Inhibition of neutrophil migration soon after initiation of treatment withleflunomide or methotrexate in patients with rheumatoid arthritis - Findings in a prospective, randomized, double-blind clinical trial in fifteen patients

Objective, Leflunomide is a novel immunomodulating drug that has recently b een approved as a disease-modifying antirheumatic drug for the treatment of rheumatoid arthritis (RA), The aim of this study was to determine the rela tionship between the clinical effects of leflunomide and neutrophil migrati on. Methods. The effects of leflunomide and methotrexate on neutrophil chemotax is were studied in 15 RA patients who participated in a prospective, random ized, double-blind clinical trial. When possible, neutrophil numbers were c ounted in synovial fluid (SF) samples at baseline and after 14 days, 4 mont hs, and 1 year of treatment. The chemotactic properties of peripheral blood neutrophils from RA patients treated with either leflunomide or methotrexa te were studied by the Boyden chamber technique, using the activators formy l-methionylleucyl-phenylalanine (fMLP) and interleukin-8 (IL-8), The in vit ro effects of A77 1726, the active metabolite of leflunomide, and methotrex ate on peripheral blood neutrophils from 7 healthy control subjects were al so investigated. Results. Both therapy groups exhibited clinical improvement, including rapi d reductions in SF neutrophil counts and reduced joint swelling and tendern ess. On day 14, 3 of 7 patients who received leflunomide showed no detectab le effusions, There was a significant effect on neutrophil chemotaxis (P < 0,001), which was similar for leflunomide and methotrexate. The direct effe cts on the neutrophils diminished over time. Incubation of peripheral blood neutrophils from healthy controls with A77 1726 confirmed the inhibitory e ffect on chemotaxis. Conclusion. Leflunomide treatment is beneficial in BA patients. Different m echanisms are operative in various phases of treatment, leading to decrease d recruitment of inflammatory cells in the joints.