Modified-Release Prednisone Reduces Morning Stiffness In Patients With Rheumatoid Arthritis (Capra-1 Trial)

Main Category: Arthritis / Rheumatology
Article Date: 21 Jan 2008 - 2:00 PDT

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Using modified-release prednisone instead of standard prednisone significantly reduces the duration of morning stiffness in patients with rheumatoid arthritis (RA). This is the conclusion of authors of an Article in this week's edition of The Lancet.

Circadian (day-night) rhythms of endogenous cortisol and anti-inflammatory protection are changed in patients with RA. A new-modified release delivery system has been developed which adapts the release of the administered glucocorticoid (prednisone) to the circadian rhythms of the disease symptoms, and improves the performance of the treatment.

Professor Frank Buttgereit, Charité University Medicine Berlin, Germany, and colleagues did a study of 288 patients with active RA, half of which were randomised to receive a modified-release prednisone tablet, and the other half a standard (immediate-release) prednisone tablet. The modified-release tablet was taken at bedtime and released the prednisone four hours after ingestion; this method was compared to morning administration of immediate release (standard) prednisone. Morning stiffness of the joints was then measured in both groups and the mean relative change of duration of morning stiffness at 12 weeks versus baseline was calculated.

This mean relative change was much higher for the modified group (minus 22•7%) versus the standard group (minus 0•4%). In terms of the actual time the duration of the morning stiffness was reduced for both treatments versus baseline, but the reduction was also much higher in the modified-release group (44•0 minutes). The absolute difference in minutes between the treatments at 12 weeks was 29•2 min in favour of the new modified-release tablet. The safety profile was the same for both treatments.

The authors say: "It took two years of drug engineering and phase I clinical trials to develop a formulation that could be tested in the phase III clinical trial reported here." They add that the new formulation has a special coating that bursts four hours after intake because of water penetration; but the total drug exposure and maximum concentration values are almost identical to those of standard prednisone.

They conclude: "Our results have confirmed that the new modified-release formulation is clinically and statistically better than the conventional immediate-release preparation with regard to morning stiffness of the joints. Furthermore, the effects of the new tablet taken at night were achieved in addition to the established clinical control of the disease resulting from previous treatment with conventional immediate-release prednisone."

In an accompanying Comment Professor Johannes Bijlsma and Dr Johannes Jacobs, University Medical Centre, Utrecht, Netherlands, say: "Glucocorticoids are the most effective and widely used immunosuppressive drugs worldwide in many immune-mediated diseases and vasculitidies. Might this new formulation also have benefits in those diseases? An interesting second step could be the use of this formulation in polymyalgia rheumatica, which is also characterised by severe early morning symptoms. Ultimately, the relevance of Buttgereit and colleagues' study could go far beyond rheumatic diseases."

The Lancet