Pre-treatment macrophage infiltration of the synovium predicts the clinical effect of both radiation synovectomy and intra-articular glucocorticoids

Z N Jahangier ^1*, J WG Jacobs ¹, M C Kraan ², M JG Wenting ¹, T JM Smeets ³, J WJ Bijlsma ¹, F PJG Lafeber ¹ and P P Tak ⁴

¹ University Medical Center Utrecht, Netherlands
² SPRI, United States
³ Academic Medical Center/ University of Amsterdam, Netherlands
⁴ Academical Medical Center Amsterdam, Netherlands

^* To whom correspondence should be addressed. E-mail: njahangier{at}hotmail.com.

Accepted 17 March 2006

Abstract

Objective: To explore whether pre-treatment features of synovial tissue in patients with gonarthritis could predict the clinical effect of radiation synovectomy with yttrium (⁹⁰Y) and glucocorticoids (GC) or intra- articular GC alone.

Methods: A synovial biopsy procedure was performed blindly two weeks prior to therapy in 66 patients with persistent gonarthritis, who were randomized to treatment with either 90Y and triamcinolone or placebo and triamcinolone. Immunohistochemistry was used to detect T cells, macrophages, B cells, plasma cells, fibroblast- like synoviocytes, adhesion molecules and pro- inflammatory cytokines. Stained sections were evaluated by digital image analysis. Individual patient improvement was expressed by a composite change index (CCI) (range 0-12). Successful therapy was defined as CCI 6 after 6 months.

Results: Patients with rheumatoid arthritis, psoriatic arthritis, undifferentiated arthritis, and other causes of gonarthritis were included. The overall response rate was 47%. Clinical efficacy in both therapeutic groups was similar and not dependent on diagnosis. There were no significant differences between baseline microscopic features of synovial tissue inflammation in RA vs. non- RA (i.e. all diagnoses other than RA). The number of macrophages in the synovial sublining was significantly higher in responders than in non-responders (P = 0.002), independent of treatment group and diagnosis. The clinical effect was positively correlated with pre- treatment total macrophage numbers (r = 0.28, P = 0.03), sublining macrophage numbers (r = 0.34, P = 0.005) and VCAM-1 expression (r = 0.25, P = 0.04).

Conclusion: The observations support the view that intra-articular therapy with either ⁹⁰Y and GC or GC alone is especially successful in patients with marked synovial inflammation.

Keywords: arthritis, glucocorticoids, macrophages, synovial tissue, yttrium

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