SHORT-TERM AND LONG-TERM CONSIDERATIONS CONCERNING THE MANAGEMENT OF PLAQUE PSORIASIS WITH LOW-DOSE CYCLOSPORINE

In an open multicenter studv. cyclosporin (CsA) at low doses (3 mg/kg/ day adjusted during the course of treatment on the basis of clinical r esponse 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 a nd 3 months after treatment. All patients were unsatisfactory responde rs to conventional topical therapy and had indications for systemic tr eatment. Patients entered the study only if they were within the norma l range for renal an hepatic function and blood pressure. and were fre e of any clinically obvious immunodeficiencies, malignancies or blood dyscrasia. All gave their informed consent. After remission (defined a s reduction greater-than-or-equal-to 75% of the body area involved and an improvement of at least 2 points on a 4-point scale for desquamati on, erythema and infiltration) CsA was slowly tapered off (0.5 mg/kg/d ay every 2 weeks) until total discontinuation or the reappearance of s igns of the disease; the dose of CsA was also varied in the case of an y important modification in renal and hepatic function of blood pressu re. As concomitant treatment, white petrolatum was allowed, as well as specific local therapy after CsA discontinuation. Considerable improv ement (>50% reduction in the skin area affected) was observed in 98%, and only 2% (5 patients) did not respond. Clinical remission was achie ved 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 less-than -or-equal-to 2.49 mg/kg/day and 19% after 3 months at doses greater-th an-or-equal-to 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) al lowed control over the disease (the absence of relapse) to be maintain ed for a median of 8 months in 133 patients (59%). The topical therapi es permitted after remission and during the maintenance phase (steroid s, inert topical agents and exposure to UVB radiation) were used in le ss than 50% of cases. Disease relapse (the reappearance of skin involv ement over more than 50% of the area affected at baseline) occurred in 92 of the 225 patients achieving remission. 24 of whom relapsed a med ian of 6 months after remission. when CsA had been completely withdraw n: the remaining relapses occurred about 4 months after remission, dur ing the gradual withdrawal of the drug. In none of the patients was an y '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 event s 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 sel ected and closely monitored severe psoriatic patients produces constan tly favourable results within 2-3 months. After remission, it seems ad visable to withdraw the drug gradually, to evaluate the usefulness. ef fectiveness and tolerability of a low-dose maintenance regimen aimed a t preventing the recurrence of the disease or an intermittent therapy which allows a relapse-free period of 6-8 months in 70% of patients.