**5. Indications/dosage**

In Europe, cyclosporin is indicated for the treatment of severe psoriasis in patients for whom conventional therapy is ineffective or inappropriate. After starting treatment with oral cyclosporin, psoriatic patients should not be switched to another oral cyclosporin formulation without relevant monitoring of plasma cyclosporin levels, creatinine levels, and blood pressure; indeed, except for Neoral® soft gelatin capsules and Neoral® oral solution, which are bioequivalent, the various oral forms of cyclosporin are not bioequivalent. To

treated with cyclosporin 3 mg/kg/day compared with 84% of placebo recipients had

A recent, retrospective evaluation of 193 patients with moderate-to-severe psoriasis revealed that cyclosporin 1.5–3.1 mg/kg/day (mean dosage) administered for 12–36 (mean 14) months reduced mean PASI score from 23.3 to 5.6; the PASI75 response rate was 73.9%. In this trial, 83/193 patients (43%) received cyclosporin monotherapy, whereas the remainder received polytherapy. Among monotherapy recipients, the physician's judgement of therapeutic success (total clearance of lesions) was 71% of patients, whereas that of clinical remission (clearance of lesions with some remaining pigmentation) was 19% of patients. Costs to the Italian healthcare system, based on a mean 1.5 cyclosporin courses administered over 14 months, were estimated at €2,984 per patient overall; the direct costs of cyclosporin acquisition were €2,058 per patient, which are approximately 4½–7 times less than annual treatment courses of etanercept and infliximab (Colombo et al., 2010b). To support and extend these cost findings, the design and execution of comparative economic evaluations of cyclosporin versus biological therapies in patients with moderate-to-severe psoriasis would

In smaller studies, continuous versus intermittent cyclosporin therapy was significantly more effective over a 1-year period in 51 patients with chronic plaque psoriasis (PASI75 response rate: 92% vs 62%, p=0.008), although the mean cumulative annual dose of cyclosporin was 1.4-fold greater for continuous therapy (Chaidemenos et al., 2007). Furthermore, 60 patients with clearance or near clearance of psoriasis during cyclosporin induction therapy (3–7.5 mg/kg/day for 4 months) subsequently received cyclosporin maintenance therapy 1.5 or 3 mg/kg/day, or placebo, for up to 4 months (Ellis et al., 1995). Mean time to relapse was significantly longer in the higher-dose versus lower-dose cyclosporin group (12 vs 9 weeks; p=0.04), and in the higher-dose group versus placebo recipients (12 vs 7 weeks; p=0.002). At study completion, markedly fewer patients in the higher-dose versus lower-dose versus placebo group had relapsed: 43% vs 79% vs 95% (Ellis

Rotational therapy with various systemic agents (e.g. 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 (Amor et al., 2010). While most patients require additional antipsoriatic therapy after cyclosporin cessation (Amor et al., 2010), some patients may have an extended period of remission after

In Europe, cyclosporin is indicated for the treatment of severe psoriasis in patients for whom conventional therapy is ineffective or inappropriate. After starting treatment with oral cyclosporin, psoriatic patients should not be switched to another oral cyclosporin formulation without relevant monitoring of plasma cyclosporin levels, creatinine levels, and blood pressure; indeed, except for Neoral® soft gelatin capsules and Neoral® oral solution, which are bioequivalent, the various oral forms of cyclosporin are not bioequivalent. To

relapsed (Shupack et al., 1997).

now be particularly pertinent (see section 8).

et al., 1995).

**4.4 Rotational therapy** 

**5. Indications/dosage** 

cyclosporin therapy (Ho et al., 1999, 2001).

avoid any possible confusion among healthcare professionals, and to avoid any potential for major fluctuations in cyclosporin bioavailability, cyclosporin should be prescribed by brand (Neoral® SPC, 2011).

To induce remission of psoriasis, the recommended starting dosage of oral cyclosporin is 2.5 mg/kg actual bodyweight each day, administered in two divided doses; however, when a rapid initial response is required, a starting dosage of 5 mg/kg/day can be used (Neoral® SPC, 2011). If no improvement is evident after 1 month of 2.5 mg/kg/day, the dosage can be gradually increased in 0.5–1 mg/kg increments, at intervals of 2–4 weeks, up to a maximum of 5 mg/kg/day (Menter et al., 2009; Neoral® SPC, 2011). Cyclosporin should be stopped if the response is inadequate after 6 weeks' administration of 5 mg/kg/day. However, after an initially good response, the cyclosporin dosage can be reduced for maintenance therapy in steps of 0.5–1 mg/kg, at intervals of 2 weeks, until the lowest effective dosage level is attained (Amor et al., 2010; Neoral® SPC, 2011). Intermittent cyclosporin therapy may be appropriate for some psoriatic patients: that is, when an initial satisfactory response has been attained, cyclosporin therapy can be stopped and any subsequent relapses treated with reintroduction of cyclosporin at the previously effective dosage (Neoral® SPC, 2011).

Before starting cyclosporin therapy, baseline renal function and blood pressure should be measured. Plasma creatinine should be measured every month. If an increase in plasma creatinine occurs to ≥30% above baseline, cyclosporin dosage should be reduced by 25–50%, even if levels are within the reference range (see section 7.2.2). If such dosage reduction does not successfully reduce plasma creatinine within 1 month, cyclosporin should be stopped. Similarly, if elevated blood pressure occurs and cannot be controlled by cyclosporin dosage reduction, or by intervention with antihypertensive therapy, cyclosporin cessation is advocated (Neoral® SPC, 2011).
