Tazarotene Revisited: Safety and Efficacy in Plaque Psoriasis and Its Emerging Role in Treatment Strategy
December 2018 | Volume 17 | Issue 12 | Original Article | 1280 | Copyright © December 2018
Emil A. Tanghetti MD,a Mark G. Lebwohl MD,b Linda Stein Gold MDc
aCenter for Dermatology and Laser Surgery, Sacramento, CA bIcahn School of Medicine at Mount Sinai, New York, NY cHenry Ford Hospital, Detroit, MI
BACKGROUND: Psoriasis is a chronic, immune-mediated disease that varies widely in its clinical expression. Treatment options focus on relieving symptoms, reducing inflammation, induration, and scaling, and controlling the extent of the disease. While significant data on tazarotene in psoriasis has been available for over 20 years, its main utility is in acne. OBJECTIVE: To review the clinical studies with tazarotene in psoriasis and establish its future role in the management of this chronic, incurable condition. METHODS: An English language literature review was performed utilizing Medline, EMBASE, and the Web of Science to identify relevant articles, both clinical trials and reviews. RESULTS: Tazarotene is a very effective treatment for plaque psoriasis, with significant reductions in both plaque elevation and scaling after 12 weeks. Efficacy appears to be dose and formulation dependent, and erythema less responsive. Tazarotene sustains clinical response posttreatment and may have an important role in maintenance therapy. The most common side effect is mild-to-moderate local irritation, which limited its role as a single agent for psoriasis. Efficacy is enhanced through combination with topical corticosteroids (TCS). Tazarotene may circumvent the problem of TCS tachyphylaxis, due to its sustained efficacy and provide tolerability benefits; tazarotene increases epidermal thickness and may reduce the risk of steroid-induced atrophy. In addition, tazarotene-induced irritation is reduced by the anti-inflammatory effect of TCS. A new fixed combination, well-tolerated tazarotene/halobetasol topical formulation is now available, which provides synergistic efficacy that is both rapid and sustained posttreatment. CONCLUSIONS: Tazarotene is a highly effective psoriasis treatment whose efficacy and tolerability can be enhanced through combination therapy with TCS, and a new fixed combination topical formulation of tazarotene and halobetasol may provide an optimal management approach. J Drugs Dermatol. 2018;17(12):1280-1287.
Psoriasis is a chronic and persistent, immune-mediated disease that affects approximately 2% of the population 1-3. Most patients have mild to moderate plaque psoriasis, which despite its limited cutaneous involvement, causes significant emotional and physical distress. The aim of treatment is to minimize the extent and severity of the disease such that it no longer disrupts a patient’s quality of life.Topical therapy is a key component in the management of almost all psoriasis patients. They are used first-line for mild disease and have an increasing role in moderate-to-severe psoriasis.4 Topical retinoids are used successfully to treat many derma- tological conditions and have an important, often overlooked role in psoriasis. Tretinoin had been studied in psoriasis and ichthyosiform dermatoses using relatively high concentrations (1%-3%) many years ago.5 Although some improvement in psoriatic lesions was observed, unacceptable irritation discour- aged further investigation.
Mode of Action in Psoriasis
Psoriasis is a retinoid-sensitive disease. Tazarotene is the only topical retinoid currently available for the treatment of psoriasis. On application to the skin, it is rapidly hydrolysed to its main metabolite, tazarotenic acid, which binds to retinoic acid receptors (RARs) in the nucleus. The RAR-γ nuclear receptor is the prominent receptor in the epidermis, and tazarotenic acid selectively binds to RAR-β and -γ, with less of an effect on RAR-α and no affinity for retinoid X receptors (RXR).6 By regulating gene transcription, tazarotene normalizes abnormal keratinocyte differentiation, reduces epidermal hyperproliferation, and decreases inflammation.7 Tazarotene has anti-inflammatory properties characterized by suppression of the activator protein 1 (AP-1) and affects the antimicrobial pathway system through inhibition ofToll-like receptor-2 (TLR2).7-9