Commentary: endoscopic dilatation for stricturing Crohn's disease.
Louis, Edouard ; GAST, Pierrette ; VAN KEMSEKE, Catherine et al
in Alimentary Pharmacology & Therapeutics (2012), 36(5), 494-6Detailed reference viewed: 9 (1 ULg)
What changes in inflammatory bowel disease management can be implemented today?
LOUIS, Edouard ; ; et al
in Journal of Crohn’s and Colitis [=JCC] (2012), 6 Suppl 2
Innovative ideas are required to improve the management of inflammatory bowel disease and to share best practice that can be implemented into clinical practice today. The use of biomarkers such as ... [more ▼]
Innovative ideas are required to improve the management of inflammatory bowel disease and to share best practice that can be implemented into clinical practice today. The use of biomarkers such as calprotectin to monitor disease progression and treatment response could help to improve management of inflammatory bowel disease, but several strategies need to be implemented to make this a reality in clinical practice. The use of calprotectin as a biomarker and the manipulation of the thiopurine pathway to extend the use of current therapies are examples of how basic research can translate into patient benefit. Translational research into the use of microbiota and predictive factors for response and toxicity to drugs, may provide future clinical applications. Global improvement in care in inflammatory bowel disease could also be advanced by improving service provision. For example, the establishment of 'Centres of Excellence', a global interactive inflammatory disease map, and the alignment of processes and standards of care within treatment centres may help to achieve better outcomes for patients with inflammatory bowel disease. Realization of this goal, as well as a better understanding of the aetiology of the disease, may be furthered by collaborative efforts between organizations involved in inflammatory bowel disease as well as wider collaboration across countries and globally. [less ▲]Detailed reference viewed: 106 (2 ULg)
L'asthme: une maladie complexe mettant en jeu facteurs environnementaux et terrain genetique.
LOUIS, Renaud ; SCHLEICH, FLorence ; Corhay, Jean-Louis et al
in Revue Médicale de Liège (2012), 67(5-6), 286-91
Asthma is a complex disease highly dependent of environmental exposure and genetic background. Through linkage analysis, positional cloning and genome wide association studies, novel asthma genes have ... [more ▼]
Asthma is a complex disease highly dependent of environmental exposure and genetic background. Through linkage analysis, positional cloning and genome wide association studies, novel asthma genes have come out such as ADAM-33 or ORMLD3. Important environmental factors include allergenic exposure, pollutants and especially particulate matters, tobacco, aerosol exposure, viral infections and level of exposure to endotoxin. The effects of environmental factors are modulated by the genetic sequence and numerous single nucleotide polymorphisms (SNPs). Recently, it has also become clear that environmental factors may alter gene expression by DNA methylation or histone methylation/acetylation without changing the gene sequence and thereby changing asthmatic phenotype. [less ▲]Detailed reference viewed: 222 (8 ULg)
Epidemiology of the transition from early to late Crohn's disease.
in Digestive Diseases (2012), 30(4), 376-9
Phenotypically, the transition from early to late Crohn's disease is characterized by the occurrence of complications including strictures, intra-abdominal fistulas and perianal fistulas, all of them ... [more ▼]
Phenotypically, the transition from early to late Crohn's disease is characterized by the occurrence of complications including strictures, intra-abdominal fistulas and perianal fistulas, all of them leading to various types of surgeries and currently non-reversible tissue damage. It must, however, be kept in mind that this transition is not at all a uniform and linear process. According to these simple phenotypic criteria, Crohn's disease can already be a late disease at diagnosis while in other patients, it can still be an early disease after 20 years of evolution. This simply highlights the relativity of time in this field, actually reflecting the nature, location and severity of the inflammatory process. The risk over time of the development of these complications has been described, first in cohort studies and then in population-based studies. Globally, at diagnosis, between 19 and 38% only of Crohn's disease patients have complicated Crohn's disease. After 10 years, between 56 and 65% of patients have developed either stricturing or penetrating complications. After 20 years, these numbers are between 61 and 88%. In parallel to these structural changes, changes in the immunobiology of the disease also seem to occur; the latter seem to happen quicker with major modification already within 2 years of the diagnosis. Beside these general figures, important questions remain pending. First, the real timing of these changes is still unclear. Second, the precise role of genetics and environment in the development of these changes remains to be clarified. Third, the correlation between changes in immunobiology and intestinal structural damages has not been specifically studied. [less ▲]Detailed reference viewed: 37 (6 ULg)
Le syndrome de Lynch et l'instabilité des microsatellites : revue de littérature.
; VERSET, Gontran ; POLUS, Marc et al
in Revue Médicale de Liège (2012), 67(12), 638-642Detailed reference viewed: 87 (9 ULg)
Perception gaps between patients with ulcerative colitis and healthcare professionals: an online survey.
; ; LOUIS, Edouard et al
in BMC Gastroenterology (2012), 12(1), 108
ABSTRACT: BACKGROUND: The purpose of this study was to examine the differing perspectives and perceptual gaps relating to ulcerative colitis (UC) symptoms and their management between patients and ... [more ▼]
ABSTRACT: BACKGROUND: The purpose of this study was to examine the differing perspectives and perceptual gaps relating to ulcerative colitis (UC) symptoms and their management between patients and healthcare professionals (HCPs). METHODS: Structured, cross-sectional, Web-based questionnaires designed to assess a variety of disease indices were completed by adult patients with UC and HCPs involved in the care of patients with UC from Canada, France, Germany, Ireland, Spain, and the United Kingdom. RESULTS: Surveys were completed by 775 patients, 475 physicians, and 50 nurses. Patient self-reported classification of disease severity revealed generally greater severity (mild, 32 %; moderate, 53 %) compared with physician and nurse estimates of UC severity among their caseloads (mild, 52 % and 49 %; moderate, 34 % and 37 %, respectively). Patients reported that an average of 5.5 (standard deviation, 11.0) flares (self-defined) occurred over the past year, compared with 3.4 and 3.8 flares per year estimated by physicians and nurses. Perceived flare triggers differed between patients (stress ranked first) and HCPs (natural disease course ranked first). Fifty-five percent of patients stated that UC symptoms over the past year had affected their quality of life, while physicians and nurses estimated that 35 % to 37 % of patients would have a reduced quality of life over the same period. Patients ranked urgency and pain as the most bothersome symptoms, while physicians and nurses ranked urgency and stool frequency highest. About half of patients (47 %) defined remission as experiencing no symptoms; by comparison, 62 % to 63 % of HCPs defined remission as requiring the complete absence of symptoms. HCPs (doctors/nurses in general practice and/or hospital) were regarded by patients as their main source of UC information by 72 %; however, 59 % reported not arranging regular visits to see their HCPs. CONCLUSIONS: This large survey identified important differences between patients' and HCPs' perceptions of the impact of UC symptoms on patients' lives. Notably, HCPs may underestimate the effect of specific UC symptoms on patients and may fail to recognize issues that are important to patients. [less ▲]Detailed reference viewed: 10 (0 ULg)
Adalimumab in ulcerative colitis: can pharmacodynamics be improved based on pharmacokinetics?
LOUIS, Edouard ;
in Gastroenterology (2012), 142(1), 176-8Detailed reference viewed: 33 (2 ULg)
Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease.
; ; et al
in Nature Genetics (2012), 43(11), 1066-73
More than 1,000 susceptibility loci have been identified through genome-wide association studies (GWAS) of common variants; however, the specific genes and full allelic spectrum of causal variants ... [more ▼]
More than 1,000 susceptibility loci have been identified through genome-wide association studies (GWAS) of common variants; however, the specific genes and full allelic spectrum of causal variants underlying these findings have not yet been defined. Here we used pooled next-generation sequencing to study 56 genes from regions associated with Crohn's disease in 350 cases and 350 controls. Through follow-up genotyping of 70 rare and low-frequency protein-altering variants in nine independent case-control series (16,054 Crohn's disease cases, 12,153 ulcerative colitis cases and 17,575 healthy controls), we identified four additional independent risk factors in NOD2, two additional protective variants in IL23R, a highly significant association with a protective splice variant in CARD9 (P < 1 x 10(-16), odds ratio approximately 0.29) and additional associations with coding variants in IL18RAP, CUL2, C1orf106, PTPN22 and MUC19. We extend the results of successful GWAS by identifying new, rare and probably functional variants that could aid functional experiments and predictive models. [less ▲]Detailed reference viewed: 52 (2 ULg)
Does co-treatment with immunosuppressors improve outcome in patients with Crohn's disease treated with adalimumab?
; LOUIS, Edouard ; Belaiche, Jacques et al
in Alimentary Pharmacology & Therapeutics (2012), 36(11-12), 1040-8
BACKGROUND: There is clear benefit from combination therapy with infliximab and immunosuppressive drugs (IS), but few data are available for adalimumab (ADA). AIM: To assess the efficacy of ADA ... [more ▼]
BACKGROUND: There is clear benefit from combination therapy with infliximab and immunosuppressive drugs (IS), but few data are available for adalimumab (ADA). AIM: To assess the efficacy of ADA monotherapy and ADA+IS for induction and maintenance therapy in Crohn's disease. METHODS: Retrospective study of patients with Crohn's disease treated with ADA in Oxford, UK or Liege, Belgium. Treatment periods were divided into 6-month semesters. A combination therapy semester was defined as ADA+IS for at least 3 months; successful induction meant clinical response; a semester with flare as ADA dose escalation, starting steroids, perianal complication, or surgery; and ADA failure as ADA withdrawal for secondary loss of response or intolerance. Semesters with and without flares were compared through univariate and multivariate analysis. RESULTS: Successful induction was achieved in 171/207 (83%) patients, with no significant difference between ADA+IS and ADA monotherapy (85% vs. 82%, P = 0.50). Five hundred and sixty-two semesters in 181 patients were included for maintenance analysis. ADA+IS was not associated with fewer semesters with flare (34% vs. 35%, P = 0.96), or with ADA failure (6% vs. 8%, P = 0.43). Nevertheless, combination therapy in the first semester was associated with a lower risk of ADA failure (5% vs. 10%, P = 0.04, OR = 0.48) and combination therapy beyond 6 months was associated with fewer semesters with flares (14% vs. 36%, P = 0.02, OR = 0.31). CONCLUSIONS: There may be a benefit from adalimumab+immunosuppressive drugs combination therapy during the first semester of initiating adalimumab, with a slight decrease in adalimumab failure and lower need for adalimumab dosage escalation. [less ▲]Detailed reference viewed: 34 (3 ULg)
Genetique et environnement dans les maladies inflammatoires chroniques de l'intestin.
Louis, Edouard ; VAN KEMSEKE, Catherine ; LATOUR, Pascale et al
in Revue Médicale de Liège (2012), 67(5-6), 298-304
Inflammatory bowel diseases are both environmental and genetic illnesses. More than one hundred genes or loci involved in the regulation of innate or acquired immune response as well as intestinal mucosa ... [more ▼]
Inflammatory bowel diseases are both environmental and genetic illnesses. More than one hundred genes or loci involved in the regulation of innate or acquired immune response as well as intestinal mucosa homeostasis have been identified. Environmental studies have been less numerous up to now and only smoking and appendectomy have been validated, as protector for ulcerative colitis, while smoking is clearly associated with an increased risk and more severe forms of Crohn's disease. An important role is also currently suspected for the intestinal flora and the dysbiosis described in inflammatory bowel disease could contribute to the triggering or the persistence of the inflammation. New therapeutic strategies are currently studied, particularly aiming at targeting immune, inflammatory or homeostatic pathways corresponding to the predisposing gene variants. [less ▲]Detailed reference viewed: 130 (9 ULg)
Development of the paris definition of early Crohn's disease for disease-modification trials: results of an international expert opinion process.
; ; et al
in American Journal of Gastroenterology (2012), 107(12), 1770-6
We report the findings and outputs of an international expert opinion process to develop a definition of early Crohn's disease (CD) that could be used in future disease-modification trials. Nineteen ... [more ▼]
We report the findings and outputs of an international expert opinion process to develop a definition of early Crohn's disease (CD) that could be used in future disease-modification trials. Nineteen experts on inflammatory bowel diseases held an international expert opinion meeting to discuss and agree on a definition for early CD to be used in disease-modification trials. The process included literature searches for the relevant basic-science and clinical evidence. A published preliminary definition of early CD was used as the basis for development of a proposed definition that was discussed at the expert opinion meeting. The participants then derived a final definition, based on best current knowledge, that it is hoped will be of practical use in disease-modification trials in CD. [less ▲]Detailed reference viewed: 43 (3 ULg)
Maintenance of Remission Among Patients With Crohn's Disease on Antimetabolite Therapy After Infliximab Therapy Is Stopped.
Louis, Edouard ; ; et al
in Gastroenterology (2012), 142(1), 63-70531
BACKGROUND & AIMS: It is important to determine whether infliximab therapy can be safely interrupted in patients with Crohn's disease who have undergone a period of prolonged remission. We assessed the ... [more ▼]
BACKGROUND & AIMS: It is important to determine whether infliximab therapy can be safely interrupted in patients with Crohn's disease who have undergone a period of prolonged remission. We assessed the risk of relapse after infliximab therapy was discontinued in patients on combined maintenance therapy with antimetabolites and identified factors associated with relapse. METHODS: We performed a prospective study of 115 patients with Crohn's disease who were treated for at least 1 year with scheduled infliximab and an antimetabolite and had been in corticosteroid-free remission for at least 6 months. Infliximab was stopped, and patients were followed up for at least 1 year. We associated demographic, clinical, and biologic factors with time to relapse using a Cox model. RESULTS: After a median follow-up period of 28 months, 52 of the 115 patients experienced a relapse; the 1-year relapse rate was 43.9% +/- 5.0%. Based on multivariable analysis, risk factors for relapse included male sex, the absence of surgical resection, leukocyte counts >6.0 x 10(9)/L, and levels of hemoglobin </=145 g/L, C-reactive protein >/=5.0 mg/L, and fecal calprotectin >/=300 mug/g. Patients with no more than 2 of these risk factors (approximately 29% of the study population) had a 15% risk of relapse within 1 year. Re-treatment with infliximab was effective and well tolerated in 88% of patients who experienced a relapse. CONCLUSIONS: Approximately 50% of patients with Crohn's disease who were treated for at least 1 year with infliximab and an antimetabolite agent experienced a relapse within 1 year after discontinuation of infliximab. However, patients with a low risk of relapse can be identified using a combination of clinical and biologic markers. [less ▲]Detailed reference viewed: 30 (5 ULg)
Auto-immune gastritis characteristics in a large series of patients with auto-immune thyroiditis.
VALDES SOCIN, Hernan Gonzalo ; ; LUTTERI, Laurence et al
in XXIVth Belgian Week of Gastroenterology 2012 - Abstract book (2012)Detailed reference viewed: 51 (7 ULg)
Rheumatoid arthritis and pregnancy: evolution of disease activity and pathophysiological considerations for drug use
; ; Geenen, Vincent et al
in Rheumatology (2011)
It has long been known that pregnancy and childbirth have a profound effect on the disease activity of rheumatic diseases. For clinicians, the management of patients with RA wishing to become pregnant ... [more ▼]
It has long been known that pregnancy and childbirth have a profound effect on the disease activity of rheumatic diseases. For clinicians, the management of patients with RA wishing to become pregnant involves the challenge of keeping disease activity under control and adequately adapting drug therapy during pregnancy and post-partum. This article aims to summarize the current evidence on the evolution of RA disease activity during and after pregnancy and the use of anti-rheumatic drugs around this period. Of recent interest is the potential use of anti-TNF compounds in the preconception period and during pregnancy. Accumulating experience with anti-TNF therapy in other immune-mediated inflammatory diseases, such as Crohn’s disease, provides useful insights for the use of TNF blockade in pregnant women with RA, or RA patients wishing to become pregnant. [less ▲]Detailed reference viewed: 79 (3 ULg)
Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47.
; ; et al
in Nature Genetics (2011), 43(3), 246-52
Genome-wide association studies and candidate gene studies in ulcerative colitis have identified 18 susceptibility loci. We conducted a meta-analysis of six ulcerative colitis genome-wide association ... [more ▼]
Genome-wide association studies and candidate gene studies in ulcerative colitis have identified 18 susceptibility loci. We conducted a meta-analysis of six ulcerative colitis genome-wide association study datasets, comprising 6,687 cases and 19,718 controls, and followed up the top association signals in 9,628 cases and 12,917 controls. We identified 29 additional risk loci (P < 5 x 10(-8)), increasing the number of ulcerative colitis-associated loci to 47. After annotating associated regions using GRAIL, expression quantitative trait loci data and correlations with non-synonymous SNPs, we identified many candidate genes that provide potentially important insights into disease pathogenesis, including IL1R2, IL8RA-IL8RB, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1. The total number of confirmed inflammatory bowel disease risk loci is now 99, including a minimum of 28 shared association signals between Crohn's disease and ulcerative colitis. [less ▲]Detailed reference viewed: 41 (11 ULg)
Laparoscopic antireflux surgery vs esomeprazole treatment for chronic GERD: the LOTUS randomized clinical trial.
; ; et al
in JAMA : Journal of the American Medical Association (2011), 305(19), 1969-77
CONTEXT: Gastroesophageal reflux disease (GERD) is a chronic, relapsing disease with symptoms that have negative effects on daily life. Two treatment options are long-term medication or surgery. OBJECTIVE ... [more ▼]
CONTEXT: Gastroesophageal reflux disease (GERD) is a chronic, relapsing disease with symptoms that have negative effects on daily life. Two treatment options are long-term medication or surgery. OBJECTIVE: To evaluate optimized esomeprazole therapy vs standardized laparoscopic antireflux surgery (LARS) in patients with GERD. DESIGN, SETTING, AND PARTICIPANTS: The LOTUS trial, a 5-year exploratory randomized, open, parallel-group trial conducted in academic hospitals in 11 European countries between October 2001 and April 2009 among 554 patients with well-established chronic GERD who initially responded to acid suppression. A total of 372 patients (esomeprazole, n = 192; LARS, n = 180) completed 5-year follow-up. Interventions Two hundred sixty-six patients were randomly assigned to receive esomeprazole, 20 to 40 mg/d, allowing for dose adjustments; 288 were randomly assigned to undergo LARS, of whom 248 actually underwent the operation. MAIN OUTCOME MEASURE: Time to treatment failure (for LARS, defined as need for acid suppressive therapy; for esomeprazole, inadequate symptom control after dose adjustment), expressed as estimated remission rates and analyzed using the Kaplan-Meier method. RESULTS: Estimated remission rates at 5 years were 92% (95% confidence interval [CI], 89%-96%) in the esomeprazole group and 85% (95% CI, 81%-90%) in the LARS group (log-rank P = .048). The difference between groups was no longer statistically significant following best-case scenario modeling of the effects of study dropout. The prevalence and severity of symptoms at 5 years in the esomeprazole and LARS groups, respectively, were 16% and 8% for heartburn (P = .14), 13% and 2% for acid regurgitation (P < .001), 5% and 11% for dysphagia (P < .001), 28% and 40% for bloating (P < .001), and 40% and 57% for flatulence (P < .001). Mortality during the study was low (4 deaths in the esomeprazole group and 1 death in the LARS group) and not attributed to treatment, and the percentages of patients reporting serious adverse events were similar in the esomeprazole group (24.1%) and in the LARS group (28.6%). CONCLUSION: This multicenter clinical trial demonstrated that with contemporary antireflux therapy for GERD, either by drug-induced acid suppression with esomeprazole or by LARS, most patients achieve and remain in remission at 5 years. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00251927. [less ▲]Detailed reference viewed: 33 (1 ULg)
The efficacy of shortening the dosing interval to once every six weeks in Crohn's patients losing response to maintenance dose of infliximab.
; ; et al
in Alimentary Pharmacology & Therapeutics (2011), 33(3), 349-57
Background Patients treated with infliximab for Crohn's disease (CD) frequently require intensified dosage due to loss of response. There are scant data regarding the efficacy of shortening the dosing ... [more ▼]
Background Patients treated with infliximab for Crohn's disease (CD) frequently require intensified dosage due to loss of response. There are scant data regarding the efficacy of shortening the dosing interval to 6 weeks. Aim We sought to investigate the efficacy of a once every 6 weeks' strategy compared with dose-doubling. Methods This work was a multicentre retrospective study of infliximab-treated CD patients who required dose escalation. The clinical outcome of patients treated by intensification to 5 mg/kg/6 weeks (6-week group) was compared with the outcome of patients whose infliximab was double-dosed (10 mg/kg/8 weeks or 5 mg/kg/4 weeks). Results Ninety-four patients (mean age: 29.8 years) were included in the study, 55 (59%) in the 6-week group and 39 (41%) in the double-dose group. Demographics and disease characteristics were similar between the two groups, although patients with re-emerging symptoms 5-7 weeks postinfusion were more likely to receive 5 mg/kg/6 weeks dosing (OR: 3.4, 95% CI: 1.4-8.8, P < 0.01). Early response to dose-intensification occurred in 69% of patients in the 6-week group and 67% in the double-dose group (P = N.S.). Regained response was maintained for 12 months in 40% compared with 29% of the patients respectively (P = N.S.). Conclusion In CD patients who lost response to standard infliximab dose, especially when symptoms re-emerge 5-7 weeks postinfusion, shortening the dosing interval to 6 weeks appears to be at least as effective as doubling the dose to 10 mg/kg or halving the infusion intervals to once in 4 weeks. [less ▲]Detailed reference viewed: 27 (6 ULg)
Resequencing of positional candidates identifies low frequency IL23R coding variants protecting against inflammatory bowel disease.
Momozawa, Yukihide ; Mni, Myriam ; Nakamura, Kayo et al
in Nature Genetics (2011), 43(1), 43-7
Genome-wide association studies (GWAS) have identified dozens of risk loci for many complex disorders, including Crohn's disease. However, common disease-associated SNPs explain at most approximately 20 ... [more ▼]
Genome-wide association studies (GWAS) have identified dozens of risk loci for many complex disorders, including Crohn's disease. However, common disease-associated SNPs explain at most approximately 20% of the genetic variance for Crohn's disease. Several factors may account for this unexplained heritability, including rare risk variants not adequately tagged thus far in GWAS. That rare susceptibility variants indeed contribute to variation in multifactorial phenotypes has been demonstrated for colorectal cancer, plasma high-density lipoprotein cholesterol levels, blood pressure, type 1 diabetes, hypertriglyceridemia and, in the case of Crohn's disease, for NOD2 (refs. 14,15). Here we describe the use of high-throughput resequencing of DNA pools to search for rare coding variants influencing susceptibility to Crohn's disease in 63 GWAS-identified positional candidate genes. We identify low frequency coding variants conferring protection against inflammatory bowel disease in IL23R, but we conclude that rare coding variants in positional candidates do not make a large contribution to inherited predisposition to Crohn's disease. [less ▲]Detailed reference viewed: 113 (42 ULg)
Thiopurine metabolites and TPMT activity measurement in inflammatory bowel disease.
in Alimentary Pharmacology & Therapeutics (2011), 34(9), 1138-9Detailed reference viewed: 13 (1 ULg)