Colitis, Microscopic

A new study examines how multiple factors contribute to the miscommunication and understanding of the digestive disease, microscopic colitis. It's a hidden cause of diarrhea and the development of the disease is poorly understood. Multiple factors work against the diagnosis of microscopic colitis, an inflammatory digestive disease, because the symptom distress compared to patients with other causes of chronic diarrhea remains unknown. Now, a new study published in journal Gastro Hep Advances, shows patients may be unsure of a diagnosis based on their colonoscopy results, patients may not be prescribed the proper medications, and many patients may remain symptomatic one year after colonoscopy. The study, led by corresponding author Walker Redd, MD, a clinical outcomes and epidemiology fellow in the Division of Gastroenterology and Hepatology at the UNC School of Medicine, involved a cohort of patients from April 1, 2015 to December 22, 2020 enrolled at UNC Hospitals in Chapel Hill, NC. Patients participating in a follow-up survey included 74 with biopsy-confirmed microscopic colitis and 162 patients experiencing other causes of chronic diarrhea (diarrhea controls) after colonoscopy at a one-year follow-up. "We thought it was important to better understand the burden of symptoms among those patients with microscopic colitis within the context of all patients undergoing colonoscopy to evaluate diarrhea," Redd said. Survey results in regard to a microscopic colitis diagnosis showed 10% were unaware of the diagnosis. Among the controls, 7% reported a diagnosis of microscopic colitis despite no clinical documentation. Researchers also found that 15% of controls either thought they had microscopic colitis or were unsure of their diagnosis. While most of the cases received either a letter or phone call with the pathology results, the authors emphasized the importance of considering whether patients with a new diagnosis of microscopic colitis may benefit from a follow-up visit in the gastroenterology clinic for education and treatment. These results highlight how clear communication is needed to address next steps after a diagnosis of the chronic disease. "We were surprised that certain patients were unaware of their diagnosis and that some of the patients who remained symptomatic were not being treated with prescription medications because we would hope that patients understand their colonoscopy results and receive treatment for any ongoing symptoms," said Redd. "Identifying and addressing gaps in the communication of diagnostic results is an important area for future research." What is typically experienced with microscopic colitis and other causes of chronic diarrhea are similar symptoms such as: watery diarrhea, pain in the abdomen, urgent need to have a bowel movement, fecal incontinence and weight loss. The first line therapy recommended for microscopic colitis is budesonide. However, findings show 46% of cases received that kind of treatment. Also, just 26% of diarrhea controls with significant enough symptoms to warrant diagnostic colonoscopy were offered prescription treatment -- showing how these patients were likely undertreated. In addition, many cases continued to experience ongoing loose stools, urgency, and fecal incontinence at one year, providing further evidence that patients should be offered follow-up appointments to assess how they are responding to treatment. The final finding examines the magnitude of symptoms at one year follow-up. In the study, 15% of microscopic colitis cases reported nocturnal stools, 28% abdominal pain, 40% fecal urgency, 32% weight loss, and 21% fecal incontinence. The Microscopic Colitis Disease Activity Index (MCDAI), a tool used to assess disease severity and quality of life, showed significant improvement in microscopic colitis cases compared to controls at a one-year follow up, only 37% of controls had a an improved MCDAI score. Based on these results, cases showed improvement in symptoms whether or not they were treated with budesonide. As far as controls, symptomatic follow up was either similar or more severe than cases. "Hopefully, these findings will help increase awareness of the importance of communicating diagnostic colonoscopy findings as well as assessing and treating persistent symptoms following an initial diagnostic evaluation," said Redd. There is substantial symptom overlap between microscopic colitis and other causes of chronic diarrhea, Redd said, so much so that it makes it harder for providers to reliably distinguish the disease from other common conditions, like irritable bowel syndrome. Researchers concluded that colonoscopy should be considered for certain patients with diarrhea who do not respond to initial treatment or who are at higher risk for microscopic colitis. Furthermore, follow-up appointments, education, and communication can be used to empower patients as far as understanding the implications of a new microscopic colitis diagnosis and how to manage the disease. This study was funded in part by the National Institutes of Health.

Inflammatory bowel disease (IBD) is an independent risk factor for serious infection, even at very low levels of gastrointestinal inflammation. IBD is an umbrella term for chronic inflammatory bowel diseases, with a population prevalence of around 0.5%. The main types of IBD are ulcerative colitis and Crohn's disease. Unlike irritable bowel syndrome (IBS), IBD results in visible damage to the intestinal mucous membrane. IBD is characterized by intermittent symptoms. Periods of high disease activity are sometimes followed by longer periods of low or no activity. However, the extent to which IBD patients with low disease activity are also at increased risk of serious infections, including sepsis, has been unclear. The current study, published in the journal Clinical Gastroenterology and Hepatology, included data on 55,626 individuals diagnosed with IBD. 'Serious infections' referred to infections requiring hospitalization. The difference between healed and unhealed The results show that during periods of low disease activity but active gastrointestinal inflammation, known as microscopic inflammation, there was an increased risk of being affected by serious infections compared to periods of microscopically healed intestinal mucosa. In the case of microscopic inflammation, the number of serious infections was 4.62 per 100 people per year. The corresponding figure for microscopically healed mucosa was 2.53. This corresponded to a 59% relative risk increase for residual microscopic gastrointestinal inflammation, on adjusting the results for various confounders. Interestingly, the results held true even after adjusting for the prescribed IBD medications, and were otherwise similar regardless of age group, sex, and level of education. The study's first-named and corresponding author is Karl Mårild, an associate professor in pediatrics at the University of Gothenburg's Sahlgrenska Academy and a consultant at the Gastrointestinal and Liver Clinic at Queen Silvia's Children's Hospital in Gothenburg. Healing provides important protection "We have shown that even during periods of microscopic intestinal inflammation, IBD patients have an increased risk of serious infections, including sepsis, compared to periods when they have a microscopically healed mucosa," he explains. "This is also true for patients who appear to have low-active disease in clinical terms, but who have microscopic intestinal inflammation beneath the surface. "The results indicate that achieving a fully healed intestinal mucosa in IBD may reduce the risk of serious infections. This is important, as serious infections currently contribute toward increased morbidity and mortality in both children and adults with IBD." The results from the study are based on data from a national cohort (ESPRESSO) with information from Swedish health registers, and from the quality register for IBD (SWIBREG) on people in Sweden diagnosed with IBD between 1990 and 2016. This information was linked to data from microscopic intestinal examinations of patients with IBD.

October 19, 2016 By Mark Terry , BioSpace.com Breaking News Staff On October 16, Celgene International Sarl , a wholly owned subsidiary of Celgene Corporation , released data from a Phase Ib clinical trial that evaluated its GED-0301 (mongersen) in patients with active Crohn’s disease. Although the overall results appeared positive, after a closer look, investors and analysts noted that the company did not use a placebo control in the study. As Celgene stated, “The study was designed to further enhance the understanding of GED-0301 activity in a difficult-to-treat, moderate to severe patient population. This population was more diverse than prior GED-0301 studies and included patients with endoscopically confirmed mucosal damage at entry and those who had previous surgeries. The study also included both biologic-exposed and biologic-naive patients, as well as patients with a diagnosis of Ileitis, Ileocolitis or colitis.” Everything, it seems, but a placebo or normal control group. Clinical improvement was observed by the second week. Patients who were eligible for endoscopies at week 12 had a 37 percent endoscopic response, “with no meaningful difference across treatment groups.” And in patients with greater endoscopic disease activity at the baseline, 63 percent had a decrease of 25 percent or more in SES-CD score, with 31 percent having a reduction of 50 percent or more. “We are encouraged that oral GED-0301 showed both meaningful endoscopic improvement and clinical remission at an early time point in this study,” said Scott Smith , president of Celgene Inflammation & Immunology , in a statement on October 16. “The fact that this study included nearly 50 percent biologic-experienced patients further reflects the potential of GED-0301 as a novel approach for patients with Crohn’s disease searching for alternatives.” Adam Feuerstein , however, writing for The Street, said, “Celgene wasted everyone’s time by running a Crohn’s disease study of GED-0301 without including a placebo arm. Absent a placebo arm for comparison, the GED-0301 Crohn’s data presented Tuesday (announced via press release on Monday) are largely uninterpretable.” And Feuerstein isn’t the only critic. Josh Schimmer , an analyst with Piper Jaffray , wrote in a research note, “While response and remission rates seen with ‘301 are consistent with rates seen with active drug arms of placebo controlled trials, the rates with placebo in trials can be substantial … When [approximately] 60 patients are divided across three dose arms and subsequent subset analyses are performed, the error bars become extremely wide. We were concerned by how confident Celgene was in interpreting the small dataset overall but then fall back on the ‘small patient numbers’ argument to explain away any inconsistencies in the data.” And by comparison, in a Phase II trial of filgotonib in Crohn’s disease run by Gilead Sciences and Galapagos , at the 50 percent cutoff point, the placebo group had a 14 percent endoscopic response rate. The endoscopic response rate for their compound, filgotonib, was 25 percent. Celgene is arguing that GED-0301 works against Crohn’s disease without a placebo to compare it to, and warn that comparing their trial to the Gilead-Galapagos trial could be misleading. Feuerstein writes, “Okay, that might certainly be true, but it’s also hard not to look at the 14 percent placebo response rate in the filgotinib study and wonder if GED-0301 (15 percent response rate) is also a placebo. It would certainly be more accurate and reassuring to have placebo data from the Celgene study, but it’s missing.” Celgene won’t have more data available until sometime in 2018 when a Phase III study on GED-0301 in Crohn’s reads out. Sometime next year there will be some results from a Phase II trial of the drug in ulcerative colitis, but it won’t have a placebo either. Celgene is currently trading for $100.06, down significantly from its November 2, 2015 price of $127.20 a year ago.