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See detailEfficacy and safety of a third anti-TNF monoclonal antibody in Crohn's disease after failure of two other anti-TNF.
Allez, Matthieu; Vermeire, Severine; Mozziconacci, Nicolas et al

in Alimentary Pharmacology & Therapeutics (2009)

Adalimumab (ADA) and certolizumab pegol (CZP) have demonstrated efficacy in Crohn's disease (CD) patients previously treated with infliximab (IFX). Aim: To assess the efficacy and tolerability of a third ... [more ▼]

Adalimumab (ADA) and certolizumab pegol (CZP) have demonstrated efficacy in Crohn's disease (CD) patients previously treated with infliximab (IFX). Aim: To assess the efficacy and tolerability of a third anti-TNF in CD after failure of and/or intolerance to two different anti-TNF. Methods: CD patients who received ADA or CZP after loss of response and/or intolerance to two anti-TNF were included in this retrospective study. Data were collected using a standardized questionnaire. Clinical response, duration, safety and reasons for discontinuation were assessed. Results: Sixty-seven patients treated with CZP (n=40) or ADA (n=27) were included. A clinical response was observed in 41 (61%) at week 6 and 34 patients (51%) at week 20. The probability of remaining under treatment at 3 months, 6 months and 9 months was 68%, 60% and 45%, respectively. At the end of follow-up, the third anti-TNF had been stopped in 36 patients for intolerance (n=13), or failure (n=23). Two deaths were observed. Conclusion: Treatment, with a third anti-TNF (CZP or ADA) agent, of CD patients who have experienced loss of response and/or intolerance to two anti-TNF antibodies, has favorable short- and long-term efficacy and is an option to be considered in patients with no other therapeutic options. [less ▲]

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See detailEvaluation of the GERD Impact Scale, an international, validated patient questionnaire, in daily practice. Results of the ALEGRIA study.
Louis, Edouard ULg; Tack, Jacques ULg; Vandenhoven, G. et al

in Acta Gastro-Enterologica Belgica (2009), 72(1), 3-8

BACKGROUND AND STUDY AIMS: Gastroesophageal reflux disease (GERD) is a common chronic disease that is primarily diagnosed based on symptom severity and frequency. This study gathered epidemiological data ... [more ▼]

BACKGROUND AND STUDY AIMS: Gastroesophageal reflux disease (GERD) is a common chronic disease that is primarily diagnosed based on symptom severity and frequency. This study gathered epidemiological data in a population of GERD patients and evaluated the added-value of the GERD Impact Scale (GIS), a novel, validated patient questionnaire, as a tool for initial and long-term patient management. PATIENTS AND METHODS: This observational study recruited patients (296 study centers) with symptomatic GERD and a history of erosive, or reflux, esophagitis. Symptoms were assessed by GIS and physician-subject interview and recorded at baseline (visit 1), at 4-6 weeks (visit 2) and 8-14 weeks (visit 3); also recorded at each visit was the physician's assessment of GERD severity and treatment changes. Analyses were performed on an intent-to-treat basis. RESULTS: Subjects (n = 1919; mean age, 55 years) were 54% female. Lifestyle characteristics included stress (approximately 70% of subjects), mean daily consumption of five cups of caffeine-containing beverages (approximately 70%), alcohol consumption of approximately nine units per week (approximately 50%) and smoking/ex-smoker (41%). Proton pump inhibitors were prescribed in 99% of cases: mainly esomeprazole (82%), with a median dose of 40 mg. Prescribed therapy was changed (mainly dosage levels) between visits in approximately 60% of subjects. The severity of GERD symptoms and GIS scores decreased substantially throughout the study. Mean GIS scores correlated positively with increasing GERD severity and clinical judgment at all visits. Physicians reported that the GIS helped them define the appropriate treatment for the patient and to evaluate the patient's response to treatment in 81% of cases. CONCLUSIONS: This study demonstrates the added-value and usefulness of the patient self-assessment GIS as a management tool for GERD. [less ▲]

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See detailGenetics of ulcerative colitis: the come-back of interleukin 10.
Louis, Edouard ULg; Libioulle, Cécile ULg; Reenaers, Catherine ULg et al

in Gut (2009), 58(9), 1173-6

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See detailThérapies biologiques et maladies inflammatoires chroniques intestinales
Reenaers, Catherine ULg; Louis, Edouard ULg; Belaiche, Jacques ULg

in Revue Médicale de Liège (2009), 64(5-6), 301-304

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See detailChallenges for Biomarker Discovery in Body Fluids Using SELDI-TOF-MS
De Bock, Muriel ULg; De Seny, Dominique ULg; Meuwis, Marie-Alice ULg et al

in Journal of Biomedicine & Biotechnology (2009)

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See detailPredictors of severe Crohn's disease
Loly, Catherine ULg; Belaiche, Jacques ULg; Louis, Edouard ULg

in Scandinavian Journal of Gastroenterology (2008), 43(8), 948-54

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See detailGastroenterology - Clinical and genetic factors associated with sacroiliitis in Crohn's disease
Peeters, Harald; Cruyssen, Bert Vander; Mielants, Herman et al

in Journal of Gastroenterology and Hepatology (2008), 23(1), 132-137

Background and Aim: Radiographic sacroiliitis (SI), often asymptomatic, is considered the most frequent extra-intestinal manifestation (EIM) of Crohn's disease (CD). Data on the association of SI with ... [more ▼]

Background and Aim: Radiographic sacroiliitis (SI), often asymptomatic, is considered the most frequent extra-intestinal manifestation (EIM) of Crohn's disease (CD). Data on the association of SI with other clinical features of CD are limited. Association of SI with CARD15 polymorphisms has recently been suggested. In a multicenter study, we investigated the association of SI in CD patients with clinical phenotypes, other EIM and CARD15 polymorphisms. Methods: Radiographs of the sacroiliac joints were taken in 251 CD patients from three Belgian university hospitals and scored by two blinded rheumatologists. Clinical features were obtained from medical records. Forty-three percent of patients carried at least one CARD15 polymorphism. Results: Sacroiliitis, defined as the presence of at least grade 2 unilateral changes, was diagnosed in 65 of the 244 scorable radiographs (27%). Only 16 of these patients were previously diagnosed with ankylosing spondylitis (AS). HLA-B27 positivity was observed in 53% of patients with AS and 7% of patients with radiographic SI. In univariate and multivariate analysis, associations between the presence of SI and peripheral arthritis (P = 0.005) and between AS and uveitis (P = 0.005) were found. No associations with other recorded clinical features or with CARD15 polymorphisms were observed. Conclusion: We confirm the high prevalence of radiographic sacroiliitis in a multicenter CD cohort. Uveitis is only associated with AS whereas all patients with SI are more prone to develop peripheral arthritis during their disease course, suggesting similar pathogenetic mechanisms in the development of these EIM. The previously reported association between SI and CARD15 polymorphisms was not confirmed. [less ▲]

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See detailProteomics for prediction and characterization of response to infliximab in Crohn's disease: a pilot study.
Meuwis, Marie-Alice ULg; Fillet, Marianne ULg; Lutteri, Laurence ULg et al

in Clinical Biochemistry (2008), 41(12), 960-7

OBJECTIVES: Infliximab is the first anti-TNFalpha accepted by the Food and Drug Administration for use in inflammatory bowel disease treatment. Few clinical, biological and genetic factors tend to predict ... [more ▼]

OBJECTIVES: Infliximab is the first anti-TNFalpha accepted by the Food and Drug Administration for use in inflammatory bowel disease treatment. Few clinical, biological and genetic factors tend to predict response in Crohn's disease (CD) patient subcategories, none widely predicting response to infliximab. DESIGN AND METHODS: Twenty CD patients showing clinical response or non response to infliximab were used for serum proteomic profiling on Surface Enhanced Lazer Desorption Ionisation-Time of Flight-Mass Spectrometry (SELDI-TOF-MS), each before and after treatment. Univariate and multivariate data analysis were performed for prediction and characterization of response to infliximab. RESULTS: We obtained a model of classification predicting response to treatment and selected relevant potential biomarkers, among which platelet aggregation factor 4 (PF4). We quantified PF4, sCD40L and IL-6 by ELISA for correlation studies. CONCLUSIONS: This first proteomic pilot study on response to infliximab in CD suggests association between platelet metabolism and response to infliximab and requires validation studies on a larger cohort of patients. [less ▲]

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See detailDoes the behavior of Crohn's disease change over time?
Louis, Edouard ULg; Reenaers, Catherine ULg; Belaiche, Jacques ULg

in Inflammatory Bowel Diseases (2008), 14

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See detailAre we giving biologics too much time? When should we stop treatment?
Louis, Edouard ULg; Reenaers, Catherine ULg; Belaiche, Jacques ULg

in World Journal of Gastroenterology (2008), 14

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See detailGenome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease
Barrett, Jeffrey C.; Hansoul, Sarah ULg; Nicolae, Dan L. et al

in Nature Genetics (2008), 40(8), 955-62

Several risk factors for Crohn's disease have been identified in recent genome-wide association studies. To advance gene discovery further, we combined data from three studies on Crohn's disease (a total ... [more ▼]

Several risk factors for Crohn's disease have been identified in recent genome-wide association studies. To advance gene discovery further, we combined data from three studies on Crohn's disease (a total of 3,230 cases and 4,829 controls) and carried out replication in 3,664 independent cases with a mixture of population-based and family-based controls. The results strongly confirm 11 previously reported loci and provide genome-wide significant evidence for 21 additional loci, including the regions containing STAT3, JAK2, ICOSLG, CDKAL1 and ITLN1. The expanded molecular understanding of the basis of this disease offers promise for informed therapeutic development. [less ▲]

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See detailNew biomarkers of Crohn's disease: serum biomarkers and development of diagnostic tools
Meuwis, Marie-Alice ULg; Fillet, Marianne ULg; Chapelle, Jean-Paul ULg et al

in Expert Review of Molecular Diagnostics (2008), 8

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See detailMonomeric calgranulins measured by SELDI-TOF mass spectrometry and calprotectin measured by ELISA as biomarkers in arthritis
De Seny, Dominique ULg; Fillet, Marianne ULg; Ribbens, Clio ULg et al

in Clinical Chemistry (2008), 54

BACKGROUND: SELDI-TOF mass spectrometry (MS) is a high-throughput proteomic approach with potential for identifying novel forms of serum biomarkers of arthritis. METHODS: We used SELDI-TOF MS to analyze ... [more ▼]

BACKGROUND: SELDI-TOF mass spectrometry (MS) is a high-throughput proteomic approach with potential for identifying novel forms of serum biomarkers of arthritis. METHODS: We used SELDI-TOF MS to analyze serum samples from patients with various forms of inflammatory arthritis. Several protein profiles were collected on different Bio-Rad Laboratories ProteinChip arrays (CM10 and IMAC-Cu(2+)) and were evaluated statistically to select potential biomarkers. RESULTS: SELDI-TOF MS analyses identified several calgranulin proteins [S100A8 (calgranulin A), S100A9 (calgranulin B), S100A9*, and S100A12 (calgranulin C)], serum amyloid A (SAA), SAA des-Arg (SAA-R), and SAA des-Arg/des-Ser (SAA-RS) as biomarkers and confirmed the results with other techniques, such as western blotting, immunoprecipitation, and nano-LC-MS/MS. The S100 proteins were all able to significantly differentiate samples from patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) from those of patients with inflammatory bowel diseases used as an inflammatory control (IC) group, whereas the SAA, SAA-R, and SAA-RS proteins were not, with the exception of AS. The 4 S100 proteins were coproduced in all of the pathologies and were significantly correlated with the plasma calprotectin concentration; however, these S100 proteins were correlated with the SAA peak intensities only in the RA and IC patient groups. In RA, these S100 proteins (except for S100A12) were significantly correlated with the serum concentrations of C-reactive protein, matrix metalloproteinase 3, and anti-cyclic citrullinated peptide and with the Disease Activity Score (DAS(28)). CONCLUSIONS: The SELDI-TOF MS technology is a powerful approach for analyzing the status of monomeric, truncated, or posttranslationally modified forms of arthritis biomarkers, such as the S100A8, S100A9, S100A12, and SAA proteins. The fact that the SELDI-TOF MS data were correlated with results obtained with the classic calprotectin ELISA test supports the reliability of this new proteomic technique. [less ▲]

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See detailManifestations respiratoires de la rectocolite ulcérohémorragique et de la maladie de Crohn
Guiot, Julien; Louis, Edouard ULg; Belaiche, Jacques ULg et al

in EMC Pneumologie (2008)

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See detailSensitivity of intestinal fibroblasts to TNF-related apoptosis-inducing ligand-mediated apoptosis in Crohn's disease
Reenaers, Catherine ULg; Franchimont, Nathalie; Oury, Cécile ULg et al

in Scandinavian Journal of Gastroenterology (2008), 43

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See detailAn insertion-deletion polymorphism in the Interferon Regulatory Factor 5 (IRF5) gene confers risk of inflammatory bowel diseases
Dideberg, Vinciane ULg; Kristjansdottir, G.; Milani, L. et al

in Human Molecular Genetics (2007), 16(24), 3008-3016

The interferon regulatory factor 5 (IRF5) gene encodes a transcription factor that plays an important role in the innate as well as in the cell-mediated immune responses. The IRF5 gene has been shown to ... [more ▼]

The interferon regulatory factor 5 (IRF5) gene encodes a transcription factor that plays an important role in the innate as well as in the cell-mediated immune responses. The IRF5 gene has been shown to be associated with systemic lupus erythematosus and rheumatoid arthritis. We studied whether the IRF5 gene is also associated with inflammatory bowel diseases (IBD), Crohn disease (CD) and ulcerative colitis (UC). Twelve polymorphisms in the IRF5 gene were genotyped in a cohort of 1007 IBD patients (748 CD and 254 UC) and 241 controls from Wallonia, Belgium. The same polymorphisms were genotyped in a confirmatory cohort of 311 controls and 687 IBD patients (488 CD and 192 UC) from Leuven, Belgium. A strong signal of association [P=1.9x10(-5), odds ratio (OR) 1.81 (1.37-2.39)] with IBD was observed for a 5 bp indel (CGGGG) polymorphism in the promoter region of the IRF5 gene. The association was detectable also in CD patients (P=6.8x10(-4)) and was particularly strong among the UC patients [P=5.3x10(-8), OR=2.42 (1.76-3.34)]. The association of the CGGGG indel was confirmed in the second cohort [P=3.2x10(-5), OR=1.59 (1.28-1.98)]. The insertion of one CGGGG unit is predicted to create an additional binding site for the transcription factor SP1. Using an electrophoretic mobility shift assay, we show allele-specific differences in protein binding to this repetitive DNA-stretch, which suggest a potential function role for the CGGGG indel. [less ▲]

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See detailAssessment of endoscopic activity lndex and biological lnflammatory markers in clinically active Crohn's disease with normal C-reactive protein serum level
Denis, Marie-Armelle; Reenaers, Catherine ULg; Fontaine, Fernand et al

in Inflammatory Bowel Diseases (2007), 13(9), 1100-1105

Background: Patients with clinically active Crohn's disease (CD), defined by a Crohn's Disease Activity Index (CDAI) > 150, may have normal Greactive protein (CRP) serum levels. In such cases, it is ... [more ▼]

Background: Patients with clinically active Crohn's disease (CD), defined by a Crohn's Disease Activity Index (CDAI) > 150, may have normal Greactive protein (CRP) serum levels. In such cases, it is difficult to know whether these patients have really active disease or rather functional symptoms. This distinction is important to decide the most appropriate treatment. The aim of our work was to assess intestinal and colonic lesions in such patients and to look for biological markers potentially associated with endoscopic activity of the disease. Methods: We included 28 consecutive CD patients with CDAI >150 and a normal CRP level. These patients underwent a full colonoscopy with Crohn's Disease Endoscopy Index of Severity (CDEIS) calculation, fecal calprotectin, blood fibrinogen, acid a-I glycoprotein, and erythrocyte sedimentation rate measurement. The Harvey-Bradshaw score was also calculated. Serum ILI beta, IL6, IL8, sIL2R, and sTNFR2 were measured. Results: The median CDAI was 181 (151-485). Almost all (92.9%) these patients had endoscopic lesions, but the majority had only mild lesions (CDEIS : 6). No correlation was found between CDEIS and any of the clinical or biological markers. However, all the patients with significant endoscopic lesions (defined by a CDEIS >6) had previous surgical intestinal resection and lesions involving the anastomosis. Conclusions: Patients with elevated CDAT and normal CRP have only mild mucosal lesions of CD. Most significant lesions may be observed at the anastomosis and proximal to it in previously operated patients. None of the biological markers tested was associated with these endoscopic lesions. [less ▲]

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See detailThe role of the Toll receptor pathway in susceptibility to inflammatory bowel diseases
De Jager, P. L.; Franchimont, D.; Waliszewska, A. et al

in Genes and Immunity (2007), 8(5), 387-397

The intestinal flora has long been thought to play a role either in initiating or in exacerbating the inflammatory bowel diseases (IBD). Host defenses, such as those mediated by the Toll-like receptors ... [more ▼]

The intestinal flora has long been thought to play a role either in initiating or in exacerbating the inflammatory bowel diseases (IBD). Host defenses, such as those mediated by the Toll-like receptors (TLR), are critical to the host/pathogen interaction and have been implicated in IBD pathophysiology. To explore the association of genetic variation in TLR pathways with susceptibility to IBD, we performed a replication study and pooled analyses of the putative IBD risk alleles in NFKB1 and TLR4, and we performed a haplotype-based screen for association to IBD in the TLR genes and a selection of their adaptor and signaling molecules. Our genotyping of 1539 cases of IBD and pooled analysis of 4805 cases of IBD validates the published association of a TLR4 allele with risk of IBD (odds ratio (OR): 1.30, 95% confidence interval (CI): 1.15 - 1.48; P = 0.00017) and Crohn's disease (OR: 1.33, 95% CI: 1.16 - 1.54; P = 0.000035) but not ulcerative colitis. We also describe novel suggestive evidence that TIRAP (OR: 1.16, 95% CI: 1.04 - 1.30; P = 0.007) has a modest effect on risk of IBD. Our analysis, therefore, offers additional evidence that the TLR4 pathway - in this case, TLR4 and its signaling molecule TIRAP - plays a role in susceptibility to IBD. [less ▲]

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