Glucocorticoid receptor up-regulation in early rheumatoid arthritis treated with low dose prednisone or placebo.
OBJECTIVE
Low or medium dose prednisone in early rheumatoid arthritis (RA), albeit with significant variation in clinical efficacy, reduces the progression of joint damage. The glucocorticoid receptor (GR) number in peripheral mononuclear cells (PBMC) might be helpful to predict which patients will respond to low or medium dose prednisone and therefore do not or will not need higher doses. With this in mind we determined in a double blind, placebo controlled study at baseline and yearly the GR number in PBMC.


METHODS
Eighty-one early RA patients (disease duration less than one year) were included. All patients fulfilled the ACR criteria and were disease modifying antirheumatic drugs (DMARD) and glucocorticoid-naive. They were randomly assigned to treatment with 10 mg prednisone daily or placebo. From all patients disease activity (CRP, number of tender and swollen joints), the radiological joint score, bone mineral density, and the GR number in PBMC were measured annually.


RESULTS
In females the GR number was up-regulated over time in both the prednisone and the placebo group. The same trend was observed in males. No correlations were found between the GR number in the prednisone users at the start of their treatment and changes in radiological scores or bone density after 2 years of treatment. No correlations were found between the GR number at the start and the clinical characteristics after a follow-up of 2 years.


CONCLUSIONS
The GR number in the PBMC of early RA patients did not predict which patients would be prednisone responders based on clinical or radiological parameters. However, the up-regulation of the GR number in PBMC in early RA patients towards the GR number of healthy subjects during the first two years of their disease course seems to reflect a recovery or compensatory mechanism as a response to an ongoing inflammatory process. This recovery may be not enough to efficiently control the inflammatory situation.
Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, PO Box 85000, 3508 GA Utrecht, The Netherlands. Margriet.Huisman@planet.nl
A M
AM
Huisman
A A
AA
Siewertsz van Everdingen
M J G
MJ
Wenting
F
F
Lafeber
D R Siewertsz
DR
van Reesema
J W G
JW
Jacobs
J W J
JW
Bijlsma
D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000276:immunology / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011241:Prednisone / Q000276:immunology / Q000627:therapeutic use*; D011965:Receptors, Glucocorticoid / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology*
D000893:Anti-Inflammatory Agents; D011965:Receptors, Glucocorticoid; D011241:Prednisone