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Studies Examine Potential Treatments for Ulcerative Colitis, Chronic Hepatitis C and Other Gastrointestinal Conditions

Health Outcomes Explored at DDW® 2012

SAN DIEGO, CA (May 21, 2012) — New research being presented at Digestive Disease Week® (DDW) reveals effective treatments for a number of gastrointestinal conditions, which are often chronic and costly. One study found that statin therapy may be safe and potentially beneficial in individuals with cirrhosis, a condition that elevates heart disease risk, while another produced positive outcomes by adding telaprevir to a drug regimen for the most common and difficult-to-treat form of chronic hepatitis C. Researchers also saw benefits from using a subcutaneously injected anti-tumor necrosis factor drug in patients with moderate to severe ulcerative colitis, for which existing treatment options are limited. And probiotic dairy consumption that can affect bacteria in the gut was potentially linked to changes in the activity of regions of the brain that control emotional arousal.

“Gastrointestinal disorders are often hard-to-treat diseases requiring drugs that can lead to diminished quality of life,“ said Bruce Sands, MD, MS, AGAF, chief, division of gastroenterology, Mount Sinai School of Medicine, New York, NY. “Addtionally, due to the functions of the gastrointestinal track, we are often unsure how drugs for other diseases may affect patients‘ disorders. New and better treatments are essential to improving quality of life, saving lives and reducing the impact of disease. A number of studies being presented during DDW help further our knowledge of how to best treat our patients while helping to maintain, and in some cases improve, their quality of life.“ DDW is the largest international gathering of physicians and resarchers in the field of gastroenterology, hepatology, endoscopy and gastrointestinal surgery.

Statin Therapy Decreases the Risk of Hepatic Decompensation in Cirrhosis (Abstract #595)

Statin therapy may be safe and potentially beneficial in individuals with cirrhosis, according to new research from Brigham and Women’s Hospital, Boston, MA.

While recent studies have shown that treatment with statins in patients with various liver conditions, including hepatitis C and fatty liver disease, is generally well tolerated compared to the general population, both patients and health-care professionals remain concerned about the use of these drugs in patients with liver disease, particularly cirrhosis. However, patients with liver disease are also at risk of heart disease, and treatment with statins may decrease the risk of heart attack and death.

Researchers led by Sonal Kumar, MD, gastroenterology fellow, Brigham and Women’s Hospital, aimed to evaluate the safety of statin use in patients confirmed to have advanced liver disease, defined as cirrhosis, by a liver biopsy. They compared 81 patients with cirrhosis who were treated with statins to 162 patients who were not to evaluate the effect of statins. Investigators found fewer deaths in the patients who had cirrhosis and were treated with statins. 

Recent studies have suggested that statins may reduce pressures in the liver called portal hypertension, which causes complications such as jaundice, vomiting blood due to enlarged veins in the upper gastrointestinal tract, fluid retention in the abdomen, and confusion. Researchers in this study found that among the group receiving statins, overall decompensation rates were less and the overall time to decompensation was longer. But Dr. Kumar added that further studies are needed to confirm these findings and to better understand the role statins have in patients with cirrhosis.

Despite the findings, Dr. Kumar cautioned that the study reviewed patient chart data retrospectively, and further prospective studies will be needed to clarify the role of statin therapy in cirrhosis. “We can’t conclude that everyone with liver disease should get statins, but we did find that in this population, it may not only be safe, but also beneficial to take statins,” she said. 

No pharmaceutical funding was provided for this study.

Dr. Kumar will present these data on Monday, May 21 at 8:30 a.m. PT in Room 6d of the San Diego Convention Center.

Health-related quality of life among genotype 1 treatment-naïve chronic Hepatitis C patients receiving Telaprevir (Abstract #Sa1048)

Adding telaprevir to two drugs commonly used to treat chronic hepatitis C (peginterferon alfa-2a/ribavirin) does not appear to worsen quality of life substantially compared to using only peginterferon alfa-2a/ribavirin, according to new research from an analysis of the multi-center, multi-national ADVANCE clinical trial. The study looked at patients with genotype 1 hepatitis C who had not been treated previously with telaprevir. These findings are important because genotype 1 is not only the most common form of hepatitis C virus (HCV), is it also the most difficult to treat.

Researchers led by Zobair Younossi, MD, vice president of research and chairman of department of medicine at Inova Health System, Falls Church, VA, analyzed data from 722 patients enrolled in the ADVANCE clinical trial who also had completed the EuroQol Group questionnaire at the beginning of the study and at weeks four, 12, 24, 36, 48 and 72. Patients answered questions about their health-related quality of life in five areas: mobility, self care, usual activities, pain/discomfort and anxiety/depression. Percentages of patients reporting problems in each area and mean scores were calculated.

As expected with any interferon-based regimen, quality of life scores worsened during the first 12 weeks, but returned to normal by week 72; percentages of patients reporting problems at week 12 were high in usual activities, anxiety/depression and pain/discomfort. However, the findings showed that the addition of telaprevir to peginterferon alfa-2a/ribavirin was not associated with substantially lower quality of life scores during treatment. In fact, among those undergoing a shorter treatment duration, improvements in quality of life were observed earlier. Importantly, at week 72, sustained virologic response was independently associated with improved quality of life scores.

“Although impairment of quality of life is expected with two or three drug regimens for hepatitis C, it was encouraging to see that addition of the third drug did not substantially impact quality of life,” said Dr. Younossi. “In addition, patients who received the three drugs were shown to have a substantially better sustained virologic response. Therefore, for patients with H CV genotype 1, the three-drug regimen with telaprevir not only improves sustained virologic response, but also does not seem to substantially worsen quality of life.”

The sustained virologic response is important because it is statistically significant and is a meaningful predictor of health-related quality of life, Dr. Younossi said. Sustained virologic response is linked to long-term eradication of HCV from the body while liver disease improves.

Dr. Younossi cautioned that patients should not assume that they will feel better on the telaprevir-based regimen.  As the third drug is added to peginterferon alfa-2a and ribavirin, it is associated with its own side effect profile.

He added that future research in this field should look at the impact of potential new hepatitis C treatments on patients’ quality of life.

The study was funded by Vertex Pharmaceuticals.

Dr. Younossi will present these data on Saturday, May 19 at 8 a.m. PT in Halls C-G of the San Diego Convention Center.

A phase 2/3 randomized, placebo-controlled, double-blind study to evaluate the safety and efficacy of subcutaneous golimumab induction therapy in patients with moderately to severely active ulcerative colitis (UC): Pursuit SC (Abstract #943d)
 

A large new study from the University of California, San Diego (UCSD) shows the benefit of the subcutaneously  injected anti-tumor necrosis factor (TNF) drug, golimumab (Simponi®), in the treatment of ulcerative colitis. 

Investigators led by William J. Sandborn, MD, professor of clinical medicine, UCSD; and chief, division of gastroenterology, and director, UCSD Inflammatory Bowel Disease Center, looked at adult patients with moderate to severe ulcerative colitis who previously had an inadequate response to conventional ulcerative colitis medications and had not already tried anti-TNF therapies. Anti-TNF therapies are biologic medications that block a protein called tumor necrosis factor, which plays an important role in causing ulcerative colitis. 

More than 1,000 patients were enrolled. The primary endpoint was clinical response at week six. Secondary endpoints at week six were clinical remission and mucosal healing, and change from baseline in quality of life.  Three groups were administered injection regimens of the drug to effectively identify the safety and efficacy of the therapy. Group one received 100 milligrams of the drug through the first phase of injections and 50 milligrams of the drug through the second phase. Group two received slightly higher levels with 200 milligrams during phase one and 100 milligrams during phase two. Group three was provided a placebo to allow for control.

The data demonstrated that golimumab administered subcutaneously was significantly better than a placebo in inducing clinical response, clinical remission, mucosal healing and improving quality of life in patients participating in the study. The safety of golimumab was consistent with the FDA-approved safety profile of golimumab in rheumatologic indications and of other anti-TNFs.

“These findings are important because there are limited treatment options for patients with moderate to severe ulcerative colitis who have had inadequate responses to conventional therapies,” said Dr.  Sandborn. He added that currently, there is only one biologic treatment (Remicade®) approved in the U.S. for this disease. These findings support the effectiveness of an intravenous anti-TNF therapy, infliximab, in the treatment of ulcerative colitis and demonstrate the usefulness of golimuamb to rapidly control symptoms and induce significant and meaningful clinical benefit, Dr. Sandborn said. 

Dr. Sandborn cautioned that while golimumab  is currently approved for rheumatologic conditions, it is not approved for the treatment of ulcerative colitis.

Funding for this study was provided by Janssen Research and Development, LLC.

Dr. Sandborn will present these data on Tuesday, May 22 at 9:15 a.m. PT in Room 20d of the San Diego Convention Center.

Modulation of the Brain-gut Axis After 4-week Intervention with a Probiotic Fermented Dairy Product (Abstract #589)

Probiotic dairy consumption can affect bacteria in the gut and may be linked to changes in the activity of regions of the brain that control emotional arousal and change the body’s response to emotional images, according to new research from the University of California, Los Angeles (UCLA).

Previous animal studies have shown that bacteria in the colon can influence emotional behavior, but there has not been extensive study of this issue in humans. While it is known that some probiotics help people with irritable bowel syndrome feel better, it is less known whether people feel better because of improved digestive function or if other factors are responsible.
 
Researchers led by Kirsten Tillisch, MD, assistant professor of medicine, Oppenheimer Family Center for Neurobiology of Stress, division of digestive diseases, David Geffen School of Medicine at UCLA, sought to build on previous research conducted in animals to determine whether probiotic consumption can alter brain activity in humans. They enrolled 45 healthy women aged 18 to 50 with no digestive or psychological illnesses, and studied brain scans to identify a link between probiotic ingestion and brain response.
 
Investigators studied women who were generally healthy (no abdominal pain, no complaints about bowel movements, and no known physical or mental problems) and divided them into three groups to see how they changed or did not change. The groups were no product (NoP), control milk-based non-fermented dairy product (CTRL) and probiotic dairy product (TEST). The women were asked questions about their stomach health and continued their normal regimen with the exception that they could not take any antibiotics or non-study probiotics during the time of the study. Investigators reviewed each group a month later and compared the findings.
 
The CTRL and TEST groups consumed 125 gram products twice daily for four weeks, and all the groups performed an emotional reactivity task during functional magnetic resonance imaging (MRI) in which the brain was scanned while investigators asked participants questions about overall health and mood before starting the treatment and at the end of the four-week period. The emotional reactivity task consisted of viewing negative emotional faces compared to viewing shapes. A measure called blood oxygen level-dependent response, which is an estimate of brain activity, was measured using an MRI scanner.
 
The TEST group showed less blood oxygen level-dependent response during the emotional reactivity task compared to the CTRL and NoP groups in areas of the brain involved in the processing and modulation of gastrointestinal sensation.
 
The study suggests that the probiotic may dampen the signals that come from the gut and go to the brain when faced with a negative stimulus. The probiotic used in this study may alter signaling molecules and nerve activity in the enteric nervous system. So, by changing the balance of bacteria in the gut, chronic ingestion of the probiotic may alter the body’s response to emotional stimulation.
 
“By changing what’s going on inside of the gut, we hope we can decrease the activity in the nervous system within the wall of the gut, so when we are confronted by a stimulus that may excite it, it should be more relaxed and less responsive to stress, and thus lead to less stimulation in the brain,” Dr. Tillisch said. She cautioned against over-interpretation of the findings and emphasized that one should not conclude that a probiotic is going to make you less emotional or more at ease. 

Dr. Tillisch said the findings are not surprising given that the gut and the brain are very closely connected. For example, stimulation of the autonomic nervous system associated with emotions can change the level of gut activity, creating sensations like “butterflies in the stomach.” Sensations from the gut can feed back to the brain and may stimulate emotions like anxiety or depression. The conscious awareness of these signals may be the basis for what people refer to as “gut feelings.”  A potentially threatening signal from the environment (like an angry face) creates a body response (including changes in gut activity), which feeds back to the brain, and is integrated with memories and emotions to create a conscious feeling in response to the angry face.
 
Funding for this study was provided by Danone Research.

Dr. Tillisch will present these data on Monday, May 21 at 8:27 a.m. PT in Room 20d of the San Diego Convention Center.

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DDW is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy and the Society for Surgery of the Alimentary Tract, DDW takes place May 19–22, 2012, at the San Diego Convention Center. The meeting showcases more than 5,000 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology. For more information, visit www.ddw.org.

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