Ciclosporin in psoriasis clinical practice: an international consensus statement

Abstract

The main recommendations for the use of ciclosporin in the management of psoriasis are: (i) intermittent short courses (average of 12 weeks duration) of ciclosporin are preferable; (ii) ciclosporin should be given in the dose range 2.5-5.0 mg kg(-1) day(-1) (doses greater than 5.0 mg kg(-1) day(-1) should only be given in exceptional circumstances); (iii) treatment regimens should be tailored to the needs of each patient; (iv) selection of patients should take into account psychosocial disability, as well as clinical extent of disease and failure of previous treatment; (v) each patient's renal function (as measured by serum creatinine) should be thoroughly assessed before and during treatment; (vi) each patient's blood pressure should be carefully monitored before and during treatment; (vii) adherence to treatment guidelines substantially reduces the risk of adverse events; (viii) long-term continuous ciclosporin therapy may be appropriate in a subgroup of patients; however, duration of treatment should be kept below 2 years whenever possible; and (ix) when long-term continuous ciclosporin therapy is necessary, annual evaluation of glomerular filtration rate may be useful to accurately monitor renal function.

Calcineurin Inhibitor Nephrotoxicity

“…To date, no randomized studies are available assessing the impact of CNI minimization protocols on the histologic evolution of CNI nephrotoxicity, and the relative contribution of rejection phenomena versus CNI nephrotoxicity is not known from minimization protocols. Given the finding that chronic CNI nephrotoxicity also occurs in psoriasis patients treated with lowdose cyclosporine (348), it can be expected that persistent nephrotoxicity will occur as long as the CNIs are continued.…”

Systemic Cyclosporin in the Treatment of Psoriasis

“…European guidelines recommend that the maximum period of continuous cyclosporin therapy in patients with psoriasis should be no more than 2 years (Griffiths et al 2004;Menter et al 2009;Pathirana et al 2009). This is primarily because the incidence of renal dysfunction and nonmelanoma skin cancer may increase markedly with high doses of cyclosporin administered for longer periods (Paul et al 2003;Ryan et al 2010).…”

“…Generally, such side effects are reversible after cyclosporin discontinuation, although rarely chronic renal impairment and structural abnormalities in the kidneys may persist and be irreversible . To minimise the risk of nephrotoxicity, the most widely recommended cyclosporin regimen in psoriasis is a short-term schedule of 2.5-5.0 mg/kg/day for 12-16 weeks (see section 5); this short course is repeated if subsequent disease flares occur Griffiths et al, 2004). Adhering to present guidelines about appropriate dosage and monitoring protocols for cyclosporin use in psoriatic patients will substantially reduce the risk of side effects (Griffiths et al, 2004;Menter et al, 2009;Pathirana et al, 2009).…”

“…weekly self-monitoring) is therefore important in cyclosporin-treated patients with psoriasis. If hypertension occurs, current guidelines advocate a cyclosporin dosage reduction of 25-50%, or commencement of antihypertensive therapy (Griffiths et al, 2004;Pathirana et al, 2009). Dihydropyridine calcium-channel blockers (e.g.…”

“…If plasma creatinine levels are ≥30% above baseline on two consecutive occasions, 2 weeks apart, the cyclosporin dosage should be reduced by 25-50% for at least 4 weeks; this applies even if creatinine values are within the normal reference range (Griffiths et al, 2004;Menter et al, 2009;Pathirana et al, 2009). After 4 weeks of reduced-dosage treatment, if plasma creatinine levels remain elevated, cyclosporin should be discontinued (Neoral ® SPC, 2011).…”