10
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Precision medicine in inflammatory bowel disease: concept, progress and challenges

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Crohn’s disease and ulcerative colitis are increasingly prevalent, relapsing and remitting inflammatory bowel diseases (IBDs) with variable disease courses and complications. Their aetiology remains unclear but current evidence shows an increasingly complex pathophysiology broadly centring on the genome, exposome, microbiome and immunome. Our increased understanding of disease pathogenesis is providing an ever-expanding arsenal of therapeutic options, but these can be expensive and patients can lose response or never respond to certain therapies. Therefore, there is now a growing need to personalise therapies on the basis of the underlying disease biology and a desire to shift our approach from “reactive” management driven by disease complications to “proactive” care with an aim to prevent disease sequelae. Precision medicine is the tailoring of medical treatment to the individual patient, encompassing a multitude of data-driven (and multi-omic) approaches to foster accurate clinical decision-making. In IBD, precision medicine would have significant benefits, enabling timely therapy that is both effective and appropriate for the individual. In this review, we summarise some of the key areas of progress towards precision medicine, including predicting disease susceptibility and its course, personalising therapies in IBD and monitoring response to therapy. We also highlight some of the challenges to be overcome in order to deliver this approach.

          Related collections

          Most cited references114

          • Record: found
          • Abstract: found
          • Article: not found

          Ulcerative colitis

          Ulcerative colitis is a chronic inflammatory disease affecting the colon, and its incidence is rising worldwide. The pathogenesis is multifactorial, involving genetic predisposition, epithelial barrier defects, dysregulated immune responses, and environmental factors. Patients with ulcerative colitis have mucosal inflammation starting in the rectum that can extend continuously to proximal segments of the colon. Ulcerative colitis usually presents with bloody diarrhoea and is diagnosed by colonoscopy and histological findings. The aim of management is to induce and then maintain remission, defined as resolution of symptoms and endoscopic healing. Treatments for ulcerative colitis include 5-aminosalicylic acid drugs, steroids, and immunosuppressants. Some patients can require colectomy for medically refractory disease or to treat colonic neoplasia. The therapeutic armamentarium for ulcerative colitis is expanding, and the number of drugs with new targets will rapidly increase in coming years.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Crohn's disease.

            Crohn's disease is a chronic inflammatory disease of the gastrointestinal tract, with increasing incidence worldwide. Crohn's disease might result from a complex interplay between genetic susceptibility, environmental factors, and altered gut microbiota, leading to dysregulated innate and adaptive immune responses. The typical clinical scenario is a young patient presenting with abdominal pain, chronic diarrhoea, weight loss, and fatigue. Assessment of disease extent and of prognostic factors for complications is paramount to guide therapeutic decisions. Current strategies aim for deep and long-lasting remission, with the goal of preventing complications, such as surgery, and blocking disease progression. Central to these strategies is the introduction of early immunosuppression or combination therapy with biologicals in high-risk patients, combined with a tight and frequent control of inflammation, and adjustment of therapy on the basis of that assessment (treat to target strategy). The therapeutic armamentarium for Crohn's disease is expanding, and therefore the need to develop biomarkers that can predict response to therapies will become increasingly important for personalised medicine decisions in the near future. In this Seminar, we provide a physician-oriented overview of Crohn's disease in adults, ranging from epidemiology and cause to clinical diagnosis, natural history, patient stratification and clinical management, and ending with an overview of emerging therapies and future directions for research.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease

              Genetic association studies have identified 215 risk loci for inflammatory bowel disease 1–8, which have revealed fundamental aspects of its molecular biology. We performed a genome-wide association study of 25,305 individuals, and meta-analyzed with published summary statistics, yielding a total sample size of 59,957 subjects. We identified 25 new loci, three of which contain integrin genes that encode proteins in pathways identified as important therapeutic targets in inflammatory bowel disease. The associated variants are correlated with expression changes in response to immune stimulus at two of these genes (ITGA4, ITGB8) and at previously implicated loci (ITGAL, ICAM1). In all four cases, the expression increasing allele also increases disease risk. We also identified likely causal missense variants in the primary immune deficiency gene PLCG2 and a negative regulator of inflammation, SLAMF8. Our results demonstrate that new common variant associations continue to identify genes relevant to therapeutic target identification and prioritization.
                Bookmark

                Author and article information

                Contributors
                Role: ConceptualizationRole: Writing – Original Draft PreparationRole: Writing – Review & Editing
                Role: ConceptualizationRole: Writing – Original Draft PreparationRole: Writing – Review & Editing
                Role: ConceptualizationRole: Writing – Review & Editing
                Role: ConceptualizationRole: Writing – Original Draft PreparationRole: Writing – Review & Editing
                Journal
                F1000Res
                F1000Res
                F1000Research
                F1000Research
                F1000 Research Limited (London, UK )
                2046-1402
                28 January 2020
                2020
                : 9
                : F1000 Faculty Rev-54
                Affiliations
                [1 ]Department of Gastroenterology, Wythenshawe Hospital, Manchester University NHS Foundation Trust, Southmoor Road, Wythenshawe, Manchester, M23 9LT, UK
                [2 ]Department of Gastroenterology, Monash Health, Clayton, Victoria, Australia
                [3 ]Faculty of Medicine, Nursing & Health Sciences, Monash University, Clayton, Victoria, Australia
                [4 ]Translational Gastroenterology Unit, Nuffield Department of Medicine, Experimental Medicine Division, University of Oxford, John Radcliffe Hospital, Oxford, UK
                [5 ]Department of Gastroenterology, Royal Infirmary of Edinburgh, 51 Little France Crescent, Edinburgh, EH16 4SA, UK
                Author notes

                Drafting of this review was performed by SB-B, RKB and RK. All authors contributed equally in the conception and design of this review, literature review and critical revision and editing, and final approval of the final version.

                No competing interests were disclosed.

                Author information
                https://orcid.org/0000-0002-6968-9518
                https://orcid.org/0000-0001-9683-8411
                Article
                10.12688/f1000research.20928.1
                6993839
                32047622
                3722b01d-7a68-48ad-9577-105b4251a46e
                Copyright: © 2020 Borg-Bartolo SP et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 16 January 2020
                Funding
                The author(s) declared that no grants were involved in supporting this work.
                Categories
                Review
                Articles

                inflammatory bowel disease,precision medicine,biomarkers,genomics,prognosis,therapeutics,crohn's disease,ulcerative colitis,microbiome

                Comments

                Comment on this article