Rheumatology Advance Access originally published online on July 26, 2008
Rheumatology 2008 47(10):1469-1475; doi:10.1093/rheumatology/ken261
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The value of synovial cytokine expression in predicting the clinical response to TNF antagonist therapy (infliximab)
1Academic Unit of Musculoskeletal Disease, University of Leeds, Leeds, UK.
Correspondence to: P. Emery, Leeds Teaching Hospitals NHS Trust, Academic Unit of Musculoskeletal Disease, Second Floor, Chapel Allerton Hospital, Chapeltown Road, Leeds LS7 4SA, UK. E-mail: p.emery{at}leeds.ac.uk
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Abstract |
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Objectives. Clinical response to TNF-
blockade in the treatment of RA is heterogeneous. The study aims were to determine whether pre-treatment synovial cytokine expression predicted infliximab response and whether synovial changes after therapy correlated with response.
Methods. Fifty-one patients had arthroscopic biopsies of the knee joint prior to infliximab (3 mg/kg) treatment. Synovial tissue cell numbers (CD68 and CD3 positive) and cytokine expression (TNF-, lymphotoxin-, IL-1, -β and receptor antagonist, and IL-6) pre-treatment was assessed using semi-quantitative immunohistochemistry. Changes in these parameters were assessed 16 weeks after infliximab in 32 patients who underwent repeat arthroscopic biopsy.
Results. Of the total patients, 47% (n = 24) achieved an ACR20 response; 53% (n = 27) did not. Baseline synovial TNF-, IL-1 and -β expression did not differ between the two groups. No differences in baseline TNF- levels were observed with ACR levels of response (ACR20 and ACR50/70 groups). Post-treatment biopsies (17 ACR responders, 15 ACR non-responders) revealed significant reductions in sub-lining layer TNF- expression in both response and non-response groups with significant reduction in vascularity and membrane proliferation scores. The worst ACR non-responders (<20% CRP suppression) demonstrated no reduction in any of the parameters.
Conclusion. Pre-treatment synovial TNF- or IL-1 expression does not predict TNF blockade response. Both ACR response and non-response was associated with reduction in synovial TNF--level expression. Suppression in TNF- levels was not observed in the worst non-responders. The improvements (including in vascularity), independent of ACR clinical response, are compatible with the reduced structural damage documented in all groups of patients independent of response.
KEY WORDS: Rheumatoid arthritis, Infliximab, Synovial biopsy, Tumour necrosis factor, Cytokine
Present addresses: G. Cunnane, St. James's Hospital, James's Street, Dublin 8, Ireland; J. Isaacs, Musculoskeletal Research Group, School of Clinical Medical Sciences, University of Newcastle upon Tyne, UK.
Submitted 15 October 2007;
revised version accepted 17 June 2008.
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