COMBINATION THERAPY IN RECENT-ONSET RHEUMATOID-ARTHRITIS - A RANDOMIZED DOUBLE-BLIND TRIAL OF THE ADDITION OF LOW-DOSE CYCLOSPORINE TO PATIENTS TREATED WITH LOW-DOSE CHLOROQUINE

Objective. To investigate whether there is interaction between chloroq uine and cyclosporine (CyA) at the level of efficacy and toxicity in p atients with recent onset rheumatoid arthritis (RA). Methods. Eighty-e ight patients with recent onset RA, who had shown a suboptimal clinica l response on low dose chloroquine monotherapy, were randomly assigned to additional treatment with placebo, CyA 1.25 mg/kg/day, or CyA 2.50 mg/kg/day (fixed doses) for another 24 weeks. The tender joint count was the primary outcome assessment of efficacy and the serum creatinin e of toxicity. The 1995 preliminary ACR response criteria for improvem ent were applied to evaluate individual clinical responses. Results. T wo patients in the placebo group (n = 29), 7 patients in the CyA 1.25 mg group (n = 29), and 8 patients in the CyA 2.50 mg group (n = 30) (p = 0.06) discontinued study medication prematurely for inefficacy or a dverse events. The intention-to-treat analysis revealed that the tende r joint count decreased 2.2 +/- 6.1 (mean +/- SD) joints in the placeb o group, 2.2 +/- 6.6 joints in the CyA 1.25 mg group, and 5.0 +/- 5.8 joints in the CyA 2.50 mg group (p = 0.04). The 1995 preliminary ACR r esponse criteria for clinical improvement were met by 8 (28%) patients in the placebo group, 10 (34%) patients in the CyA 1.25 mg group, and 15 (50%) patients in the CyA 2.50 mg group (p = 0.07). The serum crea tinine increased 2 +/- 7 mu mol/l in the placebo group, decreased 1 +/ - 8 mu mol/l in the CYA 1.25 mg,group, and increased 10 +/- 15 mu mol/ l in the CyA 2.50 mg group (p < 0.001). Conclusion. The addition of lo w dose CyA is moderately effective in patients with early RA already t reated with low dose chloroquine, but results in statistically signifi cant renal function loss.