L J van Vugt1,2, J M P A van den Reek1,2, M J H Coenen2,3, E M G J de Jong1,2,4. 1. Department of Dermatology, Radboud University Medical Centre, Nijmegen, the Netherlands. 2. Radboud Institute for Health Sciences (RIHS), Nijmegen, the Netherlands. 3. Department of Human Genetics, Radboud University Medical Centre, Nijmegen, the Netherlands. 4. Radboud University, Nijmegen, the Netherlands.
Abstract
BACKGROUND: Biologics are indicated for treating moderate-to-severe psoriasis. As the number of biologics registered for the treatment of 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. OBJECTIVES: To assess which genetic variants are associated with response to biologics in patients with psoriasis according to current literature. METHODS: A systematic search was performed in Embase, MEDLINE, the Cochrane Library and Web of Science. In total, 26 papers were included in this systematic review; 24 original studies and two meta-analyses. Quality was assessed using a predesigned form and risk of bias was assessed using the Newcastle-Ottawa Scale. RESULTS: The majority of studies reported a candidate gene approach, focusing on polymorphisms in genes related to the therapeutic 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 patients who were positive for HLA-Cw6 reported across three of five studies. CONCLUSIONS: Pharmacogenetic studies in psoriasis have generated divergent results. Replication of findings in larger cohorts is required. Large-scale hypothesis-free searches for genetic biomarkers are needed to uncover the complete genetic background of outcomes for treatment with biologics.
BACKGROUND: Biologics are indicated for treating moderate-to-severe psoriasis. As the number of biologics registered for the treatment of 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. OBJECTIVES: To assess which genetic variants are associated with response to biologics in patients with psoriasis according to current literature. METHODS: A systematic search was performed in Embase, MEDLINE, the Cochrane Library and Web of Science. In total, 26 papers were included in this systematic review; 24 original studies and two meta-analyses. Quality was assessed using a predesigned form and risk of bias was assessed using the Newcastle-Ottawa Scale. RESULTS: The majority of studies reported a candidate gene approach, focusing on polymorphisms in genes related to the therapeutic 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 patients who were positive for HLA-Cw6 reported across three of five studies. CONCLUSIONS: Pharmacogenetic studies in psoriasis have generated divergent results. Replication of findings in larger cohorts is required. Large-scale hypothesis-free searches for genetic biomarkers are needed to uncover the complete genetic background of outcomes for treatment with biologics.
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