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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
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
Charlie Bridgewood, Abdulla Watad, Richard J Cuthbert, Dennis McGonagle
PURPOSE OF REVIEW: The spondyloarthopathies (SpA), which encompass related diseases that were originally viewed as autoimmune, are now known to have a strong innate immune or autoinflammatory initiation phase characterized by disease localization to tissue-specific sites based on the nuances and microanatomy and immunology of those sites. This review covers recent translational advances in the field of SpA. RECENT FINDINGS: Imaging studies in SpA continue to add support for the pivotal role of enthesitis in disease initiation and expression...
June 9, 2018: Current Opinion in Rheumatology
K T Park, L Sceats, M Dehghan, A W Trickey, A Wren, J J Wong, R Bensen, B N Limketkai, K Keyashian, C Kin
BACKGROUND: Perioperative vedolizumab (VDZ) and anti-tumour necrosis factor (TNFi) therapies are implicated in causing post-operative complications in inflammatory bowel disease (IBD). AIM: To compare the risk of surgical site infections (SSIs) between VDZ- and TNFi-treated IBD patients in propensity-matched cohorts. METHODS: The Optum Research Database was used to identify IBD patients who received VDZ or TNFi within 30 days prior to abdominal surgery between January 2015 and December 2016...
June 7, 2018: Alimentary Pharmacology & Therapeutics
Fatima Nawaz, Livia R Goes, Jocelyn C Ray, Ronke Olowojesiku, Alia Sajani, Aftab A Ansari, Ian Perrone, Joseph Hiatt, Donald Van Ryk, Danlan Wei, Mia Waliszewski, Marcelo A Soares, Katija Jelicic, Mark Connors, Stephen A Migueles, Elena Martinelli, Francois Villinger, Claudia Cicala, Anthony S Fauci, James Arthos
Human gut-associated lymphoid tissues (GALT) play a key role in the acute phase of HIV infection. The propensity of HIV to replicate in these tissues, however, is not fully understood. Access and migration of naive and memory CD4+ T cells to these sites is mediated by interactions between integrin α4 β7 , expressed on CD4+ T cells, and MAdCAM, expressed on high endothelial venules. We report here that MAdCAM delivers a potent costimulatory signal to naive and memory CD4+ T cells following ligation with α4 β7 ...
June 6, 2018: Mucosal Immunology
Marcel Vetter, Markus F Neurath
BACKGROUND: Crohn's disease (CD) is a chronic immune-mediated disorder of the gastrointestinal tract. The pathophysiological understanding of this disease is limited and no curative therapy is available so far. Therefore, most patients require long-lasting or even life-long immunosuppressive therapies for the suppression of symptoms to improve quality of life and reduction of long-term risks. However, in a relevant subgroup of patients, these therapeutic goals cannot be sufficiently attained...
June 5, 2018: Digestion
Stefan Schreiber, Axel Dignass, Laurent Peyrin-Biroulet, Greg Hather, Dirk Demuth, Mahmoud Mosli, Rebecca Curtis, Javaria Mona Khalid, Edward Vincent Loftus
BACKGROUND: Selective patient recruitment can produce discrepancies between clinical trial results and real-world effectiveness. METHODS: A systematic literature review and meta-analysis were conducted to assess vedolizumab real-world effectiveness and safety in patients with ulcerative colitis (UC) or Crohn's disease (CD). MEDLINE, MEDLINE In-Process, EMBASE, and Cochrane databases were searched for real-world studies of vedolizumab in adult patients with UC/CD reporting clinical response, remission, corticosteroid-free remission, UC/CD-related surgery or hospitalization, mucosal healing, or safety published from May 1, 2014-June 22, 2017...
June 4, 2018: Journal of Gastroenterology
Neil E McCarthy, Matthias Eberl
Human γδ T-cells include some of the most common "antigen-specific" cell types in peripheral blood and are enriched yet further at mucosal barrier sites where microbial infection and tumors often originate. While the γδ T-cell compartment includes multiple subsets with highly flexible effector functions, human mucosal tissues are dominated by host stress-responsive Vδ1+ T-cells and microbe-responsive Vδ2+ T-cells. Widely recognized for their potent cytotoxicity, emerging data suggest that γδ T-cells also exert strong influences on downstream adaptive immunity to pathogens and tumors, in particular via activation of antigen-presenting cells and/or direct stimulation of other mucosal leukocytes...
2018: Frontiers in Immunology
Karien Bloem, Tiny Schaap, Ronald Boshuizen, Eva L Kneepkens, Gerrit J Wolbink, Annick de Vries, Theo Rispens
AIM: For assessment of concentrations of biopharmaceuticals, for example, therapeutic drug monitoring, dried blood sampling of capillary blood is a convenient alternative to traditional venepuncture sampling. We investigated an alternative to dried blood spot collection on filter paper: sampling capillary blood using the Mitra® microsampler. MATERIALS AND METHODS:  Therapeutic monoclonal antibodies were spiked in whole blood, sampled using filter paper and Mitra microsampler and concentrations measured using specific ELISAs...
June 4, 2018: Bioanalysis
Stephane Paul, Nicolas Williet, Thomas Di Bernado, Anne-Emmanuelle Berger, Gilles Boschetti, Jerome Filippi, Emilie Del Tedesco, Stephane Nancey, Bernard Flourie, Xavier Roblin
Background: Vedolizumab (VDZ), a humanized monoclonal antibody targeting α4β7 integrin, is effective in induction and maintenance therapy in patients with inflammatory bowel disease (IBD) who have not adequately responded to standard therapies, and high levels of vedolizumab trough levels (VTL) have been associated with clinical remission. The α4β7 integrin binds to endothelial MAdCAM-1 and is up-regulated by retinoic acid (RA). Aim: To determine the relations between soluble MAdCAM-1 (sMAdCAM-1) and RA concentrations with clinical remission during VDZ maintenance therapy...
May 31, 2018: Journal of Crohn's & Colitis
Tianrun Cai, Tzu-Chieh Lin, Allison Bond, Jie Huang, Gwendolyn Kane-Wanger, Andrew Cagan, Shawn N Murphy, Ashwin N Ananthakrishnan, Katherine P Liao
Background: The gut-selective nature of vedolizumab has raised questions regarding increased joint pain or arthralgia with its use in inflammatory bowel disease (IBD) patients. As arthralgias are seldom coded and thus difficult to study, few studies have examined the comparative risk of arthralgia between vedolizumab and tumor necrosis factor inhibitor (TNFi). Our objectives were to evaluate the application of natural language processing (NLP) to identify arthralgia in the clinical notes and to compare the risk of arthralgia between vedolizumab and TNFi in IBD...
May 26, 2018: Inflammatory Bowel Diseases
Prashanth Rawla, Tagore Sunkara, Jeffrey Pradeep Raj
Inflammatory bowel disease (IBD) is an idiopathic chronic inflammatory disease of the gastrointestinal system. The spectrum is of predominantly two types, namely, ulcerative colitis and Crohn's disease. The incidence of IBD has been increasing steadily since 1990, and so the number of agents used in their treatment. Biologics that are derived partly or completely from living biological sources such as animals and humans have become widely available, which provide therapeutic benefits to the IBD patients. Currently, monoclonal antibodies against tumor necrosis factor-alpha (infliximab, adalimumab, certolizumab, and golimumab), integrins (vedolizumab and natalizumab), and interleukin (IL)-12 and IL-23 antagonists (ustekinumab) are approved for use in IBD...
2018: Journal of Inflammation Research
James D Lord, S Alice Long, Donna M Shows, Jerill Thorpe, Katherine Schwedhelm, Janice Chen, Mariko Kita, Jane H Buckner
Integrin alpha4/beta7 on circulating lymphocytes identifies them as gut-tropic, and can be targeted by the humanized antibody vedolizumab to treat inflammatory bowel disease (IBD). We found lymphocytes expressing alpha4/beta7 were significantly more responsive to the pro-inflammatory cytokines IL-6, IL-7, and IL-21, and less responsive to the regulatory T cell (Treg)-supporting cytokine IL-2. Alpha4/beta7 was expressed by a smaller percent of FOXP3 + Helios+ thymically-derived Tregs (tTregs) than FOXP3 + Helios- peripherally-derived Tregs (pTregs) or FOXP3- effector T cells...
May 26, 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
C S Tse, E V Loftus, L E Raffals, A A Gossard, A L Lightner
BACKGROUND: Primary sclerosing cholangitis (PSC) is a chronic, progressive cholestatic biliary disease associated with inflammatory bowel disease (IBD) with no known cure. AIM: To evaluate the effect of biological therapies on PSC progression in IBD patients. METHODS: We performed a retrospective cohort study of 88 cases (75 unique patients with 12 patients treated >1 biologics) of IBD (48 ulcerative colitis, 24 Crohn's disease and 3 indeterminate colitis) with concomitant PSC who received biological therapy (42 infliximab, 19 adalimumab, 27 vedolizumab) between June 2002 and October 2017...
May 28, 2018: Alimentary Pharmacology & Therapeutics
M Belvis Jiménez, B Maldonado Pérez, F Argüelles-Arias
No abstract text is available yet for this article.
May 19, 2018: Journal of Crohn's & Colitis
Diana E Yung, Nir Horesh, Amy L Lightner, Shomron Ben-Horin, Rami Eliakim, Anastasios Koulaouzidis, Uri Kopylov
Background: Several studies have reported the surgical outcomes of inflammatory bowel disease (IBD) patients exposed to vedolizumab (VDZ) preoperatively, with conflicting results. This meta-analysis aims to evaluate the risk of postoperative complications in IBD patients preoperatively exposed to VDZ in comparison with patients exposed to anti-tumor necrosis factor (anti-TNF) treatment or no biologic therapy. Methods: A systematic review with a meta-analysis of the existing literature was conducted...
May 17, 2018: Inflammatory Bowel Diseases
Marie-Theres Binder, Emily Becker, Maximilian Wiendl, Lena Schleier, Friederike Fuchs, Moritz Leppkes, Raja Atreya, Clemens Neufert, Imke Atreya, Markus F Neurath, Sebastian Zundler
Background: Although anti-adhesion therapies are a novel mainstay in the treatment of inflammatory bowel diseases (IBDs), the mechanisms controlling integrin-dependent gut homing are poorly elucidated, and the available techniques for translational functional investigations are limited. Methods: We used dynamic adhesion assays to study adhesion of CD4+ T cells, CD8+ T cells, CD19+ B cells, and granulocytes to the addressins MAdCAM-1, VCAM-1, and ICAM-1. The effects of vedolizumab, natalizumab, etrolizumab-s, anti-CD11a, and anti-CD18 antibodies were explored...
May 18, 2018: Inflammatory Bowel Diseases
Uri Kopylov, Bram Verstockt, Luc Biedermann, Shaji Sebastian, Daniela Pugliese, Elena Sonnenberg, Peter Steinhagen, Naila Arebi, Yulia Ron, Torsten Kucharzik, Xavier Roblin, Bella Ungar, Ariella Bar-Gil Shitrit, Sandro Ardizzone, Pauliina Molander, Marina Coletta, Laurent Peyrin-Biroulet, Peter Bossuyt, Irit Avni-Biron, Emmanouela Tsoukali, Mariangela Allocca, Konstantinos Katsanos, Tim Raine, Taina Sipponen, Gionata Fiorino, Shomron Ben-Horin, Rami Eliakim, Alessandro Armuzzi, Britta Siegmund, Daniel C Baumgart, Nikolaos Kamperidis, Nitsan Maharshak, Christian Maaser, Gerassimos Mantzaris, Henit Yanai, Dimitrious K Christodoulou, Iris Dotan, Marc Ferrante
Background: Vedolizumab (VDZ) is effective for treatment of ulcerative colitis (UC) and Crohn's disease (CD). In GEMINI trials, anti-tumor necrosis factor (anti-TNF)-naïve patients had a superior response compared with anti-TNF-exposed patients. In real-world experience (RWE), the number of included anti-TNF-naïve patients was low. We aimed to evaluate the effectiveness and safety of VDZ in anti-TNF-naïve patients in an RWE setting. Methods: This retrospective multicenter European pooled cohort study included consecutive active anti-TNF-naïve IBD patients treated with VDZ...
May 18, 2018: Inflammatory Bowel Diseases
Sophie Restellini, Reena Khanna, Waqqas Afif
In patients with Crohn's disease (CD) and ulcerative colitis (UC), the use of therapeutic drug monitoring (TDM) with TNF-α antagonists has led to a personalized approach to optimize treatment and has been shown to be cost-effective. The utility of this TDM-based personalized approach for novel biologic agents, which target different inflammatory pathways, is unclear. Commercial assays for ustekinumab (UST) and vedolizumab (VDZ) are available, but there is little available guidance for clinicians regarding the use of TDM with these drugs...
May 17, 2018: Inflammatory Bowel Diseases
Brian G Feagan, Fatima Bhayat, Mona Khalid, Aimee Blake, Simon P L Travis
Background and Aims: Vedolizumab, a humanised monoclonal antibody for the treatment of inflammatory bowel disease, selectively blocks gut lymphocyte trafficking. This may reduce the risk of respiratory tract infections [RTIs] compared with systemic immunosuppressive therapies. To assess this possibility, we evaluated the rates of RTIs in clinical trials of vedolizumab. Methods: Patient-level data from Phase 3 randomised controlled trials [RCTs] of vedolizumab in ulcerative colitis [UC; GEMINI 1] and Crohn's disease [CD; GEMINI 2], and a long-term safety study [UC and CD] were pooled...
May 17, 2018: Journal of Crohn's & Colitis
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