Vaccinations in patients with immune-mediated inflammatory diseases.
; Moutschen, Michel ; et al
in Rheumatology (2010), 49(10), 1815-27
Patients with immune-mediated inflammatory diseases (IMID) such as RA, IBD or psoriasis, are at increased risk of infection, partially because of the disease itself, but mostly because of treatment with ... [more ▼]
Patients with immune-mediated inflammatory diseases (IMID) such as RA, IBD or psoriasis, are at increased risk of infection, partially because of the disease itself, but mostly because of treatment with immunomodulatory or immunosuppressive drugs. In spite of their elevated risk for vaccine-preventable disease, vaccination coverage in IMID patients is surprisingly low. This review summarizes current literature data on vaccine safety and efficacy in IMID patients treated with immunosuppressive or immunomodulatory drugs and formulates best-practice recommendations on vaccination in this population. Especially in the current era of biological therapies, including TNF-blocking agents, special consideration should be given to vaccination strategies in IMID patients. Clinical evidence indicates that immunization of IMID patients does not increase clinical or laboratory parameters of disease activity. Live vaccines are contraindicated in immunocompromized individuals, but non-live vaccines can safely be given. Although the reduced quality of the immune response in patients under immunotherapy may have a negative impact on vaccination efficacy in this population, adequate humoral response to vaccination in IMID patients has been demonstrated for hepatitis B, influenza and pneumococcal vaccination. Vaccination status is best checked and updated before the start of immunomodulatory therapy: live vaccines are not contraindicated at that time and inactivated vaccines elicit an optimal immune response in immunocompetent individuals. [less ▲]Detailed reference viewed: 45 (8 ULg)
The second European evidence-based Consensus on the diagnosis and management of Crohn's disease: Definitions and diagnosis.
; ; et al
in Journal of Crohn’s and Colitis [=JCC] (2010), 4(1), 7-27Detailed reference viewed: 22 (1 ULg)
Severe skin lesions cause patients with inflammatory bowel disease to discontinue anti-tumor necrosis factor therapy.
; ; et al
in Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of The American Gastroenterological Association (2010), 8(12), 1048-55
BACKGROUND & AIMS: Psoriasiform and eczematiform lesions are associated with anti-tumor necrosis factor (TNF)-alpha therapies. We assessed clinical characteristics, risk factors, and outcomes of skin ... [more ▼]
BACKGROUND & AIMS: Psoriasiform and eczematiform lesions are associated with anti-tumor necrosis factor (TNF)-alpha therapies. We assessed clinical characteristics, risk factors, and outcomes of skin disease in patients with inflammatory bowel diseases that presented with psoriasiform and eczematiform lesions induced by anti-TNF-alpha agents. METHODS: We studied 85 patients (69 with Crohn's disease, 15 with ulcerative colitis, and 1 with indeterminate colitis; 62 women) with inflammatory skin lesions (62 psoriasiform and 23 eczematiform lesions). RESULTS: Twenty-four patients had a history of inflammatory skin lesions and 15 had a familial history of inflammatory skin disease. Locations of eczematiform lesions varied whereas scalp and flexural varieties were mostly psoriasiform. Skin lesions emerged but inflammatory bowel disease was quiescent in 69 patients following treatment with any type of anti-TNF-alpha agent (60 with infliximab, 20 with adalimumab, and 5 with certolizumab). Topical therapy resulted in partial or total remission in 41 patients. Patients with psoriasiform lesions that were resistant to topical therapy and that changed anti-TNF-alpha therapies once or twice developed recurring lesions. Overall, uncontrolled skin lesions caused 29 patients to stop taking TNF-alpha inhibitors. CONCLUSIONS: Inflammatory skin lesions following therapy with TNF-alpha inhibitors occurred most frequently among women and patients with a personal or familial history of inflammatory skin disease; lesions did not correlate with intestinal disease activity. Recurring and intense skin lesions caused 34% of patients in this study to discontinue use of anti-TNF-alpha agents. [less ▲]Detailed reference viewed: 30 (3 ULg)
Fibrin glue is effective healing perianal fistulas in patients with Crohn's disease.
; ; et al
in Gastroenterology (2010), 138(7), 2275-8122811
BACKGROUND & AIMS: Fibrin glue is a therapeutic for fistulas that activates thrombin to form a fibrin clot, which mechanically seals the fistula tract. We assessed the efficacy and safety of a ... [more ▼]
BACKGROUND & AIMS: Fibrin glue is a therapeutic for fistulas that activates thrombin to form a fibrin clot, which mechanically seals the fistula tract. We assessed the efficacy and safety of a heterologous fibrin glue that was injected into the fistula tracts of patients with Crohn's disease (ClinicalTrials.gov No. NCT00723047). METHODS: This multicenter, open-label, randomized controlled trial included patients with a Crohn's disease activity index < or =250 and fistulas between the anus (or low rectum) and perineum, vulva, or vagina, that drained for more than 2 months. Magnetic resonance imaging or endosonography was performed to assess fistula tracts and the absence of abscesses. Patients were stratified into groups with simple or complex fistulas and randomly assigned to receive fibrin glue injections (n = 36) or only observation (n = 41) after removal of setons. The primary end point was clinical remission at week 8, defined as the absence of draining, perianal pain, or abscesses. At week 8, a fibrin glue injection was offered to patients who were not in remission. RESULTS: Clinical remission was observed in 13 of the 34 patients (38%) of the fibrin glue group compared with 6 of the 37 (16%) in the observation group; these findings demonstrate the benefit of fibrin glue (odds ratio, 3.2; 95% confidence interval: 1.1-9.8; P = .04). The benefit seemed to be greater in patients with simple fistulas. Four patients in the fibrin glue group and 6 in the observation group had adverse events. CONCLUSIONS: Fibrin glue injection is a simple, effective, and well-tolerated therapeutic option for patients with Crohn's disease and perianal fistula tracts. [less ▲]Detailed reference viewed: 42 (0 ULg)
Report of the ECCO pathogenesis workshop on anti-TNF therapy failures in inflammatory bowel diseases: definitions, frequency and pharmacological aspects.
; ; Louis, Edouard et al
in Journal of Crohn’s and Colitis [=JCC] (2010), 4(4), 355-66
The first ECCO pathogenesis workshop focused on anti-TNF therapy failures in inflammatory bowel diseases (IBDs). The overall objective was to better understand and explore primary non response and loss of ... [more ▼]
The first ECCO pathogenesis workshop focused on anti-TNF therapy failures in inflammatory bowel diseases (IBDs). The overall objective was to better understand and explore primary non response and loss of response to anti-TNF agents in IBD. The outcome of this workshop is presented into two parts. This first section addresses definitions, frequency and pharmacological aspects of anti-TNF therapy failure, including pharmacokinetics of anti-TNF monoclonal antibodies and immune and non-immune mediated clearance of anti-TNF mAbs. The second section concerns the biological roles of TNF and TNF antagonists, including mechanisms of action of anti-TNF agents, and discuss hypothesis regarding their failures and phenomenon of paradoxical inflammation, including the potential role of TNF independent inflammatory pathways. [less ▲]Detailed reference viewed: 34 (0 ULg)
Do clinical factors help to predict disease course in inflammatory bowel disease?
Louis, Edouard ; Belaiche, Jacques ; Reenaers, Catherine
in World Journal of Gastroenterology (2010), 16(21), 2600-3
While therapeutic strategies able to change the natural history of the disease are developing, it is of major importance to have available predictive factors for aggressive disease to try and target these ... [more ▼]
While therapeutic strategies able to change the natural history of the disease are developing, it is of major importance to have available predictive factors for aggressive disease to try and target these therapeutic strategies. Clinical predictors have probably been the most broadly studied. In both Crohn's disease (CD) and ulcerative colitis (UC), age at diagnosis, disease location and smoking habit are currently the strongest predictors of disease course. A younger age at onset is associated with more aggressive disease both in CD and UC. Disease location in CD is associated with different types of complications: surgery and recurrence in upper gastrointestinal and proximal small bowel disease; and surgery in distal small bowel disease and peri-anal lesions in rectal disease. In UC, extensive colitis is clearly been associated with more severe disease. Finally, active smoking globally increases disease severity in CD but decreases it in UC. Besides these important factors, others may predispose to some specific disease evolution and complications, and are also reviewed in the present paper. [less ▲]Detailed reference viewed: 30 (6 ULg)
Should patients under long-term anti-TNF therapies be followed for tuberculosis contamination?
Reenaers, Catherine ; Belaiche, Jacques ; Louis, Edouard
in Inflammatory Bowel Diseases (2010), 16(8), 1271-2Detailed reference viewed: 23 (5 ULg)
Immunosuppressant combined with infliximab in Crohn's Disease: For 6 months, for 2 years, or forever?
in Inflammatory Bowel Diseases (2010)Detailed reference viewed: 14 (5 ULg)
Dissection moléculaire de la prédisposition innée aux maladies inflamatoires chroniques de l'intestin: liason génétique, gènes candidats et études d'association du génome entier.
Georges, Michel ; LIBIOULLE, Cécile ; Louis, Edouard
in Maladies inflamatoires chroniques de l'instestin. Progrès en hépatho-Gastroentérologie (2010)Detailed reference viewed: 29 (12 ULg)
Comparison of three methods for fractionation and enrichment of low molecular weight proteins for SELDI-TOF-MS differential analysis
De Bock, Muriel ; De Seny, Dominique ; Meuwis, Marie-Alice et al
in Talanta (2010), 82
In most diseases, the clinical need for serum/plasma markers has never been so crucial, not only for diagnosis, but also for the selection of the most efficient therapies, as well as exclusion of ... [more ▼]
In most diseases, the clinical need for serum/plasma markers has never been so crucial, not only for diagnosis, but also for the selection of the most efficient therapies, as well as exclusion of ineffective or toxic treatment. Due to the high sample complexity, prefractionation is essential for exploring the deep proteome and finding specific markers. In this study, three different sample preparation methods (i.e., highly abundant protein precipitation, restricted access materials (RAM) combined with IMAC chromatography and peptide ligand affinity beads) were investigated in order to select the best fractionation step for further differential proteomic experiments focusing on the LMW proteome (MW inferior to 40,000 Da). Indeed, the aim was not to cover the entire plasma/serum proteome, but to enrich potentially interesting tissue leakage proteins. These three methods were evaluated on their reproducibility, on the SELDI-TOF-MS peptide/protein peaks generated after fractionation and on the information supplied. The studied methods appeared to give complementary information and presented good reproducibility (below 20%). Peptide ligand affinity beads were found to provide efficient depletion of HMW proteins and peak enrichment in protein/peptide profiles. [less ▲]Detailed reference viewed: 85 (19 ULg)
Génomique des maladies inflammatoires intestinales
Louis, Edouard ; Libioulle, Cécile ; Reenaers, Catherine et al
in Revue Médicale de Liège (2009), 64Detailed reference viewed: 134 (21 ULg)
The Role of PET/CT in the Monitoring and Diagnosis of Pediatric Inflammatory Bowel Disease.
Hustinx, Roland ; Louis, Edouard
in PET Clinics (2009), 3Detailed reference viewed: 23 (4 ULg)
Anti-TNF and Crohn's Disease: When Should We Stop?
Louis, Edouard ; Belaiche, Jacques ; Reenaers, Catherine
in Current Drug Targets (2009), 11(2), 148-51
When to stop anti-TNF therapy in Crohn's disease (CD)? This is a very important question both for patients and physicians. There is no published evidence to clearly and definitely answer this question ... [more ▼]
When to stop anti-TNF therapy in Crohn's disease (CD)? This is a very important question both for patients and physicians. There is no published evidence to clearly and definitely answer this question. However data on natural history of CD, long term safety of biologics, outcome after immunosuppressors (IS) cessation and some preliminary studies on biologics cessation may help us to discuss this topic. One could argue that there is currently no good reason to stop anti-TNF therapy in a patient who is in stable remission and tolerate this drug very well. The decision to stop an anti-TNF treatment is thus currently based on a compromise between the benefits/risks and cost of such long term treatment. While it appears now clearly that prolonged anti-TNF therapy is associated with favourable outcome with sustained remission, reduced surgeries and hospitalisation as well as absence of significant increase in mortality or cancers, the cost-effectiveness which is probably favourable for short and mid-term treatment (up to one year), may be less optimal for very long term treatment. In this perspective however, prospective studies should be performed to adequately assess long term evolution, disease outcome, safety and global cost of strategies based on treatment reduction with IS maintenance alone or even full treatment cessation. [less ▲]Detailed reference viewed: 68 (6 ULg)
Common variants in the NLRP3 region contribute to Crohn's disease susceptibility.
; ; et al
in Nature Genetics (2009), 41(1), 71-6
We used a candidate gene approach to identify a set of SNPs, located in a predicted regulatory region on chromosome 1q44 downstream of NLRP3 (previously known as CIAS1 and NALP3) that are associated with ... [more ▼]
We used a candidate gene approach to identify a set of SNPs, located in a predicted regulatory region on chromosome 1q44 downstream of NLRP3 (previously known as CIAS1 and NALP3) that are associated with Crohn's disease. The associations were consistently replicated in four sample sets from individuals of European descent. In the combined analysis of all samples (710 father-mother-child trios, 239 cases and 107 controls), these SNPs were strongly associated with risk of Crohn's disease (P(combined) = 3.49 x 10(-9), odds ratio = 1.78, confidence interval = 1.47-2.16 for rs10733113), reaching a level consistent with the stringent significance thresholds imposed by whole-genome association studies. In addition, we observed significant associations between SNPs in the associated regions and NLRP3 expression and IL-1beta production. Mutations in NLRP3 are known to be responsible for three rare autoinflammatory disorders. These results suggest that the NLRP3 region is also implicated in the susceptibility of more common inflammatory diseases such as Crohn's disease. [less ▲]Detailed reference viewed: 99 (19 ULg)
Genetic variation in the familial Mediterranean fever gene (MEFV) and risk for Crohn's disease and ulcerative colitis.
; ; Louis, Edouard et al
in PLoS ONE (2009), 4(9), 7154
BACKGROUND AND AIMS: The familial Mediterranean fever (FMF) gene (MEFV) encodes pyrin, a major regulator of the inflammasome platform controlling caspase-1 activation and IL-1beta processing. Pyrin has ... [more ▼]
BACKGROUND AND AIMS: The familial Mediterranean fever (FMF) gene (MEFV) encodes pyrin, a major regulator of the inflammasome platform controlling caspase-1 activation and IL-1beta processing. Pyrin has been shown to interact with the gene product of NLRP3, NALP3/cryopyrin, also an important active member of the inflammasome. The NLRP3 region was recently reported to be associated with Crohn's disease (CD) susceptibility. We therefore sought to evaluate MEFV as an inflammatory bowel disease (IBD) susceptibility gene. METHODOLOGY AND RESULTS: MEFV colonic mucosal gene expression was significantly increased in experimental colitis mice models (TNBS p<0.0003; DSS p<0.006), in biopsies from CD (p<0.02) and severe ulcerative colitis (UC) patients (p<0.008). Comprehensive genetic screening of the MEFV region in the Belgian exploratory sample set (440 CD trios, 137 UC trios, 239 CD cases, 96 UC cases, and 107 healthy controls) identified SNPs located in the MEFV 5' haplotype block that were significantly associated with UC (rs224217; p = 0.003; A allele frequency: 56% cases, 45% controls), while no CD associations were observed. Sequencing and subsequent genotyping of variants located in this associated haplotype block identified three synonymous variants (D102D/rs224225, G138G/rs224224, A165A/rs224223) and one non-synonymous variant (R202Q/rs224222) located in MEFV exon 2 that were significantly associated with UC (rs224222: p = 0.0005; A allele frequency: 32% in cases, 23% in controls). No consistent associations were observed in additional Canadian (256 CD trios, 91 UC trios) and Scottish (495 UC, 370 controls) sample sets. We note that rs224222 showed marginal association (p = 0.012; G allele frequency: 82% in cases, 70% in controls) in the Canadian sample, but with a different risk allele. None of the NLRP3 common variants were associated with UC in the Belgian-Canadian UC samples and no significant interactions were observed between NLRP3 and MEFV that could explain the observed flip-flop of the rs224222 risk allele. CONCLUSION: The differences in association levels observed between the sample sets may be a consequence of distinct founder effects or of the relative small sample size of the cohorts evaluated in this study. However, the results suggest that common variants in the MEFV region do not contribute to CD and UC susceptibility. [less ▲]Detailed reference viewed: 70 (14 ULg)
Common variants at five new loci associated with early-onset inflammatory bowel disease.
; ; et al
in Nature Genetics (2009), 41(12), 1335-40
The inflammatory bowel diseases (IBD) Crohn's disease and ulcerative colitis are common causes of morbidity in children and young adults in the western world. Here we report the results of a genome-wide ... [more ▼]
The inflammatory bowel diseases (IBD) Crohn's disease and ulcerative colitis are common causes of morbidity in children and young adults in the western world. Here we report the results of a genome-wide association study in early-onset IBD involving 3,426 affected individuals and 11,963 genetically matched controls recruited through international collaborations in Europe and North America, thereby extending the results from a previous study of 1,011 individuals with early-onset IBD. We have identified five new regions associated with early-onset IBD susceptibility, including 16p11 near the cytokine gene IL27 (rs8049439, P = 2.41 x 10(-9)), 22q12 (rs2412973, P = 1.55 x 10(-9)), 10q22 (rs1250550, P = 5.63 x 10(-9)), 2q37 (rs4676410, P = 3.64 x 10(-8)) and 19q13.11 (rs10500264, P = 4.26 x 10(-10)). Our scan also detected associations at 23 of 32 loci previously implicated in adult-onset Crohn's disease and at 8 of 17 loci implicated in adult-onset ulcerative colitis, highlighting the close pathogenetic relationship between early- and adult-onset IBD. [less ▲]Detailed reference viewed: 96 (17 ULg)
Dyspeptic symptoms in the general population: a factor and cluster analysis of symptom groupings.
; ; Louis, Edouard et al
in Neurogastroenterology & Motility : The Official Journal of the European Gastrointestinal Motility Society (2009), 21(4), 378-88
Both dyspeptic and gastro-oesophageal reflux-like symptoms are frequent in the general population, but their degree of overlap is unknown. In severe functional dyspepsia (FD), symptoms are organized in ... [more ▼]
Both dyspeptic and gastro-oesophageal reflux-like symptoms are frequent in the general population, but their degree of overlap is unknown. In severe functional dyspepsia (FD), symptoms are organized in factors associated with pathophysiological mechanisms. The aims of this study were: (i) to assess the prevalence of dyspeptic symptoms with and without overlapping reflux symptoms in the general population and their impact on daily life and on healthcare utilization; and (ii) to compare symptom groupings in the general population to FD patients. A total of 2025 subjects, representative of the Belgian general population, were used in this study. The subjects were submitted to a questionnaire with validated questions on their dyspeptic and reflux symptoms and with evaluators of impact on daily life and use of healthcare resources. Significant dyspeptic symptoms were found in 417 (20.6%). Overlapping reflux symptoms were present in 141 (33.8%). In this group, symptoms were more frequent and more severe. Dyspeptic symptoms induced weight loss (12.7%) and absenteeism (12.4%), affected daily life (61.2%) and generated use of healthcare resources, such as medical consultations (61.4%) and medication (70.9%). Factor analysis revealed a three-component structure with factor 1 including fullness, bloating and early satiety, factor 2 including nausea and vomiting and factor 3 including discomfort, pain, belching and reflux. If forced in a four-factor model, the analysis separates belching as independent factor. Dyspeptic symptoms are frequent in the general population, with overlapping reflux symptoms and increased symptom burden in about a third. [less ▲]Detailed reference viewed: 48 (3 ULg)
Le depistage generalise du cancer colorectal: une absolue necessite et une realite imminente en Communaute francaise.
Polus, Marc ; Montrieux, Christian ; Giet, Didier et al
in Revue Médicale de Liège (2009), 64(2), 96-102
Colorectal cancer is a real problem of public health. Screening is an absolute necessity. An ambitious program of screening is launched in the French Community. Faecal occult blood test will be proposed ... [more ▼]
Colorectal cancer is a real problem of public health. Screening is an absolute necessity. An ambitious program of screening is launched in the French Community. Faecal occult blood test will be proposed to average risk patients in the general population. A total colonoscopy will be performed if FOBT is positive. First step colonoscopy will be proposed to high or very high risk patients. General practitioners are in the core of the multi-disciplinary program. [less ▲]Detailed reference viewed: 102 (13 ULg)
Tailoring the treatment to the individual in Crohn's disease
Louis, Edouard ; Belaiche, Jacques ; Reenaers, Catherine
in Therapeutic advances in Gastroenterology (2009), 2Detailed reference viewed: 21 (2 ULg)