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

S Visvanathan ^1*, C L. Wagner ¹, J C Marini ¹, D van der Heijde ², D Baker ¹, T Gathany ¹, J Han ¹ and J Braun ³

¹ Centocor Research and Development, Inc., United States
² Leiden University Medical Centre, Netherlands
³ Rheumazentrum Ruhrgebiet, Germany

^* To whom correspondence should be addressed. E-mail: svisvana{at}cntus.jnj.com.

Accepted 5 July 2007

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 analyzed 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 < 0.01).

Conclusion: 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.

Keywords: ankylosing spondylitis, infliximab, interleukin-6, magnetic resonance imaging

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