A systematic review of pharmacogenetic studies on the response to biologics in psoriasis patients

Abstract

Biologics are indicated for treating moderate to severe psoriasis. As the number of biologics registered for psoriasis increases, so does the need for biomarkers to guide personalized therapeutic decisions. Genetic variants might serve as predictors for treatment response, a field of research known as pharmacogenetics. The aim of this systematic review was to assess which genetic variants are associated with the response to biologics in psoriasis patients. A systematic search was performed in EMBASE, MEDLINE, the Cochrane Library and Web of Science. Twenty-six papers were included in this systematic review: 24 original studies and two meta-analyses. Quality was assessed using a predesigned form. Risk of bias was assessed using the Newcastle-Ottawa Scale. The majority of studies reported a candidate gene approach, focusing on polymorphisms in genes related the therapeutical target or to psoriasis susceptibility. Studied populations were small and results were divergent, especially for studies investigating tumour necrosis factor inhibitors. The evidence for the role of HLA-Cw6 in ustekinumab efficacy shows minimal heterogeneity, with a higher response rate among HLA-Cw6 positive patients reported across three out of five studies. However, replication of these findings in larger cohorts is required. Large scale hypothesis-free searches for genetic biomarkers are needed to uncover the complete genetic background of biologics treatment outcome.

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