A STUDY OF THE RISK-BENEFIT RATIO OF LOW-DOSE CYCLOSPORINE-A IN SEVERE RHEUMATOID-ARTHRITIS

Although the efficacy of cyclosporin therapy in rheumatoid arthritis h as been established, there have been no long term studies of the risk/ benefit ratio of cyclosporin A in severe rheumatoid arthritis. A prosp ective, open-label one-year study included 106 patients (83 women and 23 men; mean age 53 years; mean disease duration 11 years) with rheuma toid arthritis. Mean number of previous second-line treatments was fou r and 69% of patients had failed methotrexate therapy. The initial dos age of cyclosporin was 3 mg/kg/d and was increased if needed up to 5 m g/kg/d. The dosage was reduced in the event of serum creatinine elevat ion (by more than 30% versus baseline) or diastolic blood pressure ele vation (above 95 mmHg). The statistical analysis was performed on an i ntention-to-treat basis. In the 45 patients who completed the one-year study period, the mean dosage was 3.6 +/- 1 mg/kg/d after six months and 3.3 +/- 1 mg/kg/d after one year. Significant improvements were se en in all the clinical efficacy parameters. The mean reduction in cort icosteroid dosage was 0.5 mg/d (n.s.). The study drug was discontinued prematurely in 61 patients (36 because of adverse events and 21 becau se of inefficacy). Twelve of the 56 patients with serum creatinine lev el elevation on at least one occasion and seven of the 35 patients wit h diastolic blood pressure elevation were taken off the study drug. No patients developed malignant disease. Despite high rates of occurrenc e of serum creatinine and blood pressure elevations, the marked effica cy of cyclosporin A and close monitoring of patients for adverse effec ts resulted in a favorable risk/benefit ratio with a one-year treatmen t continuation rate of 42%.