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This Article Free to Access Full Text Full Text (PDF) All Versions of this Article: ard.2007.080440v1 67/8/1139    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this link to a friend Similar articles in this journal Similar articles in PubMed Add article to my folders Download to citation manager Request Permissions Google Scholar Articles by Wijbrandts, C A Articles by Tak, P P PubMed PubMed Citation Articles by Wijbrandts, C A Articles by Tak, P P

The clinical response to infliximab in rheumatoid arthritis is in part dependent on pretreatment tumour necrosis factor expression in the synovium

¹ Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
² Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
³ Jan van Breemen Institute, Amsterdam, The Netherlands
⁴ Department of Rheumatology, Slotervaart Hospital, Amsterdam, The Netherlands
⁵ VU Medical Center, Amsterdam, The Netherlands

Correspondence to:
Professor P P Tak, Division of Clinical Immunology and Rheumatology, F4-218, Academic Medical Center/University of Amsterdam, Meibergdreef 9 1105 AZ Amsterdam, The Netherlands; P.P.Tak{at}amc.uva.nl

Objective: To determine whether the heterogeneous clinical response to tumour necrosis factor (TNF) blocking therapy in rheumatoid arthritis (RA) can be predicted by TNF expression in the synovium before initiation of treatment.

Methods: Prior to initiation of infliximab treatment, arthroscopic synovial tissue biopsies were obtained from 143 patients with active RA. At week 16, clinical response was evaluated using the 28-joint Disease Activity Score (DAS28). Immunohistochemistry was used to analyse the cell infiltrate as well as the expression of various cytokines, adhesion molecules and growth factors. Stained sections were evaluated by digital image analysis. Student t tests were used to compare responders (decrease in DAS28 1.2) with non-responders (decrease in DAS28 <1.2) and multivariable regression was used to identify the independent predictors of clinical response.

Results: Synovial tissue analysis confirmed our hypothesis that the baseline level of TNF expression is a significant predictor of response to TNF blocking therapy. TNF expression in the intimal lining layer and synovial sublining were significantly higher in responders than in non-responders (p = 0.047 and p = 0.008, respectively). The numbers of macrophages, macrophage subsets and T cells (all able to produce TNF) were also significantly higher in responders than in non-responders. The expression of interleukin (IL)1β, IL6, IL18, IL10, E-selectin, intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) was not associated with response to anti-TNF treatment.

Conclusion: The effects of TNF blockade are in part dependent on synovial TNF expression and infiltration by TNF producing inflammatory cells. Clinical response cannot be predicted completely, indicating involvement of other as yet unknown mechanisms.