**10. References**

Ameen, M., Smith, H.R. & Barker, J.N. Combined mycophenolate mofetil and cyclosporin therapy for severe recalcitrant psoriasis. *Clin Exp Dermatol* 2001;26:480–3.

at ≤5 mg/kg/day, and if renal function is monitored closely so that plasma creatinine levels remain ≤30% above baseline, any renal side effects occurring during cyclosporin therapy

Safety concerns may also exist about possible malignancies during cyclosporin administration. Again, however, it should be emphasised that the disease itself leads to long-term immunological overstimulation, such that psoriatic patients have greater risks of lymphoma and other malignancies compared to the general population. Any risk of nonmelanoma skin cancer during cyclosporin administration appears to be minimised if the duration of continuous therapy is kept to ≤2 years, and if PUVA is avoided; and some studies suggest that cyclosporin plus other immunosuppressant therapy may actually

Additional well-designed assessments of various cyclosporin schedules are now warranted

Comparative studies — i.e. vs traditional treatments (e.g. methotrexate) and/or newer

 Measures of economic and quality-of-life endpoints, such that relative cost-utility and cost-effectiveness, and important considerations such as effects on psychological

 Careful evaluation of the clinical potential of specific combination therapy schedules (e.g. cyclosporin plus topical calcipotriol; low-dose cyclosporin plus mycophenolate mofetil, with a possible view to the development of a fixed-dose combination 'pill' with enhanced tolerability). This is particularly pertinent given that most studies of

In summary, the immunosuppressive properties of cyclosporin in the transplant and nontransplant settings have been widely recognised for approximately 3½ decades. As such, there is much clinical knowledge and experience of cyclosporin use in non-dermatological settings, but in the dermatological arena, clinical experience is 'catching up'. Cyclosporin has now been used in the treatment of psoriasis for almost 15 years, and with the relatively low doses used, dermatologists appear to be moving beyond any potential safety concerns about the compound, and are increasingly embracing the established antipsoriatic efficacy of the drug. As further clinical, economic, and quality-of-life data accrue from wellconducted clinical trials of cyclosporin monotherapy and combination therapy schedules, dermatologists, policy makers, and patients are likely to gain even more confidence in the favourable efficacy and tolerability profiles of cyclosporin in the treatment of psoriasis and

Ameen, M., Smith, H.R. & Barker, J.N. Combined mycophenolate mofetil and cyclosporin therapy for severe recalcitrant psoriasis. *Clin Exp Dermatol* 2001;26:480–3.

combination therapy to date have been small-scale, uncontrolled evaluations.

will be reversible when treatment is stopped.

reduce the risks of some cancers (e.g. breast, rectal).

agents (e.g. etanercept, infliximab).

distress, can be quantified and clarified.

Long-term studies of ≥2 years' duration.

other dermatological disorders.

**10. References** 

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**15** 

*USA* 

**Topical Therapies for Psoriasis** 

 *Clinical Supply, West Point, PA, Merck Research Laboratories* 

*1Biopharmaceutics, Product Value Enhancement, Pharmaceutical Sciences and* 

*2 Global Regulatory Affairs, Upper Gwynedd, PA, Merck Research Laboratories* 

Psoriasis is a chronic and recurring inflammatory condition of the skin that affects approximately 2% of the western population (Nestle et al., 2009). The most common form is plaque type psoriasis, the treatment of which is the focus of this chapter. Patients with psoriasis often present with scaly, painful and disfiguring skin lesions (Nestle et al., 2009). Although, it is seldom life-threatening, psoriasis is associated with a high degree of morbidity - patients are embarrassed about the appearance of their skin. There are significant psychosocial issues affecting these patients, often they experience social isolation, stigmatization, alcoholism and depression. In addition, patients with psoriasis, like those with other major medical disorders, have reduced levels of employment and income as well as a decreased quality of life (Horn et al., 2007). The combined costs of long-term therapy and social costs of the disease have a major impact on healthcare systems and on society in general. There are several co-morbidities that have been linked to psoriasis and it has been hypothesized that psoriasis as a disease has important systemic manifestations (Nestle et al., 2009). The shared conditions include the metabolic syndrome, depression, and cancer. Psoriasis can also occur in association with inflammatory bowel disease (Wolf et al., 2008), diabetes mellitus (Wolf et al., 2008) and HIV infection (Maurer, 2005). Although cases have been reported, it is unclear whether cancer particularly lymphoma and skin cancer, is related to psoriasis or the long term consequences of its treatment (Gelfand et al., 2006a). The relationship between psoriasis and the risk of cardiovascular disease is of emerging significance (Gelfand et al., 2006b). While patients with mild psoriasis appears to be in no excess risk, the moderate and severe form of the disease is associated with an increase in frequency of myocardial infarction and an increase in mortality, in large part because of cardiovascular events (Gelfand et al., 2006b). If confirmed, these findings would have major implications for future preventive and therapeutic strategies. Further, it is estimated that a significant population of juvenile guttate psoriasis cases are preceded by streptococcal

For treatment purposes, psoriasis can be categorized into localized and generalized forms, based upon body surface area (BSA) involvement. For localized, mild to moderate disease, usually defined as lesions covering <10% of body surface area, topical therapy is often

**1. Introduction** 

infections (Campalani & Barker, 2005).

 \*

Corresponding Author

Amitava Mitra1\* and Ercem Atillasoy2

Vena, G.A., Cassano, N., Colombo, D., et al. Cyclosporine in chronic idiopathic urticaria: a double-blind, randomized, placebo-controlled trial. *J Am Acad Dermatol* 2006;55:705–9.
