Pharmacogenetics and pharmacogenomics in psoriasis treatment: current challenges and future prospects

ABSTRACT

Introduction: Topical, systemic, oral disease modifying, and biologic agents are part of the armamentarium to manage psoriatic disease. The choice of therapy depends upon disease severity, relevant co-morbidities and patient preference. There is great variability in patient response with these agents, and there is still no clear method of selecting the preferred therapeutic agent for efficacy or lack of adverse events.

Areas covered: This article will review the pharmacogenetic and pharmacogenomic targets that are currently known with respect to psoriasis vulgaris, and the most frequent co-morbidity of psoriasis, psoriatic arthritis.

Expert opinion: Presently, no clinically actionable biomarker exists for any therapeutic agent used to treat psoriasis or psoriatic arthritis. The lack of validated outcome measures and conflicting results of open-label studies conducted may be attributed to a multitude of issues that confound discovery. Consequently, studies have been underpowered to identify genes or genetic variants worth translating to clinical practice. In order to achieve a pharmacogenetic/pharmacogenomic signature, improvements in study design of future investigations are required, including carefully designed prospective studies. It is imperative to combine known clinical, serological, and molecular markers with consistent outcomes and an adequate health economic evaluation before they can be adopted widely in clinical practice.

KEYWORDS:

• Psoriasis
• psoriatic arthritis
• genetics
• pharmacogenetics
• pharmacogenomics

Article highlights

• The most intriguing genetic variants have been identified in key signalling pathways associated with biologic agents, in particular, TNFα and IL-12/IL-23 inhibitors.

• No convincing predictive biomarker exists for any drug used to treat psoriasis or PsA attributed small effect size, lack of replication and conflicting results.

• Improvements in study design of future investigations are required, including well-designed prospective pharmacogenetic studies.

• With accelerated advancements in genetic and genomic technologies expected to continue in the future, a real potential exists for translating genetic and/or epigenetic markers from bench to bedside.

• Clinical, serological, and molecular markers with consistent outcomes and an adequate health economic evaluation will be required before any findings can be adopted widely in clinical practice.

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Declaration of interest

P Rahman sits on the advisory boards of Amgen, Abbvie, Bristol-Myers Squibb, Pfizer, UCB, Norvartis, Eli Lilly and Celgene. 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.