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

doi:https://doi.org/10.1136/ard.2007.080440

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

Research output: Contribution to journal › Article › Academic › peer-review

129 Citations (Scopus)

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 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 language	English
Pages (from-to)	1139-1144
Journal	Annals of the rheumatic diseases
Volume	67
Issue number	8
DOIs	https://doi.org/10.1136/ard.2007.080440
Publication status	Published - 2008

Access to Document

https://doi.org/10.1136/ard.2007.080440

Cite this

Wijbrandts, C. A., Dijkgraaf, M. G. W., Kraan, M. C., Vinkenoog, M., Smeets, T. J., Dinant, H., Vos, K., Lems, W. F., Wolbink, G. J., Sijpkens, D., Dijkmans, B. A. C., & 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), 1139-1144. https://doi.org/10.1136/ard.2007.080440

@article{ac46da5a5c194f4ca27e5ae45b6d0f6c,

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

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 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",

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

year = "2008",

doi = "https://doi.org/10.1136/ard.2007.080440",

language = "English",

volume = "67",

pages = "1139--1144",

journal = "ANNALS OF THE RHEUMATIC DISEASES",

issn = "0003-4967",

publisher = "BMJ Publishing Group",

number = "8",

}

Wijbrandts, CA, Dijkgraaf, MGW, Kraan, MC, Vinkenoog, M, Smeets, TJ, Dinant, H, Vos, K, Lems, WF , Wolbink, GJ, Sijpkens, D, Dijkmans, BAC & Tak, PP 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, vol. 67, no. 8, pp. 1139-1144. https://doi.org/10.1136/ard.2007.080440

The clinical response to infliximab in rheumatoid arthritis is in part dependent on pretreatment tumour necrosis factor alpha expression in the synovium. / Wijbrandts, C. A.; Dijkgraaf, M. G. W.; Kraan, M. C. et al.
In: Annals of the rheumatic diseases, Vol. 67, No. 8, 2008, p. 1139-1144.

Research output: Contribution to journal › Article › Academic › peer-review

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.

PY - 2008

Y1 - 2008

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 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

AB - 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

U2 - https://doi.org/10.1136/ard.2007.080440

DO - https://doi.org/10.1136/ard.2007.080440

M3 - Article

C2 - 18055470

SN - 0003-4967

VL - 67

SP - 1139

EP - 1144

JO - ANNALS OF THE RHEUMATIC DISEASES

JF - ANNALS OF THE RHEUMATIC DISEASES

IS - 8

ER -