scholarly journals Results of the Seventh Scientific Workshop of ECCO: Precision medicine in IBD - disease outcome and response to therapy

2021 ◽  
Author(s):  
Bram Verstockt ◽  
Nurulamin M Noor ◽  
Urko M Marigorta ◽  
Polychronis Pavlidis ◽  
Parakkal Deepak ◽  
...  
Keyword(s):  
Precision Medicine ◽  
Response To Therapy ◽  
Treatment Algorithms ◽  
New Era ◽  
Extreme Phenotypes ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Omic Data Integration ◽  
Omic Data ◽  
Prognostic And Predictive Markers

Abstract Inflammatory bowel diseases [IBD] are a heterogeneous spectrum with two extreme phenotypes, Crohn’s disease [CD] and ulcerative colitis [UC], which both represent numerous phenotypical variations. Hence, we should no longer approach all IBD patients similarly, but rather aim to rethink clinical classifications and modify treatment algorithms to usher in a new era of precision medicine in IBD. This scientific ECCO workshop aims to provide a state-of-the-art overview on prognostic and predictive markers, shed light on key questions in biomarker development, propose best practices in IBD biomarker development [including trial design], and discuss the potential for multi-omic data integration to help drive further advances to make precision medicine a reality in IBD.

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

F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 54 ◽  
Author(s):  
Simon P. Borg-Bartolo ◽  
Ray Kiran Boyapati ◽  
Jack Satsangi ◽  
Rahul Kalla
Keyword(s):  
Precision Medicine ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Underlying Disease ◽  
Response To Therapy ◽  
Current Evidence ◽  
Disease Biology ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
The Individual

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.

scholarly journals Predictors and Early Markers of Response to Biological Therapies in Inflammatory Bowel Diseases

2021 ◽  
Vol 10 (4) ◽  
pp. 853
Author(s):  
Giuseppe Privitera ◽  
Daniela Pugliese ◽  
Gian Ludovico Rapaccini ◽  
Antonio Gasbarrini ◽  
Alessandro Armuzzi ◽  
...  
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Current Knowledge ◽  
Real Life ◽  
Response To Therapy ◽  
Significant Heterogeneity ◽  
Intestinal Damage ◽  
Biological Therapies ◽  
Early Markers ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Inflammatory bowel diseases (IBD) are chronic conditions that primarily affect the gastrointestinal tract, with a complex pathogenesis; they are characterized by a significant heterogeneity of clinical presentations and of inflammatory pathways that sustain intestinal damage. After the introduction of the first biological therapies, the pipeline of therapies for IBD has been constantly expanding, and a significant number of new molecules is expected in the next few years. Evidence from clinical trials and real-life experiences has taught us that up to 40% of patients do not respond to a specific drug. Unfortunately, to date, clinicians lack a valid tool that can predict each patient’s response to therapies and that could help them in choosing what drug to administer. Several candidate biomarkers have been investigated so far, with conflicting results: clinical, genetic, immunological, pharmacokinetic and microbial markers have been tested, but no ideal marker has been identified so far. Based on recent evidence, multiparametric models seemingly hold the greatest potential for predicting response to therapy. In this narrative review, we aim to summarize the current knowledge on predictors and early markers of response to biological therapies in IBD.

scholarly journals Nutritional Aspects in Inflammatory Bowel Diseases

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 372 ◽  
Author(s):  
Paola Balestrieri ◽  
Mentore Ribolsi ◽  
Michele Pier Luca Guarino ◽  
Sara Emerenziani ◽  
Annamaria Altomare ◽  
...  
Keyword(s):  
Nutritional Assessment ◽  
Early Adulthood ◽  
Caloric Intake ◽  
Bacterial Overgrowth ◽  
Response To Therapy ◽  
Intestinal Bacterial Overgrowth ◽  
Bowel Diseases ◽  
Poor Nutritional Status ◽  
Inflammatory Bowel

Crohn’s disease (CD) and ulcerative colitis (UC) are chronic, relapsing, inflammatory disorders of the digestive tract that characteristically develop in adolescence and early adulthood. The reported prevalence of malnutrition in inflammatory bowel disease (IBD) patients ranges between 20% and 85%. Several factors, including reduced oral food intake, malabsorption, chronic blood and proteins loss, and intestinal bacterial overgrowth, contribute to malnutrition in IBD patients. Poor nutritional status, as well as selective malnutrition or sarcopenia, is associated with poor clinical outcomes, response to therapy and, therefore, quality of life. The nutritional assessment should include a dietetic evaluation with the assessment of daily caloric intake and energy expenditure, radiological assessment, and measurement of functional capacity.

scholarly journals Combining explainable machine learning, demographic and multi-omic data to identify precision medicine strategies for inflammatory bowel disease

2021 ◽  
Author(s):  
Laura-Jayne Gardiner ◽  
Anna Paola Carrieri ◽  
Karen Bingham ◽  
Graeme Macluskie ◽  
David Bunton ◽  
...  
Keyword(s):  
Machine Learning ◽  
Precision Medicine ◽  
Human Tissue ◽  
Drug Response ◽  
Drug Efficacy ◽  
Mitogen Activated Protein Kinase ◽  
Patient Specific ◽  
Genomic Features ◽  
Inflammatory Bowel ◽  
Omic Data

Inflammatory bowel diseases (IBDs), including ulcerative colitis and Crohn's disease, affect several million individuals worldwide. These diseases are heterogeneous at the clinical, immunological and genetic levels and result from a complex interaction between the host and environmental factors. Investigating drug efficacy in cultured human fresh IBD tissues can improve our understanding of the reasons why certain medications are more or less effective for different patients. We propose an explainable machine learning (ML) approach that combines bioinformatics and domain insight, to informatively integrate multi-modal data to predict inter-patient specific variation in drug response. Using explanation of our models, we interpret the models' predictions inferring unique combinations of important features associated with human tissue pharmacological responses. The inferred multi-modal features originate from multi-omic data (genomic and transcriptomic), demographic, medicinal and pharmacological data and all are associated with drug efficacy generated by a preclinical human fresh IBD tissue assay. To pharmacologically assess patient variation in response to IBD treatment, we used the reduction in the release of the inflammatory cytokine TNFa; from the fresh IBD tissues in the presence or absence of test drugs, as a measure of drug efficacy. The TNF pathway is a common target in current therapies for IBD; we initially explored the effects of a mitogen-activated protein kinase (MAPK) inhibitor on the production of TNFa; however, we later show the approach can be applied to other targets, test drugs or mechanisms of interest. Our best model was able to predict TNFa; levels from a combination of integrated demographic, medicinal and genomic features with an error as low as 4.98% on unseen patients. We incorporated transcriptomic data to validate and expand insights from genomic features. Our results showed variations in drug effectiveness between patients that differed in gender, age or condition and linked new genetic polymorphisms in our cohort of IBD patients to variation in response to the anti-inflammatory treatment BIRB796 (Doramapimod). Our approach models drug response in a relevant human tissue model of IBD while also identifying its most predictive features as part of a transparent ML-based precision medicine strategy.

scholarly journals Precision medicine and inflammatory bowel diseases: concept, strategies, future

2021 ◽  
Vol 1 (6) ◽  
pp. 121-129
Author(s):  
G. R. Bikbavova ◽  
M. A. Livzan ◽  
D. G. Novikov ◽  
E. A. Bambulskaya
Keyword(s):  
Precision Medicine ◽  
Inflammatory Bowel Diseases ◽  
Scientific Information ◽  
Treatment Strategies ◽  
Wide Range ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
New Treatment ◽  
Personalized Approach ◽  
The Right

With the advent of modern cellular and genomic technologies, we have become participants in the integration of such areas as personalized, predictive, preventive, and precision medicine (referred to as 4P-medicine), into practical healthcare. In replace of the classic methods of diagnosis and treatment of diseases comes medicine, which makes it possible to predict (anticipate) the disease, and a personalized approach to each patient, taking into account their genetic, biochemical and physiological uniqueness. Precision medicine aims to improve the quality of medical care by opening up an individual approach to the patient and covers a wide range of areas, including drug therapy, genetics, and cause-and-effect relationships in order to make the right decisions based on evidence. 4P-medicine combines knowledge in the field of proteomics, metabolomics, genomics, bioinformatics with classical approaches of anatomy, therapy, laboratory and instrumental diagnostics as well as public health. The purpose of this review is to analyze and summarize the information available to date and to present examples of the application of modern approaches of medicine into clinical practice by diving into the example of inflammatory bowel diseases (IBD). The search for literature containing scientific information about relevant studies was conducted in the PubMed and Google Scholar systems with the use of the following keywords: precision medicine, 4P medicine, inflammatory bowel diseases. Despite significant progress in medicine in general, there is still a long way to go before implementing the principles of precision medicine in the field of IBD, since many clinicians continue to treat patients with IBD symptomatically. However, the use of specific biomarkers and new treatment strategies as described in the review, can significantly accelerate this path and contribute to the improvement of diagnostic and therapeutic approaches.

scholarly journals Treatment approaches to patients with multiple sclerosis and coexisting autoimmune disorders

2021 ◽  
Vol 14 ◽  
pp. 175628642110355
Author(s):  
Tobias Brummer ◽  
Tobias Ruck ◽  
Sven G. Meuth ◽  
Frauke Zipp ◽  
Stefan Bittner
Keyword(s):  
Multiple Sclerosis ◽  
Autoimmune Disorders ◽  
New Era ◽  
The Past ◽  
Disease Modifying Therapies ◽  
Bowel Diseases ◽  
Autoimmune Conditions ◽  
Autoimmune Condition ◽  
Inflammatory Bowel ◽  
Attending Physician

The past decades have yielded major therapeutic advances in many autoimmune conditions – such as multiple sclerosis (MS) – and thus ushered in a new era of more targeted and increasingly potent immunotherapies. Yet this growing arsenal of therapeutic immune interventions has also rendered therapy much more challenging for the attending physician, especially when treating patients with more than one autoimmune condition. Importantly, some therapeutic strategies are either approved for several autoimmune disorders or may be repurposed for other conditions, therefore opening new curative possibilities in related fields. In this article, we especially focus on frequent and therapeutically relevant concomitant autoimmune conditions faced by neurologists when treating patients with MS, namely psoriasis, rheumatoid arthritis and inflammatory bowel diseases. We provide an overview of the available disease-modifying therapies, highlight possible contraindications, show pathophysiological overlaps and finally present which therapeutics can be utilized as a combinatory treatment, in order to ‘kill two birds with one stone’.

scholarly journals Diagnostic Markers for Nonspecific Inflammatory Bowel Diseases

2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
Alicja Derkacz ◽  
Pawel Olczyk ◽  
Katarzyna Komosinska-Vassev
Keyword(s):  
Disease Activity ◽  
Inflammatory Bowel Diseases ◽  
Clinical Laboratory ◽  
Correct Diagnosis ◽  
Response To Therapy ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Laboratory Biomarkers ◽  
Diagnostic Sensitivity And Specificity ◽  
Noninvasive Biomarkers

The nonspecific inflammatory bowel diseases (IBD) represent a heterogeneous group of chronic inflammatory disorders of the gastrointestinal tract, and Leśniowski-Crohn’s disease (CD) and ulcerative colitis (UC) are among the two major clinical forms. Despite the great progress in understanding the pathogenesis of these diseases, their etiology remains unclear. Genetic, immune, and environmental factors are thought to play a key role. The correct diagnosis of nonspecific inflammatory bowel diseases as well as the determination of disease activity, risk stratification, and prediction of response to therapy still relies on a multidisciplinary approach based on clinical, laboratory, endoscopic, and histologic examination. However, considerable effort has been devoted to the development of an accurate panel of noninvasive biomarkers that have increased diagnostic sensitivity and specificity. Laboratory biomarkers useful in differentiating IBD with functional disorders and in evaluating disease activity, prognosis, and treatment selection for IBD are presented in this study.

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