Summary The value of oral cyclosporin A (CyA: Sandimmun®) in the treatment of chronic severe plaque psoriasis has already been established. Many controlled studies have addressed the issues of efficacy and safety, mostly in studies of several months duration. Patients treated for up to several years have been reported, but never in multicentre controlled studies. Guidelines have established the maximum dose permissible to reduce the risk of side-effects. However, the efficacy and safety of therapy of longer duration remain under investigation.
The results of a multicentre prospective randomized clinical study (251 patients) to evaluate the efficacy, safety and tolerability of two dose levels of CyA (2·5 or 5 mg/kg/day) for inducing remission, and for use in long-term maintenance therapy for up to 21 months, are presented. An assessment of relapse as the dose was tapered (during the last 3 months of treatment), and the reversibility of CyA-induced side-effects, is also presented (follow-up phase of 3 months).
Efficacy was evaluated by means of the psoriasis area and severity index (PASI). Safety was assessed by using the results of vital signs, physical examination, laboratory tests and physician and patient evaluation of adverse events. During the induction of remission phase of therapy, a total of 184 patients (73%) were treated successfully. The percentage of patients classified as successes at the endpoint was significantly higher in the group on 5·0 mg/kg/day (92%) than in that on 2·5 mg/kg/day (52%; P≤0·001).
A total of 215 (86%) patients reported at least one adverse event during the study. In 136 patients (54%) the reported adverse event was judged by the investigator as being related to CyA. Nineteen patients (8%) reported events that were judged as severe, and related to treatment with CyA. A total of 45 patients (18%) discontinued treatment due to adverse events. Hypertension was one of the reasons, or the reason, for discontinuation in 16 patients (6%). The occurrence of hypertension appeared unrelated to CyA dose.
One hundred and sixteen patients (46%) experienced a maximum increase in serum creatinine >30% above baseline values on at least one occasion. This increase in serum creatinine was often transient, and was one of the reasons, or the reason, for discontinuation in 24 patients (10%). An increase in serum creatinine >30% above baseline was dose-related.
The results of this study show that 5·0 mg/kg/day of CyA is significantly more effective than 2·5 mg/kg/day in the treatment of chronic plaque psoriasis. Depending on the dose group, some patients relapsed as CyA was tapered, but without rebound. Hypertension and an increase in serum creatinine were the two most frequently encountered complications of treatment.