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Crohn's and TNF

S Singh, M Fumery, W J Sandborn, M H Murad
BACKGROUND: There are limited data to inform positioning of agents for treating moderate-severe Crohn's disease (CD). AIM: We assessed comparative efficacy and safety of first-line (biologic-naïve) and second-line (prior exposure to anti-tumour necrosis factor [TNF]-α) agents) biologic therapy for moderate-severe CD, through a systematic review and network meta-analysis, and appraised quality of evidence (QoE) using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach...
June 19, 2018: Alimentary Pharmacology & Therapeutics
Christoffer Soendergaard, Jakob Benedict Seidelin, Casper Steenholdt, Ole Haagen Nielsen
Objectives: Characterise the circulating inflammatory cytokine pattern among patients failing consecutive anti-tumour necrosis factor (anti-TNF) and anti-integrin treatments to identify predictors of response. Methods: A retrospective single-centre cohort study of 28 patients with inflammatory bowel disease (IBD) receiving anti-integrin therapy (vedolizumab) subsequent to the failure of anti-TNF treatment was conducted. Blood samples were obtained immediately prior to initiation of vedolizumab therapy, and the response to treatment was evaluated after completion of the 14-week induction regimen...
2018: BMJ Open Gastroenterology
Weixun Zhou, Yan Huang, Jinping Lai, Jun Lu, Michael Feely, Xiuli Liu
An increasing number of drugs including monoclonal antibodies and small molecules, either anti-inflammatory or immunity-enhancing, have been developed to treat human diseases and the number of medications in these classes is likely to expand in the future. The two most commonly used categories of such therapies are the anti-inflammatory group (anti- tumor necrosis factor (TNF) α, anti-interleukins/interleukin receptors, and anti-integrin bodies) and the anti-tumoral agents (immune checkpoint inhibitors, anti-CD20, and anti-endothelial growth factor)...
June 2018: Gastroenterology Research
Arne Bokemeyer, Nicolas Tentrop, Peter J Barth, Frank Lenze, Karin Hengst, Johannes Kleinheinz, Dominik Bettenworth
BACKGROUND: Crohn's Disease (CD) is typically characterized by abdominal symptoms, however, besides gastrointestinal symptoms, CD patients may suffer from extraintestinal manifestations which are far less common and medical treatment can be challenging. CASE PRESENTATION: We report about a 34-year-old Crohn's Disease (CD) patient in clinical remission under adalimumab therapy who presented in the clinic for Cranio-Maxillo Surgery due to severe pain in the mandibular area...
June 18, 2018: BMC Gastroenterology
Abhijeet Yadav, Satya Kurada, Joshua Foromera, Kenneth R Falchuk, Joseph D Feuerstein
BACKGROUND: Long-term inflammatory complications of IPAA include Crohn's Disease (CD) or "CD-like" (CDL) condition. We performed a meta-analysis to evaluate the efficacy of anti-tumor necrosis factor (anti-TNF) with or without immunomodulator (IM) therapy in this group of patients. METHODS: Literature databases were searched from inception to October 4, 2017. Further searches using references from papers of interest were conducted and, abstracts from major GI conferences were searched...
May 30, 2018: Digestive and Liver Disease
Blanca Martínez Andrés, Violeta Sastre Lozano, José Francisco Sánchez Melgarejo
Sweet syndrome is a common extraintestinal manifestation in inflammatory bowel disease (IBD). In this research, a 42-year-old man case with colon Crohn's disease is been described. After failure with two anti-TNF therapies, in treatment with azathioprim, it was decided to start a therapeutic target change to Vedolizumab due to a severe outbreak refractory to corticosteroids. 24 hours after the infusion of the new drug, skin lesions appear along with leukocytes with neutrophilia, all suggestive of sweet syndrome later confirmed by histology...
June 14, 2018: Revista Española de Enfermedades Digestivas
Jianhui Liu, Honggang Wang, Yi Li, Peiliang Shi, Jianfeng Gong, Lili Gu, Weiming Zhu, Jieshou Li
Recent studies suggested that excessive Th1/17 cells concomitant with regulatory T cell deficiency might play important roles in Crohn's disease. Anti-CD52 mAb, which aims on CD52 antigen on mature immunocytes, has both T cell depletion and immunosuppressive activities. In this study, we evaluated the therapeutic effects and possible mechanisms of anti-CD52 treatment on interleukin-10 deficient mouse. Anti-mouse CD52 mAb was administered to C3H.IL-10-/- mice intraperitoneally 20μg per week for 2 weeks. The disease activity index, body weight, the histological grading of colitis, and levels of TNF-α, IFN-γ, IL-17 and IL-6 in colon were quantified after treatment...
June 13, 2018: Biological & Pharmaceutical Bulletin
Deenaz Zaidi, Hien Q Huynh, Matthew W Carroll, Shairaz Baksh, Eytan Wine
Purpose: A significant feature of pediatric inflammatory bowel diseases (IBD), which include Crohn disease (CD), and ulcerative colitis (UC), is failure to suppress inflammation. The inability to regulate inflammation renders a major challenge toward establishing effective treatments in IBD. Nuclear factor kappa-light-chain-enhancer of activated B-cells-induced inflammation is inhibited by A20 through interactions with TAX1BP1 (Tax1-binding protein 1) and A20-binding inhibitor of NF-κβ activation (ABIN)-1 (A20 binding and inhibitor of NF-κβ) and upon phosphorylation by inhibitor of nuclear factor kappa-β kinase subunit beta (IKKβ), which stabilizes it...
2018: Clinical and Experimental Gastroenterology
Xu-Feng Pei, Long-Lei Cao, Fang Huang, Xu Qiao, Jie Yu, Hui Ye, Chang-Lei Xi, Qi-Chang Zhou, Guo-Fei Zhang, Zhi-Lin Gong
OBJECTIVE: miR-22 is known to be involved in the pathogenesis of several autoimmune diseases, but it remains unclear whether miR-22 is associated with inflammatory intestinal disease (IBD). METHODS: The patients with ulcerative colitis (UC) and Crohn's disease (CD) were enrolled in this study. After the CD4+ T cells from healthy controls and active IBD patients were isolated and then transfected with miR-22 mimics/inhibitors, Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to measure expressions of miR-22, HDAC4, specific transcription factors in intestinal mucosa tissue and CD4+ T cells, while enzyme-linked immuno sorbent assay (ELISA) to detect expressions of inflammatory cytokines in PB...
April 22, 2018: Pathology, Research and Practice
Tetsuya Takagawa, Atsushi Kitani, Ivan Fuss, Beth Levine, Steven R Brant, Inga Peter, Masaki Tajima, Shiro Nakamura, Warren Strober
The LRRK2/MUC19 gene region constitutes a high-risk genetic locus for the occurrence of both inflammatory bowel diseases (IBDs) and Parkinson's disease. We show that dendritic cells (DCs) from patients with Crohn's disease (CD) and lymphoblastoid cell lines derived from patients without CD but bearing a high-risk allele (rs11564258) at this locus as heterozygotes exhibited increased LRRK2 expression in vitro. To investigate the immunological consequences of this increased LRRK2 expression, we conducted studies in transgenic mice overexpressing Lrrk2 and showed that these mice exhibited more severe colitis induced by dextran sodium sulfate (DSS) than did littermate control animals...
June 6, 2018: Science Translational Medicine
Georgia Melagraki, Georgios Leonis, Evangelos Ntougkos, Vagelis Rinotas, Christos Papaneophytou, Thomas Mavromoustakos, George Kontopidis, Eleni Douni, George Kollias, Antreas Afantitis
The overexpression of Tumor Necrosis Factor (TNF) is directly related to the development of several autoimmune diseases, such as rheumatoid and psoriatic arthritis, inflammatory bowel disease, Crohn's disease, refractory asthma, and multiple sclerosis. Receptor activator of nuclear factor kappa-B ligand (RANKL) belongs to the TNF family, and is the primary mediator of osteoclast-induced bone resorption through interaction with its receptor RANK. The function of RANKL is physiologically inhibited by the action of osteoprotegerin (OPG), which is a decoy receptor that binds to RANKL and prevents the process of osteoclastogenesis...
June 6, 2018: Current Topics in Medicinal Chemistry
J M Bae, H H Lee, B-I Lee, K-M Lee, S H Eun, M-L Cho, J S Kim, J M Park, Y-S Cho, I S Lee, S W Kim, H Choi, M-G Choi
BACKGROUND: There are increasing reports of paradoxical psoriasiform diseases secondary to anti-tumour necrosis factor (TNF) agents. AIMS: To determine the risks of paradoxical psoriasiform diseases secondary to anti-TNF agents in patients with inflammatory bowel disease (IBD). METHODS: A nationwide population study was performed using the Korea National Health Insurance Claim Data. A total of 50 502 patients with IBD were identified between 2007 and 2016...
June 5, 2018: Alimentary Pharmacology & Therapeutics
Mauricio Javier Olivares-Morales, Marjorie Katherine De La Fuente, Karen Dubois-Camacho, Daniela Parada, David Diaz-Jiménez, Alejandro Torres-Riquelme, Xiaojiang Xu, Nayaret Chamorro-Veloso, Rodrigo Naves, Maria-Julieta Gonzalez, Rodrigo Quera, Carolina Figueroa, John Anthony Cidlowski, Roberto Mauricio Vidal, Marcela Alejandra Hermoso
Crohn's disease (CD) is a chronic inflammatory bowel disorder characterized by deregulated inflammation triggered by environmental factors. Notably, adherent-invasive Escherichia coli (AIEC), a bacterium with the ability to survive within macrophages is believed to be one of such factors. Glucocorticoids are the first line treatment for CD and to date, it is unknown how they affect bactericidal and inflammatory properties of macrophages against AIEC. The aim of this study was to evaluate the impact of glucocorticoid treatment on AIEC infected macrophages...
2018: Frontiers in Immunology
Ryoki Takahashi, Takayasu Noguchi, Yoko Mizoguchi, Tadashi Shimoyama, Teruko Nakazawa, Tohru Ikuta
Despite the recent development of biological modifiers for inflammatory bowel diseases (IBD), there continues to be considerable interest in fermented medicines because of its negligible adverse effects. We previously showed that the synbiotic Gut Working Tablet (GWT) alleviates experimental colitis. Here we show that GWT is capable of ameliorating jejunoileal mucosal injury, which is frequently seen with IBD. We created experimental jejunoileal mucositis in rats by injection of methotrexate (MTX) which increases intestinal permeability, a hallmark finding of IBD...
2018: BioMed Research International
Eirini Filidou, Vasilis Valatas, Ioannis Drygiannakis, Konstantinos Arvanitidis, Stergios Vradelis, Georgios Kouklakis, George Kolios, Giorgos Bamias
Background: Colonic subepithelial myofibroblasts (cSEMFs) are mesenchymal cells with a pivotal role in the pathophysiology of Crohn's disease (CD) fibrosis. Here, we demonstrate for the first time a complete expression mapping of cytokine receptors, implicated in inflammatory bowel diseases, in primary human cSEMFs and how pro-inflammatory cytokines regulate this expression. Furthermore, we show the effect of Th1-, Th2-, Th17- and Treg-related cytokines on a fibrosis-related phenotype of cSEMFs...
June 1, 2018: Inflammatory Bowel Diseases
Dan Turner, Frank M Ruemmele, Esther Orlanski-Meyer, Anne M Griffiths, Javier Martin de Carpi, Jiri Bronsky, Gabor Veres, Marina Aloi, Caterina Strisciuglio, Christian P Braegger, Amit Assa, Claudio Romano, Séamus Hussey, Michael Stanton, Mikko Pakarinen, Lissy de Ridder, Konstantinos Katsanos, Nick Croft, Victor Navas-López, David C Wilson, Sally Lawrence, Richard K Russell
BACKGROUND: The contemporary management of ambulatory ulcerative colitis (UC) continues to be challenging with ∼20% of children needing a colectomy within childhood years. We thus aimed to standardize daily treatment of paediatric UC and inflammatory bowel diseases (IBD)-unclassified through detailed recommendations and practice points. METHODS: These guidelines are a joint effort of the European Crohn's and Colitis Organization (ECCO) and the Paediatric IBD Porto group of European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN)...
May 30, 2018: Journal of Pediatric Gastroenterology and Nutrition
Heike Schmitt, Ulrike Billmeier, Walburga Dieterich, Timo Rath, Sophia Sonnewald, Stephen Reid, Simon Hirschmann, Kai Hildner, Maximilian J Waldner, Jonas Mudter, Arndt Hartmann, Robert Grützmann, Clemens Neufert, Tino Münster, Markus F Neurath, Raja Atreya
OBJECTIVE: Anti-tumour necrosis factor (TNF) antibodies are successfully used for treatment of Crohn's disease. Nevertheless, approximately 40% of patients display failure to anti-TNF therapy. Here, we characterised molecular mechanisms that are associated with endoscopic resistance to anti-TNF therapy. DESIGN: Mucosal and blood cells were isolated from patients with Crohn's disease prior and during anti-TNF therapy. Cytokine profiles, cell surface markers, signalling proteins and cell apoptosis were assessed by microarray, immunohistochemistry, qPCR, ELISA, whole organ cultures and FACS...
May 30, 2018: Gut
Jesus K Yamamoto-Furusho
PURPOSE OF REVIEW: Treatment of inflammatory bowel disease (IBD) patients can vary depending on the degree of response, lack of response or intolerance to conventional or biological agents aimed at blocking various cytokines or integrins. Recent therapies targeting several cytokines were reviewed to evaluate efficacy in IBD patients. RECENT FINDINGS: Ustekinumab is an interleukin inhibitor which blocks the p40 subunit of IL-12 and IL-23 axis and is already approved for the treatment of Crohn's disease patients, specially those who had inadequate response or intolerance to conventional treatment with anti-TNF-α agents...
July 2018: Current Opinion in Gastroenterology
B Bhoyrul, C Lyon
BACKGROUND AND AIMS Vulval Crohn disease (VCD) is a rare extra-intestinal cutaneous manifestation of Crohn disease (CD). VCD is often unrecognised and misdiagnosed and can be difficult to treat. The aim of the study was to describe the clinical presentation, associated features and response to treatment modalities in patients with VCD. METHODS: A prospective review of patients with VCD who were referred to our specialist dermatology clinic from 2003 to 2017 was performed. Data on age at diagnosis, presenting signs, associated features and response to treatment was collected...
May 29, 2018: Journal of Gastroenterology and Hepatology
W J Sandborn, P Rutgeerts, C Gasink, D Jacobstein, B Zou, J Johanns, B E Sands, S B Hanauer, S Targan, S Ghosh, W J S de Villiers, J-F Colombel, B G Feagan
BACKGROUND: In Phase 3 studies of ustekinumab, a fully human monoclonal IL-12/23p40 antibody approved for moderate-to-severe Crohn's disease, patients entered a long-term extension after completing 8 weeks of induction and 44 weeks of maintenance treatment. Efficacy through 92 weeks and safety through 96 weeks of IM-UNITI maintenance are reported. METHODS: UNITI-1 (TNF-antagonist failures) and UNITI-2 (conventional therapy failures) patients (N = 1281) entered IM-UNITI, including 397 ustekinumab intravenous induction responders randomised to subcutaneous ustekinumab 90 mg every 12 weeks, every 8 weeks, or placebo and 884 nonrandomised patients...
May 24, 2018: Alimentary Pharmacology & Therapeutics
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