The timing of glucocorticoid administration in rheumatoid arthritis

Journal/Book: Z Rheumatol 1999; 58: 306-307. 1999;

Abstract: R. Hällgren; Section of Rheumatology Department of Internal Medicine University Hospital Uppsala Glucocorticoids have been used in the treatment of rheumatoid arthritis (RA) since more than 50 years mainly because of their ability to relieve symptoms such as joint stiffness and joint pain. The effect is brought about by their diverse anti-inflammatory and immunosuppressive properties. They are by tradition given in the morning in order to minimize the disturbance of the physiological circadian rhythm of the endogenous adrenal glucocorticoids. However the administration of hormones for therapeutical use should primarily consider the optimal timing of administration of the hormone for influencing the disease process and its symptoms. This is quite obvious in e.g. insulin treatment for diabetes mellitus. We have questioned the established regimen of giving glucocorticoids in the morning to patients with RA for a number of reasons. The main reason is due to our observation of a circadian rhythm in the serum concentrations of serum IL-6 in patients with RA; the IL-6 levels peak early in the morning and decline spontaneously towards normal levels during the afternoon and evening. Assuming that that the rhythm in serum IL-6 mirrors its production and is associated with the flare in inflammatory activity so obvious during the morning in patients with RA one should consider the optimal timing of glucocorticoid administration in RA. The plasma half life of prednisolone is about 2.5 hours and the biological half life has been calculated to be six hours. Thus based on the assumption that the inflammatory activity in RA starts to flare late at night the conventional administration of glucocorticoids does not seem to optimal. We have tested this hypothesis by comparing the short term efficacy of low dosage of prednisolone (5-7.5 mg) treatment administered in patients with RA at either 2.00 am or 7.30 am. ... le

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