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. 1997 Jan;56(1):27–31. doi: 10.1136/ard.56.1.27

The timing of glucocorticoid administration in rheumatoid arthritis

N G Arvidson 1, B Gudbjornsson 1, A Larsson 1, R Hallgren 1
PMCID: PMC1752253  PMID: 9059137

Abstract

OBJECTIVE—To test the hypothesis that the timing of prednisolone administration might be critical in determining its effect on the diurnal rheumatoid inflammatory process.
METHODS—26 patients with rheumatoid arthritis were randomly divided into two equal groups and allocated to low doses of prednisolone at either 2.00 am or 7.30 am. Because of the diurnal variation in disease activity in rheumatoid arthritis, assessments of the two study groups were performed at 7.30 am both at the start of the study (day 1) and after four doses of prednisolone (day 5). The study protocol differences in the time period from the last dose of prednisolone to assessment were 5.5 hours in the 2.00 am group and 24 hours in the 7.30 am group.
RESULTS—Administration of low doses of prednisolone (5 or 7.5 mg daily) at 2.00 am had favourable effects on the duration of morning stiffness (P << 0.001), joint pain (P < 0.001), Lansbury index (P << 0.001), Ritchie index (P << 0.001), and morning serum concentrations of IL-6 (P < 0.01). The other study group showed minor but significant effects on morning stiffness (P < 0.05) and circulating concentrations of IL-6 (P < 0.05). Modest and similar improvements of C reactive protein, serum amyloid protein A, and erythrocyte sedimentation rate were seen in both study groups.
CONCLUSIONS—Administration of low doses of glucocorticoids with a rather short biological half life seems to improve acute rheumatoid arthritis symptoms if it precedes the period of circadian flare in inflammatory activity, as defined by enhanced IL-6 synthesis. Further studies are needed to test the relative merits of different timing protocols of glucocorticoid administration in rheumatoid arthritis.



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The individual values for morning stiffness, pain at rest, Lansbury index, and serum IL-6 in patients with rheumatoid arthritis before (day 1) and after (day 5) treatment with prednisolone at daily doses of 5 mg or 7.5 mg (circles). The patients who received prednisolone at 2.00 am or at 7.30 am are indicated.

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