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 cyclosporine efficacy is currently observed. To evaluate individual therapeutic potency of cyclosporine, pharmacodynamic approaches were performed with use of peripheral blood mononuclear cells (PBMCs) from patients with psoriasis.


METHODS
Cyclosporine effects on PBMC-blastogenesis were examined in 33 patients with psoriasis. The drug concentration that gave 50% inhibition of mitogen-stimulated PBMC proliferation in vitro (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 in the psoriasis area and the severity index (PASI) 16 weeks after cyclosporine therapy began was measured.


RESULTS
Cyclosporine IC50 values in 33 patients deviated widely, from 0.1 to 120.6 ng/ml. We classified these patients into two groups on the basis of their PBMC sensitivity 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 cyclosporine therapy in the patients with high sensitivity was significantly higher than that in the patients with low sensitivity (p < 0.0007). 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.


CONCLUSIONS
The results showed that we could use PBMCs to pharmacodynamically predict the patients with a poor response to cyclosporine therapy. These patients may require larger doses of cyclosporine or alternative approaches to treatment. The patients with PBMCs sensitive to cyclosporine should be evaluated for treatment with smaller doses of the drug to avoid serious side effects.
Hirano
T
T
Department of Clinical Pharmacology, Tokyo University of Pharmacy and Life Science, Japan.
Oka
K
K
Umezawa
Y
Y
Hirata
M
M
Oh-i
T
T
Koga
M
M
D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects*; D011237:Predictive Value of Tests; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology*; D012720:Severity of Illness Index
D007166:Immunosuppressive Agents; D016572:Cyclosporine