Hypothalamic-Pituitary-Adrenal Axis Function in Patients with Rheumatoid Arthritis Treated with Different Glucocorticoid Approaches

Glucocorticoids (GCs) continue to be an important treatment option in rheumatoid arthritis (RA) - despite their multitude of side effects. Amongst those, suppression of the hypothalamic-pituitary-adrenal (HPA) axis plays a dominant role. In clinical practice, low-dose GC therapy of 5 mg or less per day seems to be safest in eschewing these undesirable effects and assuring function of the HPA axis. Further research has shown that, apart from dosage, the degree of HPA axis suppression by exogenous GCs is not only dependent on the duration of therapy, but that it also underlies a significant diurnal variation. The recent development of a novel modified-release (MR) prednisone formula reflects an attempt at targeting these circadian neuroendocrine pathways of the HPA axis' function and their interplay with the immune system in RA. Data from a subset of 28 patients included in the CAPRA-1 study indicated that chronotherapy with MR prednisone has no adverse effect on HPA function. Whether adapting GC therapy to a pathophysiological circadian pattern might even be beneficial will have to be further investigated.