Abstract
In an open multicenter study, cyclosporin (CsA) at low doses (3 mg/kg/day adjusted during the course of treatment on the basis of clinical response and tolerability up to a maximum of 5 mg/kg/day) was given to 293 evaluable patients with severe plaque-form psoriasis (M/F 215/78, aged 19–80 years, 2–53 years from diagnosis) in order to evaluate its safety and efficacy over a median follow-up of 7 months of treatment and 3 months after treatment. All patients were unsatisfactory responders to conventional topical therapy and had indications for systemic treatment. Patients entered the study only if they were within the normal range for renal an hepatic function and blood pressure, and were free of any clinically obvious immunodeficiencies, malignancies or blood dyscrasia. All gave their informed consent. After remission (defined as reduction ≥ 75% of the body area involved and an improvement of at least 2 points on a 4-point scale for desquamation, erythema and infiltration) CsA was slowly tapered off (0.5 mg/kg/day every 2 weeks) until total discontinuation or the reappearance of signs of the disease; the dose of CsA was also varied in the case of any important modification in renal and hepatic function of blood pressure. As concomitant treatment, white petrolatum was allowed, as well as specific local therapy after CsA discontinuation. Considerable improvement ( > 50% reduction in the skin area affected) was observed in 98% and only 2% (5 patients) did not respond. Clinical remission was achieved in 225 patients (77%): of these, 73% after a median of 2 months at CsA doses of 2.5–3.49 mg/kg/day, 8% after 4 months at doses < 2.49 mg/kg/day and 19% after 3 months at doses ≥ 3.5 mg/kg/day. After remission, the gradual withdrawal of the drug over a period of 3 months (0.5 mg/kg/day every 2 weeks) allowed control over the disease (the absence of relapse) to be maintained for a median of 8 months in 133 patients (59%). The topical therapies permitted after remission and during the maintenance phase (steroids, inert topical agents and exposure to UVB radiation) were used in less than 50% of cases. Disease relapse (the reappearance of skin involvement over more than 50% of the area affected at baseline) occurred in 92 of the 225 patients achieving remission, 24 of whom relapsed a median of 6 months after remission, when CsA had been completely withdrawn; the remaining relapses occurred about 4 months after remission, during the gradual withdrawal of the drug. In none of the patients was any ‘rebound’ effect observed. In 11 patients who relapsed twice during the course of observation, the administration of successive cycles of equal doses of CsA proved to be equally efficacious. The adverse events reported by 26% of the patients were mild or moderate and reversible with the adjustment of posology or discontinuation of the treatment (3% of cases). In conclusion, CsA at 3 mg/kg/day given to carefully selected and closely monitored severe psoriatic patients produces constantly favourable results within 2-3 months. After remission, it seems advisable to withdraw the drug gradually, to evaluate the usefulness, effectiveness and tolerability of a low-dose maintenance regimen aimed at preventing the recurrence of the disease or an intermittent therapy which allows a relapse-free period of 6–8 months in 70% of patients.
