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Crohn's and TNF

Bindu Madhavi Mudduluru, Shalin Shah, Steven Shamah, Arun Swaminath
Tumor necrosis factor alpha (TNF alpha) antagonists are biologic agents used in the management of inflammatory conditions such as rheumatoid arthritis, seronegative spondyloarthropathies and inflammatory bowel disease. These agents have been recently shown to cause a syndrome called anti-TNF induced lupus (ATIL), a rare condition which has similar clinical manifestations to idiopathic systemic lupus erythematosus (SLE). Given that extra-intestinal manifestations of inflammatory bowel disease include arthritis, it can be difficult to separate arthritis due to underlying disease from drug-induced arthritis...
October 17, 2016: Postgraduate Medicine
Gabriella Bröms, Fredrik Granath, Olof Stephansson, Helle Kieler
BACKGROUND: The inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC) have been associated with an increased risk of preterm birth. MATERIAL AND METHODS: We identified all 246 singleton preterm births among women with IBD between July 2006 and December 2010 as cases and an equal number of controls with IBD from the Swedish national health registers, matched by maternal age, parity and IBD diagnosis (CD/UC). From register data and medical charts, we obtained information on reproductive history, comorbidity, disease activity and drug treatment (corticosteroids, 5-aminosalicylates, sulfasalazine, thiopurines and anti-TNF) as risk factors for preterm birth...
December 2016: Scandinavian Journal of Gastroenterology
Tiffany Y Loh, Philip R Cohen
BACKGROUND: Tumor necrosis factor-α (TNF-α) inhibitors, such as infliximab, adalimumab, and certolizumab pegol are effective agents in the treatment of inflammatory bowel disease. Some individuals undergoing anti-TNF-α therapy for Crohn's disease or ulcerative colitis develop psoriasiform lesions. This is a paradoxical finding, as classical psoriasis is known to respond to these agents. PURPOSE: The clinical features of anti-TNF-α-induced psoriatic dermatitis are described...
September 9, 2016: Curēus
Lisa S Thomas, Stephan R Targan, Masato Tsuda, Qi T Yu, Brenda C Salumbides, Talin Haritunians, Emebet Mengesha, Dermot P B McGovern, Kathrin S Michelsen
TL1A contributes to the pathogenesis of several chronic inflammatory diseases, including those of the bowel by enhancing TH1, TH17, and TH2 responses. TL1A mediates a strong costimulation of these TH subsets, particularly of mucosal CCR9(+) T cells. However, the signaling pathways that TL1A induces in different TH subsets are incompletely understood. We investigated the function of TL1A on human TH17 cells. TL1A, together with TGF-β, IL-6, and IL-23, enhanced the secretion of IL-17 and IFN-γ from human CD4(+) memory T cells...
October 12, 2016: Journal of Leukocyte Biology
Shih-Yao Chen, Ai-Li Shiau, Chao-Liang Wu, Chrong-Reen Wang
Rheumatoid arthritis (RA) and Crohn's disease (CD) are autoimmune disorders with a crosstalk between their pathogenesis such as increased expression of TNF in the target organs. Despite a successful clinical trial with an oral Smad7 antisense oligonucleotide in CD, intraarticular (i.a.) modulation of Smad7 expression has not been performed in rheumatoid joint yet. In this study, contradictory to the findings in CD mucosa, higher levels of pSmad2/3 were found in RA synovium. In vitro experiments with synovial fibroblasts revealed that higher acetylated Smad7 expression was associated with lower activation status...
October 12, 2016: Scientific Reports
Irina Udalova, Claudia Monaco, Jagdeep Nanchahal, Marc Feldmann
Tumor necrosis factor (TNF) is one of the most important cytokines produced by macrophages. TNF is a very important component of host defense, released very rapidly after all types of injuries and stimuli. The kinetics of TNF release are short, and so it is perhaps not surprising that prolonged TNF production is associated with pathology. This was first elucidated in rheumatoid arthritis but extends to other chronic inflammatory diseases such as Crohn's disease and psoriasis. In this chapter, the discovery of anti-TNF therapy is reviewed, with its benefit but also its limitations...
August 2016: Microbiology Spectrum
Marisa Iborra, Javier Pérez-Gisbert, Marta Maia Bosca-Watts, Alicia López-García, Valle García-Sánchez, Antonio López-Sanromán, Esther Hinojosa, Lucía Márquez, Santiago García-López, María Chaparro, Montserrat Aceituno, Margalida Calafat, Jordi Guardiola, Blanca Belloc, Yolanda Ber, Luis Bujanda, Belén Beltrán, Cristina Rodríguez-Gutiérrez, Jesús Barrio, José Luis Cabriada, Montserrat Rivero, Raquel Camargo, Manuel van Domselaar, Albert Villoria, Hugo Salata Schuterman, David Hervás, Pilar Nos
BACKGROUND: Ulcerative colitis (UC) treatment is focused to achieve mucosal healing, avoiding disease progression. The study aimed to evaluate the real-world effectiveness of adalimumab (ADA) in UC and to identify predictors of remission to ADA. METHODS: This cohort study used data from the ENEIDA registry. Clinical response, clinical remission, endoscopic remission, adverse events (AE), colectomy, and hospitalisations were evaluated; baseline characteristics and biological parameters were compared to determine predictors of response...
October 8, 2016: Journal of Gastroenterology
Gabrielle Brown, Eva Wang, Argentina Leon, Monica Huynh, Mackenzie Wehner, Rebecca Matro, Eleni Linos, Wilson Liao, Anna Haemel
BACKGROUND: Tumor necrosis factor-α (TNF-α) inhibitors have been reported to induce new-onset psoriasis. OBJECTIVE: To better define the demographic, clinical features, and treatment approach of TNF-α inhibitor-induced psoriasis. METHODS: Systematic review of published cases of TNF-α inhibitor-induced psoriasis. RESULTS: We identified 88 articles with 216 cases of new-onset TNF-α inhibitor-induced psoriasis. The mean age at psoriasis onset was 38...
October 5, 2016: Journal of the American Academy of Dermatology
A Stallmach, C Langbein, R Atreya, T Bruns, A Dignass, K Ende, J Hampe, F Hartmann, M F Neurath, J Maul, J C Preiss, R Schmelz, B Siegmund, H Schulze, N Teich, U von Arnim, D C Baumgart, C Schmidt
BACKGROUND: Vedolizumab, a monoclonal antibody targeting the α4β7-integrin, is effective in inducing and maintaining clinical remission in Crohn's disease and ulcerative colitis according to randomised clinical trials. AIM: To determine the long-term effectiveness of vedolizumab in a real-world clinical setting. METHODS: This observational registry assessed the clinical outcome in patients treated with vedolizumab for clinically active Crohn's disease (n = 67) or ulcerative colitis (n = 60)...
October 7, 2016: Alimentary Pharmacology & Therapeutics
Piotr Eder, Liliana Łykowska-Szuber, Katarzyna Katulska, Kamila Stawczyk-Eder, Iwona Krela-Kaźmierczak, Katarzyna Klimczak, Aleksandra Szymczak, Marek Stajgis, Krzysztof Linke
INTRODUCTION: Objective assessment of Crohn's disease (CD) activity in patients treated with anti-tumour necrosis factor (anti-TNF) antibodies is crucial for the prediction of its long-term results. Mucosal healing estimated endoscopically has a strong predictive value; however, only combined assessment together with transmural healing in magnetic resonance enterography (MRE) gives full information about the whole spectrum of inflammatory lesions in CD. AIM: To assess the usefulness of intestinal healing phenomenon in CD, defined as improvement both in endoscopy and MRE, after anti-TNF induction therapy, in predicting long-term results of 1-year treatment...
2016: Przegla̜d Gastroenterologiczny
Gaurav Kanojia, Rimko Ten Have, Arjen Bakker, Koen Wagner, Henderik W Frijlink, Gideon F A Kersten, Jean-Pierre Amorij
In prospect of developing an oral dosage form of Infliximab, for treatment of Crohn's disease and rheumatoid arthritis, freeze-drying (vial vs Lyoguard trays) and spray-drying were investigated as production method for stable powders. Dextran and inulin were used in combination with sucrose as stabilizing excipients. The drying processes did not affect Infliximab in these formulations, i.e. both the physical integrity and biological activity (TNF binding) were retained. Accelerated stability studies (1 month at 60°C) showed that the TNF binding ability of Infliximab was conserved in the freeze-dried formulations, whereas the liquid counterpart lost all TNF binding...
2016: PloS One
Yana Davidov, Bella Ungar, Haggai Bar Yoseph, Dan Carter, Ola Haj-Natour, Miri Yavzori, Yehuda Chowers, Rami Eliakim, Shomron BenHorin, 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 the study was to establish whether early induction infliximab levels and anti-infliximab antibodies (ATI) 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...
October 4, 2016: Journal of Crohn's & Colitis
Paweł Moćko, Paweł Kawalec, Beata Smela-Lipińska, Andrzej Pilc
INTRODUCTION: The aim of this systematic review (SR) and meta-analysis was to assess the efficacy and safety of vedolizumab in the treatment of Crohn's disease (CD). MATERIAL AND METHODS: A systematic literature search was conducted in Medline/PubMed, Embase and Cochrane Library until 25 January, 2015. Included studies were critically appraised according to the PRISMA protocol. Assessment in specified subgroups of CD patients and meta-analysis with Revman software were performed...
October 1, 2016: Archives of Medical Science: AMS
Natashia M Seemann, Sebastian K King, Abdul Elkadri, Thomas Walters, Joel Fish, Jacob C Langer
BACKGROUND/PURPOSE: Perianal Crohn's disease (PCD) can affect both quality of life and psychological wellbeing. A subset of pediatric patients with complex PCD require surgical intervention, although appropriate timing and treatment regimens remain unclear. This study aimed to describe a large pediatric cohort in a tertiary center to determine the range of surgical management in children with complex PCD. METHODS: A retrospective review of children requiring operative intervention for PCD over 13 years (2002-2014) was performed...
September 15, 2016: Journal of Pediatric Surgery
Qi Zhang, Cuiping Zhang, Fangzhi Chang, Kun Liang, Xiaoyan Yin, Xiaoyu Li, Kun Zhao, Qinghui Niu, Zibin Tian
Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is a chronically intestinal autoimmune disease, the pathological mechanisms of which are not very clear. Wild type p-53 induced phosphatase 1 (Wip1), a serine/threonine protein phosphatase, has been reported to negatively regulate the inflammation in sepsis. However, the role of Wip1 in IBD is not very clear. Therefore, colonic tissues and peripheral blood from patients with IBD and healthy controls were collected to analyzed mRNA and protein expression of Wip1 using the method of qPCR and immunohistochemistry...
July 25, 2016: Cellular Immunology
Erika Lehtola, Johanna Haapamäki, Martti A Färkkilä
BACKGROUND: Biological medications, particularly TNF-α inhibitors, are used increasingly for active inflammatory bowel disease (IBD). Even though they are superior to many older medications in achieving remission and mucosal healing, primary nonresponse and loss of response remain significant problems, and a remarkable proportion of patients still need surgery at some point. OBJECTIVE: To study the outcome of IBD patients treated with TNF-α inhibitors, either infliximab or adalimumab, with a two-year follow-up...
December 2016: Scandinavian Journal of Gastroenterology
J Greene, G M O'Kane, D N Carney, E Aherne, G C O'Toole
Patients with inflammatory bowel disease (IBD) have an increased risk of developing malignancy. The use of immunosuppressive therapies and tumour necrosis factor (TNF) inhibitors in these patients may provide a further risk for the development of malignancy. We report the clinical and pathological findings of a high grade osteosarcoma in a patient with Crohns disease receiving TNF inhibitor therapy. In this case, a 32-year old female presented with a painful right knee after receiving maintenance adalimumab for Crohns disease for a period of six years...
2016: Irish Medical Journal
Ibrahim Hatemi, Gulen Hatemi, Aykut F Çelik
PURPOSE OF REVIEW: Gastrointestinal system can be involved in primary and secondary vasculitides. The recent data regarding the pathophysiology, clinical findings, diagnosis, management, and outcome of gastrointestinal involvement in different types of vasculitis are reviewed. RECENT FINDINGS: Diagnosis of gastrointestinal vasculitis may be difficult and relies mostly on imaging, because biopsy samples are hard to obtain and superficial mucosal biopsies have a low yield...
September 28, 2016: Current Opinion in Rheumatology
Christopher Alexakis, Kristiana Gordon, Russell Mellor, Heung Chong, Peter Mortimer, Richard Pollok
BACKGROUND AND AIMS: Ano-genital granulomatosis is a rare chronic granulomatous condition of the skin that causes lymphoedema of the external genitalia. There is a reported association with Crohn's disease. Mechanisms of disease, and optimal methods of treatment are poorly understood. METHODS: A retrospective case note review of 25 male patients with ano-genital granulomatosis presenting with genital lymphoedema was performed to determine the clinical and histopathological features of this condition and its relationship to intestinal Crohn's disease...
September 28, 2016: Journal of Crohn's & Colitis
Severine Vermeire, Edward V Loftus, Jean-Frédéric Colombel, Brian G Feagan, William J Sandborn, Bruce E Sands, Silvio Danese, Geert R D'Haens, Arthur Kaser, Remo Panaccione, David T Rubin, Ira Shafran, Megan McAuliffe, Arpeat Kaviya, Serap Sankoh, Reema Mody, Brihad Abhyankar, Michael Smyth
BACKGROUND AND AIMS: Vedolizumab is a gut-selective α4β7 integrin antagonist therapy for ulcerative colitis and Crohn's disease. The GEMINI long-term safety (LTS) trial is an ongoing open-label study investigating the safety of vedolizumab. We present interim exploratory analyses of efficacy in patients with Crohn's disease. METHODS: Patients from the C13004, GEMINI 2, and GEMINI 3 studies and vedolizumab-naïve patients could enrol in GEMINI LTS and received vedolizumab every 4 weeks...
September 28, 2016: Journal of Crohn's & Colitis
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