New Treatment Methods for Patients with Inflammatory Bowel Disease

28/05/07 Inflammatory bowel disease, or IBD, is an umbrella term referring to a group of disorders that cause inflammation of the intestines, including ulcerative colitis, diverticular disease and perianal fistula. Nearly one million Americans experience some form of IBD every year, which is often chronic or recurring. Research presented at Digestive Disease Week 2007 (DDW) looks at preventative measures and potential treatment options for these painful and debilitating conditions. DDW is the largest international gathering of physicians and researchers in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery.

"Inflammatory bowel diseases are serious and complex diseases with varied preventative and treatment options, and we are pleased to see more attention directed toward improving the lives of people suffering from these conditions," said Mar'a Abreu, M.D., Director, Inflammatory Bowel Disease Center, Associate Professor of Medicine, Mount Sinai School of Medicine. "The studies presented provide evidence that scientists are beginning to capitalize on previous research to better understand, prevent and treat intestinal inflammation."

Can Patients with Diverticular Disease Eat Nuts, Corn and Popcorn

Diverticulosis is a common disease of the large intestine characterized by pouches in the colon that bulge outward through weak spots in the colon musculature. These pouches can become inflamed, a complication referred to as diverticulitis, or they can bleed, often profusely. Patients with diverticulosis, particularly those who have complications, are frequently advised to avoid nuts and seeds; however, there is little evidence to support this recommendation. The aim of this study, conducted by researchers from the University of Washington School of Medicine and Harvard Medical School, was to prospectively evaluate whether nut, corn and popcorn consumption were associated with complications of diverticular disease.

From the Health Professionals Follow-up Study cohort, investigators selected 47,228 U.S. men aged 40-75 years at baseline (in 1986) and free of diverticular disease, gastrointestinal cancer and inflammatory bowel disease. Men reporting newly diagnosed diverticulosis or diverticular complications on biennial follow-up questionnaires were sent supplemental questionnaires outlining details of diagnosis and treatment. Recent consumption of nuts, corn and popcorn was determined from a validated 131-item semi-quantitative food frequency questionnaire mailed to the participants every four years. Study endpoints included diverticular bleeding and diverticulitis.

During 18 years of follow-up, researchers identified 383 cases of diverticular bleeding and 801 cases of diverticulitis. Among men with diverticular bleeding no associations were observed for consumption of nuts, corn, popcorn or combined consumption. Again, among men with diverticulitis, no associations were found for corn consumption. However, after adjusting for other known or potential risk factors for diverticular complications, men with the highest popcorn intake (at least two times per week) had a 28 percent decrease in the risk of diverticulitis compared with men with the lowest intake (less than once per month). Similar statistically significant negative associations with diverticulitis were seen for men with the highest nut intake and the highest combined intake of nuts, corn and popcorn.

"In the past, many doctors have recommended that individuals with diverticulosis or diverticular complications avoid nuts and seeds because they believed that these foods could lodge in diverticula and incite inflammation or bleeding," said Lisa L. Strate M.D., M.P.H., of the University of Washington Division of Gastroenterology in Seattle, Wash. and lead author of this study. "However, data from this large, prospective cohort suggest that these foods do not increase the risk of diverticular complications. In fact, frequent popcorn and nut consumption were associated with a decreased risk of diverticulitis."

Dr. Strate presented this study.

Randomized, Placebo-Controlled Trial of the PPARγ Ligand Rosiglitazone for Active Ulcerative Colitis

Currently, 5-aminosalicylic acid (5-ASA) is the most common treatment for ulcerative colitis (UC), a form of inflammatory bowel disease (IBD). However, not all patients respond to this treatment. Ligands to peroxisome proliferators-activated receptors (PPARy) - a type of therapy widely used to treat type-2 diabetes by lowering the body's resistance to insulin - has been proposed to have anti-inflammatory properties in the colon. This study aimed to determine the effectiveness of the PPARy ligand rosiglitazone (Avandia®) in patients with UC.

Researchers from the University of Pennsylvania in Philadelphia, Pa. led a multicenter, randomized, double-blind, placebo-controlled clinical trial of 105 patients with mild-to-moderately active UC. Patients who have not responded to or were intolerant of 5-ASA were given either 4mg of rosiglitazone or a placebo twice daily for 12 weeks. A Disease Activity Index (DAI) was used to measure the disease activity during the trial and efficacy was assessed by measuring clinical response, clinical remission, endoscopic remission and overall quality of life.

The team found that rosiglitazone was an effective treatment for mild-to-moderately active UC in patients who did not respond to 5-ASA. After 12 weeks of therapy, clinical response was achieved in 23 patients (44%) treated with rosiglitazone and 12 patients (23%) treated with placebo. Patients treated with rosiglitazone had higher rates of clinical remission, but not endoscopic remission. Furthermore, patients who took rosiglitazone also experienced improvement in endoscopic appearance, stool frequency, bleeding rates and the physician's global assessment. Clinical improvement was evident as early as four weeks. While the patients' quality of life was not improved at week four or 12, significant changes were seen at week eight.

"As physicians and scientists, we seek to provide patients with safe and effective treatment options," said James Lewis, M.D., M.S.C.E., of the University of Pennsylvania and lead author of this study. "With that goal in mind, the benefits observed with rosiglitazone in animal models of colitis led us to examine whether this commonly prescribed treatment for type-2 diabetes could relieve the symptoms of ulcerative colitis. This study suggests that rosiglitazone may be a safe and effective short-term therapy for selected patients with ulcerative colitis; however, further testing of maintenance therapy with rosiglitazone is needed."

Dr. Lewis presented this study.

Expanded Adipose-Derived Stem Cells (Cx401) for the Treatment of Complex Perianal Fistula. A Phase II Clinical Trial

Complex anal fistulas, abnormal connections between the anal canal and the skin, is a chronic and highly debilitating condition affecting primarily young people and seriously compromising their quality of life. Management of complex fistulas is a challenge due to the limitations of current treatments, such as surgery and biological therapies, which are not satisfactory. Medical treatment (combination of antibiotics, antiseptics and anti-inflammatory drugs) only provides temporary relief and is usually not successful in clearing up the condition. Moreover, as a result of limited or aggressive surgical treatment, a dilemma stands between permanent recurrence and fecal incontinence. On the other hand, long-term efficacy of biological treatment is limited and adverse events can occur. The use of expanded adipose-derived mesenchymal stem cells (Cx401) is a novel cell therapy based on immunoregulation and cell proliferation, which helps repair damaged tissue.

In a multicenter, randomized, controlled trial, researchers from three Mayor Hospitals in Madrid, Spain and led by La Paz University Hospital, evaluated the efficacy and safety of Cx401 in 49 adult patients with complex perianal fistula from cryptoglandular diseases (conditions pertaining to the anal gland, n=35) or Crohn's disease (an inflammatory disease of the GI tract, n=14). Patients received fibrin glue (biological product that can stimulate wound healing) alone or in addition to Cx401 (20 million stem cells) intralesionally. If not healed, a second dose of fibrin glue or 40 million cells plus fibrin glue was administered. Fistula healing was evaluated at eight weeks. Healing was defined as absence of drainage (spontaneous or by gentle compression) and complete re-epithelization of the external openings. Recurrence rates and quality of life parameters were also analyzed.

This study found that the proportion of patients whose fistulas were healed was significantly higher with Cx401 (71%) than with fibrin glue (16%). Cx401 efficacy was observed in the cryptoglandular and the Crohn's subpopulations. Very remarkably, at the one-year follow-up, the recurrence rate in the Cx401 group was only 17.6 percent and the impact of Cx401 administration on the patient's quality of life was significant. At eight weeks after treatment, not a single adverse event related to the stem cells (Cx401) was observed.

"The safety profile of the product turned out to be very promising. We propose this strategy as a novel approach for the healing of patients with perianal fistula, a chronic and highly debilitating disease with unmet needs," said Damian Garcia-Olmo, M.D., of La Paz University Hospital and lead author of this study. "Overall, we were able to determine that a dose of 20 to 60 million adipose-derived stem cells in combination with fibrin glue is an effective and safe treatment for complex perianal fistula."