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Corticosteroids in rheumatoid arthritis

Effective anti-inflammatory agents but doubts about safety remain
Elaine M Dennison, Wellcome training research fellow and Cyrus Cooper, Professor of rheumatology

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The millennium brings with it the 50th anniversary of Hench’s discovery that corticosteroids might be used to treat rheumatoid arthritis.1 Attitudes towards such use have waxed and waned since then. Initial hope that steroids might dramatically alter the long term course of the disorder gave way to a recognition of the serious adverse effects that accompany high dose treatment. As a result the use of low dose corticosteroids in arthritis remains highly controversial.

Corticosteroids are used widely in medicine today. A recent survey in general practice found that 1.4% of patients aged over 54 were using corticosteroids at a mean dose of 8 mg daily2: rheumatoid arthritis was the indication in 23% of cases. Although rheumatologists claim to use steroids relatively infrequently, audits of patients attending outpatient departments suggest a high prevalence of use (as great as 80%).3,4 What, then, is the quality of the evidence to support the use of corticosteroids in rheumatoid arthritis?

This question is best answered by considering the balance between the risks and benefits of steroid use for short periods (two to three months), with the objective of suppressing generalised flares of synovitis, and for longer periods (two years or more) in an attempt to modify the progression of structural disease. The best controlled data on efficacy and safety originate from long term studies that examine endpoints such as the progression of erosive disease. Yet many rheumatologists use short term courses of steroids, either as a “bridge” to suppress inflammation while other disease modifying drugs take effect or to combat acute flares of the disease.5

Direct comparison between the studies addressing both issues is hampered by differences in disease duration, severity, and concurrent treatment among patients recruited. One of the earliest clinical trials compared cortisone with aspirin over three years6: both regimens improved patient function and reduced the erythrocyte sedimentation rate, with no clear benefit attributable to cortisone. More recently, a Dutch trial comparing prednisolone 10 mg daily with placebo as an adjunct to intramuscular gold reported clinical improvement in both groups over 12 weeks; this was greatest among those treated with prednisolone.7 However, there appeared to be a rebound deterioration when the dose of prednisolone was tapered. Finally, the Arthritis and Rheumatism Council trial randomised 128 patients to prednisolone 7.5 mg daily or placebo in addition to non-steroidal and disease modifying agents.8 Symptomatic benefit was maintained for only 6-9 months of the two year follow up.

A meta-analysis of the effectiveness of low dose corticosteroids in rheumatoid arthritis based on 9 of 34 studies identified in a rigorous search strategy9 compared the effectiveness of prednisolone to either placebo or active drug controls (aspirin, chloroquine, or deflazacort). Although corticosteroids tended to be better at reducing the number of tender or swollen joints and the erythrocyte sedimentation rate, these differences were not significant.

Whether corticosteroids attenuate the progression of erosive damage is also unresolved. In the Arthritis and Rheumatism Council study prednisolone had a pronounced and significant (P