Effects of oral prednisolone on biomarkers in synovial tissue and clinical improvement in rheumatoid arthritis.
OBJECTIVE
To create greater understanding of the changes in synovial tissue parameters that occur in conjunction with clinical response by using an effective therapy, in order to facilitate the planning of future studies with therapeutic agents for rheumatoid arthritis (RA).


METHODS
Twenty-one patients with active RA were randomized to receive either oral prednisolone (n = 10) or placebo (n = 11) for 2 weeks. In all patients, synovial tissue biopsy specimens were obtained by arthroscopy directly before treatment and after 14 days of treatment. Immunohistochemical analysis was performed to characterize the cell infiltrate and vascularity. Stained tissue sections were analyzed by digital imaging. Statistical analysis was performed using an analysis of covariance model.


RESULTS
After treatment, the mean Disease Activity Score in 28 joints (DAS28) was 2.0 units lower (95% confidence interval [95% CI] 1.0-3.0) in patients who received prednisolone than in those who received placebo. In the prednisolone group, the mean (+/-SD) DAS28 decreased from 6.27 +/- 0.95 to 4.11 +/- 1.43 after therapy; minimal change was observed in the placebo group. For macrophages, the estimated effect of prednisolone was large. Patients receiving active treatment had fewer (mean 628 cells/mm(2) [95% CI 328-927]) macrophages after therapy compared with those receiving placebo. A reduction in the total number of CD68+ macrophages, from 1,038 +/- 283 cells/mm(2) before treatment to 533 +/- 248 cells/mm(2) after treatment, was observed in the prednisolone group. There were clear trends toward decreased infiltration by T cells, plasma cells, and fibroblast-like synoviocytes after active treatment. We observed a trend toward a reduction in alphavbeta3+ newly formed blood vessels and expression of vascular growth factors after prednisolone therapy.


CONCLUSIONS
Prednisolone therapy in RA is associated with a marked reduction in macrophage infiltration in synovial tissue, suggesting that synovial macrophage numbers could be used as a biomarker for clinical efficacy.
Gerlag
Danielle M
DM
Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands. d.m.gerlag@amc.uva.nl
Haringman
Jasper J
JJ
Smeets
Tom J M
TJ
Zwinderman
A H
AH
Kraan
Maarten C
MC
Laud
Peter J
PJ
Morgan
Shethah
S
Nash
Anthony F P
AF
Tak
Paul P
PP
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D002452:Cell Count; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007596:Joints / Q000187:drug effects / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013583:Synovial Membrane / Q000187:drug effects* / Q000378:metabolism; D013585:Synovitis / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology
D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D011239:Prednisolone