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The efficacy of cyclosporin A (CyA) in severe psoriasis was analysed in 457 adult patients included in five European multicentre dose-finding studies. Initial CyA doses were 1.25 mg/kg/day in 33 patients, 2.5-3 mg/kg/day in 285 and 5 mg/kg/day in 139. After 3 months of treatment, the reduction of the Psoriasis Area and Severity Index (PASI) score was 35 +/- 6% with 1.25 mg/kg/day of CyA, 57 +/- 2% with 2.5 mg or 3 mg/kg/day and 86 +/- 2% with 5 mg/kg/day (P less than 0.001). The rates of success, defined by a PASI score reduction greater than or equal to 75% or a score less than or equal to 8, were 24%, 52% and 88%, respectively. There were no differences in age, initial severity or duration of psoriasis. The improvement was maintained for 9 months or more in the majority of patients receiving continuous CyA therapy.

Cyclosporin A (CyA) trough (pre-dose) levels were measured in whole blood with a radioimmunoassay (RIA) using specific monoclonal antibody in 193 patients receiving CyA for the treatment of psoriasis. These patients received either CyA 2.5 mg/kg/day (n = 134) or 5 mg/kg/day (n = 59). In addition, a subgroup of 94 patients also had CyA trough levels measured using a non-specific polyclonal RIA. Within each CyA dose group, no difference was detected between mean CyA trough levels in relation to success or failure nor to the presence or absence of renal dysfunction with the use of either the specific or non-specific RIA. Based on the experience in transplantation, CyA thresholds of 100 and 200 ng/ml (specific) were selected for the assessment of efficacy and renal dysfunction. The success rate was higher by 10-15% when the CyA level was above, rather than below, 100 ng/ml in both the CyA 2.5 mg and 5 mg/kg/day groups. A slightly increased incidence of renal dysfunction was only found in the 5 mg/kg/day group when the CyA level was above 200 ng/ml. Because of its low predictive value, measurement of the level of CyA was not particularly useful for monitoring patients with psoriasis treated with low-dose CyA.

Serum creatinine and blood pressure were measured in patients who had severe psoriasis and who were treated with cyclosporin A (CyA) in initial doses of 1.25 mg (n = 34), 2.5 or 3 mg (n = 314), or 5 (n = 215) mg/kg/day. Of the 563 patients involved, 201 were treated for more than 3 months, and 100 received CyA continuously for 12 months or more. Sixty-eight additional patients were included as controls and received placebo (n = 42) or etretinate (n = 26). At doses of 2.5 and 5 mg/kg/day, CyA induced slight but significant dose-dependent increases in serum creatinine and blood pressure. Creatinine increases of 50% or more over baseline values were detected in 4% of the patients receiving 2.5 mg/kg/day and in 13% of those receiving 5 mg/kg/day. After an initial rise during the first weeks of treatment, mean creatinine level remained stable over 1 year provided that the CyA dose was reduced whenever creatinine levels increased by 30% or more over baseline. The incidence of hypertension was 10.6% and did not vary whether the CyA dose was 2.5 or 5 mg/kg/day. The first elevated blood pressures were recorded early after starting CyA therapy (median: 1 month). However, 3 months after stopping treatment, the increases in creatinine as well as in blood pressure were reversible and the levels did not significantly differ from baseline values.

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 400 mg 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. [ABSTRACT FROM AUTHOR]

Kidney biopsies were obtained from 14 adult patients treated with cyclosporin A (CyA) for psoriasis. These biopsies were compared with those from 16 psoriatic patients of the same age, but who were not receiving treatment with CyA. Patients receiving CyA had a maximum mean dose of 5&middot1 mg/kg/day for a mean duration of 15 months (range 3–37 months). Minimal or slight interstitial fibrosis, tubular atrophy or arteriolopathy were seen in the biopsies of patients receiving CyA as well as in those of the controls. No relevant CyA-related structural alterations of the kidney were detected. [ABSTRACT FROM AUTHOR]