A standardized set of criteria to identify clinical response in ankylosing spondylitis (AS) following treatment is needed. The Assessment in Ankylosing Spondylitis Working Group has developed improvement criteria (ASAS-IC) consisting of 4 domains: physical function, pain, patient global, and inflammation, each measured on a 100mm visual analog scale. This study investigates whether this criteria reflect clinically relevant improvement based on the opinion of a panel of experts in the field of AS.

Methods: 55 patients with AS, who had participated in a NSAID efficacy trial with a flare design, were presented to the expert panel in a 3-round Delphi-exercise. The response rate according to the final consensus of the experts was compared with the response rate according to the ASAS-IC.

Results: 40 experts completed the 3 Delphi-rounds. The experts considered twice as many patients as a responder than the ASAS-IC did (42 versus 21). Overall agreement between experts and ASAS-IC was 62%. Considering the end-of-trial efficacy assessment by patient and physician as the gold standard, the candidate criteria sets showed an agreement of 71 to 82%, sensitivity of 67 to 83%, and specificity of 81 to 88%. The ASAS-IC showed an agreement of 70%, sensitivity of 62% and specificity of 89%.

Conclusion: The ASAS-IC appears to be highly specific with lower sensitivity. Although less patients were considered responders using the ASAS-IC criteria, all responders by ASAS-IC were also considered responder the expert panel as well as by patients themselves and by their physicians, independently of each other.

Editorial Comments: As clinical trials in ankylosing spondylitis become more common, it is critical to develop a standardized set of criteria to identify clinical response to an intervention. This study is an important attempt to critically evaluate the proposed ASAS-IC criteria, using clinical data from real patients.

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OP00025 DIFFERENTIAL EFFECT OF INFLIXIMAB ON THE T AND B CELL SYNOVIAL INFILTRATION IN SPONDYLOARTHROPATHY:HISTOLOGIC EVALUATION OF PERIPHERAL ARTHRITIS IN A PLACEBO-CONTROLLED TRIAL
E. Kruithof, D. Baeten, F. Van den Bosch, H. Mielants, E.M. Veys, F. De Keyser

This study evaluates the synovial histology in patients with spondyloarthropathy following treatment with infliximab. 13 of 40 patients participating in a double-blind, placebo-controlled trial, who were treated with 5 mg/kg infliximab or placebo at week 0, 2, and 6, underwent serial synovial biopsies at baseline, week 1 and week 12. All 13 patients (n=10, infliximab; n=3, placebo) had active synovitis of the knee. The histologic and immunohistochemical evaluation included lining layer thickness, inflammatory infiltration and phenotypic markers, as well as vascularity, neovascularization markers and adhesion molecules.

All 10 inflixmab-treated patients had a significant clinical improvement. Synovial tissue evaluations at week 12 were compared to those at baseline. The infliximab-treated group showed a reduction in lining layer thickness (p=0.015) and VCAM-1, but not ICAM-1, expression in the synovial lining (p=0.034). In the sublining layer, there was a significant decrease in overall cell infiltration (p=0.018), CD3+ cells (p=0.026), neutrophils (p=0.041) and CD68+ macrophages (p=0.034), with a similar trend for follicles, CD4+ cells and CD8+ cells. In contrast to observations in RA synovium, no such trend was observed for CD20+ B cells nor CD38+ and CD138+ plasma cells. Additionally, the placebo group showed no significant immunohistochemical or histologic changes.

Conclusion: These data support the immunomodulatory role of infliximab on peripheral arthritis in SpA.

Editorial Comments: Although only a small number of patients were studied (particularly control patients), this is one of the few studies available on synovial histopathology in AS in general, and after TNF inhibition, in particular. Infliximab-induced changes in synovial thickening, inflammation and vascularity reported here were, in general, similar to those observed with TNF inhibition in RA. The failure of infliximab to downregulate B cells/plasma cells is interesting though the significance is unclear, since AS is not associated with autoantibody production.

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