INDIVIDUAL PHARMACODYNAMICS ASSESSED BY ANTILYMPHOCYTE ACTION PREDICTS CLINICAL CYCLOSPORINE EFFICACY IN PSORIASIS

Background: Cyclosporine (INN, ciclosporin) use for psoriasis has been proposed and clinically examined. However, individual variation in cy closporine efficacy is currently observed, To evaluate individual ther apeutic potency of cyclosporine, pharmacodynamic approaches were perfo rmed with use of peripheral blood mononuclear cells (PBMCs) from patie nts with psoriasis, Methods: Cyclosporine effects on PBMC-blastogenesi s were examined in 33 patients with psoriasis, The drug concentration that gave 50% inhibition of mitogen-stimulated PBMC proliferation in v itro (IC50, in nanograms per milliliter) was evaluated in each patient . Cyclosporine was administered at an initial dose of 5 mg/kg/day, and the dose was tapered for 16 weeks to 3 mg/kg/day, The recovery rate i n the psoriasis area and the severity index (PASI) 16 weeks after cycl osporine therapy began was measured. Results: Cyclosporine IC50 values in 33 patients deviated widely, from 0.1 to 120.6 ng/ml, We classifie d these patients into two groups on the basis of their PBMC sensitivit y to cyclosporine with use of the median cyclosporine IC50 (3.0 ng/ml) of these patients as the cutoff point, The PASI recovery rate after c yclosporine therapy in the patients with high sensitivity was signific antly higher than that in the patients with low sensitivity (p < 0.000 7), Moreover, a significant negative correlation between the IC50 and the PASI recovery rate was observed in these 33 patients (r = -0.73; p < 0.0001), Blood trough levels and side effects of cyclosporine were not significantly different between the two patient groups. Conclusion s: The results showed that we could use PBMCs to pharmacodynamically p redict the patients with a poor response to cyclosporine therapy. Thes e patients may require larger doses of cyclosporine or alternative app roaches to treatment. The patients with PBMCs sensitive to cyclosporin e should be evaluated for treatment with smaller doses of the drug to avoid serious side effects.