May 4, 2010 Research being presented at Digestive Disease Week® (DDW®) shows that using telaprevir in the treatment regimen for hepatitis C virus (HCV) is highly effective, particularly in difficult-to-treat cases. Further studies show that aspirin may be a factor in the development of inflammatory bowel disease. DDW is the largest international gathering of physicians and researchers in the field of gastroenterology, hepatology, endoscopy and gastrointestinal surgery.
"Treatment for hepatitis C has historically been challenging, with available treatment options being uncomfortable for the patient and sometimes ineffective, but the science presented here offers hope for the patients living with the infection and the doctors who treat them," said Philip S. Schoenfeld, MD, MSEd, MSc (Epi), associate professor of medicine University of Michigan School of Medicine. "Inflammatory bowel disease, including Crohn's disease, has been historically difficult to treat, partly because we're still learning how the disease occurs. These data will help us better understand this debilitating disease."
Final Results of A Rollover Study Assessing Telaprevir in Combination with Peginterferon Alfa-2A and Ribavirin in Chronic Hepatitis C Patients with Well-Characterized Null Response, Partial Response, Virtual Breakthrough, or Relapse After Prior PR Treatment (Abstract #311)
Researchers at Duke Clinical Research Institute found that patients who had not improved with standard HCV treatment significantly improved response rates when telaprevir was added to the standard treatment regimen.
A previous study had suggested that patients who had failed prior treatments benefited from telaprevir, but the Duke researchers did not have records from these patients to know the full details of their previous treatment. In this study, researchers studied patients from previous telaprevir trials during which patients received standard treatment with peginterferon and ribavirin, but placebo instead of telaprevir, a drug frequently used in the treatment of HCV.
Researchers looked at 117 patients, all of whom received treatment with the combination of pegylated interferon alfa, ribavirin and telaprevir. All patients received 12 weeks of the triple combination and then 12 to 36 more weeks of pegylated interferon alfa and ribavirin.
Telaprevir was discontinued after 12 weeks, and the patients continued for 12 or 36 more weeks of peginterferon alfa and ribavirin. Results showed that null responders -- patients who did not respond to previous treatment (< 1-log10 decrease in HCV RNA at week four or < 2-log10 at week 12) -- needed 48 weeks of treatment, but 57 percent of null responders were cured with this regimen.
The other groups received the 12 weeks of triple combination therapy plus 12 more weeks of peginterferon alfa and ribavirin. For patients who were partial responders to previous therapy, 60 percent were cured with the triple combination. For patients who relapsed with previous therapy, 92 percent were cured with the triple combination.
"The results seen in this trial were encouraging for all patient groups studied," said Andrew J. Muir, MD, director of GI/hepatology research at Duke Clinical Research Institute, Duke University. "This study is yet another indication that telaprevir is consistently showing potential efficacy as a new treatment option for patients who have failed treatment, but also reinforces the additional side effects that come with adding this drug to standard treatments."
The study was funded by Vertex Pharmaceuticals, which is developing telaprevir.
Dr. Muir will present these data on Monday, May 3 at 9 a.m. CT in 383-385, Ernest N. Morial Convention Center.
Improved Sustained Virologic Response (SVR) in "Difficult to Cure" Patients Treated with Telaprevir (T) in Combination with Peginterferon Alfa-2a (P) and Ribavirin (R): An Analysis from the PROVE3 Study (Abstract #T2002)
A new study from Duke Clinical Research Institute shows that telaprevir is effective in difficult-to-treat populations with HCV. Researchers focused on populations traditionally referred to as difficult to treat, including patients with a high viral load (very severe infection), cirrhosis, older or obese patients, or African Americans, and found they all experienced improved response rates. The findings are significant because previous studies have not achieved such high response rates.
This research was a secondary analysis of a large prospective, randomized, controlled trial, PROVE3, which enrolled patients who did not respond to previous standard treatment with peginterferon alfa and ribavirin. Patients (453) were assigned to one of four treatment approaches, which included varying combinations of telaprevir in combination with peginterferon alfa and ribavirin, as well as peginterferon alfa, ribavirin and placebo.
"These findings, if confirmed in larger phase III studies, could provide a meaningful treatment option for clinicians to consider when dealing with patients who have failed an initial standard of care treatment regimen," said Andrew J. Muir, MD, director of GI/hepatology research at Duke Clinical Research Institute, Duke University.
Dr. Muir cautioned that this study is a secondary analysis, and the numbers in each subgroup are small; they need to be further confirmed in larger trials. The study was funded by Vertex Pharmaceuticals, which is developing telaprevir.
Dr. Muir will present these data on Tuesday, May 4 at from 8:00 a.m. CT in Hall F, Ernest N. Morial Convention Center.
Aspirin in the Etiology of Crohn's Disease and Ulcerative Colitis -- Results from a European Prospective Cohort Study (Abstract #96)
Regular aspirin use may be one of many factors involved in the development of Crohn's disease, according to new research from the University of East Anglia in the U.K. Crohn's disease is a serious condition that causes inflammation and swelling in any part of the digestive system that can result in debilitating symptoms. Previous experimental research has shown that aspirin can directly damage the bowel wall, impair its energy supply and possibly limit the bowel's blood supply.
Researchers led by Andrew Hart, MD, senior lecturer in gastroenterology at the University of East Anglia, analyzed data from the European Prospective Investigation into Cancer & Nutrition (EPIC) of more than 200,000 healthy participants from European countries for risk factors involved in the development of Crohn's disease and ulcerative colitis (UC). A total of 62 participants developed Crohn's disease and 126 developed UC. By comparing the frequency of regular aspirin use in participants who developed Crohn's disease and UC and those who did not, researchers found regular aspirin use was positively associated with the risk of developing Crohn's disease. There was no association between aspirin use and UC.
The findings demonstrate that participants who took aspirin regularly for at least one year were nearly five times more likely to be diagnosed with Crohn's disease than those who did not. However, smokers in the study who took aspirin did not develop Crohn's, even though smoking by itself is seen as a risk factor of the disease. Researchers hypothesize that the blood-thickening effects of smoking and the blood thinning effects of aspirin may counteract the harmful properties of both.
"This work suggests that regular use of aspirin may be one of many factors in the development of some cases of Crohn's disease," said Dr. Hart. "We are working to understand the etiology of Crohn's disease looking at many factors including aspirin and diet."
These results need to be tested in different populations in the world before a definitive link can be made. Dr. Hart and colleagues caution that not everyone taking aspirin will develop Crohn's disease and that aspirin has many beneficial effects, including helping to prevent heart attacks and strokes.
Dr. Simon Chan will present these data on Sunday, May 2 at 10:45 a.m. CT in 295-296, Ernest N. Morial Convention Center.
Chemokine Receptor Antagonist CCX282-B (Traficet-EN) Maintained Remission of Crohn's Disease in PROTECT-1 Study (Abstract #647)
New research from the PROTECT-1 study (Prospective Randomized Oral Therapy Evaluation in Crohn's Disease Trial) demonstrates the effectiveness of Traficet-EN (CCX282-B) in maintaining remission of Crohn's disease over 36 weeks. Previously the drug was shown to reduce the severity of Crohn's disease in a 12 week induction study.
PROTECT-1 is a double-blind placebo-controlled trial of 436 patients with moderate to severe Crohn's disease, a condition that causes inflammation and swelling in the digestive system that can result in debilitating symptoms. Traficet-EN targets the chemokine receptor 9 (CCR9) that is involved in attracting specific inflammatory cells to the gastrointestinal tract during inflammatory bowel disease. The drug targets specific cells that are involved in this inflammatory condition of Crohn's disease, while leaving the rest of the immune system unaltered.
Following the 12-week induction study, patients who experienced at least a 70 point reduction on the Crohn's Disease Activity Index were re-randomized to examine Traficet-EN efficacy in maintaining remission of the disease. For this period of the study, 241 patients were re-randomized: 146 received Traficet-EN and 95 received placebo. Traficet-EN maintained remission rate at ~50 percent, whereas the remission rate in patients on placebo decreased progressively from 50 percent at baseline to 31 percent at 36 weeks. At 36 weeks, 47 percent of subjects on Traficet-EN were in remission, constituting a statistically significant difference (p=0.01).
In addition to greater remission levels, patients taking Traficet-EN required less corticosteroid therapy compared to placebo. In patients with Crohn's disease, symptoms typically flare up, often requiring initiation or increase of corticosteroids. At 36 weeks, 41 percent of subjects on Traficet-EN were in corticosteroid-free remission versus 28 percent on placebo (p=0.04).
"Traficet-EN's efficacy as an oral treatment in preserving remission in people with Crohn's disease is a significant advance in the treatment of this disease," said Pirow Bekker, MD, PhD, senior vice president of medical and clinical affairs at ChemoCentryx. "In addition to being a novel therapeutic approach for treating Crohn's disease, this study validates the selective targeting of chemokine receptors to treat major inflammatory and autoimmune diseases."
Current treatments available for Crohn's disease are administered intravenously or by injection, whereas Traficet-EN is an oral capsule. Steroids are also often used in the treatment of Crohn's disease. While they are effective at reducing symptoms of the disease, they have significant side effects including osteoporosis and increased risk of infection. Additionally, over the course of treatment, Traficet-EN was well tolerated by patients and there were no reports of serious infections.
Dr. Bekker noted that this study did not directly compare Traficet-EN to other drugs, so the relative efficacy and safety of the compound compared to other treatments are unknown at this time. The study was funded by ChemoCentryx, which is developing Traficet-EN.
Satish Keshav, MD, PhD will present these data on Tuesday, May 4 at 11:15 a.m. CT in Auditorium AB, Ernest N. Morial Convention Center.
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