Future Pharmacology, Vol. 5, Pages 39: Design of an Array to Evaluate Biomarkers of Response to Biological Treatments in Inflammatory Bowel Disease

Future Pharmacology doi: 10.3390/futurepharmacol5030039

Authors:
Andrea Rodríguez-Lopez
Eva González-Iglesias
Jesús Novalbos
Susana Almenara
Francisco Abad-Santos

Background: Inflammatory bowel disease (IBD) is defined as recurrent inflammatory bowel disorders, the most common of which are Crohn’s disease (CD) and ulcerative colitis (UC). Tumor necrosis factor inhibitors (anti-TNFs), primarily adalimumab (ADA), infliximab (IFX), ustekinumab (UST), and vedolizumab (VLZ), are used to treat moderate-to-severe cases of IBD in patients who either do not tolerate or fail to respond to conventional therapies. However, about one-third of patients are primary non-responders to these treatments, and an additional 30% lose response over time. Several studies have investigated the role of genetic variability in explaining these differences in treatment response among patients. The aim of this study was to design an array of 60 single-nucleotide variants (SNVs) to validate the biomarkers described in the literature in a population of more than 400 IBD patients treated with biological drugs. Method: The primary focus of this study was the most recent reviews published in PubMed, with all relevant SNVs selected for the array design. Subsequently, studies presenting original data on the association between variants and the response to biological treatment were identified. Results: A total of 55.9% of SNVs have been studied in CD, 18.6% have been in UC, and 25.4% have been studied in both pathologies. A total of 44.1% of SNVs have been observed to influence the response to IFX, 16.9% influence the response to ADA, and 37.3% influence the response to both IFX and ADA; however, only one study (1.7%) reported an influence on the response to UST and none reported an influence on the response to VLZ. Conclusions: An array comprising 38 genes and 59 SNVs has been designed to be used to validate biomarkers associated with responses to biologic drug treatments in IBD.

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Andrea Rodríguez-Lopez www.mdpi.com