Drug treatment for rheumatoid arthritis (RA) usually includes a nonsteroidal anti-inflammatory drug (NSAID) and a disease-modifying antirheumatic drug. Newer agents include tumor necrosis factor-3 blocking agents and interleukin-1 receptor antagonists. Glucocorticoids have been less popular because of their many side effects and a concern that inhibiting inflammation may not delay joint damage. Recent studies have shown that glucocorticoids reduced the progression of joint damage when used in conjunction with disease-modifying antirheumatic drugs, suggesting that glucocorticoids may also have beneficial disease-modifying effects. The side effects of glucocorticoids, such as osteoporosis and gastrointestinal complications, can now be minimized by using protective drugs. Van Everdingen and colleagues used a randomized, placebo-controlled, double-blind study to test the efficacy and side-effects of low-dose glucocorticoid therapy in previously untreated patients with early active RA.

Patients with RA for less than one year who had not received treatment were given either 10 mg of oral prednisone (n = 40) or placebo (n = 41). Both groups were given 500 mg of elementary calcium in the evening. Patients were followed for two years with regular clinical, disability, and radiologic measurements. Patients were permitted to use concomitant NSAID therapy and were prescribed sulfasalazine after six months as a rescue medication, based on clinical criteria of rheumatoid arthritis activity. Four patients in the prednisone group and six patients in the placebo group withdrew from the study. After six months, 39 of the 71 patients (20 in the placebo group and 19 in the prednisone group) who completed the study were given sulfasalazine as additional anti-rheumatic therapy.

Although the prednisone group showed a greater improvement in most clinical variables at 12 and 24 months, the only statistically significant differences in the two groups were improvement in grip strength and in the 28-joint score for tenderness. The overall use of physiotherapy, intra-articular joint injections, and NSAIDs at 12 and 24 months was lower in the prednisone group than in the placebo group. Radiologic scores showed significantly less progression of disease in the prednisone group at 12 months. The prednisone group had significantly more weight gain and mean serum glucose elevation compared with the placebo group. New osteoporotic fractures were more common among the prednisone group.

The authors conclude that, although glucocorticoids alone showed improvement in most disease variables and slowed radiologically detected joint changes, glucocorticoids are not appropriate for monotherapy; they may, however, be useful to optimally affect disease progression when used with disease-modifying antirheumatic drugs. Further study is needed.

In an accompanying editorial, Pincus and associates support the long-term use of low-dose prednisone (5 mg or less) in most patients with RA, but clarification is needed to differentiate symptomatic benefit from real disease-modifying properties. They propose that until more studies are done, the use of low-dose glucocorticoid treatment should probably depend on individual patient characteristics and the individual clinician's estimates of benefits and risks.