Influence of long-term leflunomide treatment on serum amyloid concentration in rheumatoid arthritis patients

Rheumatoid arthritis (RA) is a chronic, inflammatory disease that requires intervention with disease-modifying antirheumatic drugs (DMARDs) to stop disease progression. Leflunomide (LEF) is a DMARD with anti-inflammatory and immunomodulatory properties. As its primary mode of action, LEF reversibly inhibits dihydroorotate dehydrogenase, a key enzyme in de novo biosynthesis of pyrimidine in cells. Serum amyloid A protein (SAA) is elevated in inflammatory states and high SAA levels indicate a risk of developing secondary amyloidosis. The aim of this study was to investigate the effects of long-term LEF treatment on SAA levels and disease activity in a group of RA patients. The study group consisted of 50 consecutive RA patients (43 F, 7 M) treated with leflunomide. All patients had a clinical evaluation and SAA measurements taken at two consecutive visits during months 0, 1, 3, 6 and 12. Mean SAA concentrations decreased significantly in the first months of LEF therapy (up to the 6th month) with a more pronounced effect in patients with higher SAA levels. However, by the 12th month of treatment, the mean SAA level did not differ significantly from the SAA level at the start of treatment. At the same time though, other clinical and laboratory parameters of RA activity indicated that the disease activity decreased. Results demonstrated that in patients with active RA LEF therapy provided a significant, long-term reduction of inflammatory activity, as measured by the classic parameters of disease activity. During the treatment, SAA concentrations decreased significantly, followed by a slight increase, in spite of a reduction in other classical indicators of inflammatory response.