Pretreatment macrophage infiltration of the synovium predicts the clinical effect of both radiation synovectomy and intra-articular glucocorticoids
- Z N Jahangier2,
- J W G Jacobs1,
- M C Kraan3,
- M J G Wenting1,
- T J Smeets2,
- J W J Bijlsma1,
- F P J G Lafeber1,
- P P Tak2
- 1Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands
- 2Division of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
- 3Schering Plough Research Institute, Kenilworth, New Jersey, USA
- Correspondence to:
Z N Jahangier
Department of Rheumatology & Clinical Immunology, F02.127, University Medical Center Utrecht, Box 85500, 3508 GA Utrecht, The Netherlands;
- Accepted 17 March 2006
- Published Online First 20 April 2006
Objective: To explore whether pretreatment features of synovial tissue in patients with gonarthritis could predict the clinical effect of radiation synovectomy with yttrium-90 (90Y) and glucocorticoids or with intra-articular glucocorticoids alone.
Methods: A synovial biopsy was carried out blindly 2 weeks before treatment in 66 patients with persistent gonarthritis, who were randomised to treatment either with 90Y and triamcinolone or with 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 using a composite change index (CCI; range 0–12). Successful treatment 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. No significant differences were noted between baseline microscopic features of synovial tissue inflammation in patients with rheumatoid arthritis and in those with non-rheumatoid arthritis (ie, all diagnoses other than rheumatoid arthritis). 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 pretreatment total macrophage numbers (r = 0.28; p = 0.03), sublining macrophage numbers (r = 0.34; p = 0.005) and vascular cell adhesion molecule 1 expression (r = 0.25; p = 0.04).
Conclusion: The observations support the view that intra-articular treatment either with 90Y and glucocorticoids or with glucocorticoids alone is especially successful in patients with marked synovial inflammation.
- anti-ICAM1, anti-intercellular adhesion molecule 1
- anti-VCAM1, anti-vascular cell adhesion molecule 1
- CCI, composite change index
- DMARD, disease-modifying antirheumatic drug
- FLS, fibroblast-like synoviocytes
- IOD, integrated optical density
- mAb, monoclonal antibody
- RCT, randomised clinical trial
- RSO, radiation synovectomy
- TNF, tumour necrosis factor
- 90Y, yttrium-90
Published Online First 20 April 2006
Funding: This study was supported by a grant from The Netherlands Organization for Scientific Research (NWO).
Competing interests: None declared.