**7. Sequential therapy**

Sequential therapy is a strategy to treat psoriasis using a specific combination of therapeutic agents in a particular sequence with the aim of achieving initial efficacy followed by a safe maintenance regimen (Koo 1999). This treatment strategy maximizes efficacy of each medication while minimizing long term side effects. The strategy involves three main steps – 1) clearing phase, 2) transitional phase and 3) maintenance phase (Koo 1999). A combination of topical, systemic and phototherapy agents can be used to achieve the desired outcome, depending on the severity of the disease (Lebwohl et. al., 2004).

The clearing phase involves the use of a rapid acting agent such as a potent or super-potent topical steroid at the maximum dermatologic dose with the main aim of promptly controlling an acute outbreak of psoriasis. This is followed by the transitional phase, in which a well tolerated maintenance agent such as acitrein or vitamin D analogue is introduced and administered along with the clearing agent. The clearing agent is slowly tapered off in this phase of treatment. The transitional phase can be challenging as it requires prevention of breakthrough of the disease, while tapering off the clearing agent and adjusting dose of the maintenance agent to ensure long term control with minimal side effects. Finally, in the third phase of the treatment, the patient is retained on the maintenance therapy, with additional therapy such as phototherapy, as needed (Koo 1999).

Several combinations of therapeutic agents and regimen for sequential therapy have been proposed in literature (Lebwohl et. al., 2004; Bhutani et. al., 2011). However the choice of treatment agents needs careful consideration based on the severity and type of the disease, and the need to balance safety and efficacy. Recently, a sequential treatment regimen of clobetasol and calcitriol has been shown to be efficacious and safe for the management of moderate-to-severe plaque psoriasis (Brodell et. at., 2011). In a multicentre, open-label study in subjects aged 18-80 years with moderate-to-severe plaque psoriasis, the patients applied

Topical Therapies for Psoriasis 325

3. Effective management of psoriasis frequently necessitates combining therapies in order to achieve optimum response while minimizing any side-effects. Thus any new topical therapy should have appropriate safety and efficacy when used in combination with

4. In order to increase patient adherence to therapy, new topical formulations should have appropriate cosmetic elegance such as ease of use, no or minimal staining potential on

6. Due to the availability of a wide variety of therapies and presence of generic products in the market, competitive cost of any new medication is paramount in influencing

As is summarized in this chapter, there are several treatment options for psoriasis and exciting novel targets (e.g. PDE4 and JAK) are being investigated as potential topical treatment options. Also, combination topical products and combination of topical and phototherapy have been shown to provide more effective treatment options. The epidermal hyperproliferation in psoriatic patients may increase the variability in drug penetration across the skin. Hence novel drug delivery approaches such as liposomes, iontophoresis, and electroporation are being investigated for improved delivery. Recent research has emphasized the importance of treatment adherence in the management of psoriasis. Adherence to treatment is likely to be a far more important determinant of success than are small differences in drug delivery, especially in actual clinical use as opposed to the well controlled environment of clinical trials. Several guidances have been developed to optimize topical treatment of psoriasis and hence enable more effective management of psoriasis. Since patients prefer a less messy vehicle, adherence and outcomes are likely to be better with the more novel formulation options such as foams and sprays compared with the

The authors are employees of Merck Research Laboratories, a division of Merck Sharp and Dohme Corporation, which markets certain topical therapies discussed in the chapter.

Bagel J. (2009). Topical therapies for the treatment of plaque psoriasis. *Cutis*, 84, Suppl 4, 3-13. Barker JN, Ashton RE, Marks R, Harris RI, Berth-Jones J. (1999). Topical maxacalcitol for the

Bäumer W, Hoppmann J, Rundfeldt C, Kietzmann M. (2007). Highly selective

study with active comparator. *Br J Dermatol*, 141, 2, 274-278.

psoriasis. *Inflamm Allergy Drug Targets*, 6, 17-26.

treatment of psoriasis vulgaris: a placebo controlled, double-blind, dose finding

phosphodiesterase 4 inhibitors for the treatment of allergic skin diseases and

clothing and bedding, quick absorption on application and being less greasy; 5. Formulations which can be used on many areas of the body including hair-bearing sites

are preferred as patients often have psoriasis plaques in multiple areas;

another topical medication, systemic therapy and/or phototherapy;

the first four weeks of treatment;

physician's and patient's choice of product.

traditionally recommended ointment.

**10. Declaration of interest** 

**11. References** 

**9. Conclusion** 

therapies which can be once daily application and show quick response, such as within

clobetasol propionate (0.05% spray) twice daily for up to four weeks. At the end of four weeks, if the patient's overall disease severity was assessed as clear, almost clear, mild or moderate, the patients were treated with calcitriol (3 μg/g ointment) twice daily for an additional eight weeks (upto week 12) or unless the patient's disease was assessed as severe or returned to the baseline score, at which time the treatment was discontinued. Patients were evaluated at baseline and at 2, 4, 8 and 12 weeks. In 84% of the patients who completed the 12 week study, this treatment resulted in at least one grade improvement in disease severity and hence was considered successful as per predefined criteria. There was a significant decrease in the percent body surface area affected, from 7.1% at baseline to 3.9% at week 12. The sequential treatment regimen was also well tolerated with no unexpected adverse events. Most reported adverse events and skin irritations were mild in severity (Brodell et. at., 2011).
