Histological evidence that infliximab treatment leads to downregulation of inflammation and tissue remodelling of the synovial membrane in spondyloarthropathy.
OBJECTIVE
To confirm and extend the immunopathological evidence of effects of infliximab on the synovium in active spondyloarthropathy.


METHODS
Synovial biopsies obtained in patients with spondyloarthropathy at baseline and week 12 were stained and scored by two independent observers. Two study populations were evaluated: I, a cohort of 10 patients treated with 5 mg/kg infliximab at week 0, 2, and 6, plus three placebo treated patients; and II, a pooled cohort of 20 patients fulfilling identical inclusion and exclusion criteria and treated with the same loading dose regimen.


RESULTS
In study population I, treatment with infliximab induced reduction in synovial lining layer thickness (p = 0.015), endothelial activation (E-selectin, p = 0.034), and inflammatory cell infiltration with neutrophils (p = 0.041), macrophages (p = 0.034), and T cells (p = 0.026), but not with B cells and plasma cells; no such trends were observed in the placebo treated patients. Besides confirming the highly significant downregulation of inflammation, analysis of cohort II showed structural changes such as normalisation of lining layer thickness (p = 0.030), reduction in the number of blood vessels (p = 0.039), and downregulation of follicular organisation (p = 0.050). No differences in histopathological response were observed between spondyloarthropathy subtypes.


CONCLUSIONS
Profound immunomodulatory changes in the synovium parallel the clinical benefit in patients with spondyloarthropathy treated with infliximab, independently of the subtype. The study provides histological evidence that TNF alpha blockade not only downregulates inflammation but also leads to tissue remodelling.
Kruithof
E
E
Department of Rheumatology, Ghent University Hospital, De Pintelaan 185, 9000 Gent, Belgium. elli.kruithof@UGent.be
Baeten
D
D
Van den Bosch
F
F
Mielants
H
H
Veys
E M
EM
De Keyser
F
F
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001706:Biopsy; D004311:Double-Blind Method; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006801:Humans; D000069285:Infliximab; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D025242:Spondylarthropathies / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D013583:Synovial Membrane / Q000098:blood supply / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D013585:Synovitis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab