BARCELONA, Spain—A new modified-release (MR) tablet form of prednisone reduces the duration of morning stiffness in patients with rheumatoid arthritis (RA) compared with immediate release (IR) prednisone, according to new research presented at the 2007 EULAR meeting in Barcelona, Spain.¹ Taken at bedtime, the new formulation releases prednisone after a 4-hour delay, so the medication is released during the night, report researchers led by Frank Buttgereit, MD, at Charité University Hospital, in Berlin, Germany. The result is a substantial reduction in morning stiffness.

"The new MR prednisone provides a clinically relevant reduction of morning stiffness added to the known therapeutic effects of IR prednisone," the researchers conclude. "In addition, the bedtime administration mode is convenient for the patient." A 9-month, open-label, follow-up study is currently being evaluated.

New formulation gets more efficacy from the same prednisone dose

The researchers studied 288 RA patients, average age of 55 and mean disease duration of 115.3 months, who were pretreated with steroids and disease-modifying antirheumatic drugs (DMARDs). Patients received daily prednisone doses for 3 months ranging from 3 to 10 mg that were equivalent to prestudy doses. The primary outcome measure was duration of morning stiffness as recorded in patient diaries. The secondary endpoints included interleukin-6 and C-reactive protein levels, Disease Activity Score, physician's global assessment, Disability Index as measured by the Health Assessment Questionnaire (HAQ), quality of life as measured by Short Form 36 (SF36), pain, use of analgesics, and quality of sleep. Researchers monitored adverse events and performed routine blood work.

New approach taps into circadian rhythms

The mean relative change in duration of morning stiffness from MR prednisone from baseline to end of treatment was significantly higher than what was seen with IR prednisone, 22.7% versus 0.4%, respectively. A 10% difference became apparent at week 2. In more than half of subjects, the duration of morning stiffness was reduced by about one third, the study showed.

Interleukin-6 was decreased by 30% (P<.0001) in the group who took the MR form of prednisone, but it remained unchanged in the IR group. There were no differences in any other efficacy variables. Both treatments had similar safety profiles.

Coming soon to a doctor's office near you?

The new prednisone formulation is making its way through the approval process and may be available this year or next, Dr. Buttgereit told CIAOMed.
 
He noted that steroids are more than 60 years old, but the quest for safer steroids continues. "There are quite a lot of things going on in terms of improving benefit and risk ratio of glucocorticoids and glucocorticoid receptor ligands," he said. These include selective glucocorticoid receptor agonists and nitrosoglucocorticoids, but the MR prednisone is closer to regulatory approval.

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Reference

1. Buttgreit F, Doering G, Schaeffler A, et al. New modified release (MR) tablet formulation of prednisone significantly reduces duration of morning stiffness compared to standard prednisone in subjects with rheumatoid arthritis (RA). Presented at: EULAR 2007 Meeting; June 13-16, 2007; Barcelona, Spain. Abstract OP0007.