P R Rutgeerts

..Treatments that do not heal (or at least improve) ulcers are not to be continued if they have been given a reasonable time to work. Biomarkers like C-reactive protein and calprotectin can be useful surrogates in this setting...

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

..In this paper, we report the effect of certolizumab pegol on health-related quality of life (HRQoL)...

..Other adverse events associated with anti-TNF strategies are demyelinating disease and worsening of congestive heart failure. Malignancy rates in patients treated with anti-TNF strategies do not seem to be increased...

..A treatment algorithm for fistulizing Crohn's disease must therefore involve the early and optimal use of immunosuppression and of infliximab. Medical and surgical co-operation is also critical to achieve the best possible outcome...

..We propose that future studies should focus on healing and disease course as primary outcome measures...

..There is no evidence that malignancy rates in patients treated with antitumour necrosis factor strategies are increased...

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..We investigated the efficacy and safety of ornidazole, a nitroimidazole antibiotic, for the prevention of clinical recurrence of Crohn's disease after curative ileocolonic resection in a placebo-controlled double-blind clinical trial...

..Onercept is a recombinant, soluble human p55 receptor to tumor necrosis factor-alpha...

..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...

..Careful monitoring of safety of repeated and long-term use of these agents, interfering with very basic physiological events, is mandatory...

..The efficacy of each therapy must be shown in carefully designed clinical programs. Biological therapies carry a definite safety risk, so their place in treatment algorithms must be defined carefully...

..We aimed to study the influence of immunosuppressives discontinuation in patients in remission with combination therapy in an open-label, randomized, controlled trial...

..Materials and..

..Therefore, patients not responding to these agents within 5-7 d should be considered for colectomy and responders should be closely monitored for infections...

..It is not clear which factors influence treatment outcome. We assessed whether variants in NOD2/CARD15 are predictive for differences in clinical response...

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

..Few prospective data are available to support the clinical relevance of mucosal healing in patients with Crohn's disease. This study examined whether complete healing, determined by endoscopy, predicts a better outcome in Crohn's disease...

..In clinical practice assessing mucosal healing should be considered in patients with persistent symptoms despite adequate therapy and when treatment discontinuation is being considered...

..Concomitant use of immunosuppressives (IS) reduces the risk of ATI formation...

..001). Myenteric plexitis was the only consistent predictor of endoscopic recurrence. CONCLUSIONS: The presence of myenteric plexitis in proximal margins of ileocolonic resection specimens is predictive of early endoscopic CD recurrence...

..The aim of this study was to measure mucosal butyrate oxidation in UC (involved and noninvolved colon) and in pouchitis and to study the relationship with endoscopic as well as histological disease activity...

..However, whether we need to include CRP as an inclusion criterion for future trials with biologicals is still a matter of debate...

..The advent of newer anti-TNF agents is only postponing the answer...

..Since nothing is known about the transmission of these variants within families, this was the subject of our study in Flemish patients with inflammatory bowel disease (IBD) and their healthy relatives...

..Taken together, our data suggest that 4-1BB/4-1BBL interactions contribute to the persistence of gut inflammation in CD...

..Whereas the validity and reproducibility of the IBDQ have been extensively studied, there are limited data on its short-term responsiveness and cutoff values for remission and partial clinical response...

..We examined the influence of recently discovered CD-associated susceptibility loci on changes in disease behavior and evaluated whether a genetic risk model for disease progression could be generated...

..We observed two main staining patterns, both of which were present in IBD and were associated with specific phenotypes of the disease...

..Further studies are warranted to confirm these results in a larger cohort...

..Since about 80% of the cumulative urinary (15)N was recovered within 24 h, it was concluded that the biomarker (15)N-LU was useful to monitor processes in the proximal colon rather than in the distal colon...

..Our data confirm the central role of TNF in gut barrier modulation in inflammatory conditions in vivo...

..Infliximab (IFX) treatment induces mucosal healing (MH) in patients with Crohn's disease (CD) but the impact of MH on the long-term outcome of IFX treatment in CD is still debated...

..alpha-Enolase has been proposed as a target antigen in IBD. We evaluated the prevalence and diagnostic value of anti-alpha-enolase antibodies in IBD and related disorders...

..The purpose of the study was to investigate the influence of RS type 3 (retrograded amylose) alone or combined with wheat bran on gastric emptying (GE) and protein assimilation...

..Therefore, we investigated the effect of infliximab (IFX) therapy on Forkhead box protein3 (Foxp3) T cells in blood and intestinal mucosa from Crohn's disease (CD) and ulcerative colitis (UC)...

..We investigated the impact of anti-inflammatory therapy with infliximab on the mucosal gene expression of AMPs in IBD...

..Predictors of response could improve selection of patients with a higher probability of favorable outcomes and could improve the safety profile. We aimed to develop a predictive model for the response to infliximab in CD...

..boulardii intake. CONCLUSION: The results obtained in present study have indicated that colonic amino acid fermentation can be reduced by the administration of lactulose as a fermentable carbohydrate...

..In summary, high local expression of IDO may represent an anti-inflammatory mechanism tempting to counterbalance the tissue-damaging effects of activated T-cells infiltrating the colonic mucosa in IBD...

..CONCLUSIONS: In this large cohort of infliximab-treated CD patients, young age, Crohn's colitis, and concomitant immunosuppressive treatment were identified as independent variables favoring short-term response to infliximab...

..CONCLUSIONS: CSA is an effective treatment of the majority of patients with severe attacks of UC, although the toxicity and even mortality associated with its use necessitates careful evaluation, selection, and follow-up...

..We conclude that IL-10 exhibits poor anti- and even potential proinflammatory effects on ileal Crohn's disease lamina propria. These data might explain the lack of therapeutic efficacy when IL-10 is given to Crohn's disease patients...

..Concomitant immunosuppressive therapy reduces the magnitude of the immunogenic response...

..Our single center, randomized, double-blind, controlled trial aimed to evaluate the additional clinical benefit of 4 mg/kg over 2 mg/kg IV cyclosporine in the acute treatment of severe UC...

..However, currently, they have no place in the diagnostic work up. Their real promise may lie in their use as surrogate markers of complicated aggressive disease as shown in various retrospective studies, but prospective data are lacking...

..In the near future, these novel biological agents may prove valuable therapeutic tools in the management of refractory IBD...

..Future well designed collaborative trials with specified end points are needed to optimize clinical practice in the prevention of postoperative Crohn's disease recurrence...

..Our aim was to test whether a combination of CD-associated genes involved in innate immunity and/or antibody responses to microbial antigens may be valuable in identifying healthy relatives at risk...

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..Goal: We sought to examine whether metronidazole for 3 months together with azathioprine (AZA) for 12 months is superior to metronidazole alone to reduce recurrence of postoperative CD in "high-risk" patients...

..The incorporation of differently labeled substrates into a single test meal allows the assessment of different gastrointestinal processes in the overall assimilation of proteins...

..As illustrated by unexpected but devastating brain infections with anti-adhesion molecules, clinicians should be aware that the powerful immunomodulatory capacity of biologicals necessitates a rigorous safety follow-up...

..The histological features in the liver of PSC patients are similar to those observed in cystic fibrosis (CF). Our aim was to study whether variants in the CFTR gene are associated with the occurrence and/or evolution of PSC...

..This is underscored by the finding of the association between CARD15 variants and Crohn's disease (CD) and D299G in Toll-like receptor (TLR) 4 and IBD. Our aims were to study nonsynonymous polymorphisms in other TLR genes in IBD...

..Our objective is to report the outcome of infliximab (IFX) in ulcerative colitis (UC) patients from a single center and to identify predictors of early clinical response...

..Whereas prolonged exposure to steroids predisposes to an increased rate of peri-operative complications it is still debated whether cyclosporine or infliximab increase peri-operative morbidity in ulcerative colitis...

..Despite the advent of the anti-TNF agent, infliximab, an important unmet medical need characterizes the medical treatment of inflammatory bowel diseases. This review aims to summarize recent progress in the field...

..The purpose of this review is to summarize recent evidence describing specific complications associated with the use of biological therapy derived from controlled trials and from post-marketing surveillance...

..Therapies aiming at neutralisation of IFN-gamma or IL-12 are therefore unlikely to replace anti-TNF, but they might provide an additive or synergistic effect...

..6%. Interestingly, 48.5% of patients do not show antibodies against ASCA or pANCA. Most of these patients remain diagnosed with IC during their further clinical course, perhaps reflecting a distinct clinicoserological entity...

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..This instillation study shows that lactose[15N,15N]ureide is a tool with good properties to investigate the effect of different types of carbohydrates on nitrogen metabolism in the proximal colon in vivo...

..Probiotics are an attractive treatment option for IBD but studies so far are small and data are not yet convincing...

..We studied mutation prevalence, assessed phenotypic expression, and performed conditional analysis to examine evidence for gene-gene interactions...

..Until there are more data, the use of CRP and of other biomarkers should be seen as an additional tool that aids clinical observation and physical examination, but that cannot replace it...

..Dry bowel preparation and VCTC is a promising approach towards a patient-friendly colon cancer-screening setup...

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..We investigated whether a simpler tool, the Harvey-Bradshaw Index, was equally effective in assessing disease severity...

..We discuss the safety aspects of the biological agents in this chapter and, where available, give ways to prevent and/or treat them...

..To focus on the emerging clinical evidence for the use of traditional immunosuppressives and biologicals in the treatment of inflammatory bowel disease...

..Specific medical therapy aimed at preventing or reversing intestinal fibrosis is not yet available, but candidate molecules are emerging from research in the liver and in other organs...

..An effort should be made to collect genomic DNA from all patients enrolled in clinical drug trials after appropriate informed consent for pharmacogenetic studies...

..Some studies suggested an association between the month of birth and the later development of IBD. We studied this putative relationship in a large cohort of Belgian patients with Crohn's disease (CD)...

..Nevertheless, the importance and necessity of pharmacogenetic studies will increase further as more therapeutic classes are being developed...

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..In chronic inflammatory conditions such as Crohn's disease, the migration of leukocytes from the circulation into the parenchyma and their activation within inflammatory sites are mediated in part by alpha4 integrins...

..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...

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

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

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..In all other CD patients and for UC patients in general, continuation seems beneficial. These results support a novel differential algorithm for long-term azathioprine therapy in IBD...

..Anti-Sacharomyces cerevisiae antibodies (ASCA) represent the immunologic marker correlated with Crohn's disease because of their high specificity (80-95%). The aim of this study is to confirm their value in a Romanian population with IBD...

..These data support the notion of an underlying intestinal mucosal barrier hyperresponsiveness in a subset of patients with CD, independent of inflammation...

..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...

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

..Our results identify a major new susceptibility locus for CD, and suggest that genetic variants associated with disease risk at this locus could modulate cis-acting regulatory elements of PTGER4...

..Impairment of health-related quality of life, employment, and productivity has been documented in patients with moderate to severe ulcerative colitis...

..Certolizumab pegol is a pegylated humanized Fab' fragment that binds tumor necrosis factor alpha...

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..We aimed to compare the effectiveness of early use of combined immunosuppression with conventional management in patients with active Crohn's disease who had not previously received glucocorticoids, antimetabolites, or infliximab...

..Maintenance therapy for Crohn disease features the use of immunosuppressive drugs, which are associated with an increased risk of infection. Identification of safe and effective maintenance strategies is a priority...

..We could not confirm an association between the LTA locus and clinical or biological response to infliximab in a large cohort of CD patients...