Anti-TNF-α antibody Infliximab and glucocorticoids reduce serum vascular endothelial growth factor (VEGF) levels in patients with rheumatoid arthritis: a pilot study

Background

Pannus growth in rheumatoid arthritis (RA) is critically dependent upon accompanying neovascularization. Vascular endothelial growth factor (VEGF) is a potent angiogenic promoter, which is thought to play a crucial role in synovial angiogenesis in rheumatoid arthritis (RA). Serum VEGF levels are elevated in RA patients, and therapy with the anti-TNF-α antibody infliximab reduces serum VEGF levels in these patients.

Objective

The study was conducted to compare the early effect of oral glucocorticoids (GC) with anti-TNF-α therapy (infliximab) on serum VEGF levels in patients with RA.

Methods

Five RA patients (5/8) who had no prior treatment with DMARDs or glucocorticoids (GC) were administered 20 mg/day prednisolone. Three patients who failed more than one disease-modifying antirheumatic drug (DMARD) therapy received infusion with infliximab (200 mg). VEGF serum levels were measured using ELISA before treatment and at day 10 or 13 during prednisolone therapy or 14 days after the first infliximab infusion.

Results

Serum VEGF levels in therapy naïve RA patients (GC group) were higher than those in pretreated patients who received infliximab (median serum VEGF level: 1106 pg/ml versus 320 pg/ml; P = 0,09). Treatment with infliximab as well as glucocorticoids significantly decreased serum VEGF levels after 10–14 days in RA patients (median serum VEGF level after treatment: GC group 559 pg/ml, infliximab group 92 pg/ml; P = 0.01 versus without treatment or preinfusion).

Conclusions

Treatment with oral glucocorticoids leads to an early and drastic reduction in serum VEGF levels in therapy naïve RA patients. TNF-α inhibition by infliximab could reduce low serum VEGF levels in pretreated RA patients independent of the initial serum VEGF concentration. This is the first report comparing the effect of both therapies on serum VEGF levels, indicating a possible therapeutic inhibition of angiogenesis in RA.