*Flat Dysplastic Lesions Identified In Ulcerative Colitis Patients By Narrow Band Imaging Colonoscopy Flat Dysplastic Lesions Identified In Ulcerative Colitis Patients By Narrow Band Imaging Colonoscopy
Article Date: 20 Nov 2007 - 7:00 PST
A pilot study from researchers at Kyushu University in Fukuoka, Japan, found that narrow band imaging (NBI) colonoscopy used in cancer surveillance for ulcerative colitis patients can identify flat dysplastic lesions. The research appears in the November issue of Gastrointestinal Endoscopy, the monthly peer-reviewed scientific journal of the American Society for Gastrointestinal Endoscopy.
Narrow band imaging (NBI) is a novel illumination technology for endoscopy characterized by light with wavelengths of narrow bands that improves the visibility of capillaries, veins and other subtle tissue structures by optimizing the absorbance and scattering characteristics of light. It enhances vasculature within and beneath the mucosa, or lining, of the gastrointestinal (GI) tract. Random biopsy has been a recommended procedure for cancer surveillance in patients with ulcerative colitis. Some studies have shown that chromoscopy, a dye spraying technique used with colonoscopy, with targeted biopsy identified dysplastic lesions (cell abnormalities that indicate progression to cancer) more frequently than did conventional colonoscopy in long-standing ulcerative colitis.
"Our pilot study indicated that the GI mucosal surface structure pattern classified as tortuous, discerned by NBI colonoscopy with a magnifying instrument, may be a clue for the identification of dysplasia in ulcerative colitis," said study lead author Takayuki Matsumoto, MD, Kyushu University. "Because NBI colonoscopy is an easily applicable procedure without specific dye, it may be an alternative to magnifying chromoscopy for cancer surveillance in patients with ulcerative colitis. The value of the procedure for surveillance colonoscopy needs to be examined prospectively in a larger number of patients."
Ulcerative colitis is a chronic (ongoing) disease of the colon, or large intestine. The disease is marked by inflammation and ulceration of the colon mucosa, or innermost lining. Because the inflammation makes the colon empty frequently, symptoms typically include diarrhea (sometimes bloody) and often crampy abdominal pain. According to the Crohn's and Colitis Foundation of America, approximately half a million people in the United States have ulcerative colitis. Researchers do not know what causes the disease and there is no cure. The goal of treatment is to reduce the inflammatory response. Ulcerative colitis is a risk factor for developing colon cancer.
Patients and Methods
In this pilot study of 46 patients with ulcerative colitis, researchers applied NBI colonoscopy to cancer surveillance to investigate whether flat dysplastic lesions in ulcerative colitis could be identified by the procedure.
Patients, aged 18 to 67 years, who had left-sided colitis or pancolitis for more than seven years and who had clinically inactive disease were recruited for the study. Patients were examined by NBI colonoscopy. A magnifying colonoscope was connected to a prototype NBI system. Researchers first searched for sharply demarcated, protruding lesions under conventional colonoscopy and then changed the mode of observation to NBI colonoscopy.
Protruding lesions and flat mucosa were observed by NBI magnifying colonoscopy at a maximum of x70 magnification. The flat areas of interest were identified by a brownish or discolored area distinct from the surrounding mucosa. Otherwise, indistinctive flat mucosa was assessed. The surface structure was classified into honeycomb-like, villous, or tortuous pattern. The honeycomb-like pattern was defined as a crowding of round capillary vessels in honeycomb appearances. The villous pattern was characterized by a cerebriform structure (like the brain in form). The tortuous pattern was defined as a pattern composed of round or ovoid structures of various sizes. The grade of dysplasia was determined in the biopsy specimens obtained from the protrusions and from the flat mucosa.
Results
A total of 296 sites (20 protruding lesions and 276 flat areas) were examined by NBI colonoscopy. The surface pattern was determined to be honeycomb like in 161 sites, villous in 85 sites, and tortuous in 50 sites. Five dysplastic lesions were detected in three patients. A patient had three dysplastic lesions and the other two had a dysplastic lesion each. The positive rate of dysplasia was higher in protrusions (2/20 sites, 10%) than in flat mucosa (3/276 sites, 1.1%, P = .038; however, correction for the multiple testing of data removes this significance). When the surface pattern was taken into account, the rate of positive dysplasia was higher in the tortuous pattern (4/50 sites, 8%) than in the honeycomb-like or villous patterns (1/246 sites, 0.4%, P = .003).
The tortuous pattern determined by NBI colonoscopy may be a clue for the identification of dysplasia during surveillance for ulcerative colitis.
http://www.medicalnewstoday.com/articles/89383.php∞

*Asacol? 800mg Mr Tablets Approved For Ulcerative Colitis (UC), Maintenance Of Remission Of UC And Crohn's Ileo-Colitis Asacol? 800mg Mr Tablets Approved For Ulcerative Colitis (UC), Maintenance Of Remission Of UC And Crohn's Ileo-Colitis
Article Date: 11 Oct 2007 - 8:00 PDT
Procter & Gamble Pharmaceuticals (NYSE: P&G) announced today that Asacol? (mesalazine) 800mg Modified Release (MR) tablets have been approved for the treatment of mild to moderate ulcerative colitis (UC) and maintenance of remission of UC and Crohn's ileo-colitis in the United Kingdom by the Medicines and Healthcare products Regulatory Agency (MHRA).
Asacol 800mg MR tablets have been approved for moderately active UC patients at the new high 4.8 grams per day dose based on the ASCEND (Assessing the Safety and Clinical Efficacy of a New Dose of 5-ASA) I and II clinical trials that demonstrated Asacol 800mg MR tablets given at 4.8g per day resulted in faster symptom relief compared to 2.4g per day in moderately active UC patients.1 Median time to symptom resolution was 9 days for rectal bleeding and 12 days for resolution of abnormal stool frequency for moderately active UC patients receiving Asacol 800mg MR tablets given at 4.8g per day compared to 16 days and 15 days respectively, with those who received mesalazine 400mg tablets dosed at 2.4g per day.1 Importantly, there were no significant differences in the overall serious side effect profile with Asacol 800mg MR tablets dosed at 4.8g per day compared to mesalazine 400mg dosed at 2.4g per day.2
"This is a clinically useful advance for patients with ulcerative colitis," said Simon Travis, DPhil, FRCP, Consultant Physician and Gastroenterologist at the John Radcliffe Hospital in Oxford. "Symptoms of rectal bleeding and diarrhoea resolve faster on higher dose Asacol, without increasing side effects for acute, moderately active UC patients."
"Procter & Gamble is delighted to bring this new option to ulcerative colitis patients," said Hans van Zoonen, Vice President Pharmaceuticals and Personal Healthcare, Europe. "We firmly believe that Asacol 800mg MR tablets will bring faster symptom relief to moderately active UC patients. The development of the 800mg tablet is part of our commitment to provide patients with more dosing choice and convenient options. Asacol is a key pillar to our growing GI franchise, one of three strategic focus areas within P&G Pharmaceuticals," he added.
Asacol 800mg MR tablets are indicated for the treatment of mild and moderate acute exacerbations of ulcerative colitis, to be administered at 2.4g/day and 4.8g/day, respectively, in divided doses. Asacol 800mg MR tablets, administered up to 2.4g/day, are also indicated for the maintenance of remission of ulcerative colitis and Crohn's ileo-colitis.
Procter & Gamble will advise healthcare professionals as soon as the new product is available for prescription to patients.
http://www.medicalnewstoday.com/articles/85294.php?nfid=30587∞

*PDL BioPharma Announces Long-Term Nuvion(R) Data Presented At 2007 Digestive Disease Week PDL BioPharma Announces Long-Term Nuvion(R) Data Presented At 2007 Digestive Disease Week
23 May 2007
Data presented at the Digestive Disease Week (DDW) meeting this week in Washington D.C. by Dr. William Sandborn from the Mayo Clinic suggest that Nuvion (visilizumab), an antibody in development as a treatment for intravenous steroid-refractory ulcerative colitis (IVSR-UC), administered on day 1 and day 2, produced a sustained clinical response up to 310 days and was adequately tolerated. The results presented were from long-term follow up of 138 patients who had received Nuvion in a Phase 1 and Phase 1/2 study as a treatment for IVSR-UC, which contributes to the majority of an estimated 30,000 colectomy procedures performed in the U.S. each year. In addition, early data also will be presented at the meeting regarding the Nuvion antibody's potential as a treatment for Crohn's disease.
"The data presented by Professor Sandborn further support our decision to advance Nuvion into a Phase 3 program in patients with IV steroid-refractory ulcerative colitis," said Mark McCamish, M.D., Ph.D., PDL's senior vice president and chief medical officer. "Patients with severe ulcerative colitis face surgical intervention or colectomy, and positive results from our Phase 3 program would lead to a welcomed treatment for these difficult-to-treat patients who currently have very limited non-surgical options."
Nuvion is a humanized monoclonal antibody designed to target and modulate the action of T cells, the cells believed to cause inflammation leading to ulcerative colitis, with the aim of significantly reducing the symptoms of the disease and potentially delaying or avoiding the need for colectomy, or surgical removal of the colon. An estimated 60,000 colectomy procedures are performed in the U.S. and Europe every year. In April, after review of the current data from an external data monitoring committee, PDL announced that it would advance the Nuvion antibody into a second pivotal study in patients with IVSR-UC, the most severe form of this inflammatory bowel disease that attacks the colon.
Summary of Results (Abstract T1279)
In the study presented by Dr. Sandborn, 138 subjects with IVSR-UC were treated with visilizumab at 5, 7.5, 10, 12.5 or 15 mg/kg intravenously on two consecutive days (Days 1 and 2). Eighty-nine (64.5%) of the 138 patients demonstrated a clinical response at day 30. Clinical response was defined by using one of two standard measures to determine the severity of the patient's ulcerative colitis.
Patients were followed for a median of 356 days, ranging from 21 to 792. During the follow-up period, 53% (73/138) received medical or surgical rescue therapy. Only 28 (35%) of the Day 30 responders ended up undergoing rescue therapy during subsequent observation. Encouraging new data presented at DDW from this study show the median time to first rescue therapy was 310 days. Forty-six (33%) patients underwent colectomy (colon removal), either as first rescue therapy or subsequent to failed medical rescue.
The Nuvion antibody was adequately tolerated, with 120 (87%) patients experiencing transient, mild to moderate infusion reactions due to cytokine release within the first three days of treatment. These symptoms were minimized with pre-medication and hydration. A total of 17 (12%) patients also experienced serious or opportunistic infections, including localized mucocutaneous herpes and candida infections, but there were no disseminated opportunistic infections. The Nuvion antibody also produced a transient decline in T cells, which generally lasted less than 30 days.
Additional Nuvion Data Presentations
Two additional presentations at DDW support the potential of Nuvion as a treatment for inflammatory bowel diseases:
-- On Monday, May 21, Lloyd F. Mayer, M.D., Professor and Chairman of the Immunobiology Center, Professor of Medicine and Chief of the Divisions of Clinical Immunology and Gastroenterology at the Mount Sinai School of Medicine in New York, presented results of a study (Abstract M1679) demonstrating that in in vitro culture experiment, the Nuvion antibody induced expansion of CD8+ T cells, and the CD8+ T cells possessed regulatory T cell activity. If confirmed in human studies, this mechanism may contribute to the observed long-term response to the Nuvion antibody in some patients with IVSR-UC, Dr. Mayer concluded.
-- On Wednesday, May 23, Daniel C. Baumgart M.D., Charite Medical Center, Virchow Hospital, Berlin, Germany, will deliver an oral presentation of data supporting the efficacy and safety of the Nuvion antibody in patients with moderate-to-severe, refractory Crohn's disease (Abstract 1032). The data from this study are intriguing, and PDL is assessing options for further study in this patient population.
http://www.medilexicon.com/medicalnews.php?newsid=71791∞

*Analysis Of Ulcerative Colitis (UC) Remission Rates From Long-term Safety Study Of LIALDA? (mesalamine) Presented At DDW Analysis Of Ulcerative Colitis (UC) Remission Rates From Long-term Safety Study Of LIALDA? (mesalamine) Presented At DDW
24 May 2007
A long-term phase III, open-label 12-14 month extension study (303) presented at the British Society of Gastroenterology (BSG) meeting in Glasgow, Scotland in March 2007 showed Shire plc's (LSE: SHP, NASDAQ: SHPGY, TSX: SHQ) LIALDA? (mesalamine) is well tolerated in mild to moderate UC patients. Today, secondary endpoints of study 303 were presented as post-hoc analyses at Digestive Disease Week (DDW).
Approved by the FDA on January 16, 2007, for the induction of remission in patients with active, mild to moderate UC, LIALDA is the first-and-only FDA-approved once-daily oral mesalamine for the treatment of ulcerative colitis. Safety and effectiveness have been established for up to eight weeks. LIALDA is being evaluated for longer term use.
Long-term remission and relapse rates on LIALDA (abstract # T1296)
A post-hoc analysis of study 303 evaluated maintenance of remission and relapse rates over 12 months. Remission was defined using stringent clinical and endoscopic criteria: modified UC Disease Activity Index (UC-DAI) score of ≤1, with scores of 0 for rectal bleeding and stool frequency, a combined Physician's Global Assessment and sigmoidoscopy score of ≤1, with a sigmoidoscopy score reduction of ≥1 point from baseline and no mucosal friability. Relapse was defined as withdrawing from the study due to a need for alternative therapy for UC.
Overall, a total of 459 patients entered the maintenance phase of study 303. Of these patients, 362 patients met the stringent remission criteria (clinical and endoscopic as defined above) at baseline (in parent studies 301 and 302 - LIALDA's eight-week, phase III, placebo-controlled trials that demonstrated efficacy for the induction of remission in active, mild to moderate UC) and received LIALDA once daily (2.4g/day; n=171) or twice daily (2.4g/day; n=191) for 12 months as part of study 303.
The analysis found that 67.8 percent of the 171 patients on once-daily LIALDA remained in remission and 88.7 percent of these patients remained relapse free at the end of 12 months.
"Earlier studies showed that LIALDA is effective at inducing remission in patients with active, mild to moderate UC. We were encouraged when we did this secondary analysis and found that more than two-thirds of patients in the maintenance phase of study 303 remained in remission and nearly 90 percent of patients did not relapse," says Asher Kornbluth, M.D., Associate Clinical Professor of Medicine at The Mount Sinai Medical Center.
Long-term remission rates regardless of 5-ASA treatment (abstract # T1295)
Another post-hoc analysis of the 303 extension study investigated those patients on a 5-ASA who achieved remission or were deemed to be sufficiently controlled by the physician in study 301 (patients received LIALDA) and study 302 [patients received LIALDA or Asacol? (mesalamine)] to determine if they had remained in remission when staying on or changing to LIALDA for 12 months.
A total of 198 patients who received LIALDA or Asacol in the parent studies entered the maintenance phase of study 303 directly. Of these patients, 151 were in clinical and endoscopic remission, while 47 were considered well enough by their physician to receive maintenance treatment.
Study findings show approximately 75 percent (n=148/198) of patients remained in remission on LIALDA after 12 months, regardless of whether they were previously on LIALDA or Asacol: 73.4 percent (58/79) for patients previously on LIALDA once or twice daily (2.4g/day); 74.7 percent (62/83) for patients previously on LIALDA once daily (4.8g/day); and 77.8 percent (28/36) for patients previously on Asacol three times daily (2.4g/day).
Cumulative analysis across three studies with LIALDA as sole therapy (abstract # T1297)
Another post-hoc analysis assessed long-term remission and relapse rates (secondary endpoints) of study 303. The analysis evaluated data from patients taking Lialda from all three studies: 301, 302, and 303. Patients in the parent studies (301 and 302) who did not achieve remission after eight weeks on Lialda were eligible for enrollment in the acute phase of study 303. In this acute phase, they were given a higher dose of Lialda (4.8g/day, once daily) for an additional eight weeks to induce remission. In total, 63.6 percent of patients (n=220/346) treated with Lialda for up to 16 weeks achieved remission.
Those patients, who achieved remission either in the parent studies (n=125), or the acute phase of study 303 (n=95), were allowed to enter the 12-month maintenance phase of study 303. Of the 220 patients who were in remission, 218 patients actually entered the maintenance phase.
A combined analysis of both long-term remission rates and relapse rates showed that of the patients who started on Lialda therapy, 56.6 percent achieved remission and remained relapse free for at least one year.
http://www.medilexicon.com/medicalnews.php?newsid=71889∞

*PDL BioPharma Advances Nuvion(R) Into Second Pivotal Study In Intravenous Steroid-Refractory Ulcerative Colitis PDL BioPharma Advances Nuvion(R) Into Second Pivotal Study In Intravenous Steroid-Refractory Ulcerative Colitis
27 Apr 2007
PDL BioPharma, Inc. (PDL) (Nasdaq: PDLI) today announced that the company will advance its Nuvion(R) (visilizumab) antibody in patients with intravenous steroid- refractory ulcerative colitis (IVSR-UC) into a phase 3 program. Advancement of the program follows guidance from an independent external Data Monitoring Committee (DMC) based on a planned safety and futility assessment of data from 60 patients enrolled in an ongoing phase 2/3 clinical trial of the Nuvion antibody in patients with IVSR-UC. As a result, the company will continue with enrollment in this ongoing phase 2/3 trial, known as RESTORE 1, while starting a second pivotal trial in the same patient population, known as RESTORE 2.
"We are pleased to continue development of Nuvion in this important indication," said Mark A. McCamish, M.D., Ph.D., senior vice president and chief medical officer, PDL BioPharma. "There is a significant unmet medical need in patients with IVSR-UC, as patients at this stage of the disease have exhausted other treatment options and are facing surgery to remove their colons."
Nuvion is a humanized monoclonal antibody designed to target and modulate the action of T cells, the cells believed to cause inflammation leading to ulcerative colitis (UC), with the aim of significantly reducing the symptoms of the disease and potentially delaying the need for colectomy, or surgical removal of the colon. An estimated 60,000 UC patients a year in both the U.S. and Europe undergo colectomies.
Long-term follow-up data from PDL's earlier Nuvion studies in this patient population will be presented at the upcoming Digestive Disease Week congress, which will be held from May 19 - 24, 2007 in Washington, D.C.
http://www.medilexicon.com/medicalnews.php?newsid=69083∞

*LIALDA(TM) (mesalamine) With MMX(TM) Technology The First Oral Once-Daily Mesalamine For Active, Mild To Moderate Ulcerative Colitis Now Available LIALDA(TM) (mesalamine) With MMX(TM) Technology The First Oral Once-Daily Mesalamine For Active, Mild To Moderate Ulcerative Colitis Now Available
20 Mar 2007
Shire plc (London: SHP, Nasdaq: SHPGY, Toronto: SHQ) today announced the availability of LIALDATM (mesalamine) with MMXTM Technology, indicated for the induction of remission in patients with active, mild to moderate ulcerative colitis (UC), a type of inflammatory bowel disease. LIALDA is the first and only FDA-approved once daily oral formulation of mesalamine. The U.S. Food and Drug Administration (FDA) approved LIALDA on January 16, 2007.
LIALDA is available to patients by prescription for oral administration in dosages of 2.4 g/day and 4.8 g/day, allowing patients to take as few as two tablets once daily. Other currently available mesalamines require three to four times daily dosing and six to 16 pills a day. A study found that patients who are not compliant with their mesalamine medications have a five-fold greater risk of disease flares, a serious worsening of symptoms, than compliant patients.
"In clinical trials, LIALDA was superior to placebo in inducing remission. Additionally, LIALDA's convenient once daily dosing may help address the compliance issues facing so many ulcerative colitis patients," said Mike Cola, President of Shire's Specialty Pharmaceuticals business. "Shire is pleased to offer this latest advancement in the treatment of ulcerative colitis, which complements our existing GI portfolio and reinforces our commitment to improving the treatment of gastrointestinal diseases."
"Although not everyone's experience is the same, taking the pills for my disease seemed to consume my life - my next dosage was constantly on my mind," said Becky Pace, a LIALDA clinical trial patient. "I could not believe taking medication once a day would help as much as it did. LIALDA brought my disease into remission."
http://www.medilexicon.com/medicalnews.php?newsid=65546∞