Pharmacogenetics of treatments for inflammatory bowel disease

Abstract

Introduction: Inflammatory bowel disease is a chronic inflammation of the gut whose pathogenesis is still unclear. Although no curative therapy is currently available, a number of drugs are used in induction and maintenance therapy; however, for most of these drugs, a high inter-individual variability in response is observed. Among the factors of this variability, genetics plays an important role. Areas covered: This review summarizes the results of pharmacogenetic studies, considering the most important drugs used and in particular aminosalycilates, glucocorticoids, thiopurines, monoclonal antibodies and thalidomide. Most studies used a candidate gene approach, even if significant breakthroughs have been obtained recently from applying genome-wide studies. When available, also investigations considering epigenetics and pharmacogenetic dosing guidelines have been included. Expert opinion: Only for thiopurines, genetic markers identified as predictors of efficacy or adverse events have allowed the development of dosing guidelines. For the other drugs, encouraging results are available and great expectations rely on the study of epigenetics and integration with pharmacokinetic information, especially useful for biologics. However, to improve therapy of IBD patients with these drugs, for implementation in the clinics of pharmacogenetics, informatic clinical decision support systems and training about pharmacogenetics of health providers are needed.

NGS study of glucocorticoids response genes in inflammatory bowel disease patients

“…Pharmacogenetics in IBD is the subject of a significant amount of research, which consistently concludes that there is a lack of sufficiently strong biomarkers for GC therapy that are useful in clinical practice, thus emphasizing the need for further research [7,14,17]. Although the mechanism of GC action involves dozens of genes, so far intensive pharmacogenetic studies of these drugs have focused mainly on single genes, and have produced contradictory results.…”

“…On average, only every second adult patient with IBD is sensitive to GCs, close to 20% of subjects are GC resistant, and approximately 30-40% of patients become dependent on these drugs [6]. Personalized medicine could be very promising in CD and UC therapy outcome, but except for thiopurine drugs with pharmacogenetics dosing guidelines, we do not have genetic biomarkers for IBD treatment [7,8].…”

Emerging Insights on the Interaction Between Anticancer and Immunosuppressant Drugs and Intestinal Microbiota in Pediatric Patients

“…The main therapies include aminosalicylates and glucocorticoids used as first‐line agents, whereas thiopurines are efficacious for maintaining remission; more recently, monoclonal antibodies directed toward TNF‐α (infliximab and adalimumab), the common p40 subunit of IL‐12 and IL‐23 (ustekinumab) and the integrin (vedolizumab) have been introduced . The effects of all these drugs are characterized by a high interpatient variability, associated with a significant number of side effects …”

“…41,42 The effects of all these drugs are characterized by a high interpatient variability, associated with a significant number of side effects. 43 Microbiota and IBD susceptibility Although IBD etiology remains unresolved, a general consensus supports the important role of gut dysbiosis in promoting and determining chronic intestinal inflammation. [44][45][46]…”

Intestinal Anti-Inflammatory Effect of a Peptide Derived from Gastrointestinal Digestion of Buffalo (Bubalus bubalis) Mozzarella Cheese

“…Although the etiology of IBD is still unknown, it arises as a result of the interaction of environmental or genetic factors and the immune responses [2]. IBD treatment involves the use of anti-inflammatory drugs (such as 5-aminosalicylic acid), corticosteroids, monoclonal antibodies [anti-tumor necrosis factor (TNF)-α antibodies] and vascular adhesion molecules [2,3] (anti-integrin antibodies). However, these drugs are not curative therapies and are mainly used as induction and maintenance therapy.…”