Steroids Score in Slowing Early Rheumatoid Arthritis

LIVERPOOL, England, Jan. 26 -- Low-dose glucocorticoid agents given along with standard disease-modifying drugs (DMARDs) reduced the progression of early rheumatoid arthritis for up to two years, Cochrane reviewers reported.

All the studies reviewed, except one, showed a numerical benefit in favor of the steroids, which were generally used along with DMARDs, according to a report in the January issue of the Cochrane Database of Systematic Reviews.

From an average of all the studies, the reduction of erosion progression was 60% or more when the glucocorticoids were used along with DMARDs, said John Kirwan, M.D., of Liverpool Women's Hospital here, and colleagues.

These findings were derived from a Medline search (1966 to 2005) and the Cochrane Controlled Trials Register, which produced 15 studies including 1,414 patients, older than 18.

The comparisons included either placebo or active controls (non-steroidal anti-inflammatory drugs (NSAIDS), DMARDs, but no steroids) with x-rays of hands, feet, or hands and feet. Most of the trials studied disease progression up to two years.

The daily dose of steroid was 10 mg or less of prednisone equivalent. The mean cumulative dose was 2,300 mg prednisone equivalent (range 270 mg-5,800 mg) over the first year. In most cases the drugs were added to other disease-modifying anti-rheumatoid drugs.

The standardized mean difference in progression was 0.40 in favor of steroids (95% CI 0.27-0.54), the researchers reported.

In studies of 806 patients lasting two years, the standardized mean difference in progression in favor of glucocorticoids at one year was 0.45 (CI 0.24-0.66). At two years, it was 0.42 (0.30-0.55), the researchers reported.

The proportion of benefit gained by steroids in reducing he progress of erosion from an average of all the studies over one year was 59.8% (CI, 45.4%- 74.1%), the researchers said.

Using data from trials lasting two years, the proportion of benefit gained by steroids in reducing erosion progression at one year was 67.2% (48.9%-85.4%). Over two years, it was 61.3% (46.5%-76.1%).

Furthermore, the researchers said, this benefit was achieved in patients who were for the most part receiving disease-modifying anti-rheumatoid drug treatment. It therefore represents a gain over and above any benefit from the disease-modifying drugs alone.

However, Dr. Kirwan added, the beneficial effects of glucocorticoids were generally achieved when used with the disease-modifying drugs.

Steroids were also found beneficial in an analysis of studies in which they were given along with and compared with disease-modifying anti-rheumatoid drugs plus NSAIDs. There was a significant benefit when step-down glucocorticoids taken with the disease modifiers plus NSAIDs were compared with disease modifying drugs plus NSAIDs, and in patients taking only NSAIDs, the investigators said.

The principle analysis included all studies with all types of glucocorticoid administration, even though it is possible, even likely, that the efficacy of glucocorticoids depends on the route of administration and the use of concomitant medications, the investigators said.

It should be recognized that the link between radiological benefit and overall long-term functional benefit is not firmly established, and it does not necessarily follow that patients will gain long-term functional improvement, the researchers said.

Although the potential for high doses of these drugs to cause adverse effects is well known, the doses used in many of these studies were low, they said. Nevertheless, the potential for adverse effects at low doses is less clear, they said.

Safety data from recent randomized controlled clinical trials of low dose glucocorticoid treatment in rheumatoid arthritis suggest that adverse effects associated with these drugs are modest, and often not statistically different from those of placebo.

The most immediate concern, reduced bone mineral density, can now be readily treated, they said. "Therefore, we believe the evidence that glucocorticoids given in addition to standard therapy can substantially reduce the rate of erosion progression in rheumatoid arthritis is convincing, and that the use of such treatment should be made readily available to patients," the investigators said.

It also seems likely that patients with a disease duration of three or four years might benefit, but it would be inappropriate to extrapolate into longer disease durations without more firm evidence of benefit, the researchers said.

Nevertheless, they added, there remains concern about potential long-term adverse reactions to glucocorticoid therapy, such as increased cardiovascular risk, and this issue requires further research.