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Prednisone Chronotherapy Safe in RA Patients

No worsening of HPA-axis suppression after 12 months of modified-release PM dosing

MONDAY, Aug. 16 (HealthDay News) -- Long-term, chronotherapy with a modified-release (MR) prednisone does not appear to increase the risk of hypothalamus-pituitary-adrenal (HPA) axis insufficiency in patients on daily prednisone for rheumatoid arthritis (RA), according to research published in the August issue of the Journal of Rheumatology. This formulation of prednisone is taken at bedtime but results in peak blood levels at about 2 a.m., mimicking the timing of the endogenous cortisol cycle.

To examine the impact of long-term, low-dose chronotherapy with MR prednisone on the HPA axis in patients with RA, Rieke Alten, M.D., of the Charité University Medicine in Berlin, and colleagues performed corticotropin-releasing hormone (CRH) tests on 28 patients on immediate-release (IR) prednisone at baseline; at three months on IR or MR prednisone; and after nine months on MR prednisone.

The researchers found that the mean increase in cortisol plasma concentrations after corticorelin injection was 5.5 µg/dL with IR prednisone at baseline, and 5.3 µg/dL with MR prednisone at one year. Responses were not influenced by switching from IR to MR prednisone or by long-term treatment with MR prednisone. Patients with low responsiveness to CRH testing prior to MR prednisone treatment did not experience worsening adrenal impairment with nighttime-release prednisone.

"Treatment with nighttime-release prednisone did not change adrenocortical function over 12 months. We presume that chronotherapy with this nighttime-release prednisone may improve the efficacy of long-term low-dose glucocorticoid treatment in patients with RA," the authors write.

The research was supported by Merck KGaA and Nitec Pharma AG. Several authors disclosed financial relationships with pharmaceutical companies, including Merck and Nitec.

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