The Place of Cyclosporin in the Treatment of Severe Psoriasis

Abstract

The degree of efficacy of cyclosporin in psoriasis is dose related. While doses of 2.5 to 5 mg/kg/day result in significant clearing of psoriasis within 4 to 8 weeks, response to treatment is more rapid and dramatic with higher doses (> 5 mg/kg/day). A gradual recurrence of psoriasis, without rebound, usually occurs within weeks to months after discontinuation of therapy. Tachyphylaxis has not been reported. An initial dose of 3 to 5 mg/kg/day is recommended for the treatment of severe psoriasis and 5 mg/kg/day for the treatment of erythrodermic psoriasis, because it maximises the probability of therapeutic efficacy while minimising the likelihood of significant adverse effects. Although there appears to be no correlation between cyclosporin whole blood trough concentrations and clinical response, the drug concentrations in skin appear to approximate the peak plasma concentrations. Cyclosporin has been shown to be more effective than systemic retinoids in the treatment of psoriasis vulgaris. Psoriatic erythroderma may respond extremely rapidly to oral cyclosporin. Psoriatic arthropathy and nail disease also improve during cyclosporin therapy. Patients on cyclosporin treatment must be carefully selected and monitored for renal function, with due consideration given to drug interactions. The currently available formulation of cyclosporin does not ensure constant and predictable drug exposure because its gastrointestinal absorption is affected by biliary secretion, ingested food and gastrointestinal motility. A new microemulsion-based formulation (Neoral®)1 capable of guaranteeing more consistent bioavailability has been developed, and is under investigation. There is no significant cyclosporin-sparing effect when etretinate and UVB are used adjunctively. Furthermore, the combination of cyclosporin-UVB should be used with caution because of an increased risk of nonmelanoma skin cancer. The addition of topical corticosteroids results in more rapid clearing of psoriasis plaques, although relapse rates remain unchanged. The combination with calcipotriol has been evaluated in a placebo-controlled study, and it seems to have a cyclosporin-sparing effect. Cyclosporin is useful in short term intermittent therapy to control acute psoriatic flares and/or to induce a remission. Alternative agents can then be used for maintenance treatment, thus reducing the risk of toxicity associated with long term cyclosporin therapy.