A Systematic Review of Pharmacogenetic Studies on the Response to Biologics in Patients with Psoriasis

Psoriasis is a common skin disease in which the body produces too much of a protein called ‘tumour necrosis factor alpha’ (TNF‐alpha) which in turn causes inflammation. Biologics are relatively new, powerful drugs used for treating moderate to severe psoriasis due to their ability to reduce the activity of TNF‐alpha. There are several different types of biologic and finding the best one for the individual patient is a process of trial and error, which may lead to a long period with treatment not working as well as hoped and unnecessary costs. Different people's genes (genetic variants) might explain why not everyone responds the same way to a biologic, and might also help predict whether a specific biologic is likely to be successful for a patient. This area of medicine is known as pharmacogenetics. This study, from the Netherlands, is a review of other published studies, looking at the association between genetic variants and effectiveness of treatment with the different biologics. 26 studies were included in the review, looking at the biologics dalimumab, etanercept, infliximab and ustekinumab. No studies on two other biologics, secukinumab or ixekizumab, were identified. Many of the studies focused on variants in genes related to the working mechanisms of TNF‐alpha. Associations between some variants of TNF‐alpha and biologics were found in some studies, but often these results were conflicting in other studies. The authors conclude that pharmacogenetic studies in psoriasis have differing results. The genetic variant HLA‐Cw6 may be promising as a predictor for efficacy of ustekinumab, but larger studies are needed to confirm this. Large scale searches for genetic biomarkers are needed to uncover the complete genetic background of biologics treatment outcome.