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https://www.readbyqxmd.com/read/28914560/thiopurine-metabolite-levels-in-patients-with-atopic-dermatitis-and-or-chronic-hand-foot-eczema-treated-with-azathioprine
#1
F M Garritsen, J van der Schaft, C A F Bruijnzeel-Koomen, R H van Schaik, M de Graaf, M P H van den Broek, M S de Bruin-Weller
BACKGROUND: Azathioprine is frequently used in severe eczema. It is converted in the liver into active metabolites, including 6-thioguanine nucleotide (6-TGN) and methylated 6-methylmercaptopurine (6-MMP). In the past, the therapeutic potential of azathioprine may have not been fully utilized. Recent investigations on inflammatory bowel disease have led to a better understanding of azathioprine metabolism and optimizing treatment. OBJECTIVE: To investigate whether measuring thiopurine metabolites in circulation can improve the effectiveness and safety of azathioprine treatment in patients with atopic dermatitis and/or chronic hand/foot eczema...
September 15, 2017: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/28914446/risk-factors-for-thiopurine-induced-myelosuppression-and-infections-in-inflammatory-bowel-disease-patients-with-a-normal-tpmt-genotype
#2
M M T J Broekman, M J H Coenen, G J Wanten, C J van Marrewijk, O H Klungel, A L M Verbeek, P M Hooymans, H-J Guchelaar, H Scheffer, L J J Derijks, D R Wong, D J de Jong
BACKGROUND: Leucopenia is a common side effect in patients treated with thiopurines. Variants in the thiopurine S-methyltransferase (TPMT) gene are the best-known risk factor, but only explain up to 25% of leucopenia cases. AIM: To identify the clinical risk factors for thiopurine-induced leucopenia in patients without a common TPMT variant, and explore if these patients are at increased risk for infections. METHODS: Post hoc analysis of the Thiopurine response Optimisation by Pharmacogenetic testing in Inflammatory bowel disease Clinics (TOPIC) trial...
September 15, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28903549/nudt15-variants-cause-hematopoietic-toxicity-with-low-6-tgn-levels-in-children-with-acute-lymphoblastic-leukemia
#3
Eun Sang Yi, Young Bae Choi, Rihwa Choi, Na Hee Lee, Ji Won Lee, Keon Hee Yoo, Ki Woong Sung, Soo-Youn Lee, Hong Hoe Koo
Purpose: We aimed to identify the impact of NUDT15 variants on thiopurine intolerance and 6-thioguanine nucleotide (6-TGN) levels in Korean children with acute lymphoblastic leukemia (ALL). Materials and Methods: Genotyping of NUDT15 was tested in 258 patients with ALL registered at Samsung Medical Center. Patients were classified into normal-activity (wild-type), intermediate-activity (heterozygous variant), and low-activity groups (homozygous or compound heterozygous variant)...
September 13, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28903094/effectiveness-of-mesalazine-thiopurines-and-tumour-necrosis-factor-antagonists-in-preventing-post-operative-crohn-s-disease-recurrence-in-a-real-life-setting
#4
Mariangela Allocca, Rosario Landi, Stefanos Bonovas, Gionata Fiorino, Alfredo Papa, Antonino Spinelli, Federica Furfaro, Laurent Peyrin-Biroulet, Alessandro Armuzzi, Silvio Danese
BACKGROUND: Most Crohn's disease (CD) patients develop endoscopic recurrence within one year of intestinal resection. The best treatment method to prevent post-operative CD recurrence remains uncertain. METHODS: A total of 155 CD patients from 2 referral centres, who were undergoing intestinal resection with ileo-colonic anastomosis (January 2004-January 2015), were included. All subjects received preventive therapy with tumour necrosis factor antagonists (anti-TNFs), thiopurinesor mesalazine...
September 14, 2017: Digestion
https://www.readbyqxmd.com/read/28901267/therapeutic-drug-monitoring-in-pediatric-ibd-current-application-and-future-perspectives
#5
Sara Lega, Matteo Bramuzzo, Marla Dubinsky
As the paradigm for IBD management is evolving from symptom control to the more ambitious goal of complete deep remission, the concept of personalized medicine, as a mean to deliver individualized treatment with the best effectiveness and safety profile, is becoming paramount. Therapeutic drug monitoring (TDM) is an essential part of personalized medicine wherein serum drug concentrations are used to guide drug dosing on an individual basis. The concept of TDM has been introduced in the field of IBD along with thiopurines, over a decade ago, and evolved around anti-TNFs therapies...
September 11, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28884254/elderly-onset-and-adult-onset-ulcerative-colitis-are-more-similar-than-previously-reported-in-a-nationwide-cohort
#6
Vinayak Kumar, Yash Shah, Dhruvan Patel, Nabeel Khan
BACKGROUND: Elderly-onset ulcerative colitis (EO-UC) is recognized as a distinct subpopulation of UC. To our knowledge, there have been no nationwide studies of EO-UC populations in the USA. AIMS: We aim to characterize differences in presentation at diagnosis and clinical course between EO-UC and adult-onset UC (AO-UC) patients in a national cohort. METHODS: Complete medical records of patients newly diagnosed with UC from October 2001 to October 2011 in the Veterans Affairs health system were obtained...
September 7, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28877179/adherence-to-6-mercaptopurine-in-children-and-adolescents-with-acute-lymphoblastic-leukemia
#7
Mervat Alsous, Rana Abu Farha, Eman Alefishat, Suha Al Omar, Deema Momani, Alia Gharabli, James McElnay, Robert Horne, Rawad Rihani
OBJECTIVE: Studies on children with Acute Lymphoblastic Leukemia (ALL) reported non-adherence in 2-54% of cases. The primary objective of this study was to assess rates of adherence to 6-MP using two different methods in children and adolescents with ALL. Secondary aim was to identify factors that influence adherence to 6-MP in children with ALL. METHODS: All eligible children with ALL who are (≤ 19) years old and receive 6-MP therapy for at least 1 month were approached to participate in the study...
2017: PloS One
https://www.readbyqxmd.com/read/28857898/prevalence-of-thiopurine-s-methyltransferase-gene-polymorphisms-in-patients-with-inflammatory-bowel-disease-from-the-island-of-crete-greece
#8
Constantina Coucoutsi, George Emmanouil, George Goulielmos, Ourania Sfakianaki, Ioannis E Koutroubakis, Elias A Kouroumalis
BACKGROUND: There is evidence that genotyping for the thiopurine S-methyltransferase (TPMT) gene variants is useful for the prediction of response to thiopurine analogs (azathioprine and 6-mercaptopurine) in patients with inflammatory bowel disease (IBD). The aim of the present study was to determine the prevalence of TPMT gene polymorphisms in a genetic homogenous population of IBD patients in Crete and to correlate the results with adverse reactions to thiopurine drugs. PATIENTS AND METHODS: Genotyping for the most common TPMT variants TPMT*2, TPMT*3A, TPMT3*C, and TPMT*3B was performed using the PCR-restriction fragment length polymorphism method in 223 consecutive IBD patients and 119 age-matched and sex-matched healthy controls...
August 29, 2017: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28852307/treating-children-with-inflammatory-bowel-disease-current-and-new-perspectives
#9
REVIEW
Graziella Guariso, Marco Gasparetto
Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gut characterised by alternating periods of remission and relapse. Whilst the mechanism underlying this disease is yet to be fully understood, old and newer generation treatments can only target selected pathways of this complex inflammatory process. This narrative review aims to provide an update on the most recent advances in treatment of paediatric IBD. A MEDLINE search was conducted using "paediatric inflammatory bowel disease", "paediatric Crohn's disease", "paediatric ulcerative colitis", "treatment", "therapy", "immunosuppressant", "biologic", "monitoring" and "biomarkers" as key words...
August 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28843236/a-practical-non-extraction-direct-liquid-chromatography-method-for-determination-of-thiopurine-s-methyltransferase-activity-in-inflammatory-bowel-disease
#10
Fariborz Bahrehmand, Amir Kiani, Asad Vaisi-Raygani, Homayoun Bashiri, Mehdi Zobeiri, Ali Moini, Tayebeh Pourmotabbed
Thiopurine drugs remain pivotal therapies for the wide varieties of diseases such as inflammatory bowel disease (IBD). Here, thiopurine S-methyltransferase (TPMT) phenotype, the main metabolizing enzyme of thiopurine-drugs, was studied. This is for the first time that TPMT activity is measured in Iranian IBD patients. We used an improved direct liquid chromatography assay without need for solvent extraction and minimize excess labor handling making it ideal for use in routine referral medical centers. TPMT activity in whole blood was determined by a non-extraction HPLC method...
June 2017: Acta Medica Iranica
https://www.readbyqxmd.com/read/28839910/postoperative-prophylaxis-in-crohn-s-disease-after-intestinal-resection-a-retrospective-analysis
#11
Anthony O'Connor, Peter J Hamlin, Jennifer Taylor, Christian Selinger, Nigel Scott, Alexander C Ford
INTRODUCTION: Up to 80% of patients with Crohn's disease (CD) may require surgery at some point in their lives, and it is estimated that as many as 40% may require several surgeries. It has been suggested that prophylactic medication decreases the rate of clinical and endoscopic recurrence following intestinal resection. This study aims to describe real-world clinical outcomes observed from a pragmatic, individualised strategy in postoperative CD. METHODS: All patients undergoing intestinal resection for CD between 2009 and 2013 were identified...
July 2017: Frontline Gastroenterology
https://www.readbyqxmd.com/read/28839871/monitoring-thiopurine-metabolites-in-inflammatory-bowel-disease
#12
REVIEW
Yago González-Lama, Javier P Gisbert
Thiopurines (azathioprine and mercaptopurine) are one of the immunosuppressive mainstays for the treatment of inflammatory bowel disease. In spite of its widespread use, thiopurine metabolism is still not fully understood, and a significant proportion of patients suffer toxicity or lack of efficacy. Different enzymatic pathways with individual variations constitute a pharmacogenetic model that seems to be suitable for monitoring and therapeutic intervention. This review is focused on current concepts and recent research that may help clinicians to rationally optimise thiopurine treatment in patients with inflammatory bowel disease...
October 2016: Frontline Gastroenterology
https://www.readbyqxmd.com/read/28838785/external-validation-of-a-thiopurine-monitoring-algorithm-on-the-sonic-clinical-trial-dataset
#13
Akbar K Waljee, Kay Sauder, Yiwei Zhang, Ji Zhu, Peter D R Higgins
No abstract text is available yet for this article.
August 21, 2017: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28838644/laparoscopic-ileocaecal-resection-versus-infliximab-for-terminal-ileitis-in-crohn-s-disease-a-randomised-controlled-open-label-multicentre-trial
#14
Cyriel Y Ponsioen, E Joline de Groof, Emma J Eshuis, Tjibbe J Gardenbroek, Patrick M M Bossuyt, Ailsa Hart, Janindra Warusavitarne, Christianne J Buskens, Ad A van Bodegraven, Menno A Brink, Esther C J Consten, Bart A van Wagensveld, Marno C M Rijk, Rogier M P H Crolla, Casper G Noomen, Alexander P J Houdijk, Rosalie C Mallant, Maarten Boom, Willem A Marsman, Hein B Stockmann, Bregje Mol, A Jeroen de Groof, Pieter C Stokkers, Geert R D'Haens, Willem A Bemelman
BACKGROUND: Treatment of patients with ileocaecal Crohn's disease who have not responded to conventional therapy is commonly scaled up to biological agents, but surgery can also offer excellent short-term and long-term results. We compared laparoscopic ileocaecal resection with infliximab to assess how they affect health-related quality of life. METHODS: In this randomised controlled, open-label trial, in 29 teaching hospitals and tertiary care centres in the Netherlands and the UK, adults with non-stricturing, ileocaecal Crohn's disease, in whom conventional therapy has failed were randomly allocated (1:1) by an internet randomisation module with biased-coin minimisation for participating centres and perianal fistula to receive laparoscopic ileocaecal resection or infliximab...
August 21, 2017: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28838412/intestinal-and-nonintestinal-cancer-risks-for-patients-with-crohn-s-disease
#15
REVIEW
Sushil K Garg, Fernando S Velayos, John B Kisiel
Crohn's disease (CD) is a chronic inflammatory disease that confers a higher risk of cancer than in the general population. New, large, population-based studies in the past decade show that patients with CD are at higher risk of colorectal, small bowel, melanoma, and cervical cancer. Patients who use thiopurines are at additional risk of development of lymphoma and nonmelanoma skin cancer. Preventive surveillance for cancers of the colorectum, skin, and uterine cervix is advised.
September 2017: Gastroenterology Clinics of North America
https://www.readbyqxmd.com/read/28837522/risk-factors-and-clinical-outcomes-in-patients-with-ibd-with-melanoma
#16
Loes H C Nissen, Marieke Pierik, Lauranne A A P Derikx, Elke de Jong, Wietske Kievit, Tim R A van den Heuvel, Alexander R van Rosendael, Elsemieke I Plasmeijer, Pieter Dewint, Rob H A Verhoeven, Lucy I H Overbeek, Iris D Nagtegaal, Frank Hoentjen, Andrea E van der Meulen-de Jong
BACKGROUND: Patients with inflammatory bowel disease (IBD) are at increased risk to develop malignant melanoma and this risk may increase with use of anti-tumor necrosis factor (TNF) therapy. Impaired survival of immunosuppressed melanoma patients is reported in transplant and rheumatology patients. This study aims to (1) identify risk factors for melanoma development in patients with IBD, (2) compare clinical characteristics of melanoma in patients with IBD to the general population, and (3) assess the influence of immunosuppressive medication on survival...
August 22, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28833287/changes-in-medical-management-and-colectomy-rates-a-population-based-cohort-study-on-the-epidemiology-and-natural-history-of-ulcerative-colitis-in-%C3%A3-rebro-sweden-1963-2010
#17
C Eriksson, Y Cao, S Rundquist, Y Zhulina, I Henriksson, S Montgomery, J Halfvarson
BACKGROUND: Whether the epidemiology of ulcerative colitis (UC) has changed during recent decades is partly unknown. AIM: To depict temporal trends in the epidemiology and medical treatment of UC as well as the long-term risk of progression in disease extent and colectomy, during 1963-2010. METHODS: Patients were identified by evaluation of all medical records in the archive of the Colitis Clinic, Örebro University Hospital. Comparisons were made between three time periods, 1963-1975, 1976-1990 and 1991-2005...
August 17, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28818801/development-and-validation-of-a-reliable-method-for-thiopurine-methyltransferase-tpmt-enzyme-activity-in-human-whole-blood-by-lc-ms-ms-an-application-for-phenotypic-and-genotypic-correlations
#18
Supaporn Wiwattanakul, Santirhat Prommas, Nuttawut Jenjirattithigarn, Siwalee Santon, Apichaya Puangpetch, Samart Pakakasama, Usanarat Anurathapan, Chonlaphat Sukasem
A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the determination of thiopurine methyltransferase (TPMT) activity in human whole blood lysate, based on conversion of 6-mercaptopurine (6-MP) by TPMT to 6-methylmercaptopurine (6-MMP) using S-adenosyl-l-methionine (SAM) as the methyl donor. This method was improved from the previous laborious method for washing of red cell lysate preparation to develop whole blood EDTA lysate. In addition, the TPMT incubation was optimized and the chromatography was performed in a short runtime of 7min on a C18-column by detection via triple quadrupole mass spectrometry...
October 25, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28811125/pharmacokinetics-and-pharmacodynamics-of-thiopurines-in-an-in%C3%A2-vitro-model-of-human-hepatocytes-insights-from-an-innovative-mass-spectrometry-assay
#19
Marco Pelin, Elena Genova, Laura Fusco, Monzer Marisat, Ute Hofmann, Diego Favretto, Marianna Lucafò, Andrea Taddio, Stefano Martelossi, Alessandro Ventura, Gabriele Stocco, Matthias Schwab, Giuliana Decorti
AIM: To apply an innovative LC-MS/MS method to quantify thiopurine metabolites in human hepatocytes and to associate them to cytotoxicity. METHODS: Immortalized human hepatocytes (IHH cells) were treated for 48 and 96 h, with 1.4 × 10(-4) M azathioprine and 1.1 × 10(-3) M mercaptopurine, concentrations corresponding to the IC50 values calculated after 96 h exposure in previous cytotoxicity analysis. After treatments, cells were collected for LC-MS/MS analysis to quantify 11 thiopurine metabolites with different level of phosphorylation and viable cells were counted by trypan blue exclusion assay to determine thiopurines in vitro effect on cell growth and survival...
August 12, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28805309/safety-of-herpes-zoster-vaccination-among-inflammatory-bowel-disease-patients-being-treated-with-anti-tnf-medications
#20
N Khan, Y Shah, C Trivedi, J D Lewis
BACKGROUND: The risk of herpes zoster (HZ) is elevated in inflammatory bowel disease (IBD) patients treated with anti-TNF medications. While it is optimal to give herpes zoster vaccine prior to initiation of therapy clinical circumstances may not always allow this. AIM: To determine the safety of giving herpes zoster vaccine while patients are on anti-TNF therapy. METHODS: We conducted a retrospective cohort study involving IBD patients who were followed in the Veterans Affairs (VA) healthcare system between 2001 and 2016...
August 14, 2017: Alimentary Pharmacology & Therapeutics
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