S B Hanauer

..More than two-thirds of ulcerative colitis patients experience at least one relapse over a period of 10 years. Treatments that reduce the likelihood of relapses also reduce the risk of long-term complications...

..The effect of different treatment regimens on antibody responses to infliximab and their clinical significance was examined by using data from ACCENT I...

..Elucidation of immunological and genetic factors indicate multiple points at which the inflammatory cascade may be interrupted, yielding the possibility of precise, targeted therapies for IBD...

..A randomized, double-blind, placebo-controlled, dose-ranging trial was performed to evaluate the efficacy of adalimumab induction therapy in patients with CD...

..6 g/day of mesalazine, although the absence of dose-related side effects allows continuation of the same inductive dose through maintenance treatment without dose-related toxicity...

..Other biological agents that have targeted T cells such as visiluzimab and abatacept were not demonstrated to be effective in controlled trials...

..The availability of novel anti-TNF agents and potential combined toxicities question the risk/benefit of combination therapies...

..8 g/day is more effective than 2.4 g/day in patients with mildly to moderately active UC and in the subgroup with moderate disease...

..Future studies are still needed to best identify predictors of response to individual agents with differing mechanisms of action, as well as to optimize the risk-benefit of long-term maintenance therapy...

..Treatment should be optimized according to the patient status and response with whichever level of therapy is introduced and maintained...

..Recent data regarding potential chemoprevention in long-standing ulcerative colitis and management of postoperative complications and pouchitis will also be discussed...

..Patients who remain indeterminate between ulcerative colitis and Crohn's disease also continue to be a diagnostic challenge...

..Currently, a broad range of options allows physicians to tailor treatment to each patient's needs and preferences. Such considerations are essential for maximizing adherence to therapy...

..The ability to monitor thiopurine metabolites may make it possible to optimize therapeutic response by guiding clinicians on dose escalation...

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..Thirteen additional loci demonstrated nominal (MLod > 1.0, P < 0.016) evidence for linkage. This screen provides strong evidence that there are several major susceptibility loci contributing to the genetic risk for CD and UC...

..CONCLUSIONS: Patients with moderately active ulcerative colitis treated with 4.8 g/day of mesalamine (800 mg tablet) are significantly more likely to achieve overall improvement at 6 wk compared to patients treated with 2.4 g/day...

..Undoubtedly, with the success of infliximab, the role of biologic therapy will continue to expand in the future treatment of IBD...

..As further investigations continue to discern microbiological and immunoinflammatory targets, future therapies may include both probiotics and novel biological agents...

..The combination of conventional and novel approaches now offers the potential of modifying the natural history of these diseases...

..Physicians should use caution when providing higher doses of the pro-drug forms of 5-ASA to their patients, as this could lead to increased diarrhea...

..Inhibition of tumor necrosis factor is a proposed mechanism for the anti-inflammatory properties of thalidomide. We performed an open-label trial of thalidomide in refractory Crohn's disease...

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..This review discusses the results of controlled clinical trials of anti-TNF agents for Crohn's disease...

..Thiazolidinedione ligands for the gamma subtype of peroxisome proliferator-activated receptors (PPARgamma), widely used to treat type 2 diabetes mellitus, have been proposed as novel therapies for ulcerative colitis (UC)...

..Concomitant use of loperamide with diphenoxylate and atropine should be avoided in early pregnancy...

..In PRECiSE 2, patients were also eligible for enrolment if prior infliximab therapy was terminated due to loss of response...

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..Alizyme expect to initiate a phase III trial in 2005...

..Aminosalicylates have been suggested as chemopreventive agents for colorectal cancer (CRC) in ulcerative colitis (UC). We studied the effect of aminosalicylate use on dysplasia and CRC risk in chronic UC...

..The aim of the current trial was to compare 6-mercaptopurine (6-MP) and mesalamine with placebo for the prevention of clinical, endoscopic, and radiographic recurrence of Crohn's disease after resection and ileocolic anastomosis...

..We did a randomised controlled trial to assess the benefit of maintenance infliximab therapy in patients with active Crohn's disease who respond to a single infusion of infliximab...

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..Evidence for therapeutic efficacy in Crohn's disease is presented as a prologue to considerations necessary to determine the benefits and risks of early aggressive treatment versus sequential approaches based upon disease severity...

..The aim of this study was to perform a meta-analysis of the efficacy results from 3 placebo-controlled multicenter clinical trials of slow-release mesalamine (Pentasa) for the acute treatment of mild to moderate Crohn's disease...

..The well-recognized multitude of adverse effects from corticosteroids are eliminated or minimized when rapidly metabolized steroids, such as budesonide, are used...

..46 [0.39-0.57]). CONCLUSION: Nonadherence is associated with multiple concomitant medications, male gender, and single status. These patient characteristics may be helpful in targeting those patients at higher risk for nonadherence...

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..Post-operative trials are certainly needed to ascertain the impact on the inevitability of disease recurrence...

..Meta-analyses have not clarified the situation, possibly because they have combined studies of different design. This debate critically examines the evidence for and against the use of mesalamine in CD...

..DIAGNOSIS: Acute mesenteric ischemia secondary to superior mesenteric vein thrombosis. MANAGEMENT: Resection of necrotic bowel, antibiotics and systemic anticoagulation...

..Given the imperfect nature of this random approach, recent work has focused on improved surveillance techniques and suggests that neoplasia is endoscopically visible in many patients...

..We describe the use of allopurinol in AZA/6-MP nonresponders to deliberately shunt metabolism of 6-MP toward 6-thioguanine (6-TGN) and improve clinical responses...

..The final recommendations are based on the data available at the time of the production of the document and may be updated with pertinent scientific developments at a later time...

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..4 g. The evidence provided by the ASCEND studies support the rationale for a 'top-down' dosing strategy for UC where more potent therapies are introduced at an earlier stage of moderately severe disease...

..These findings provide a unique opportunity to refine the localization and identify a major susceptibility gene for a complex genetic disorder...

..The maintenance benefits of mesalazine appear to be limited to patients 'induced into remission' with mesalazine and in some post-operative settings...

..Patients do, however, live a normal life span. The goal of therapy is to optimize the quality of life, minimize disease activity and disease-related complications, and avoid therapeutic toxicity...

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..Loperamide is generally well tolerated at recommended nonprescription doses, with the most common side effects related to the impact on bowel motility (abdominal pain, distention, bloating, nausea, vomiting, and constipation)...

..The management of low-grade (LGD) and indefinite dysplasia (IND) in patients with ulcerative colitis (UC) remains controversial, as outcomes after a diagnosis of LGD or IND in previous studies vary widely...

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..CONCLUSIONS: Fecal lactoferrin is sensitive and specific for detecting inflammation in chronic IBD. This noninvasive test may prove useful in screening for inflammation in patients presenting with abdominal pain and diarrhea...

..Infliximab therapy may cause a lupus-like syndrome that is reversible upon discontinuing this agent. These findings support recent evidence identifying TNF-alpha as an inhibitor of autoantibody formation...

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..DIAGNOSIS: Crohn's disease flare complicated by an intra-abdominal abscess. MANAGEMENT: Antibiotics (ceftizoxime, metronidazole and amoxicillin/clavulanate potassium), parenteral nutrition and ileocecectomy...

..To report on the results of a prospective longitudinal study of a new bowel-sparing procedure (side-to-side isoperistaltic strictureplasty [SSIS]) in patients with extensive Crohn's disease...

..The potential of aggressive initial therapy followed by step-down maintenance therapy affords the potential to modify the disease course, a possibility that has not been accomplished by current therapeutic algorithims...

..This is the first report of an association between TNFAIP3 polymorphisms and autoimmunity in African-Americans...

..12). Thus, the existence of an inflammatory bowel disease locus on chromosome 3p26 is supported by significant linkage, transmission/disequilibrium and partitioning of linkage evidence...

..Infliximab and adalimumab are anti-TNF agents approved in the US and Europe for the treatment of Crohn's disease, and infliximab is also approved for the treatment of UC...

..Certolizumab pegol is a pegylated humanized Fab' fragment with a high binding affinity for tumor necrosis factor alpha that does not induce apoptosis of T cells or monocytes...

..This analysis of Crohn's disease patients treated with infliximab in ACCENT I compared episodic and scheduled treatment strategies under conditions that simulate clinical practice...

..Patients with evidence of active infection should not receive infliximab until the infection is adequately treated, and all patients should be screened for tuberculosis prior to initiating infliximab therapy...

..The efficacy of the nonabsorbable antibiotic rifaximin in patients with active acute or chronic pouchitis is unknown...

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

..Our data provide strong evidence that extensive ulcerative colitis represents a pathophysiologic subset of IBD...

..Although the remission rate did not significantly differ from the placebo response in this study, there was a significant change in the mean CDAI from baseline in the combined treatment groups relative to the placebo...

..Here we also evaluate the current preferable treatment practices, based on scientifically valid research and collective clinical experience, for the management of mild to moderate Crohn's disease...

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..There was a numerical trend for patients with better mucosal healing to have a lower rate of Crohn's disease-related hospitalizations...

..CONCLUSION: Budesonide 6 mg/day is effective for prolonging time to relapse and for significantly reducing rates of relapse at 3 and 6 months but not 12 months in patients with CD in medically induced remission...

..Natalizumab, a humanized monoclonal IgG(4) antibody to alpha4 integrin, was investigated as a treatment of active Crohn's disease (CD). The safety of natalizumab given in combination with infliximab has not previously been studied...

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..Tetomilast (OPC-6535), a novel thiazole compound, inhibits phosphodiesterase-4 and proinflammatory functions of leukocytes including superoxide production and cytokine release...

..The impact of infliximab induction and maintenance therapy on health-related quality of life (HRQL) was evaluated in patients with ulcerative colitis (UC)...

..No anti-TNF agent has been evaluated prospectively in patients with Crohn disease who had responded to another anti-TNF agent and then lost that response or were intolerant of the agent...

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