DPP-4 inhibitor Class of Diabetes Medications Linked To Increase Risk of Inflammatory Bowel Disease

MedicalResearch.com Interview with:
Devin Abrahami,
graduate student
Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal
Department of Epidemiology, Biostatistics, and Occupational Health
McGill University, Montreal, QC, Canada

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: The goal of our study was to assess whether a class of antidiabetic drugs, the dipeptidyl peptidase-4 (DPP-4) inhibitors, is associated with the risk of inflammatory bowel disease (IBD). While these drugs control blood sugar levels in patients with type 2 diabetes, there is some evidence that they may also be involved in immune function, and possibly in conditions such as IBD.

In our study, we found that the use of DPP-4 inhibitors was associated with a 75% increased risk of IBD, with the highest risk observed after three to four years of use. Continue reading

IQuity Releasing First RNA-Based Blood Test for Inflammatory Bowel Disease

MedicalResearch.com Interview with:
Iquity IncChase Spurlock, PhD, CEO of IQuity Inc. and
Thomas M. Aune, PhD,
Co-Founder of IQuity Inc.

MedicalResearch.com: Why did you develop IsolateIBS-IBD?

Response: Isolate IBS-IBD arose from work started at Vanderbilt University, which found that autoimmune diseases exhibit distinct RNA patterns in blood and that these patterns often are specific for a particular disease. In our longitudinal and cross-sectional studies of many human conditions that span both autoimmune and non-autoimmune disease categories, we found that differences detected at the level of RNA can provide an accurate snapshot of a person’s disease. Using RNA, we can tell at a very early stage if a pattern exists that indicates a specific disease. With this information, providers can initiate treatment plans sooner and have an additional tool in their toolbox when making diagnostic determinations.

We developed this test because the symptoms of IBS and IBD are very similar, which can make it difficult and time-consuming for doctors to achieve an accurate diagnosis. IsolateIBS-IBD helps providers distinguish between the two conditions. It shouldn’t be viewed as a replacement or stand-alone test — doctors still need to use it in conjunction with clinical observation combined with traditional tests and procedures like a CT scan or endoscopic examination of the colon — but it can dramatically speed the diagnostic process. IQuity delivers results to providers within seven days of receiving the patient’s sample in the laboratory, allowing doctors to begin discussing a course of treatment as soon as possible.  Continue reading

With Increasing Westernization, Inflammatory Bowel Disease Becoming a Global Health Issue

MedicalResearch.com Interview with:

Gilaad Kaplan, MD, MPH, FRCPC Associate Professor  CIHR New Investigator & AI-HS Population Health Investigator Co-Director, Environmental Health Research Group Snyder Institute for Chronic Diseases & Institute of Public Health Departments of Medicine & Community Health Sciences University of Calgary

Dr. Kaplan

Gilaad Kaplan, MD, MPH, FRCPC
Associate Professor
CIHR New Investigator & AI-HS Population Health Investigator
Co-Director, Environmental Health Research Group
Snyder Institute for Chronic Diseases & Institute of Public Health
Departments of Medicine & Community Health Sciences
University of Calgary

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The aim of the study was to provide a global perspective on the epidemiology of the inflammatory bowel diseases in the 21st century.

During the 20th century IBD was considered a disease of the Western world. At the turn of the 21st century, IBD has become a global disease with accelerating number of cases in the developing world as it transition towards a westernized society.

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Hidradenitis Suppurativa and Inflammatory Bowel Disease Strongly Linked

MedicalResearch.com Interview with:

Alexander Egeberg, MD PhD National Allergy Research Centre, Departments of Dermato-Allergology and Cardiology Herlev and Gentofte University Hospital, University of Copenhagen Hellerup, Denmark

Dr. Alexander Egeberg

Alexander Egeberg, MD PhD
Gentofte Hospital
Department of Dermatology and Allergy
Denmark

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease. Inflammatory bowel disease (IBD) has been associated with increased prevalence of HS, but data has been limited to small studies and even less is known about the concurrence and risk of new-onset IBD in patients with pre-existing HS.

In our study, we found a higher prevalence of Crohn’s disease and ulcerative colitis in patients with HS. Notably, there was a more than two-fold increased risk of new-onset Crohn’s disease and a 63% increased risk of new-onset ulcerative colitis in patients with Hidradenitis suppurativa compared with the general population.

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Patient-Centered Medical Home Improved Quality of Life in Inflammatory Bowel Disease

Miguel Regueiro, M.D., AGAF, FACG, FACP Professor of Medicine and Professor, Clinical and Translational Science University of Pittsburgh School of Medicine Senior Medical Lead of Specialty Medical Homes University of Pittsburgh Medical Center IBD Clinical Medical Director Division of Gastroenterology, Hepatology, and Nutrition Mezzanine Level, C Wing, 200 Lothrop Street Pittsburgh PA, 15213

Dr. Miguel Regueiro

MedicalResearch.com Interview with:
Miguel Regueiro, M.D., AGAF, FACG, FACP
Professor of Medicine and Professor, Clinical and Translational Science
University of Pittsburgh School of Medicine
Senior Medical Lead of Specialty Medical Homes
University of Pittsburgh Medical Center
IBD Clinical Medical Director
Division of Gastroenterology, Hepatology, and Nutrition
Pittsburgh PA, 15213

MedicalResearch.com: What is the background for this study?

Response: The background for the study is that we created an Inflammatory Bowel Disease (IBD) patient centered medical home in conjunction with our UPMC Health Plan. The IBD medical home has been designated UPMC IBD Total Care and provides whole person care for patients with ulcerative colitis and Crohn’s disease. Unlike primary care medical homes, the gastroenterologist is the principle care provider in this specialty medical home model. We created this medical home to improve the IBD patient experience, provide high quality care, and decrease utilization and cost.

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pH Sensing Molecules May Play a Role in Initiating Inflammatory Bowel Disorders

MedicalResearch.com Interview with:
Cheryl de Valliere, PhD
University Hospital Zurich
Division of Gastroenterology and Hepatology
Zurich Switzerland
and co-authors
Gerhard Rogler, Jesus Cosin Roger, Pedro A. Ruiz

MedicalResearch.com: What is the background for this study?

Response: Inflammatory Bowel Disease (IBD), including ulcerative colitis and Crohn’s disease, gives rise to chronic relapsing inflammation of the gastrointestinal (GI) tract, resulting in a disruption of the epithelial barrier function and exacerbated innate and adaptive immune responses. One of the most important features under these inflammatory conditions is the presence of hypoxic areas where oxygen levels are lower than in normal tissue. It has been widely reported that the main transcription factor regulating cellular responses to hypoxia, hypoxia inducible factor (HIF)-1, is significantly induced in patients with IBD compared with healthy subjects. Furthermore, hypoxia is not only linked to inflammation, but also influences the local tissue pH, leading to an reduction of the pH in the inflamed mucosa compared with the non-inflamed one.

A family of pH-sensing G-protein coupled receptors (GPCRs), including the receptor T-cell death-associated gene 8 (TDAG8) and the ovarian cancer G-protein coupled receptor 1 (OGR1 or GPR68), play an important role in physiological pH homeostasis. At low extracellular pH, second messenger signaling pathways are activated by protons binding to the histidine residues located on the extracellular region of the receptor. Recent studies have reported a link between IBD and this family of pH-sensing receptors. Indeed, TDAG8 has been identified as an IBD risk gene and we have previously reported an increased expression of OGR1 in patients with IBD compared with healthy subjects.

To better understand the basic mucosal inflammatory mechanisms, and foster the development of new treatment options (e.g. pH receptor blockers and OGR1 antagonists) for chronic mucosal inflammatory diseases, we investigated the effects of hypoxia on pH-sensing OGR1 in the intestinal mucosa and associated cells.

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How Do Patients Decide Among Biologics for Inflammatory Bowel Disease?

MedicalResearch.com Interview with:

Christopher V. Almario, MD, MSHPM</strong> Assistant Professor of Medicine Division of Digestive and Liver Diseases, Cedars-Sinai Medical Center Cedars-Sinai Center for Outcomes Research and Education Los Angeles, CA

Dr. Christopher V. Almario

Christopher V. Almario, MD, MSHPM
Assistant Professor of Medicine
Division of Digestive and Liver Diseases, Cedars-Sinai Medical Center
Cedars-Sinai Center for Outcomes Research and Education
Los Angeles, CA

MedicalResearch.com: What is the background for this study?

Response: Recent drug approvals have increased the availability of biologic therapies for inflammatory bowel disease (IBD). However, the growing number of biologics has also made it more difficult for both patients and healthcare providers to navigate treatment options and to ultimately choose the most appropriate therapy.

In this study, we wanted to examine patient decision-making surrounding IBD biologic therapies using conjoint analysis, which is a form of tradeoff analysis that determines how respondents make complex decisions by presenting them with competing product profiles. Here, we quantified the relative importance of 9 biologic therapy attributes (e.g., how the medicine works, how the medicine is received, long-term effectiveness, side-effect profile, etc.) in the decision-making process.

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Adherent-Invasive E. coli May Markedly Raise Risk of Crohn’s Disease

MedicalResearch.com Interview with:

Brian K. Coombes, PhD Professor & University Scholar Associate Chair, Graduate Education Department of Biochemistry & Biomedical Sciences Assistant Dean, Biochemistry Graduate Program Canada Research Chair in Infectious Disease Pathogenesis

Dr. Brian Coombes

Brian K. Coombes, PhD
Professor & University Scholar
Associate Chair, Graduate Education
Department of Biochemistry & Biomedical Sciences
Assistant Dean, Biochemistry Graduate Program
Canada Research Chair in Infectious Disease Pathogenesis

MedicalResearch.com: What is the background for this study?

Response: North Americans have among the highest reported prevalence and incidence of inflammatory bowel disease (IBD) in the world. This is a lifelong disease that often strikes people in their early years, leading to decades of suffering, increased risk of colorectal cancer, and 50% increased risk of premature death. Compared to the general population, quality of life for those with Crohn’s disease is low across all dimensions of health. The need to understand the root origins of this disease and to use this information to invigorate a new pipeline of treatments and preventions has never been more pressing.

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Gut and Brain Communicate To Drive Irritable Bowel Syndrome

MedicalResearch.com Interview with:

Laureate Professor Nicholas J. Talley, MBBS (Hons.)(NSW), MD (NSW), PhD (Syd), MMedSci (Clin Epi)(Newc.), FRACP, FAFPHM, FAHMS, FRCP (Lond. & Edin.), FACP, FACG, AGAF, FAMS, FRCPI (Hon), GAICD Pro Vice-Chancellor, Global Research, University of Newcastle, Australia Professor of Medicine, Faculty of Health and Medicine, University of Newcastle, Australia

Prof. Nicholas Talley

Laureate Professor Nicholas J. Talley, MBBS (Hons.)(NSW), MD (NSW), PhD (Syd), MMedSci (Clin Epi)(Newc.), FRACP, FAFPHM, FAHMS, FRCP (Lond. & Edin.), FACP, FACG, AGAF, FAMS, FRCPI (Hon), GAICD
Pro Vice-Chancellor, Global Research,
University of Newcastle, Australia
Professor of Medicine, Faculty of Health and Medicine, University of Newcastle, Australia
President, Royal Australasian College of Physicians
Chair, Committee of Presidents of Medical Colleges
Hon. Treasurer, Australian Academy of Health and Medical Sciences
Editor-in-Chief, Medical Journal of Australia
Senior Staff Specialist, John Hunter Hospital, Newcastle, Australia
Professor of Medicine and Professor of Epidemiology, Joint Supplemental Consultant Gastroenterology and Health Sciences Research, Mayo Clinic, Rochester, MN, USA

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Functional gastrointestinal diseases (FGIDs) like the irritable bowl syndrome (IBS) are very common, cause major distress including pain and psychological dysfunction, impact on quality of life and drive high health care costs. We speculated that there are two distinct types of functional gastrointestinal disease that others have not recognized.

For example, IBS in a subgroup may first begin with gut symptoms (pain, diarrhea, constipation, bloating etc) in those free of psychological distress and only later does new onset anxiety or depression develop, implicating gut disease as the primary driver of the entire symptom complex (a gut-to-brain disease). On the other hand, we speculated there is another quite different subgroup where disease begins with anxiety or depression and only later do new onset gut symptoms develop, and this is likely primarily a central nervous system cause (probably through the stress system), or a brain-to-gut disease. This is exactly what we found, with gut disease occurring first followed by new onset psychological distress in about two thirds of people from the community over a one year follow-up.

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Stem Cell Therapy May Be Most Effective, and Most Toxic, Treatment For Crohn’s Disease

Dr. Chris J. Hawkey, DM, FRCP, FMedSci. University of Nottingham and Nottingham University Hospital England

Dr. Chris Hawkey

MedicalResearch.com Interview with:
Dr. Chris J. Hawkey, DM, FRCP, FMedSci.
University of Nottingham and Nottingham University Hospital
England

Medical Research: What is the background for this study?

 Dr. Hawkey: ASTIC (The Autologous Stem Cell Transplantation International Crohn’s Disease) systematically investigated the effect of immunoablation and autologous haemopoietic stem cell transplantation (HSCT) on objective signs of disease, symptoms and need for treatment and is the only controlled trial to have done so. The body’s immune system normally protects us from infections but in Crohn’s disease it turns on itself.  The treatment involves wiping out the body’s immune system (immunoablation) and replacing it with the patient’s own (autologous haemopoietic stem cell transplantation) innocent stem cells, a sort of immunological spring clean. Patients were randomly assigned to undergo transplantation (n=23) or just continue on best conventional treatment (n=22).

ASTIC was stimulated by reports which suggested that long-term regression of disease amounting to potential cure could be achieved. But the treatment is hazardous with major potentially lethal risks, so recruitment to the trial was cautious and only the most resistant cases were studied. And we used the most stringent criteria ever developed for the trial’s primary endpoint.

Medical Research: What are the main findings?

 Dr. Hawkey: In fact the criteria we used for success were so stringent (no symptoms, no signs of disease on total bowel examination and no need for treatment) that few patients achieved them. Nevertheless, there were improvements in the individual measures underlying this composite endpoint. Objective signs of disease disappeared so that the gut looked normal from mouth to anus in about a quarter of actively treated patients vs no controls. Eight vs two patients were adjudicated free of active disease on endoscopy and radiology at final assessment (p=0.054). Patients were able to come off drug treatments: by the end of a year 61% of HSCT patients off immunosuppressive drugs for >3 months vs 23% of controls (p=0.012). Ten vs two patients had lost symptoms of active disease, eight vs two for of them for > 3 months (p=0.052).

But treatment was challenging: there were 76 serious adverse events in HSCT patients (particularly infections) vs 38 in controls. One HSCT patient died.

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Isotretinoin Associated With Lower Risk of Inflammatory Bowel Disease

Shadi Rashtak, MD Department of Dermatology Mayo Clinic College of Medicine Rochester, MinnesotaMedicalResearch.com Interview with:
Shadi Rashtak, MD
Department of Dermatology
Mayo Clinic College of Medicine
Rochester, Minnesota


Medical Research:  What are the main findings of the study?

Dr. Rashtak: We found that among a population of mainly acne patients those who received isotretinoin had a lower risk of inflammatory bowel disease as compared to those who did not take this medication. We carefully reviewed the medical records of patients to ensure that this finding was not simply because the drug was avoided in patients with a previous personal or family history of IBD.

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