Study Identifies How Medical Marijuana May Ease IBD Symptoms

MedicalResearch.com Interview with:

Beth A. McCormick, Ph.D. Professor and Vice Chair | Department of Microbiology & Physiological Systems Founding Executive Director | University of Massachusetts Center for Microbiome Research Board of Editors | Gastroenterology University of Massachusetts Medical School Worcester, MA 01655

Dr. McCormick

Beth A. McCormick, Ph.D.
Professor and Vice Chair | Department of Microbiology & Physiological Systems
Founding Executive Director | University of Massachusetts Center for Microbiome Research
Board of Editors | Gastroenterology
University of Massachusetts Medical School
Worcester, MA 01655

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

Response: There has been extensive, but to date mostly anecdotal, support for a beneficial role for cannabinoids and cannabis-derived agents to provide benefit for symptoms in individuals suffering from intestinal inflammatory disease (IBD).

Our studies have provided one possible rationale for these previous findings: that there is a constitutively active efflux system at the luminal surface of cells that line the intestine that pumps out one class of lipids of the family known as endocannabinoids. In doing so, the intestine floods this surface with these endocannabinoids in a manner that counteracts the actions of a particular potent stimulators of intestinal inflammation that appears to be over-active in certain forms of IBD. This is most significant because a number of cannabinoids and cannabis-derived agents can mimic the actions of this class of endocannabinoids. Moreover, while cannabinoids and endocannabinoids have been shown to provide anti-inflammatory actions, these studies have identified one mechanism used by the body to localize and focus this protective function at a critical site where pro-inflammatory and anti-inflammatory events intersect, providing new insights into how to treat that imbalance in these process that occurs in certain forms of IBD.

Therefore, there is the immediate opportunity to use this research to identify new therapeutic strategies to treat individuals suffering from IBD that could include either agents extracted from marijuana plants or novel molecules selected based upon superior properties made obvious by this newly defined mechanism.

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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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Risk of Inflammatory Bowel Disease Lower In Rural Households

MedicalResearch.com Interview with:

Eric I. Benchimol, MD, PhD, FRCPC Associate Professor of Pediatrics and Epidemiology, University of Ottawa Division of Gastroenterology, Hepatology and Nutrition Children's Hospital of Eastern Ontario Ottawa, ON Canada

Dr. Benchimol

Eric I. Benchimol, MD, PhD, FRCPC
Associate Professor of Pediatrics and Epidemiology, University of Ottawa
Division of Gastroenterology, Hepatology and Nutrition
Children’s Hospital of Eastern Ontario
Ottawa, ON Canada

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

Response: We found that living in a rural household (compared to urban households) was protective against developing inflammatory bowel disease (IBD). People living in a rural household were around 10% less likely to get IBD (Crohn’s disease and ulcerative colitis).

While our finding that IBD was more common in people living in urban households was similar to other studies from around the world, there were a number of new, interesting findings:

  1. Living in a rural household was most protective against pediatric-onset IBD. In fact, it was not protective in IBD with onset between ages 18-39, 40-64, or 65 and older at diagnosis.
  2. Living in a rural household in the first 5 years of life was highly protective against IBD later in life.

These findings indicate the importance of early life environmental exposures in the subsequent development of IBD. This effect has been seen in the inflammatory bowel disease literature when examining other environmental risk factors, particularly early-life antibiotic use and air pollution. These risk factors seem to have the strongest effect of increasing the risk of childhood-onset IBD, and not adult-onset disease.

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Tofacitinib -XELJANZ: Potential New Treatment Option For Moderate To Severe Ulcerative Colitis

MedicalResearch.com Interview with:

William J. Sandborn, MD Professor of Medicine and Adjunct Professor of Surgery Chief, Division of Gastroenterology Vice Chair for Clinical Operations, Department of Medicine Director, UCSD IBD Center University of California San Diego and UC San Diego Health System

Dr. Sandborn

William J. Sandborn, MD
Professor of Medicine and Adjunct Professor of Surgery
Chief, Division of Gastroenterology
Vice Chair for Clinical Operations, Department of Medicine
Director, UCSD IBD Center
University of California San Diego and
UC San Diego Health System

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

Response: There is still a substantial unmet need for new treatments for patients with ulcerative colitis.

A previous Phase II study had suggested that tofacitinib might be effective for short term therapy of ulcerative colitis. The patients in that study for the most part had not failed anti-TNF therapy. Now we report the findings from 3 large Phase III trials, two short term trials and one long term trial, demonstrating that tofacitinib 10 mg twice daily is effective for short term therapy, and that both 5 mg and 10 mg twice daily is effective for long term therapy. We also demonstrated that tofacitinib is effective both in patients who have not failed anti-TNF therapy and patients who have failed anti-TNF therapy.

The study demonstrated induction of clinical remission, clinical response and mucosal healing (flexible sigmoidoscopy improvement) over the short term, and maintenance of clinical remission, clinical response, and mucosal healing over the long term.

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Protective Bacteria May Reverse Inflammation In Some Forms of IBD

MedicalResearch.com Interview with:
Justin E. Wilson, Ph.D 
On behalf of the authors
Research Assistant Professor – Laboratory of Jenny Ting
Department of Genetics
Lineberger Comprehensive Cancer Center
The University of North Carolina at Chapel Hill
Chapel Hill, NC 27599

MedicalResearch.com: Could you provide me with some background on this project? Why did you decide to do this research project? What prior work led up to this latest paper?

Response: Previous work from our lab and others discovered two major points about NLRP12:
a) NLRP12 suppresses inflammation in response to bacterial components
b) NLRP12 provides protection against the inflammatory bowel disease colitis and colitis-associated colon cancer (i.e., Nlrp12-defcient mice have greater colon inflammation and inflammation-driven colon cancer).
Therefore, we wanted to know if Nlrp12 was regulating inflammation in the colon by responding to the trillions of intestinal microbes collective referred to as the microbiome. Mounting evidence also indicates that the immune system both responds to and influences the composition of the intestinal microbiome during intestinal health and disease, and we hypothesized that NLRP12 could be one of the important immune components during this process. Moreover, we were also interested in this topic because targeting the microbiome to treat inflammatory disorders and other diseases is an attractive method that has many advantages over immune suppression.

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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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Stelara Found Effective in Inducing and Maintaining Remission in Crohn’s Disease

MedicalResearch.com Interview with:

William J. Sandborn, MD Professor of Medicine and Adjunct Professor of Surgery Chief, Division of Gastroenterology Director, UCSD IBD Center University of California San Diego and UC San Diego Health System

Dr. William Sandborn

William J. Sandborn, MD
Professor of Medicine and Adjunct Professor of Surgery
Chief, Division of Gastroenterology
Director, UCSD IBD Center
University of California San Diego and UC San Diego Health System

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

Dr. Sandborn: The Phase 3 IM-UNITI study investigated the efficacy and safety of Stelara (ustekinumab) in the treatment of moderate to severe Crohn’s disease as an every 8 or 12 week maintenance therapy.

The study showed a significant proportion of adults with moderate to severe Crohn’s disease who received Stelara maintenance treatment achieved clinical remission.

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Treatment With TNF-α inhibitors Raises Short Term Risk Of Infection in Inflammatory Bowel Disease

MedicalResearch.com Interview with:
Nynne Nyboe Andersen, MD, PhD student
Department of Epidemiology Research
Statens Serum Institut
Copenhagen, Denmark

Medical Research: What is the background for this study? What are the main findings?

Dr. Andersen: The use of TNF-α inhibitors, including infliximab, adalimumab and certolizumab pegol to treat people with inflammatory bowel disease is increasing worldwide and has upgraded the medical treatment modalities. However, concerns about their safety, including an increased risk of serious infections have persisted because they suppress the immune system. Previous meta-analyses based on randomized controlled trials did not suggest an increased risk of serious infections in people with inflammatory bowel disease treated with TNF-α inhibitors compared to placebo. However, the trials included in the meta-analyses were designed to investigate efficacy, and not to analyze risk of rare adverse events such as serious infections and often represent selected populations. Therefore, observational studies are essential to evaluate safety in a real world setting; however, results from these studies have been conflicting. Thus, as the risk of infections associated with TNF-α inhibitor treatment in people with inflammatory bowel disease is unclear we aimed at investigating this potential risk in a population-based setting based on the entire Danish inflammatory bowel disease population.

In a propensity score matched cohort we found a significant 63% increased risk of serious infections within 90 days after treatment initiation. When we prolonged follow-up to 356 days the risk was attenuated and no longer significant.  For site-specific serious infections, we found increased point estimates for sepsis, urological/gynecological infections, and skin and soft tissue infections; but these results should be interpreted cautiously because of limited power.

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Do Emulsifiers in Food Additives Play A Role In Inflammatory Bowel Diseases?

Benoit Chassaing, Ph.D. Post-Doctoral Fellow Dr.  Gewirtz's lab. Institute for Biomedical Sciences Center for Inflammation, Immunity, & Infection Georgia State University Atlanta GA 30303MedicalResearch.com Interview with:
Benoit Chassaing, Ph.D.
Post-Doctoral Fellow Dr.  Gewirtz’s lab.
Institute for Biomedical Sciences
Center for Inflammation, Immunity, & Infection
Georgia State University Atlanta GA 30303

Medical Research: What is the background for this study? What are the main findings?

Dr. Chassaing: A key feature of inflammatory bowel diseases and metabolic syndrome is alteration of the gut microbiota in a manner that promotes inflammation. Importantly, incidence of IBD and metabolic syndrome has been markedly increasing since about the mid-20th century, and this dramatic increase has occurred amidst constant human genetics, suggesting a pivotal role for an environmental factor. We considered that any modern additions to the food supply might play an important role, and addition of emulsifiers to food seems to fit the time frame of increased incidence in these diseases. We found that emulsifiers, which are added to most processed foods to aid texture and extend shelf life, can alter the gut microbiota composition and localization to induce intestinal inflammation that promotes development of inflammatory bowel disease and metabolic syndrome.

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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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Inflammatory Bowel Disease: Call to Standardize Perioperative Steroids

Elizabeth C. Wick, MD Assistant Professor,Department of Surgery The Johns Hopkins Hospital, Baltimore, MarylandMedicalResearch.com Interview with:
Elizabeth C. Wick, MD
Assistant Professor,Department of Surgery
The Johns Hopkins Hospital, Baltimore, Maryland

 

MedicalResearch.com: What are the main findings of the study?

Dr. Wick: The main finding is the high variability in physician practice for prescribing steroids and the lack of clear guidance as to best practice in the literature.
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Crohn’s Disease: Thalidomide in Refractory Pediatric Disease

MedicalResearch.com Interview with
Marzia Lazzerini, PhD
Institute for Maternal and Child Health IRCCS “Burlo Garofolo,”
Trieste, Italy

MedicalResearch.com: What are the main findings of the study?

Answer: In children and adolescent with Crohn’s disease refractory to first and second line treatment, thalidomide was effective in inducing and maintaining clinical remission. About 60% of children achieved clinical remission, and clinical remission was  maintained for a mean time of 180 weeks. The main reason to stop thalidomide was peripheral neuropathy.
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