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The clinical response to infliximab in rheumatoid arthritis is in part dependent on pretreatment tumour necrosis factor alpha expression in the synovium.
Ann Rheum Dis. 2008 Aug; 67(8):1139-44.AR

Abstract

OBJECTIVE

To determine whether the heterogeneous clinical response to tumour necrosis factor (TNF)alpha blocking therapy in rheumatoid arthritis (RA) can be predicted by TNFalpha 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 > or =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 TNFalpha expression is a significant predictor of response to TNFalpha blocking therapy. TNFalpha 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 TNFalpha) were also significantly higher in responders than in non-responders. The expression of interleukin (IL)1beta, 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-TNFalpha treatment.

CONCLUSION

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

Authors+Show Affiliations

Division of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18055470

Citation

Wijbrandts, C A., et al. "The Clinical Response to Infliximab in Rheumatoid Arthritis Is in Part Dependent On Pretreatment Tumour Necrosis Factor Alpha Expression in the Synovium." Annals of the Rheumatic Diseases, vol. 67, no. 8, 2008, pp. 1139-44.
Wijbrandts CA, Dijkgraaf MG, Kraan MC, et al. The clinical response to infliximab in rheumatoid arthritis is in part dependent on pretreatment tumour necrosis factor alpha expression in the synovium. Ann Rheum Dis. 2008;67(8):1139-44.
Wijbrandts, C. A., Dijkgraaf, M. G., Kraan, M. C., Vinkenoog, M., Smeets, T. J., Dinant, H., Vos, K., Lems, W. F., Wolbink, G. J., Sijpkens, D., Dijkmans, B. A., & Tak, P. P. (2008). The clinical response to infliximab in rheumatoid arthritis is in part dependent on pretreatment tumour necrosis factor alpha expression in the synovium. Annals of the Rheumatic Diseases, 67(8), 1139-44.
Wijbrandts CA, et al. The Clinical Response to Infliximab in Rheumatoid Arthritis Is in Part Dependent On Pretreatment Tumour Necrosis Factor Alpha Expression in the Synovium. Ann Rheum Dis. 2008;67(8):1139-44. PubMed PMID: 18055470.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The clinical response to infliximab in rheumatoid arthritis is in part dependent on pretreatment tumour necrosis factor alpha expression in the synovium. AU - Wijbrandts,C A, AU - Dijkgraaf,M G W, AU - Kraan,M C, AU - Vinkenoog,M, AU - Smeets,T J, AU - Dinant,H, AU - Vos,K, AU - Lems,W F, AU - Wolbink,G J, AU - Sijpkens,D, AU - Dijkmans,B A C, AU - Tak,P P, Y1 - 2007/11/29/ PY - 2007/12/7/pubmed PY - 2008/8/12/medline PY - 2007/12/7/entrez SP - 1139 EP - 44 JF - Annals of the rheumatic diseases JO - Ann Rheum Dis VL - 67 IS - 8 N2 - OBJECTIVE: To determine whether the heterogeneous clinical response to tumour necrosis factor (TNF)alpha blocking therapy in rheumatoid arthritis (RA) can be predicted by TNFalpha 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 > or =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 TNFalpha expression is a significant predictor of response to TNFalpha blocking therapy. TNFalpha 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 TNFalpha) were also significantly higher in responders than in non-responders. The expression of interleukin (IL)1beta, 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-TNFalpha treatment. CONCLUSION: The effects of TNFalpha blockade are in part dependent on synovial TNFalpha expression and infiltration by TNFalpha producing inflammatory cells. Clinical response cannot be predicted completely, indicating involvement of other as yet unknown mechanisms. SN - 1468-2060 UR - https://www.unboundmedicine.com/medline/citation/18055470/The_clinical_response_to_infliximab_in_rheumatoid_arthritis_is_in_part_dependent_on_pretreatment_tumour_necrosis_factor_alpha_expression_in_the_synovium_ L2 - https://ard.bmj.com/lookup/pmidlookup?view=long&amp;pmid=18055470 DB - PRIME DP - Unbound Medicine ER -