The value of synovial cytokine expression in predicting the clinical response to TNF antagonist therapy (infliximab).
OBJECTIVE
Clinical response to TNF-alpha 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-alpha, lymphotoxin-alpha, IL-1alpha, -beta 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-alpha, IL-1alpha and -beta expression did not differ between the two groups. No differences in baseline TNF-alpha 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-alpha 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.


CONCLUSIONS
Pre-treatment synovial TNF-alpha or IL-1 expression does not predict TNF blockade response. Both ACR response and non-response was associated with reduction in synovial TNF-alpha-level expression. Suppression in TNF-alpha 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.
Buch
M H
MH
Academic Unit of Musculoskeletal Disease, University of Leeds, Leeds, UK.
Reece
R J
RJ
Quinn
M A
MA
English
A
A
Cunnane
G
G
Henshaw
K
K
Bingham
S J
SJ
Bejarano
V
V
Isaacs
J
J
Emery
P
P
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001182:Arthroscopy; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012720:Severity of Illness Index; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D015415:Biomarkers; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab