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

C. A. Wijbrandts, M. G. W. Dijkgraaf, M. C. Kraan, M. Vinkenoog, T. J. Smeets, H. Dinant, K. Vos, W. F. Lems, G. J. Wolbink, D. Sijpkens, B. A. C. Dijkmans, P. P. Tak

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Objective: To determine whether the heterogeneous clinical response to tumour necrosis factor (TNF)alpha blocking therapy in rheumatoid arthritis (RA) can be predicted by TNF alpha 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 alpha expression is a significant predictor of response to TNF alpha blocking therapy. TNF alpha 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 alpha) were also significantly higher in responders than in non-responders. The expression of interleukin (IL)1 beta, 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 alpha treatment. Conclusion: The effects of TNF alpha blockade are in part dependent on synovial TNF alpha expression and infiltration by TNF alpha producing inflammatory cells. Clinical response cannot be predicted completely, indicating involvement of other as yet unknown mechanisms
Original languageEnglish
Pages (from-to)1139-1144
JournalAnnals of the rheumatic diseases
Issue number8
Publication statusPublished - 2008

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