Pharmacokinetics of tazarotene and acitretin in psoriasis

ABSTRACT

Introduction: Psoriasis is a prevalent cutaneous condition with severe physical and psychological manifestations. Since the advent of biologics, clinical outcomes in psoriasis have improved. However, retinoids are useful in the correct clinical context. Tazarotene and acitretin are currently the only US Food and Drug Administration approved retinoids for treatment of psoriasis. Both topical tazarotene and oral acitretin act on retinoic acid receptors and retinoid-X-receptors, resulting in altered gene expression of inflammatory cytokines and inhibition of keratinocyte proliferation.

Areas covered: This article provides an in-depth pharmacologic and clinical review on the use of tazarotene and acitretin in psoriasis. The PubMed database was searched using combinations of keywords: acitretin, bioavailability, dosing, efficacy, etretinate, interactions, mechanism, pharmacodynamics, pharmacokinetics, pharmacogenetics, psoriasis, safety, tazarotene, tolerability, and toxicity.

Expert opinion: Tazarotene and acitretin are effective treatments for psoriasis. Benefits include lack of immunosuppression and success treating inflammatory psoriasis. When combined with other topical and systemic agents, both retinoids improve clinical efficacy while lowering the treatment threshold. However, topical adherence and bothersome side effects can limit retinoid use. Acitretin and tazarotene both improve outcomes through a unique mechanism that especially benefits subsets of patients, despite side effects and limitations.

KEYWORDS:

• Acitretin
• efficacy
• etretinate
• pharmacodynamics
• pharmacokinetics
• pharmacology
• retinoid
• psoriasis
• tazarotene

Article highlights

• Tazarotene (topical) and acitretin (oral) are retinoids which are useful in the treatment of psoriasis. Both retinoids act on the retinoic acid and retinoid-X receptors and suppress keratinocyte proliferation and inflammatory cytokine production via altered gene expression.

• When retinoids are used in combination with other treatments such as corticosteroids, methotrexate, and biologics, the overall dose needed to treat is lowered in comparison to either agent alone.

• Retinoids are particularly efficacious for inflammatory types of psoriasis in comparison to plaque psoriasis. However, bothersome side effects and teratogenic potential limit use in clinical practice.

• Though biologics have revolutionized the treatment of psoriasis, patients with immunosuppression can benefit from management with retinoids. The chemoprevention of cutaneous malignancies and lack of systemic immune system modulation are beneficial pharmacologic properties.

• Retinoids continue to have a major role in specific populations and subtypes of psoriasis, especially when utilized in combination therapy.

This box summarizes key points contained in the article.

Declaration of Interest

SR Feldman has received research, speaking and/or consulting support from a variety of companies including Galderma, GSK/Stiefel, Almirall, Leo Pharma, Boehringer Ingelheim, Mylan, Celgene, Pfizer, Valeant, Abbvie, Samsung, Janssen, Lilly, Menlo, Merck, Novartis, Regeneron, Sanofi, Novan, Qurient, National Biological Corporation, Caremark, Advance Medical, Sun Pharma, Suncare Research, Informa, UpToDate and National Psoriasis Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.