Intermittent short courses of cyclosporin (Neoral®) for psoriasis unresponsive to topical therapy: a 1-year multicentre, randomized study

Abstract

We performed a 1-year study to determine whether intermittent short courses of the microemulsion formulation of cyclosporin (Neoral) could effectively control plaque psoriasis and whether tapering or abrupt cessation of cyclosporin therapy would influence time to relapse. Four hundred patients with plaque psoriasis were included in this open, multicentre, randomized study. All patients commenced cyclosporin at a dose of 2.5 mg/kg daily. Cyclosporin dosage could be increased to a maximum of 5 mg/kg daily. Treatment was continued until clearance of psoriasis or for a maximum of 12 weeks. Patients were then randomly assigned either to stop cyclosporin abruptly or to have the dose reduced by 1 mg/kg daily each week until cessation. On relapse, patients were given another course of cyclosporin. Patients were followed for at least 1 year, during which they could receive as many treatment courses as necessary. The number of patients who required one, two, three and four treatment courses was 400, 259, 117 and 26, respectively. The median time to relapse after the end of the first treatment period was 109 days in the group of patients randomized to stop cyclosporin abruptly and 113 days in patients randomized to taper off cyclosporin (P = 0.038). More than 30% of patients had not relapsed 6 months after having stopped treatment. After each treatment course, the Kaplan-Meier probability of achieving 75% or more reduction in disease area by day 84 of treatment was 83%, 76%, 73% and 66%, respectively. Mean serum creatinine concentration and blood pressure did not show any clinically significant changes over time. Our results show that intermittent short-course therapy with Neoral, when used in conjunction with topical therapy, is well tolerated and provides effective control of plaque psoriasis for 1 year. Tapering off cyclosporin on treatment cessation induces a slight delay in psoriasis relapse.

Cyclosporin a (Sandimmun Neoral) in Therapy for Psoriasis and Psoriatic Arthritis

“…ЦсА блокирует актива-цию Т-хелперов и Т-клеток-регуляторов, естественных киллеров и моноцитов [12]. Кроме того, он угнетает высво-бождение гистамина из тучных клеток, снижает активность различных клеточных молекул адгезии, подавляет антиген-презентирующие клетки [13].…”

Systemic Cyclosporin in the Treatment of Psoriasis

“…Such hypertension is generally reversible after the cyclosporin dosage is reduced, or after antihypertensive medications are added (Ho et al, 1999;. Importantly, besides specific drug therapy, psoriasis per se may contribute to an increased risk of hypertension, since psoriatic patients have increased incidences of obesity and metabolic syndrome (Gelfand et al, 2006).…”

“…Overall, the Kaplan-Meier probability of achieving a ≥75% decrease in disease area after 12 weeks' treatment was 83% after the first cyclosporin course, 76% after the second, 73% after the third, and 66% after the fourth [ Fig. 2] (Ho et al, 1999).…”

“…2. Maintained efficacy of intermittent short-term cyclosporin therapy during a large, 1-year, multicentre, randomised trial in patients with plaque psoriasis (Ho et al, 1999). Values shown are the probability of a PASI75 response after 12 weeks' treatment with cyclosporin 2.5-5 mg/kg/day.…”

“…acitretin, fumaric acid esters, methotrexate, mycophenolate mofetil) has occasionally been advocated as a means of reducing the duration, and any potential toxicity, of cyclosporin therapy . While most patients require additional antipsoriatic therapy after cyclosporin cessation , some patients may have an extended period of remission after cyclosporin therapy (Ho et al, 1999(Ho et al, , 2001). …”