Gert Van Assche

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

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

..This may enhance both therapeutic efficacy and the risk of infection or malignancy, so the balance of risk and benefit must be judged for individual patients...

..This migration is regulated by cell adhesion molecules (CAMs), and selective antimigration therapies have been developed. This study investigated the effect of infliximab therapy on the mucosal gene expression of CAMs in IBD...

..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...

..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...

..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...

..However, a subset of patients shows incomplete or no response to this agent. In this study we investigated whether we could identify a mucosal gene panel to predict (non)response to IFX in CD...

..In case reports, thiopurine analogs and infliximab (IFX) have been proposed as effective therapy in this setting. We analyzed the long-term efficacy of IFX in Belgian patients with refractory pouch complications...

..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...

..We aimed to investigate the predictive role of serologic and histologic markers on disease relapse in UC patients with endoscopically inactive disease...

..6%, respectively, p<0.0001) and more often had concomitant immune-mediated diseases and a trend for more seroreactivity towards ASCA...

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

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

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

....

..Infliximab (IFX) and adalimumab (ADA) are attractive treatment options in patients with inflammatory bowel disease (IBD) also during pregnancy but there is still limited data on the benefit/risk profile of IFX and ADA during pregnancy...

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

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

....

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

....

..C-reactive protein (CRP) is a marker used to identify and follow individuals with CD. We analyzed changes in levels of CRP in a large cohort of patients with CD undergoing treatment with infliximab...

..Histology showed severe mesenteric granulomatosis, dilated lymph vessels and granulomatous vasculitis. After the resection our patient improved without further albumin infusions and the oedema resolved...

..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...

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

..Expression is localized in B cells, suggesting that IL-15 regulates B-cell functions during bowel inflammation. No change in release of sIL-15Rα is observed in patients treated with IFX...

..Genetic variants in autophagy genes IRGM and ATG16L1 have been associated with susceptibility to Crohn's disease. We therefore investigated whether variants in autophagy genes contribute to granuloma formation...

..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...

..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...

..During the course of their disease, about 30% of patients with ulcerative colitis (UC) will undergo proctocolectomy with ileal pouch-anal anastomosis (IPAA). We evaluated the outcome of IPAA in a Belgian referral center...

..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)...

..Magnetic resonance imaging (MRI) is used to assess the outcome of infliximab (IFX) therapy in patients with perianal fistulizing Crohn's disease (pfCD). However, few long-term data are available about its efficacy...

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

..The primary end point was the incidence of infusion reactions in both groups...

..Finally, it remains unclear if and when a biologic agent can be stopped in patients with long-standing remission...

..We investigated long-term outcome including colectomy rates in outpatients treated with IFX for refractory UC in a single referral centre, and evaluated if predictors could be identified...

..CONCLUSIONS: CSA is an effective short- to medium-term treatment for patients with severe UC but at 7 years, 88% of patients will require a colectomy. Azathioprine-naive patients have better outcomes...

..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...

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

..These data provide support for caspase-dependent apoptosis induction being the mechanism of action of infliximab in vivo...

..It is still unknown how well they correlate and whether scoring both endoscopy and histology better reflects the true disease activity than each of the methods separately...

..We aimed to prospectively assess the safety and tolerance of infliximab infusion in patients with IBD in a specialized unit adhering to strict standard operation procedures including switch to accelerated 1h infusions...

..This activity is likely to be important for the clinical effect of this biodrug...

..Two patients developed drug-induced lupus erythematosus. Antinuclear antibodies were associated with the female sex and skin manifestations...

..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 investigated the role of antimicrobial and antiglycan antibodies and polymorphisms in microbial pattern recognition receptor genes...

..There was staining of the brain lesion for polyomavirus. This case report, along with two others, suggests that anti-alpha4-integrin therapy can result in JC virus-induced PML...

..Data on the optimal use of conventional therapies in Crohn's disease are lacking in guidelines. An educational programme was established to explore questions raised in clinical practice and to provide practical answers...

..Fecal calprotectin is a marker of inflammation in inflammatory bowel disease (IBD). Since mucosal healing has become a goal of treatment in IBD we examined how reliably calprotectin levels reflect mucosal disease activity...

..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 data also provide evidence that glycolipid biosynthesis is involved in the inflammatory cascade in these inflammatory bowel disease (IBD) models...

..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...

..Patients experienced clinical benefit along with signs of endoscopic improvement, but further controlled trials are needed to determine the therapeutic benefit of this compound...

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

..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...

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

..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...

..Basic scientists on the other hand prefer classifications that would allow to better understand the pathophysiology of the different manifestations of Crohn's disease and ulcerative colitis...

..We investigated the efficacy of adalimumab for inducing and maintaining mucosal healing in patients with Crohn's disease (CD)...

..A study was undertaken to evaluate prospectively the impact of elective switching of patients with Crohn's disease well controlled with intravenous infliximab to subcutaneous adalimumab in a controlled trial...

..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...

..Moreover, serum VEGF (sVEGF) levels are increased in IBD and correlate with disease activity. Both VEGF expression and sVEGF levels may be influenced by VEGF gene polymorphisms...

....

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

..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...

..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...

..Therefore, long-term benefit to risk profiles need to be established for all novel drugs...

..Whether complete fistula fibrosis occurs over time with repeated infliximab infusions needs further study...

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

..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...

..However, at present there is insufficient evidence to maintain patients on life-long 5-ASA maintenance treatment for this indication...

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

..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...

..Thus, the chemokine network shows complementarity rather than redundancy...

..CONCLUSIONS: Simple Endoscopic Score for Crohn's Disease is a simple, reproducible, and easy-to-use endoscopic scoring system for Crohn's disease...

..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...

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

....

..The aim was to investigate the pathogenic role of TNF in hapten-induced colitis models and to study the relationship between apoptosis induction and disease remission...