in the 16 pivotal premarketing stud ies reviewed. Average NSAID doses were, on the other hand, lower in pr emarketing trials (eg, naproxen 500 mg/d vs 773 mg/d in the Arthritis, Rheumatism, and Aging Medical System clinical practices). Conclusions : Aspirin therapy, in doses commonly employed in practice, has an exce llent safety profile in rheumatoid arthritis, and it is the least cost ly NSAID. The safety advantage is explained primarily by a dose effect and secondarily by possible differences between formulations. Newer m anagement strategies for rheumatoid arthritis emphasize NSAID use as s ymptomatic therapy and use of disease-modifying anti-rheumatic drug th erapy for antiinflammatory objectives. Thus, the original recommendati on for ''anti-inflammatory'' doses of aspirin now is less easily justi fied. Aspirin therapy merits reconsideration as adjunctive therapy for the management of rheumatoid arthritis.