TNF-α blockade in early rheumatoid significantly reduces serum VEGF and ultrasonographic measures of synovitis and joint vascularity by 18 weeks
© BioMed Central Ltd 2002
Received: 15 January 2002
Published: 4 February 2002
This study compared the ability of ultrasonographic methods and serological measurement of vascular endothelial growth factor (VEGF) to discriminate between early rheumatoid arthritis (RA) patients receiving infliximab or placebo infusions added to pre-existing methotrexate (MTX) treatment over the first 18 weeks of therapy. Twenty-four patients with early RA (<3 years duration) on stable doses of methotrexate were randomised in a double-blinded study to receive infusions of infliximab (5 mg/kg) or placebo at entry then weeks 2, 6, and 14. At baseline and 18 weeks blood was taken and serum stored. At the same time points, metacarpophalangeal joints were imaged over the dorsal surface in longitudinal and transverse planes by high resolution ultrasound (HRUS) and power Doppler to assess synovial thickness, the presence of synovial vascularity and the number of vascularised erosions. At 18 weeks, there was a median reduction in DAS28 of 1.21 from baseline in the infliximab group and 0.39 in the placebo group (P = 0.157). In the infliximab group 54% achieved ACR20 responses versus 18% in the placebo group (P = 0.08). In contrast, median reduction in synovial thickness as assessed by HRUS was 50% in the infliximab group as compared with an increase of 1.2% in the placebo group (P = 0.014). Median colour Doppler area diminished by 98.4% in the infliximab group as compared with a reduction of only 30.7% in the placebo group (P = 0.017). The total number of vascularised erosions decreased by a median of 1.0 in the infliximab group with no change from baseline in the placebo group (P = 0.001). Median serum VEGF was reduced by 31.5% in the infliximab group and 3.1% in the placebo group (P = 0.007). In this cohort, changes in serum VEGF and sonographic measures of synovial thickening and joint vascularity showed a marked reduction in the infliximab treated group compared with the placebo and methotrexate treated group. These findings indicate that reversal of inflammatory and joint destructive mechanisms are already apparent at an early stage of treatment with infliximab.