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Randomized Controlled Trial
. 2008 Apr;67(4):511-7.
doi: 10.1136/ard.2007.071605. Epub 2007 Jul 20.

Inflammatory biomarkers, disease activity and spinal disease measures in patients with ankylosing spondylitis after treatment with infliximab

S Visvanathan  1 , C Wagner, J C Marini, D Baker, T Gathany, J Han, D van der Heijde, J Braun
Affiliations
Randomized Controlled Trial

Inflammatory biomarkers, disease activity and spinal disease measures in patients with ankylosing spondylitis after treatment with infliximab

S Visvanathan et al. Ann Rheum Dis. 2008 Apr.

Abstract

Objective: To evaluate the relationship between biomarker levels and disease activity and the spinal inflammation detected by magnetic resonance imaging (MRI) in patients with ankylosing spondylitis (AS).

Methods: Patients with AS were randomly assigned in a 3:8 ratio to receive infusions of placebo or 5 mg/kg infliximab at weeks 0, 2, 6, 12 and 18. Sera were collected for biomarker analysis at weeks 0, 2 and 24 and were analysed for levels of interleukin-6 (IL-6), vascular endothelial growth factor (VEGF) and C-reactive protein (CRP). Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores and pre- and post-gadolinium T1 and short tau inversion recovery MRIs were collected at baseline and week 24.

Results: Significantly greater reductions in IL-6, VEGF and CRP were observed at weeks 2 and 24 in the infliximab group compared with the placebo group (all p<0.001). Baseline IL-6 levels >7.38 pg/ml and CRP levels >1.5 mg/dl were associated with increased rates of clinical response after 24 weeks. Multiple regression analyses showed that reductions from baseline to week 2 in IL-6, but not CRP or VEGF, were significantly associated with reductions in MRI activity and BASDAI scores from baseline to week 24 in the infliximab group (p<0.001).

Conclusions: Significant reductions in IL-6, VEGF and CRP were observed with infliximab compared with placebo. High levels of baseline IL-6 and CRP were associated with clinical response after infliximab treatment. Early reductions in IL-6 were significantly associated with improvements in disease activity and the spinal inflammation detected by MRI.

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Conflict of interest statement

Competing interests: DvdH and JB have received research funding and/or consulting fees from Centocor and/or Schering-Plough Research Institute. SV, CW, JCM, DB, JH and TG are employees of Centocor Research and Development, Inc. and own Johnson & Johnson stock.

Figures

Figure 1
Figure 1. Baseline magnetic resonance imaging (MRI) activity and BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) scores for quantiles of baseline interleukin (IL)-6 and C-reactive protein (CRP). Horizontal solid lines are medians, and horizontal dotted lines are means. The boxes show the interquartile ranges. The error bars show the standard deviations. P-values show the difference between quantiles of each biomarker using an analysis of variance on the van der Waerden normal scores.
Figure 2
Figure 2. Median percentage change from baseline in (A) interferon-γ, (B) interleukin-6, (C) vascular endothelial growth factor and (D) C-reactive protein.
Figure 3
Figure 3. Comparison of the percentage of ASAS 20 (20% improvement in the ASsessment in Ankylosing Spondylitis working group criteria) (A,B) and BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) 50 (C,D) responders between categories of baseline interleukin (IL)-6 and C-reactive protein (CRP) divided at the medians.
See this image and copyright information in PMC

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