Effects of oral prednisolone on biomarkers in synovial tissue and clinical improvement in rheumatoid arthritis†
Corresponding Author
Danielle M. Gerlag
Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
Division of Clinical Immunology and Rheumatology, F4-218, Academic Medical Center/University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, The NetherlandsSearch for more papers by this authorJasper J. Haringman
Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorTom J. M. Smeets
Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorA. H. Zwinderman
Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorMaarten C. Kraan
Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorPaul P. Tak
Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorCorresponding Author
Danielle M. Gerlag
Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
Division of Clinical Immunology and Rheumatology, F4-218, Academic Medical Center/University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, The NetherlandsSearch for more papers by this authorJasper J. Haringman
Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorTom J. M. Smeets
Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorA. H. Zwinderman
Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorMaarten C. Kraan
Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorPaul P. Tak
Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
Search for more papers by this authorPresented in part at the 67th Annual Scientific Meeting of the American College of Rheumatology, Orlando, FL, October 2003.
Abstract
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/mm2 [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/mm2 before treatment to 533 ± 248 cells/mm2 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 αvβ3+ newly formed blood vessels and expression of vascular growth factors after prednisolone therapy.
Conclusion
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.
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