Low-dose Infliximab (3 mg/kg) Significantly Reduces Spinal Inflammation on Magnetic Resonance Imaging in Patients with Ankylosing Spondylitis: A Randomized Placebo-controlled Study

Abstract

To evaluate the influence of low-dose infliximab (IFX) on spinal inflammation scored by magnetic resonance imaging (MRI). The dose recommended for rheumatoid arthritis (3 mg/kg) is also clinically effective for ankylosing spondylitis (AS), although effects on spinal inflammation as defined by MRI have yet to be described in a placebo-controlled trial. In a 12-week double-blind period, patients were randomized 1:1 to receive either IFX 3 mg/kg at 0, 2, and 6 weeks, or placebo. Spinal inflammation in discovertebral units (DVU) was measured by the Spondyloarthritis Research Consortium of Canada (SPARCC) MRI Index at baseline and 12 weeks by 3 readers blinded to timepoint and treatment allocation. We also compared reliability and discrimination of the SPARCC MRI index based on evaluation of the entire spine (23 DVU score) compared to assessment of only the 6 most severely affected DVU (6 DVU score). At Week 12, patients treated with IFX experienced mean reductions of 55.1% and 57.2% in the 6 DVU and 23 DVU SPARCC scores, respectively, compared with a mean increase of 5.8% and decrease of 3.4% in 6 DVU and 23 DVU scores, respectively, for patients taking placebo (p < 0.001). A large treatment effect (Guyatt's effect size >or= 1.7) and high reliability was evident and comparable between 6 DVU and 23 DVU scoring methods. Treatment with low-dose IFX leads to a large treatment effect on spinal inflammation as measured by MRI. Scoring for inflammation of only the most severely affected regions of the spine by MRI is comparable to assessment of the entire spine.