LONG-TERM LOW-DOSE CYCLOSPORINE THERAPY FOR SEVERE PSORIASIS - EFFECTS ON RENAL-FUNCTION AND STRUCTURE

Background: The effectiveness of cyclosporine in the treatment of seve re psoriasis is well known. Objective: We evaluated the efficacy and t oxicity of systemic cyclosporine in patients with severe psoriasis, ob serving short-term (12 weeks) and long-term (3 to 5 years) effects. Me thods: To further elucidate efficacy and safety, 42 patients with seve re psoriasis were treated initially with cyclosporine 5 to 6 mg/kg per day for 12 weeks. A subset of 14 patients continued maintenance treat ment for 3.5 years to study the long-term effects of cyclosporine on r enal function and structure. Renal biopsies were performed after 2.5 y ears and 3.5 years of treatment. Renal histologic findings were correl ated with renal function. Results: By weeks 8 and 12, 64% (n=27) and 8 6% (n=36) of patients, respectively, were rated clear or almost clear of the psoriasis. However, a subpopulation of 15 patients did not resp ond to 5 mg/kg daily but improved when the dose was increased to 6 mg/ kg daily. Clearance or near clearance was achieved in 67% of this subp opulation after 4 weeks. For the 29 patients whose glomerular filtrati on rate (GFR) was measured, mean GFR fell by 7% from baseline to week 4 (p <0.05). This change was reversible when dosage was reduced by 1 m g/kg per day in each of these patients. Patients older than 45 years o f age experienced significant elevation of mean diastolic blood pressu re and had reduced GFR and increased serum creatinine. After 2.5 years , of the 14 patients who continued maintenance treatment, two had biop sy specimens that showed moderate interstitial fibrosis and tubular at rophy. The re mainder showed only minimal to mild structural damage. A fter 3.5 years of cyclosporine treatment, repeat renal biopsy specimen s revealed slight increases in structural changes in nine subjects. Th ese changes correlated with increasing age and drug-induced hypertensi on. Conclusion: We conclude that 5 mg/kg of cyclosporine daily is usua lly an effective initial dose for psoriasis. Patients who do not respo nd will often benefit from elevation of the dose to 6 mg/kg daily. Old er patients experience cyclosporine-induced hypertension and changes i n renal function and structure more frequently than do younger patient s.