CDP571, a humanized monoclonal antibody to tumour necrosis factor-alpha, for steroid-dependent Crohn's disease: a randomized, double-blind, placebo-controlled trial.

Background: More than 50% of patients with Crohn's disease become either steroid resistant or dependent. Accordingly, development of new treatments for steroid-dependent Crohn's disease is a research priority.

Aim: To evaluate CDP571, a humanized antibody to tumour necrosis factor-alpha, for the treatment of steroid-dependent Crohn's disease.

Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn's disease: the CLASSIC-I trial.

Background & Aims: Tumor necrosis factor blockade has been shown to be an effective treatment strategy in Crohn's disease (CD). Adalimumab is a human immunoglobulin G1 (IgG(1)) monoclonal antibody targeting tumor necrosis factor (TNF). A randomized, double-blind, placebo-controlled, dose-ranging trial was performed to evaluate the efficacy of adalimumab induction therapy in patients with CD.

Safety of celecoxib in patients with ulcerative colitis in remission: a randomized, placebo-controlled, pilot study.

Background & Aims: The safety of selective cyclooxygenase-2 inhibitors in patients with ulcerative colitis in remission is unknown.

Methods: We performed a placebo-controlled pilot trial to evaluate the safety of celecoxib in patients with ulcerative colitis in remission who had a present or past history of nonspecific arthritis, arthralgia, or other condition amenable to nonsteroidal anti-inflammatory drug therapy. A total of 222 patients with ulcerative colitis in remission were randomized to receive oral celecoxib 200 mg or placebo twice daily for 14 days.

Crohn Disease: mural attenuation and thickness at contrast-enhanced CT Enterography--correlation with endoscopic and histologic findings of inflammation.

Purpose: To determine retrospectively if quantitative measures of small-bowel mural attenuation and thickness at computed tomographic (CT) enterography correlate with endoscopic and histologic findings of small-bowel inflammation and to estimate the performance of these measures in predicting inflammatory Crohn disease.

Materials And Methods: The institutional review board approved this HIPAA-compliant retrospective study, which was conducted with patient informed consent. CT enterography data in 96 patients (31 male patients and 65 female patients) who underwent ileoscopy with or without biopsy were examined for CT signs of active Crohn disease.

Survival and cause specific mortality in patients with inflammatory bowel disease: a long term outcome study in Olmsted County, Minnesota, 1940-2004.

Background And Aims: We followed a population based cohort of patients with inflammatory bowel disease (IBD) from Olmsted County, Minnesota, in order to analyse long term survival and cause specific mortality.

Material And Methods: A total of 692 patients were followed for a median of 14 years. Standardised mortality ratios (SMRs, observed/expected deaths) were calculated for specific causes of death.

Preliminary data on the use of apheresis in inflammatory bowel disease.

In patients with inflammatory bowel disease (IBD), centrifugation has been attempted to remove leukocyte components from whole blood; however, the use of selective filters has proved to result in more active modification of cellular immunity in that 4 times as many white blood cells are removed, which may result in a greater therapeutic effect. Selective apheresis for treatment of IBD, in particular ulcerative colitis (UC), has been used in Japan and some European countries for several years; pilot studies with Adacolumn, a selective therapeutic granulocyte/monocyte apheresis device, in patients with IBD have recently been completed in the United States with favorable results. Unlike conventional pharmacological treatments, selective apheresis may be associated with a relatively low rate of adverse events.

Budesonide in the treatment of inflammatory bowel disease: the first year of experience in clinical practice.

Background: Delayed release budesonide was approved by the FDA for the treatment of mildly to moderately active Crohn's disease involving the ileum and ascending colon. Controlled trials have demonstrated that budesonide is effective in inducing remission and for maintenance of remission, with less frequent steroid side effects than conventional steroids. We sought to determine the benefit of this medication in clinical practice and to identify any non-FDA-approved uses that may warrant further study.

Infliximab for induction and maintenance therapy for ulcerative colitis.

Background: Infliximab, a chimeric monoclonal antibody directed against tumor necrosis factor alpha, is an established treatment for Crohn's disease but not ulcerative colitis.

Methods: Two randomized, double-blind, placebo-controlled studies--the Active Ulcerative Colitis Trials 1 and 2 (ACT 1 and ACT 2, respectively)--evaluated the efficacy of infliximab for induction and maintenance therapy in adults with ulcerative colitis. In each study, 364 patients with moderate-to-severe active ulcerative colitis despite treatment with concurrent medications received placebo or infliximab (5 mg or 10 mg per kilogram of body weight) intravenously at weeks 0, 2, and 6 and then every eight weeks through week 46 (in ACT 1) or week 22 (in ACT 2).

Positioning novel biologic, probiotic, and apheresis therapies for Crohn's disease and ulcerative colitis.

Traditional medications for inflammatory bowel disease are small molecule drugs, most of which were developed for use in other diseases before being found to be efficacious for the treatment of ulcerative colitis or Crohn's disease. Recently, several exciting alternative approaches to the medical treatment of inflammatory bowel disease have been developed. These include biologic, probiotic, and apheresis therapies that offer certain advantages over traditional drug therapy for inflammatory bowel disease.

Acute pancreatitis in patients with Crohn's disease: clinical features and outcomes.

Background: Acute pancreatitis has occasionally been associated with Crohn's disease (CD), but whether a causal association exists remains unclear. We sought to determine the frequency of etiologies in a consecutive series of patients with CD with acute pancreatitis.

Methods: A centralized diagnostic index was used to identify all patients with CD with acute pancreatitis that were evaluated at Mayo Clinic Rochester between 1976 and 2001.

Delayed-release oral mesalamine at 4.8 g/day (800 mg tablet) for the treatment of moderately active ulcerative colitis: the ASCEND II trial.

Background And Aims: Preliminary data have shown that delayed release oral mesalamine (Asacol) dosed at 4.8 g/day provided additional efficacy benefit compared to 1.6 g/day in patients with mildly to moderately active ulcerative colitis.

Natalizumab induction and maintenance therapy for Crohn's disease.

Background: Natalizumab, a humanized monoclonal antibody against alpha4 integrin, inhibits leukocyte adhesion and migration into inflamed tissue.

Methods: We conducted two controlled trials to evaluate natalizumab as induction and maintenance therapy in patients with active Crohn's disease. In the first trial, 905 patients were randomly assigned to receive 300 mg of natalizumab or placebo at weeks 0, 4, and 8.

State of the art: IBD therapy and clinical trials in IBD.

Inflammatory bowel diseases (IBD) encompass Crohn's disease and ulcerative colitis, which are diseases characterized by chronic intestinal inflammation. IBD is believed to result from predisposing genetic and environmental factors (specific antigens and pathogen-associated molecular patterns) acting on the immunoregulatory system and causing inflammation of the gastrointestinal mucosa. IBD may be the result of an imbalance of effector (proinflammatory) and regulatory T-cell responses.

Design issues and outcomes in IBD clinical trials.

Successful clinical trials in inflammatory bowel disease are based on precise definitions of study populations, standardized and well-defined interventions, reliable indices of disease activity, and clearly stipulated outcome measures. Interpretation of research results is often complicated by the differentiation of goals of therapy (remission induction and maintenance, quality of life) and the multitude of patient subsets. Choosing the correct patient subtype to enroll in a clinical trial is critical to the results of a study, its conclusions, and its applicability to the clinical setting.

A cost-effectiveness analysis of alternative disease management strategies in patients with Crohn's disease treated with azathioprine or 6-mercaptopurine.

Background: Azathioprine (AZA) is effective for the maintenance of a steroid free remission in Crohn's disease (CD). Thiopurine methyltransferase (TPMT) is important for the metabolism of AZA and influences the production of active AZA metabolites. AZA dose selection based on pharmacogenetic testing of TPMT and metabolite monitoring (MM) may offer a safety and efficacy advantage over traditional dosing strategies.

Total laparoscopic proctocolectomy with Brooke ileostomy: a novel incisionless surgical treatment for patients with ulcerative colitis.

Background: This report describes the clinical benefits and safety of a novel (incisionless) laparoscopic operation for chronic ulcerative colitis.

Methods: The medical records for four patients with the diagnosis of chronic ulcerative colitis who underwent "incisionless" laparoscopic proctocolectomy with Brooke ileostomy were reviewed. A novel technique was used for successfully performance of four total proctocloectomies with end ileostomies that did not require abdominal incisions.

Correlation of C-reactive protein with clinical, endoscopic, histologic, and radiographic activity in inflammatory bowel disease.

Introduction: We sought to examine the relationship between C-reactive protein (CRP) and clinical, endoscopic, histologic, and radiographic activity in inflammatory bowel disease (IBD).

Methods: All IBD patients at our institution between January 2002 and August 2003 who had a CRP, colonoscopy, and either small bowel follow-through (SBFT) or CT enterography (CTE) performed within 14 days were identified. Clinical activity was assessed retrospectively through review of the medical record.

Endoscopic factors in the diagnosis of colorectal dysplasia in chronic inflammatory bowel disease.

Background: Surveillance colonoscopy in inflammatory bowel diseases (IBDs) is advocated for early diagnosis of neoplasia but is imperfect because some patients develop cancer despite surveillance. We sought to determine if any endoscopic factors during surveillance colonoscopy were associated with the diagnosis of colorectal dysplasia before the development of cancer.

Methods: We reviewed the Mayo Clinic endoscopic database and medical records of patients with IBD who underwent surveillance colonoscopy between January 2002 and November 2003.

Intentional infliximab use during pregnancy for induction or maintenance of remission in Crohn's disease.

Aim: To study the effects of infliximab on pregnancy and foetal outcome.

Methods: We conducted a retrospective chart review of women with Crohn's disease treated intentionally with infliximab during pregnancy. The primary outcome measure was the occurrence of congenital malformations.

New concepts in anti-tumor necrosis factor therapy for inflammatory bowel disease.

Crohn's disease is a T helper type 1 response immune disease characterized by increased production of interleukin-12 tumor necrosis factor-a (TNF-a), and interferon-g. Clinical trials have demonstrated that inhibition of TNF is effective for the treatment of Crohn's disease. Adverse events reported in patients treated with anti-TNF agents include immunogenicity, acute infusion reactions, delayed hypersensitivity-type reactions, autoimmune diseases including drug-induced lupus and demyelination, and infection.

A randomized, double-blind, placebo-controlled trial of CDP571, a humanized monoclonal antibody to tumour necrosis factor-alpha, in patients with corticosteroid-dependent Crohn's disease.

Aim: To evaluate CDP571, a humanized monoclonal antibody to tumour necrosis factor-alpha, for the treatment of corticosteroid-dependent Crohn's disease.

Methods: Patients with corticosteroid-dependent Crohn's disease (use of prednisolone 15-40 mg/day or budesonide 9 mg/day for at least 8 weeks, a previous failed attempt to discontinue corticosteroids within 8 weeks, and Crohn's Disease Activity Index score 150 points or less) were enrolled in a 16-week, randomized, double-blind, placebo-controlled trial. The patients received intravenous CDP571 (20 mg/kg at week 0 and 10 mg/kg at week 8) or placebo.

Budesonide as maintenance treatment in Crohn's disease: a placebo-controlled trial.

Aim: To assess the efficacy and safety of budesonide capsules 6 mg daily for prolongation of time to relapse and maintenance of remission in patients with Crohn's disease (CD) affecting the ileum and/or ascending colon.

Methods: In a double-blind, placebo-controlled, multicentre trial, 110 patients with CD, who had previously achieved remission in a placebo-controlled trial of budesonide 9 mg daily, were randomly assigned to receive budesonide 6 mg once daily or placebo for 52 weeks. Primary outcome measure was time to relapse [CD activity index (CDAI) of >150 plus an increase of at least 60 points from study entry or withdrawal due to clinical deterioration].