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Crohn's and TNF

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https://www.readbyqxmd.com/read/28542350/t0001-a-variant-of-tnfr2-fc-fusion-protein-exhibits-improved-fc-effector-functions-through-increased-binding-to-membrane-bound-tnf%C3%AE
#1
Yijun Shen, Gang Li, Chunying Gu, Ben Chen, Aihua Chen, Hua Li, Bei Gao, Chencai Liang, Jingsong Wu, Tong Yang, Li Jin, Yong Su
T0001 is a recombinant human TNFR-Fc fusion protein mutant; it exhibits higher affinity to TNFα than etanercept and is now being tested in a Phase 1 study in China (ClinicalTrials.gov Identifier: NCT02481180). T0001 can inhibit the binding of soluble TNFα (sTNFα) or membrane-bound TNFα (mTNFα) to TNF receptors. When bound to mTNFα, the Fc-bearing TNFα antagonists have the potential to induce Fc-mediated effects, such as antibody-dependent cellular cytotoxicity (ADCC) and complement-mediated cytotoxicity (CDC) as well as outside-to-inside signals (apoptosis mainly)...
2017: PloS One
https://www.readbyqxmd.com/read/28542298/early-anti-tnf-immunomodulator-therapy-is-associated-with-better-long-term-clinical-outcomes-in-asian-patients-with-crohn-s-disease-with-poor-prognostic-factors
#2
Eun Hye Oh, Kyunghwan Oh, Minkyu Han, Hyungil Seo, Kiju Chang, Sun-Ho Lee, Gwang-Un Kim, Eun Mi Song, Myeongsook Seo, Ho-Su Lee, Sung Wook Hwang, Sang Hyoung Park, Dong-Hoon Yang, Kyung-Jo Kim, Jeong-Sik Byeon, Seung-Jae Myung, Suk-Kyun Yang, Byong Duk Ye
Although early treatment of Crohn's disease (CD) patients with anti-tumor necrosis factor (TNF) agents or immunomodulators (IMs) may improve long-term outcomes, especially those with poor prognostic factors, their effectiveness in Asians remains unclear. In this study, Korean patients with CD naïve to both intestinal surgery and intestinal complications, and with at least two risk factors for progression (diagnosis at age <40 years, systemic corticosteroid treatment <3 months after diagnosis, and perianal fistula at diagnosis) were retrospectively analyzed...
2017: PloS One
https://www.readbyqxmd.com/read/28528528/ustekinumab-a-review-in-moderate-to-severe-crohn-s-disease
#3
Yvette N Lamb, Sean T Duggan
Ustekinumab (Stelara(®)) has been recently approved in the EU and the USA as intravenous induction and subcutaneous maintenance therapy for adult patients with moderately to severely active Crohn's disease who have failed or were intolerant to treatment with immunomodulators, corticosteroids or at least one tumour necrosis factor (TNF) antagonist. Ustekinumab, a monoclonal antibody to the shared p40 subunit of the proinflammatory interleukin (IL)-12 and IL-23 cytokines, has a unique mechanism of action distinct from that of TNF antagonists...
May 20, 2017: Drugs
https://www.readbyqxmd.com/read/28523450/a-review-of-the-clinical-pharmacokinetics-pharmacodynamics-and-immunogenicity-of-vedolizumab
#4
REVIEW
Maria Rosario, Nathanael L Dirks, Catherine Milch, Asit Parikh, Michael Bargfrede, Tim Wyant, Eric Fedyk, Irving Fox
Vedolizumab is a humanized anti-α4β7 integrin monoclonal antibody that selectively blocks trafficking of memory T cells to inflamed gut tissue by inhibiting the α4β7-mucosal addressin cell adhesion molecule-1 (MAdCAM-1) interaction. Approved for treating patients with moderately to severely active ulcerative colitis (UC) or Crohn's disease (CD), vedolizumab is administered as a 300 mg intravenous infusion. Vedolizumab undergoes a rapid, saturable, non-linear, target-mediated elimination process at low concentrations and a slower, linear, non-specific elimination process at higher concentrations...
May 18, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28522957/crohn-s-disease-and-smoldering-multiple-myeloma-a-case-report-and-literature-review
#5
So Young Park, Jae Min Kim, Hyun Joon Kang, Minje Kim, Jae Joon Han, Chi Hoon Maeng, Sun Kyung Baek, Hwi-Joong Yoon, Si-Young Kim, Hyo Jong Kim
Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) that presents with abdominal pain, weight loss, and diarrhea. Although the etiology has not been fully elucidated, both environmental and genetic causes are known to be involved. In chronic inflammatory conditions such as IBD, B lymphocytes are chronically stimulated, and they induce monoclonal expansion of plasma cells, sometimes resulting in monoclonal gammopathy of undetermined significance. Immunomodulators that are commonly used to control inflammation, such as tumor necrosis factor-α (TNF-α) blockers could increase the possibility of hematologic malignancy...
April 2017: Intestinal Research
https://www.readbyqxmd.com/read/28522944/preoperative-use-of-anti-tumor-necrosis-factor-therapy-in-crohn-s-disease-promises-and-pitfalls
#6
REVIEW
Paulo Gustavo Kotze, Subrata Ghosh, Willem A Bemelman, Remo Panaccione
Recent advances in medical and surgical therapy were achieved during the last two decades in the management of Crohn's disease (CD). Anti-tumor necrosis factor (anti-TNF) agents are widely used worldwide. However, a significant proportion of patients still need surgical resections. The impact of previous exposure to these agents on the perioperative and postoperative outcomes is still controversial. In this critical review, we aimed to position the strategy of intentional preoperative use of anti-TNF agents in the management of CD...
April 2017: Intestinal Research
https://www.readbyqxmd.com/read/28516874/long-term-effects-of-interleukin-17a-inhibition-with-secukinumab-in-active-ankylosing-spondylitis-3-year-efficacy-and-safety-results-from-an-extension-of-the-phase-3-measure-1-trial
#7
Xenofon Baraliakos, Alan J Kivitz, Atul A Deodhar, Jürgen Braun, James C Wei, Eumorphia Maria Delicha, Zsolt Talloczy, Brian Porter
OBJECTIVES: Secukinumab, a fully human anti-IL-17A monoclonal antibody, provided rapid and sustained improvements in signs and symptoms of ankylosing spondylitis (AS) over 2 years in the Phase 3 MEASURE 1 trial. Here, we report efficacy and safety after 3 years of treatment. METHODS: AS subjects completing 2 years of treatment every 4 weeks with subcutaneous secukinumab 150 or 75 mg (following intravenous loading or initial placebo treatment to 16/24 weeks) entered a separate 3-year extension study (NCT01863732)...
May 15, 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28509816/variations-in-health-insurance-policies-regarding-biologic-therapy-use-in-inflammatory-bowel-disease
#8
Abhijeet Yadav, Joshua Foromera, Ilana Feuerstein, Kenneth R Falchuk, Joseph D Feuerstein
BACKGROUND: The American Gastroenterological Association (AGA) has developed guidelines for the management of ulcerative colitis and Crohn's disease (CD) recommending anti-TNF therapy in moderate-severe disease. However, which drug is used is often dictated by insurance company policies. We sought to determine the insurance policy requirements prior to approval of biologic therapies. METHODS: Using the National Association of Insurance Commissioners report of the top 125 insurance companies by market share in 2014, we reviewed the first 50 that had online policies regarding anti-TNF and vedolizumab available...
June 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28509767/variations-in-health-insurance-policies-regarding-biologic-therapy-use-in-inflammatory-bowel-disease
#9
Abhijeet Yadav, Joshua Foromera, Ilana Feuerstein, Kenneth R Falchuk, Joseph D Feuerstein
BACKGROUND: The American Gastroenterological Association (AGA) has developed guidelines for the management of ulcerative colitis and Crohn's disease (CD) recommending anti-TNF therapy in moderate-severe disease. However, which drug is used is often dictated by insurance company policies. We sought to determine the insurance policy requirements prior to approval of biologic therapies. METHODS: Using the National Association of Insurance Commissioners report of the top 125 insurance companies by market share in 2014, we reviewed the first 50 that had online policies regarding anti-TNF and vedolizumab available...
May 15, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28505128/a-proposal-for-a-study-on-treatment-selection-and-lifestyle-recommendations-in-chronic-inflammatory-diseases-a-danish-multidisciplinary-collaboration-on-prognostic-factors-and-personalised-medicine
#10
Vibeke Andersen, Uffe Holmskov, Signe Bek Sørensen, Mohamad Jawhara, Karina W Andersen, Anette Bygum, Lone Hvid, Jakob Grauslund, Jimmi Wied, Henning Glerup, Ulrich Fredberg, Jan Alexander Villadsen, Søren Geill Kjær, Jan Fallingborg, Seyed A G R Moghadd, Torben Knudsen, Jacob Brodersen, Jesper Frøjk, Jens F Dahlerup, Ole Haagen Nielsen, Robin Christensen, Anders Bo Bojesen, Grith Lykke Sorensen, Steffen Thiel, Nils J Færgeman, Ivan Brandslund, Allan Stensballe, Erik Berg Schmidt, Andre Franke, David Ellinghaus, Philip Rosenstiel, Jeroen Raes, Berit Heitmann, Mette Boye, Charlotte Lindgaard Nielsen, Lars Werner, Jens Kjeldsen, Torkell Ellingsen
Chronic inflammatory diseases (CIDs), including Crohn's disease and ulcerative colitis (inflammatory bowel diseases, IBD), rheumatoid arthritis, psoriasis, psoriatic arthritis, spondyloarthritides, hidradenitis suppurativa, and immune-mediated uveitis, are treated with biologics targeting the pro-inflammatory molecule tumour necrosis factor-α (TNF) (i.e., TNF inhibitors). Approximately one-third of the patients do not respond to the treatment. Genetics and lifestyle may affect the treatment results. The aims of this multidisciplinary collaboration are to identify (1) molecular signatures of prognostic value to help tailor treatment decisions to an individual likely to initiate TNF inhibitor therapy, followed by (2) lifestyle factors that support achievement of optimised treatment outcome...
May 15, 2017: Nutrients
https://www.readbyqxmd.com/read/28502609/switching-from-originator-infliximab-to-biosimilar-ct-p13-compared-with-maintained-treatment-with-originator-infliximab-nor-switch-a-52-week-randomised-double-blind-non-inferiority-trial
#11
Kristin K Jørgensen, Inge C Olsen, Guro L Goll, Merete Lorentzen, Nils Bolstad, Espen A Haavardsholm, Knut E A Lundin, Cato Mørk, Jørgen Jahnsen, Tore K Kvien
BACKGROUND: TNF inhibitors have improved treatment of Crohn's disease, ulcerative colitis, spondyloarthritis, rheumatoid arthritis, psoriatic arthritis, and chronic plaque psoriasis, but are expensive therapies. The aim of NOR-SWITCH was to examine switching from originator infliximab to the less expensive biosimilar CT-P13 regarding efficacy, safety, and immunogenicity. METHODS: The study is a randomised, non-inferiority, double-blind, phase 4 trial with 52 weeks of follow-up...
May 11, 2017: Lancet
https://www.readbyqxmd.com/read/28477389/paradoxical-ulcerative-colitis-during-adalimumab-treatment-of-psoriasis-resolved-by-switch-to-ustekinumab
#12
A G A Kolios, L Biedermann, A Weber, A A Navarini, J Meier, A Cozzio, L E French
Here we report the case of a psoriasis patient who developed an ulcerative colitis (UC) most likely caused by Adalimumab. After cessation of Adalimumab, colitis improved significantly. However, since psoriasis worsened, the patient was switched to Ustekinumab which resulted in complete cessation of colitis. During the two-year follow-up under Ustekinumab therapy no further gastrointestinal complaints occurred. Paradoxical psoriasis manifestations in inflammatory bowel disease (IBD) under TNF-inhibitor therapy have been reported and rarely paradoxical IBD occurred (mostly Crohn's disease) in rheumatologic patients treated with Infliximab or Etanercept...
May 6, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/28470787/the-benefit-of-combination-therapy-depends-on-disease-phenotype-and-duration-in-crohn-s-disease
#13
A N Ananthakrishnan, A Sakuraba, E L Barnes, J Pekow, L Raffals, M D Long, R S Sandler
BACKGROUND: The impact of combination therapy on disease-related morbidity in patients with established Crohn's disease (CD) or ulcerative colitis (UC) remains to be well-defined. AIM: To examine the effect of combination therapy on disease outcomes in CD and UC. METHODS: Using a multicenter prospective cohort, we classified CD and UC patients as being on monotherapy with anti-TNF or on combination with an immunomodulator. The primary outcome was a composite of new IBD-related surgery, hospitalisations, penetrating complications, need for corticosteroids or new biological at 1 year...
May 3, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28463854/surgical-rates-in-the-era-of-biological-therapy-up-down-or-unchanged
#14
Pablo Olivera, Antonino Spinelli, Corinne Gower-Rousseau, Silvio Danese, Laurent Peyrin-Biroulet
PURPOSE OF REVIEW: The aim of this review is to summarize data regarding surgical trends in inflammatory bowel disease in the prebiologic and biologic era, with a focus on population-based studies and randomized controlled trials (RCTs). RECENT FINDINGS: There is paucity of data in RCTs regarding surgical rates, with only a few clinical trials reporting them. From the available data, meta-analyses of RCTs have concluded that antitumor necrosis α agents (anti-TNF) reduce surgical rates in ulcerative colitis and Crohn's disease...
May 1, 2017: Current Opinion in Gastroenterology
https://www.readbyqxmd.com/read/28458159/celastrol-reduces-il-1%C3%AE-induced-matrix-catabolism-oxidative-stress-and-inflammation-in-human-nucleus-pulposus-cells-and-attenuates-rat-intervertebral-disc-degeneration-in-vivo
#15
Jian Chen, Jun Xuan, Yun-Tao Gu, Ke-Si Shi, Jun-Jun Xie, Jiao-Xiang Chen, Zeng-Ming Zheng, Yu Chen, Xi-Bang Chen, Yao-Sen Wu, Xiao-Lei Zhang, Xiang-Yang Wang
Celastrol has been reported to exert therapeutic potential on pro-inflammatory diseases including asthma, Crohn's disease, arthritis and neurodegenerative disorders via inhibiting NF-κB pathway. While the effect of celastrol on intervertebral disc degeneration (IDD), which is also a pro-inflammatory disease, remains unknown. In this study, we evaluated the effect of celastrol on IDD in IL-1β treated human nucleus pulposus cells in vitro as well as in puncture induced rat IDD model in vivo. Our results showed that celastrol reduced the expression of catabolic genes (MMP-3, 9, 13, ADAMTS-4, 5), oxidative stress factors (COX-2, iNOS) and pro-inflammatory factors (IL-6, TNF-a) induced by IL-1β in nucleus pulposus cells, also phosphorylation of IκBα and p65 were attenuated by celastrol, indicating NF-κB pathway was inhibited by celastrol in nucleus pulposus cells...
April 27, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28453765/ccl20-is-negatively-regulated-by-tgf-%C3%AE-1-in-intestinal-epithelial-cells-and-reduced-in-crohn-s-disease-patients-with-a-successful-response-to-mongersen-a-smad7-antisense-oligonucleotide
#16
Irene Marafini, Ivan Monteleone, Vincenzo Dinallo, Davide Di Fusco, Veronica De Simone, Federica Laudisi, Massimo Claudio Fantini, Antonio Di Sabatino, Francesco Pallone, Giovanni Monteleone
Background and Aims: The chemokine CCL20 is over-produced in epithelium of Crohn's disease [CD] patients and contributes to recruiting immune cells to inflamed gut. Tumour necrosis factor-α [TNF-α] is a powerful inducer of CCL20 in intestinal epithelial cells. In CD, high levels of Smad7 block the activity of transforming growth factor-β1 [TGF-β1], a negative regulator of TNF signalling. We investigated whether intestinal epithelial cell-derived CCL20 is negatively regulated by TGF-β1 and whether Smad7 knock-down reduces CCL20 in CD...
May 1, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28453755/association-of-induction-infliximab-levels-with-clinical-response-in-perianal-crohn-s-disease
#17
Yana Davidov, Bella Ungar, Haggai Bar-Yoseph, Dan Carter, Ola Haj-Natour, Miri Yavzori, Yehuda Chowers, Rami Eliakim, Shomron Ben-Horin, Uri Kopylov
Background: The association of infliximab [IFX] trough levels with clinical and endoscopic outcomes in inflammatory bowel disease is well established. However, there is scarce data regarding the association of perianal fistula response with IFX. The aim of this study was to establish whether early induction infliximab levels and anti-infliximab antibodies [ATIs] are associated with perianal fistula response. Methods: Consecutive CD patients with perianal fistulae that were treated with IFX between 2008 and 2016 were included in the study...
May 1, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28452812/genetic-and-environmental-factors-significant-for-the-presentation-and-development-of-inflammatory-bowel-disease
#18
Sanja Dragasevic, Biljana Stankovic, Tomica Milosavljevic, Aleksandra Sokic-Milutinovic, Snezana Lukic, Tamara Alempijevic, Branka Zukic, Nikola Kotur, Gordana Nikcevic, Sonja Pavlovic, Dragan Popovic
OBJECTIVES: The aim of the study was to evaluate associations between inflammatory bowel disease (IBD) presentation and variants in NOD2, TLR4, TNF-α, IL-6, IL-1β, and IL-RN genes in order to identify possible environmental factors that may affect IBD occurrence, investigate potential predictors for surgical treatment of IBD, and correlate the presence of granulomas in biopsy specimens with clinical characteristics of Crohn's disease (CD) patients. PATIENTS AND METHODS: We genotyped 167 IBD patients using PCR-based methodology and tested for disease genotype-phenotype associations...
April 27, 2017: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28434894/-a-real-world-study-focused-on-the-effectiveness-and-safety-of-adalimumab-as-first-line-anti-tnf-treatment-for-pediatric-crohn-s-disease
#19
Víctor Manuel Navas-López, Gemma Pujol Muncunill, Enrique Llerena, María Navalón Rubio, David Gil-Ortega, Vicente Varea-Calderón, Carlos Sierra Salinas, Javier Martin-de-Carpi
BACKGROUND AND OBJECTIVES: Adalimumab (ADA), a monoclonal humanised anti-TNF antibody, is usually prescribed as a second-line treatment in paediatric Crohn's disease (CD) patients who have become unresponsive or developed intolerance to infliximab (IFX). In the case series reported, more than 70% of patients had initially been treated with IFX. Data on short- and long-term effectiveness of ADA in anti-TNF naïve patients is limited. The aim of this study is to describe our experience with ADA as a first-line anti-TNF in paediatric CD patients...
April 20, 2017: Anales de Pediatría: Publicación Oficial de la Asociación Española de Pediatría (A.E.P.)
https://www.readbyqxmd.com/read/28425943/beneficial-effect-of-voluntary-exercise-on-experimental-colitis-in-mice-fed-a-high-fat-diet-the-role-of-irisin-adiponectin-and-proinflammatory-biomarkers
#20
Agnieszka Irena Mazur-Bialy, Jan Bilski, Dagmara Wojcik, Bartosz Brzozowski, Marcin Surmiak, Magdalena Hubalewska-Mazgaj, Anna Chmura, Marcin Magierowski, Katarzyna Magierowska, Tomasz Mach, Tomasz Brzozowski
Inflammatory bowel diseases (IBDs) are a heterogeneous group of disorders exhibited by two major phenotypic forms: Crohn's disease and ulcerative colitis. Although the aetiology of IBD is unknown, several factors coming from the adipose tissue and skeletal muscles, such as cytokines, adipokines and myokines, were suggested in the pathogenesis of ulcerative colitis; however, it has not been extensively studied whether voluntary exercise can ameliorate that disorder. We explored the effect of moderate exercise (i...
April 20, 2017: Nutrients
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