Current Effective Topical Therapies in the Management of Psoriasis

Anil Kurian, MN¹ and Benjamin Barankin, MD, FRCPC²

¹Department of Medicine, McMaster University, Hamilton, ON, Canada
²Toronto Dermatology Centre, Toronto, ON, Canada

ABSTRACT
Topical therapy forms the cornerstone of treatment in the management of psoriasis. It plays a significant role as monotherapy in mild to moderate psoriasis, and it is used predominantly as adjunctive therapy in moderate to severe forms of the disease. Over the past decade, the topical treatment of psoriasis has evolved from the age-old applications, such as coal tar, to the more cosmetically acceptable and efficacious options containing topical corticosteroids, vitamin D analogues, and combined agents. With the advent of topical therapies in tailored vehicles and sophisticated delivery modes, the outlook for effectively managing psoriasis with topical approaches appears promising. To ensure therapeutic success, patient education about the disease, treatment options, proper administration, and adverse effects is essential, which will alleviate the common problem of poor patient adherence and promote more optimal clinical outcomes.

Key Words:
psoriasis, topical therapies, corticosteroids, vitamin D analogues, steroid foams

Psoriasis is a chronic, recurring inflammatory disease that affects the skin, scalp, and joints.1 The typical lesions are pruritic, erythematous, and exhibit well-demarcated papules and plaques with silvery-white scales.² Psoriasis affects 2% of the population and ranges in severity from mild to severe; patients with moderate to severe disease experience significant deterioration in quality of life. It affects men and women equally. The age of onset of psoriasis follows a bimodal distribution (peaks between ages 20 to 30 years and again between the ages of 50 to 60).³ Both genetic and environmental factors have been implicated in the pathophysiology of psoriasis. About 35% of patients with psoriasis have a family history of the disease. Several environmental factors can trigger psoriasis in susceptible individuals: infection (most commonly streptococcal infection); trauma to the skin (Koebner phenomenon); drug reaction (e.g., lithium, beta blockers, anti-malarial drugs, non-steroidal anti- inflammatory drugs, and glucocorticoids); and stress.²

The clinical presentation of psoriasis varies depending on the morphologic subclass. Plaque psoriasis is the most common subtype and is usually concentrated on the extensor surfaces (i.e., elbows, knees, and lumbar back), scalp, genital areas, palms, soles, joints, and nails.³ Removal of scale causes sites of punctate bleeding (Auspitz’ sign), a sign of historic note. Therapy varies depending on disease severity and the degree of body surface area involvement. However, the vast majority of patients (approximately 80-90%) present with relatively mild disease and have only limited involvement of the skin, which can be well- controlled with topical therapy.⁴

Topical Treatment Options

Corticosteroids

For decades, topical cor t icosteroids, par t icularly hig h-potency steroids, have been the mainstay in the topical treatment of psoriasis. Their efficacy can be attributed to multiple mechanisms of action, including anti-inflammatory, immunosuppressive, and antiproliferative effects.⁵ In choosing an appropriate corticosteroid potency and its vehicle, the disease severity, location being treated, and patient preference should be considered.⁶ Psoriatic patients with thick, chronic plaques often require treatment with the highest potency corticosteroids. Steroids are also excellent constituents to compound with other effective antipsoriatic agents, such as salicylic acid and liquor carbonis detergens (LCD).

Vitamin D3 Derivatives

Vitamin D analogs are known to play an important role in the
treatment of chronic plaque psoriasis through the stimulation of cellular differentiation, inhibition of proliferation, and immunomodulation.⁷ Their discovery was prompted by the realization that oral vitamin D had a therapeutic effect on psoriatic plaques. However, parent vitamin D3 might not be suitable for treating psoriasis owing to the potential for hypercalcemia.⁵ Hence, several vitamin D3 analogues have been developed for the treatment of psoriasis. Vitamin D analogues, such as calcipotriol and calcitriol, inhibit corneocyte proliferation and stimulate corneocyte differentiation in vitro.⁷ In addition, these analogues have only minimal effects on calcium levels and calcium excretion.

Tar

Coal tar has been used since ancient times for the treatment of
various skin diseases, and its utility for the treatment of psoriasis dates back approximately 100 years.⁶ Although the mechanism of action of coal tar is not well understood, it is known to suppress DNA synthesis by lessening the mitotic labeling index of keratinocytes.6 Many formulations of coal tar exist, however, these products lack patient acceptance due to cosmetic inelegance, including staining of clothes and a potent tar odor that is present in almost all products. Additional potential adverse effects include irritant contact dermatitis, folliculitis, and photosensitivity to ultraviolet A light.

Retinoids

Retinoids are a unique drug class within the armamentarium
of antipsoriatic treatments, which is largely dominated by immunomodulator y therapies. The mechanism of action of retinoids in psoriasis may include direct suppression of inflammation, as well as inhibition of proliferation and normalization of differentiation in the epidermal layer.⁵ The topical retinoid approved for psoriasis is tazarotene, and it is available as a gel or cream in 0.05% and 0.1% formulations.

Calcineurin Inhibitors

There are two topical preparations of calcineurin inhibitors:
tacrolimus ointment (0.03% and 0.1%) and pimecrolimus cream (1.0%). The initial trials indicated treatment efficacy in patients with psoriasis when used under occlusion. Hence, it led to the belief that the penetration of topical calcineurin inhibitors into thick psoriatic plaques was limited. Consequently, tacrolimus and pimecrolimus have been used in areas of skin where greater topical penetration is improved, such as in flexural or facial skin.⁷

The main side-effects of calcineurin inhibitors in some patients are a burning sensation and pruritus with initial treatments; however, the discomfort generally diminishes with ongoing use.⁷

Newer Topical Treatment Options

Calcipotriol + Betamethasone Dipropionate Gel (Xamiol®/Taclonex® Scalp)

Xamiol® is a lipophilic gel that is specially formulated for the
scalp and contains the active ingredients calcipotriol 0.005% and betamethasone dipropionate 0.05%.⁸ Calcipotriol binds to the intracellular vitamin D receptor, forming a heterodimer unit. These units migrate to the nucleus, where they bind the vitamin D response element, which directly regulates the genes involved in epidermal proliferation, inflammation, and keratinization.⁷

Betamethasone dipropionate is a potent topical steroid that binds to glucocorticoid receptors in the cytoplasm, then rapidly translocates to the nucleus where they inhibit or stimulate genes that regulate inflammation.⁸ As a result, the production of cytokines (such as interleukin-1 and interleukin-8, tumor necrosis factor-alpha, and gamma-interferon) are inhibited; and nitric oxide, prostaglandins, and levels of leukotrienes are reduced. Both vitamin D and corticosteroids can increase the number of T regulatory cells that are diminished in psoriatic skin.

A study comparing Xamiol® w ith Dovonex®/Daivonex® (calcipotriol/calcipotriene alone) demonstrated that the proportion of patients with ‘clear’ or ‘minimal’ disease at week 8 was significantly greater in the Xamiol® group (68.6%) as compared with the Dovonex® group (31.4%; P < 0.001).⁹

Additionally, the rate of improvement was more rapid and adverse events were less with Xamiol®.

A second study investigated the clinical efficacy of the two- compound scalp therapy (Xamiol®) after only 1 week of treatment.10 The percentage of patients who had ‘absent’ or ‘very mild’ disease (according to Investigator’s Global Assessment) after 1 week of treatment was significantly higher with the two-compound scalp formulation (30.6%) compared with betamethasone (24.1%; P < 0.001), calcipotriol (10.0%; P < 0.001), or vehicle (6.9%; P < 0.001).10 The results showed that the two-compound formulation demonstrated significant efficacy in treating scalp psoriasis after a 1 week period, with a faster onset of effect, than either of the individual components in the same vehicle.

Calcitriol Ointment (Silkis®/Vectical®)

Topical vitamin D modulators are among the most widely used
medications for the treatment of psoriasis. Calcitriol 3 µg/g ointment is a synthetic topical vitamin D analog considered to be as effective as other vitamin D analogs, but calcitriol has the advantage of increased tolerability in sensitive regions, such as the face, hairline, and postauricular and flexural areas.11 The use of a tolerable vitamin D3 analog in sensitive skin areas may minimize the need for corticosteroids and allow for better individualization in developing a psoriasis management regimen.

Calcitriol ointment has been extensively evaluated for the treatment of chronic plaque-type psoriasis and has been shown to be effective, safe, and well-tolerated in a number of short-term and long-term clinical trials.12 Pharmacokinetic studies in patients with psoriasis and healthy control subjects have demonstrated that topical calcitriol ointment produces little systemic drug absorption and does not result in systemic hypercalcemia even when applied to approximately one-third of the body surface area.¹²

In two randomized, double-blind clinical trials, twice-daily application of calcitriol ointment for 8 weeks resulted in clearing or minimal residual psoriasis in approximately 34% of patients, compared with 12% to 22.5% of patients treated with the vehicle ointment.12 The calcitriol ointment was shown to have a local safety profile comparable to its vehicle. Treatment-related side- effects were relatively minor and included erythema, pruritus, and general skin discomfort.

In another study, patients who received calcitriol ointment exhibited improvement in psoriasis symptoms that was similar to the corticosteroid betamethasone propionate, but were much less likely to have relapsed 8 weeks after treatment discontinuation.¹³

Clobetasol Proprionate 0.05% Spray and Shampoo (Clobex®)

Ultrapotent topical corticosteroids are the most widely used
psoriasis treatments and new formulations provide efficacious, safe, and tolerable options that may increase patient satisfaction and adherence to therapy. Although skin moisturizing is often described as an important benefit of ointments, the available evidence suggests that reduction of inflammation achieved with the anti-inflammator y agent is the key factor driving improvement outcomes, such that the newer clobetasol propionate (CP) formulations are roughly equal in efficacy to conventional ointments and cream formulations in clinical trial settings.¹⁴

All of the newer topical clobetasol propionate formulations produce clearing or near-clearing of psoriasis for a large proportion of patients within 2-4 weeks, with response, safety, and tolerability rates that are at least comparable to those observed with older topical clobetasol propionate ointments and creams.14 CP spray is the only clobetasol propionate 0.05% formulation currently approved for up to 4 weeks of treatment in moderate to severe plaque psoriasis patients whose benefit/risk ratio supports the additional 2 weeks of therapy. Previous studies have indicated that the additional 2 weeks of treatment with CP spray greatly increased efficacy without adversely affecting the safety profile of the drug.¹⁵

The CP spray may have an important role in the treatment of large areas of affected skin (up to 15-20% of body surface area), expanding the range of topical therapies for psoriasis patients. CP spray also resulted in greater improvements in quality of life (DLQI) scores at the end of treatment when compared with other formulations.¹⁵

CP 0.05% shampoo is also efficacious and safe for the management of moderate scalp psoriasis.¹⁶ CP shampoo effectively helps to prevent the relapse of scalp psoriasis and the short-contact shampoo formulation of clobetasol propionate can be utilized for extended periods without leading to notable side- effects.¹⁶ This treatment also leads to high patient satisfaction, which may increase adherence and result in even greater overall treatment efficacy.

Steroid Foams

Steroid foam preparations are newer formulations that provide
commonly prescribed topical steroids in a low residue vehicle.¹⁷

Despite the availability of numerous topical agents for the treatment of relatively localized psoriasis, patients are frequently dissatisfied due to the lack of efficacy and difficulty in using prescribed treatments. Patient compliance is reported to be low in the psoriatic population (approximately 40% non-compliance), the reason most often given by patients is that the treatments interfere with their lifestyle or require significant behavioral changes.¹⁸

Foam formulations of corticosteroids offer cosmetic advantages over traditional topical vehicles (ointments and creams), including quality of life variables such as minimal residue after application, quick drying, ease of application, and lack of fragrance. Other findings included that patients using foam preparations spent less time applying medication as compared with other topical medications. Furthermore, no significant difference in cost was found between foam and cream/solution after controlling for body surface area.¹⁸

In preliminary studies, steroid foams have also been shown to be more efficacious treatment vehicles by demonstrating more rapid penetration and greater total absorption than conventional delivery modes (i.e., lotions and creams).¹⁷ These advantages may lead to improved compliance and efficacy of treatment. The most frequently reported adverse events with steroid foam preparations are application-site reactions, such as burning, stinging, or itching. However, ethanol-free steroid foam formulations are also being developed to minimize these side-effects.¹⁸

Conclusion

With the advent of new topical treatments and varying vehicle delivery advances, the outlook for effectively managing psoriasis with topical therapies looks positive. To ensure therapeutic success, proper patient education about the disease, available treatment options, vehicle selection, and adverse effects is essential. Focusing on these areas will help to adequately address the primary reasons for poor patient adherence to topical therapy and inevitably result in more optimal clinical outcomes.

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