Efficacy and tolerability of multiple-dose SDZ IMM 125 in patients with severe psoriasis

Summary Although cyclosporin is effective in immunosuppression following organ transplantation and in the treatment of psoriasis, its use is limited by its side-effects, notably impaired renal function and hypertension. As SDZ IMM 125, a new derivative of the cyclosporin family, showed considerable immunosuppressive activity in experimental studies, with less effect on renal function, it was considered a potential successor to cyclosporin for both indications. In this multicentre, double-blind, placebo-controlled study, the efficacy and tolerability of 40, 100, 200 and 400mg SDZ IMM 125 daily were studied in 59 patients with psoriasis. Patients were followed for a period of 5 weeks (4 weeks treatment, and 1 week post-treatment observation). A dose-dependent effect of SDZ IMM 125 was observed. A significant correlation was found between the dose of SDZ IMM 125 and changes in the sum of severity scores of three indicator plaques. There was a significant decrease in the body surface area affected by psoriasis in the 400-mg group (P < 0.01), whereas a decrease of the global psoriasis severity was observed in the 200-mg (P < 0.01) and the 400-mg groups (P < 0.001). No serious adverse events occurred during the 4 weeks of treatment. Three patients discontinued treatment because of adverse events (one sore throat, two influenza). Clinical adverse events were similar to those reported with cyclosporin, the most frequent being gastrointestinal disturbances. Estimation of renal function indices showed that increases from baseline values were dose dependent, and appeared to be similar to those seen with cyclosporin. Changes in liver function tests showed a clearcut dose-dependent increase of some liver enzymes, principally alanine aminotransferase (ALAT). SDZ IMM 125 is effective in clearing psoriasis. However, long-term studies comparing the efficacy and safety of SDZ IMM 125 and cyclosporin must be performed, to determine whether SDZ IMM 125 has a better risk-benefit ratio than cyclosporin.