To study therapeutic potential of a novel basic drug leflunomide in suppression of activity and progression of rheumatoid arthritis (RA).
Leflunomide efficacy was investigated in a 36 month trial including 50 patients with moderate and high activity RA. Monthly registrations were made of the articular syndrome quantitative parameters (Richi's index, number of painful and swollen joints, severity of pain and general condition of the patient), morning stiffness duration, ESR, CRP, RF. Leflunomide efficacy was assessed by EULAR and ACR criteria. Dynamics of the extrajoint manifestations observed in 70% patients before therapy were examined clinically and by device tests. Speed of progression of erosive arthritis was quantified by a modified Sharp's method in hand and foot joints, carpal bones each 6 months. Arava tolerance was controlled clinically and by laboratory tests.
Leflunomide was found effective in 94% RA patients. A rapid (within the first month) and significant improvement in parameters of articular syndrome and CRP level was observed. To month 4 of therapy 1/5 patients achieved remission by EULAR criteria, to month 12--1/3 patients. By ACR criteria, 6-month leflunomide treatment produced good and exellent results in 71% patients which persisted up to the 36th month of therapy. The effect was better in shorter history of RA, moderate RA, in the absence of osteolyses and ankyloses. Leflunomide significantly reduced RF concentration in the serum, suppressed extrajoint RA manifestations (except Sjogren's syndrome). The mean number of new joint erosions for 6 consecutive months was 2.93 +/- 3.2, 1.41 +/- 1.8, 0.78 +/- 2.0 (median 0), while progression coefficient corresponded to slow progression to the treatment month 18. No new erosions occurred after 12 months of arava treatment in 41% patients and after 18 months--in 62%.
Leflunomide is well tolerated. The drug was discontinued because of cutaneous pruritus and diarrhea in 5 and 1 patients, respectively.