Hypothalamus-Pituitary-Adrenal Axis Function in Patients with Rheumatoid Arthritis Treated with Nighttime-Release Prednisone

Abstract

Objective.To investigate the effects of longterm low-dose chronotherapy with modified-release (MR) prednisone for rheumatoid arthritis (RA) on the hypothalamus-pituitary-adrenal (HPA) axis as part of the Circadian Administration of Prednisone in Rheumatoid Arthritis (CAPRA-1) study. This consisted of a 3-month active-controlled phase and a 9-month open-label extension with MR prednisone including patients previously treated with prednisone (ClinicalTrials.gov number NCT00146640).Methods.Corticotropin-releasing hormone (CRH) tests were performed on 28 patients at 3 timepoints: at baseline on prestudy immediate-release (IR) prednisone, after the 3-month double-blind phase on either IR prednisone or MR prednisone, and after the 9-month open-label extension on MR prednisone. Changes of cortisol were assessed and compared to individual patients’ efficacy and safety data.Results.The increase (mean, SD) of cortisol plasma concentrations after injection of corticorelin was 5.5 (4.37) μg/dl on IR prednisone at baseline (n = 21) and 5.3 (4.07) μg/dl on MR prednisone at 12 months (n = 22). Numbers of normal/suppressed/no response reactions did not differ among treatments. Switching from IR to MR prednisone did not influence responses, nor did longterm treatment of up to 12 months with MR prednisone. No worsening of adrenal impairment was observed on treatment with nighttime-release prednisone in patients with low responsiveness to CRH testing before the treatment with MR prednisone.Conclusion.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 longterm low-dose glucocorticoid treatment in patients with RA.