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 chloroquine and cyclosporine (CyA) at the level of efficacy and toxicity in patients with recent onset rheumatoid arthritis (RA).

METHODS

Eighty-eight patients with recent onset RA, who had shown a suboptimal clinical 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 creatinine of toxicity. The 1995 preliminary ACR response criteria for improvement were applied to evaluate individual clinical responses.

RESULTS

Two 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 adverse events. The intention-to-treat analysis revealed that the tender joint count decreased 2.2 +/- 6.1 (mean +/- SD) joints in the placebo 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 response 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 creatinine increased 2 +/- 7 micromol/l in the placebo group, decreased 1 +/- 8 micromol/l in the CyA 1.25 mg group, and increased 10 +/- 15 micromol/l in the CyA 2.50 mg group (p < 0.001).

CONCLUSION

The addition of low dose CyA is moderately effective in patients with early RA already treated with low dose chloroquine, but results in statistically significant renal function loss.