Association between Genetic Polymorphisms and Response to Anti-TNFs in Patients with Inflammatory Bowel Disease

Abstract

Tumor necrosis factor (TNF) α is a major proinflammatory cytokine involved in the immune response in inflammatory bowel disease (IBD). Anti-TNF drugs such as infliximab and adalimumab are used to treat IBD; however, approximately 30% of patients do not respond to treatment. Individual genetic differences could contribute to lack of efficacy. Genetic studies have tried to uncover the factors underlying differences in response, however, knowledge remains limited, and the results obtained should be validated, so that pharmacogenetic information can be applied in clinical practice. In this review, we gather current knowledge in the pharmacogenetics of anti-TNF drugs in patients with IBD. We observed a connection between the major genes described as possible predictors of response to anti-TNF drugs in IBD and the cytokines and molecules involved in the T helper (Th) 17 pathway.

Is Polymorphism in the Apoptosis and Inflammatory Pathway Genes Associated With a Primary Response to Anti-TNF Therapy in Crohn’s Disease Patients?

“…In recent years, numerous studies concerning IBD pharmacogenetics have highlighted the need to better understand the mechanism of response to biological treatment, as well as to develop personalized therapeutic strategies ( Parsi et al, 2002 ; Horiuchi et al, 2010 ; Trent, 2010 ; Bek et al, 2016 ; Prieto-Perez et al, 2016 ; De Lange et al, 2017 ). Up to now, many genes have been investigated, particularly the members of the TNF family.…”

Pre-Treatment Biomarkers of Anti-Tumour Necrosis Factor Therapy Response in Crohn’s Disease—A Systematic Review and Gene Ontology Analysis

“…Genomic and expression markers of anti-TNF failure in CD patients are the topic of several recent reviews [16,17,18,19,20]. However, here, for the first time we merge these potential biomarkers from different levels of expression into common interaction networks and analyse the networks with gene ontology tools, aiming at finding common biological pathways behind the therapy non-response.…”

“…Genetic background and gene expression are therefore also under investigation [7,8,9,10,11,12,13]. There are several recent reviews on the topic, focusing either on clinical prediction of anti-TNF response [2,4,5,14,15] or summarizing genomic and/or expression data and proposing predictive sets of anti-TNF response markers [16,17,18,19,20]. Here, for the first time we integrate genomic and expression markers that could predict non-response to anti-TNF treatment in CD patients prior to treatment initiation into common interaction networks.…”

Dendritic cell profiles in the inflamed colonic mucosa predict the responses to tumor necrosis factor alpha inhibitors in inflammatory bowel disease

“… 40 , 53 , Interestingly, many genetic polymorphisms linked to primary resistance to TNFa inhibitors have been identified in the Th17 pathway. 54 …”