Circadian 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 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.
MEDICA.de; Source: Lancet