EFFICACY AND SAFETY OF ORAL CYCLOSPORINE-A (CYA SANDIMMUN(R)) FOR LONG-TERM TREATMENT OF CHRONIC SEVERE PLAQUE PSORIASIS

The value of oral cyclosporin A (CyA; Sandimmun(R)) in th(: treatment of chronic severe plaque psoriasis has already been established. Many controlled studies have addressed the issues of efficacy and safety, m ostly in studies of several months duration. Patients treated for up t o several years have been reported, but never in multicentre controlle d 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 C yA (2.5 or 5 mg/kg/day) for inducing remission, and for use in long-te rm maintenance therapy for up to 21 months, are presented. An assessme nt of relapse as the dose was tapered (during the last 3 months of tr: atment), and the reversibility of CyA-induced side-effects, is also pr esented (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 t he induction of remission phase of therapy, a total of 184 patients (7 3%) were treated successfully. The percentage of patients classified a s 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 tot al of 215 (86%) patients reported at least one adverse event during th e study. In 136 patients (54%) the reported adverse event was judged b y the investigator as being related to CyA. Nineteen patients (8%) rep orted events that were judged as severe, and rc:lated to treatment wit h CyA. A total of 45 patients (18%) discontinued treatment due to adve rse events. Hypertension was one of the reasons, or the reason, for di scontinuation in 16 patients (6%). The occurrence of hypertension appe ared unrelated to CyA dose. One hundred and sixteen patients (46%) exp erienced a maximum increase in serum creatinine >30% above baseline va lues on at least one occasion. This increase in serum creatinine was o ften transient, and was one of the reasons, or the reason, for discont inuation in 24 patients (10%). An increase in serum creatinine >30% ab ove baseline was doserelated. 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 grou p, some patients relapsed as CyA was tapered, but without rebound. Hyp ertension and an increase in serum creatinine were the two most freque ntly encountered complications of treatment.