Topical Antipsoriatic Treatments in 2007

L. Kircik, MD¹, L. Guenther, MD, FRCPC², D. R. Thomas, MD, FRCPC³

1. Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN, USA
2. Division of Dermatology, University of Western Ontario, London, ON, Canada
3. Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada

Background

The number of patients with psoriasis is increasing, while the number of medical dermatologists is shrinking. There are more than 1 million psoriasis patients in Canada, with 620,000 visits to a health care professional in 2006 for treatment of this condition. Approximately 35% of these visits were with dermatologists; the remainder was handled primarily by family practitioners.

Disease Severity

There are a wide range of definitions of disease severity for psoriasis. In light of the various measures that are currently available, patients can be separated into two categories: those treated with local (topical) therapy and those treated with systemic therapy. This article will deal with topical therapy.

Topical Treatment Options and the Treatment Triangle

Topical medications, either as monotherapy or in combination, are the most commonly prescribed treatments by both dermatologists and family practitioners. The treatment triangle brings together evidence-based medicine, patient preference, and the physician’s expertise in order to determine the most appropriate treatment approach. Given the increasingly limited access to dermatologists, adequate education on all available treatment options must be provided to family practitioners in order for them to adequately manage the psoriatic population in Canada.

Commonly Used Topical Antipsoriatic Therapies

• Emollients/ Keratolytics
• Topical Steroids
• Tars
• Anthralin
• Tazarotene
• Calcipotriol
• Calcipotriol + Betamethasone Dipropionate
• Calcineurin inhibitors

Emollients

The use of emollients improves the skin barrier function by restoring hydration and forming a protective layer that guards against infection and other irritants. Additional benefits include:

• improvement of itching
• removal of superficial scales, resulting in a smoother appearance to the skin
• improvement of penetration of other topical medications.

Topical Corticosteroids

Corticosteroids are potent compounds widely used for their
anti-inflammatory, immunosuppressive and antiproliferative
effects.

• Efficacy and safety have been confirmed when used as monotherapy in short-term courses and when given intermittently for more lengthy periods.
• Studies have shown improved efficacy when applied in the late afternoon or evening.

Tar

Tar slows the proliferation of skin cells and reduces inflammation, itching and scaling. While tar compounds are very effective for treating scalp psoriasis, they have several limitations:

• They are odiferous.
• They can irritate and stain.
• They can cause folliculitis.
• There is concern that they may be carcinogenic.

Anthralin

Anthralin reduces the rapid acceleration of skin growth, as seen in psoriasis.

• An effective treatment for mild-to-moderate disease, however, patients are slow to respond.
• Skin irritation and staining are common side-effects.
• Its availability is limited and is rarely used by outpatients.

Tazarotene

• It is a retinoid with the ability to mediate skin cell proliferation and differentiation
• It is mostly used in non-psoriasis indications
• It may cause irritation to psoriatic lesions
• Its effects can be enhanced when used in combination with topical corticosteroids, calcipotriol and phototherapy.

Calcipotriol

• A vitamin D analogue that acts to modulate both epidermal proliferation and differentiation.
• Twice daily application has been shown to be more effective than tar, short contact anthralin, and some corticosteroids.

Compounding

Use of calcipotriol in combination with steroids enhances efficacy. However, compounding should be used with caution. Ad hoc mixtures of calcipotriol plus steroids (including betamethasone dipropionate and betamethasone valerate) have been shown to be unstable. The valerate steroid activity disappeared within 24 hours, while the dipropionate steroid activity was more than one-third depleted after only 4 weeks.

Calcipotriol plus Betamethasone Dipropionate

• Available as a stable commercial preparation.
• Phase III trials involving more than 6,000 psoriasis patients have demonstrated clear or almost clear responses in 50% of those treated after 4 weeks of therapy.
• Reduction in Psoriasis Area and Severity Index (PASI) score was consistent throughout the study population: approximately 40% after 1 week and 70% after 4 weeks. The PASI is a visual rating system that is determined by assessing the amount of body surface area affected by psoriasis, redness, thickness, and degree of scaling.
• Response rates were uniform across patients of differing age, sex, races, and baseline disease severity.
• Combination therapy with calcipotriol and betamethasone dipropionate can enhance the rate and degree of improvement for patients undergoing treatment with UVB, PUVA, methotrexate, cyclosporine, retinoids, or alefacept.
• The addition of calcipotriol and betamethasone dipropionate can have a dose sparing effect, reducing some of the side-effects produced by many antipsoriatic treatments.
• Many dermatologists agree that including calcipotriol and betamethasone dipropionate in combination therapy produces synergistic effects.
• Can be considered as first-line topical therapy due to once daily application, quick onset of action, and favorable safety and efficacy profiles over 52 weeks of “as needed” use.

Topical Calcineurin Inhibitors

• Calcineurin inhibitors are immunosuppressive agents that interfere with T-cell signaling and affect the body’s inflammatory responses.
• Studies have indicated therapeutic benefits for psoriasis, especially on the face, and in the groin and skin folds.

Noncompliance and Nonadherence

Noncompliance or nonadherence to treatment can influence outcomes in all disease states. They unquestionably lower response to treatment, and this is of particular concern with topical medications. When the illness has the severity potential of psoriasis, physicians need to find treatment options that best suit each patient.

There is no reliable method to ensure or improve compliance in patients with psoriasis. Some clinical strategies to promote compliance include:

• encouraging patient feedback and input surrounding their treatment.
• selecting fast-acting topical therapies.
• selecting treatments that facilitate ease of use, i.e., once-daily dosing.
• referring patients to national organizations for support.

Conclusion

Advancements in topical antipsoriatic therapies have provided safer and more effective treatment options, especially when used in combination. Consequently, much research is underway to investigate novel treatment combinations for psoriasis in the hope that it will provide further enhancements in efficacy that will lead to improved patient compliance.