The value of synovial cytokine expression in predicting the clinical response to TNF antagonist therapy (infliximab)

Objectives. Clinical response to TNF-α 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-α, lymphotoxin-α, IL-1α, -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-α, IL-1α and -β expression did not differ between the two groups. No differences in baseline TNF-α 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-α expression in both response and non-response groups with significant reduction in vascularity and membrane proliferation scores. The worst ACR non-responders (