Modified-release formulation of prednisone reduces morning stiffness in RA

Last Updated: 2008-01-17 18:30:13 -0400 (Reuters Health)

NEW YORK (Reuters Health) – A delayed-release prednisone tablet taken at night is more effective than immediate-release prednisone taken in the morning in reducing morning joint stiffness in patients with rheumatoid arthritis (RA), a phase III clinical trial has demonstrated.

The modified-release formulation (SKYE Pharma) "allows glucocorticoid release to be adapted to the circadian rhythms of endogenous cortisol and symptoms of the disease, both of which have their peaks during the early morning hours," Dr. Frank Buttgereit and associates explain in the January 19th issue of The Lancet.

Dr. Buttgereit, at Charite University Medicine Berlin, and his team enrolled patients with RA from 29 centers in Germany and Poland. Mean disease duration was 9.6 years, mean morning stiffness was 173 minutes, and mean maximum daily pain score was 59/100. The patients had been taking glucocorticoids (up to 10 mg prednisone equivalent) for at least 3 months and a DMARD if tolerated.

Using a double-dummy technique, patients were randomly assigned to either the modified-release prednisone or to immediate release prednisone (144 in each arm).

After 12 weeks, the mean relative change in duration of morning stiffness was significantly higher with the delayed-release prednisone (-22.7% versus -0.4%, p = 0.045). Absolute mean reductions were 44 minutes and 23 minutes, respectively.

The difference in duration of morning stiffness between groups was significant at 2 weeks, Dr. Buttgereit’s group reports, plateauing from week 7 on.

Safety profiles and effects on other symptoms were comparable in the two groups.

Authors of an accompanying editorial call these results "clearly relevant for daily clinical practice."

Because glucocorticoids are the most effective immunosuppressants for many immune-mediated diseases and vasculitides, Drs. Johannes W. J. Bijlsma and Johannes W. G. Jacobs, from University Medical Centre Utrecht, the Netherlands, state, "Ultimately, the relevance of Buttgereit and colleagues’ study could go far beyond rheumatic diseases."

Lancet 2008;371:183-184,205-214.