Pharmacogenetics of Psoriasis Treatment

Abstract

Psoriasis is a chronic systemic, immune-mediated disorder of unknown aetiology, usually presenting with typical inlammatory skin lesions and/or joint manifestations, but systemic inlammation that may lead to the development of co-morbidities may also be present. First-line therapy encompasses local cutaneous treatment and phototherapy, but with more severe symptoms or systemic course, systemic treatment with methotrexate (MTX), immunosuppressant cyclosporine, retinoid acitretin or biologicals may be used. Treatment response varies between patients in terms of eicacy and/or toxicity, which could, among other reasons, be due to genetic diferences between patients. Approximately 10-30% of patients experience adverse drug reactions with MTX treatment, leading to discontinuation of MTX mostly due to hepatotoxicity. Around 15% of patients experience adverse events when treated with biologicals; however, the most frequent reason for discontinuation is ineicacy or loss of the initially favourable response over time. Ineicacy or occurrence of adverse drug reactions cannot be predicted, so genetic biomarkers of drug response in combination with clinical data could be helpful in treatment planning. Several polymorphic genes have already been associated with treatment outcome, most of them involved in drug metabolism, transport and target pathways. Genetic biomarkers could be helpful in personalized care of psoriasis patients in order to prevent adverse events or predict ineicacy of a certain drug.