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Thiopurine

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https://www.readbyqxmd.com/read/29453848/postoperative-recurrence-of-crohn-s-disease-pathophysiology-diagnosis-and-treatment
#1
Antonio Di Sario, Paola Sassaroli, Luigi Daretti, Giulia Annulli, Laura Schiada, Giorgia Falcioni, Emanuele Bendia, Simone Antuono, Antonio Benedetti
BACKGROUND: Up to 80% of Crohn`s disease (CD) patients require at least one surgical intervention in their lifetime and up to 70% of these patients develop postoperative endoscopic recurrence within 1 year. The most important predictors of early postoperative recurrence are represented by smoking, prior intestinal surgery, penetrating disease and perianal location. Genetic factors, gut microbiota structure and immunological alterations may be involved in the pathogenesis of postoperative recurrence of CD, although their specific roles have to be determined yet...
February 16, 2018: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/29449434/msh6-haploinsufficiency-at-relapse-contributes-to-the-development-of-thiopurine-resistance-in-pediatric-b-lymphoblastic-leukemia
#2
Nikki A Evensen, P Pallavi Madhusoodhan, Julia Meyer, Jason Saliba, Ashfiyah Chowdhury, David J Araten, Jacob Nersting, Teena Bhatla, Tiffaney L Vincent, David Teachey, Stephen P Hunger, Jun Yang, Kjeld Schmiegelow, William L Carroll
Survival of children with relapsed acute lymphoblastic leukemia is poor and understanding mechanisms underlying resistance is essential in developing new therapy. Relapse-specific heterozygous deletions in MSH6, a crucial part of DNA Mismatch Repair, are frequently detected. Our aim was to determine whether MSH6 deletion results in a hypermutator phenotype associated with generation of secondary mutations involved in drug resistance or leads to a failure to initiate apoptosis directly in response to chemotherapeutic agents...
February 15, 2018: Haematologica
https://www.readbyqxmd.com/read/29444714/thiopurine-s-methyltransferase-activity-in-nigerians-phenotypes-and-activity-reference-values
#3
Ayorinde Adehin, Oluseye O Bolaji
OBJECTIVES: This study assessed the activity of thiopurine S-methyltransferase (TPMT) in Nigerians with a view to providing data on susceptibility to thiopurine toxicity, and as well generate reference activity values for clinical use. RESULTS: TPMT activity, expressed as the amount of 6MMP in ng/mL after 1 h incubation at 37 °C per haemoglobin (U/g Hb), varied between 2.34 and 63.50 U/g Hb in the study population. Poor metabolic phenotypes, characterised by an activity values below 8...
February 14, 2018: BMC Research Notes
https://www.readbyqxmd.com/read/29440001/risk-of-malignancy-associated-with-paediatric-use-of-tumour-necrosis-factor-inhibitors
#4
Timothy Beukelman, Fenglong Xie, Lang Chen, Daniel B Horton, James D Lewis, Ronac Mamtani, Melissa M Mannion, Kenneth G Saag, Jeffrey R Curtis
OBJECTIVE: To determine whether tumour necrosis factor inhibitor (TNFi) use is associated with an increased rate of incident malignancy compared with no TNFi use in the treatment of juvenile idiopathic arthritis (JIA), paediatric inflammatory bowel disease (pIBD) and paediatric plaque psoriasis (pPsO). METHODS: We performed a retrospective cohort study of administrative claims data from the USA from 2000 to 2014. Exposure to TNFi was considered permanent from the first observed exposure onward...
February 9, 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29436466/evaluation-of-prescriber-responses-to-pharmacogenomics-clinical-decision-support-for-thiopurine-s-methyltransferase-testing
#5
Samuel Ubanyionwu, Christine M Formea, Benjamin Anderson, Kelly Wix, Ross Dierkhising, Pedro J Caraballo
PURPOSE: Results of a study of prescribers' responses to a pharmacogenomics-based clinical decision support (CDS) alert designed to prompt thiopurine S -methyltransferase (TPMT) status testing are reported. METHODS: A single-center, retrospective, chart review-based study was conducted to evaluate prescriber compliance with a pretest CDS alert that warned of potential thiopurine drug toxicity resulting from deficient TPMT activity due to TPMT gene polymorphism. The CDS alert was triggered when prescribers ordered thiopurine drugs for patients whose records did not indicate TPMT status or when historical thiopurine use was documented in the electronic health record...
February 15, 2018: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/29425801/analytical-and-clinical-validation-of-an-lc-ms-ms-method-to-measure-thiopurine-s-methyltransferase-activity-by-quantifying-d3-6-mmp
#6
Jing Ma, Christiaan W Sies, Linda S Pike
BACKGROUND: Identification of patients with thiopurine S-methyltransferase (TPMT) deficiency prior to thiopurine drug therapy has become routine clinical practice worldwide. To measure TPMT activity, traditional radiochemical assays have been replaced by chromatographic methods. METHOD: Inspired by the increasing number of isotope labelled sources that may be of benefit for the TPMT assay, a new LC-MS/MS method for TPMT activity was developed and validated. Isotope labelled d3-S-adenosyl-l-methionine (d3-SAM) was selected for the enzymatic methylation of mercaptopurine during sample incubation; d3-6-methylmercaptopurine (d3-6-MMP) with d2-2, 8-hypoxanthine as the internal standard was quantified to ascertain individual TPMT activity...
February 6, 2018: Clinical Biochemistry
https://www.readbyqxmd.com/read/29421584/effective-long-term-solution-to-therapeutic-remission-in-inflammatory-bowel-disease-role-of-azathioprine
#7
REVIEW
Lyla Adam, Alisa Phulukdaree, Prashilla Soma
Azathioprine (AZA) is a well-known immunosuppressant used for many years for its ability to ensure long term disease remission in inflammatory bowel diseases (IBD) at an affordable cost to the public. However, the side effect profile has raised many concerns with numerous investigations into the risk, cause and prevention of these effects. Much of the side effect profile of AZA can be linked to a single nucleotide polymorphism (SNP) in the thiopurine methyltransferase (TPMT) gene which ensures the breakdown and efficacy of AZA...
February 5, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29417629/editorial-weighing-the-global-risk-of-cancer-with-thiopurines-in-inflammatory-bowel-disease
#8
EDITORIAL
D Laharie, P Riviere
No abstract text is available yet for this article.
March 2018: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29417626/editorial-weighing-the-global-risk-of-cancer-with-thiopurines-in-inflammatory-bowel-disease-authors-reply
#9
EDITORIAL
X Y Qiu, M J Lu, H J Zhang
No abstract text is available yet for this article.
March 2018: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29416770/hprt1-activity-loss-is-associated-with-resistance-to-thiopurine-in-all
#10
Fan Yang, Houshun Fang, Dan Wang, Yao Chen, Yonggong Zhai, Bin-Bing S Zhou, Hui Li
Acute lymphoblastic leukemia (ALL) is an aggressive hematological tumor resulting from the malignant transformation of lymphoid progenitors. Thiopurine is a widely used drug in the maintaining treatment of ALL. After a period of chemotherapy, 20% of pediatric patients and over 50% of adult patients will relapse. To investigate the mechanisms of drug resistance in vitro, we established the thiopurine resistant cell lines Reh-6MPR (6-MP Resistant cell) and Reh-6TGR (6-TG Resistant cell) by stepwise selection of the ALL cell line Reh...
January 5, 2018: Oncotarget
https://www.readbyqxmd.com/read/29401561/evaluation-of-stability-of-thiopurine-metabolites-using-a-validated-lc-ms-ms-method
#11
In Young Yoo, Kyunghoon Lee, Ok Ja Ji, Hye In Woo, Soo Youn Lee
Measurement of thiopurine metabolites is helpful to monitor adverse effects and assess compliance in patients on thiopurine treatment. The purpose of this study was to develop and validate an analytical method for measurement of thiopurine metabolites, thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine nucleotide (6-MMPN), in RBCs. We developed and validated a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of 6-TGN and 6-MMPN and evaluated the stability of the thiopurine metabolites in RBC and whole blood states without any preprocessing at various storage conditions...
May 2018: Annals of Laboratory Medicine
https://www.readbyqxmd.com/read/29398872/influence-of-nudt15-variants-on-hematological-pictures-of-patients-with-inflammatory-bowel-disease-treated-with-thiopurines
#12
Yuichiro Kojima, Yosuke Hirotsu, Wataru Omata, Makoto Sugimori, Shinya Takaoka, Hiroshi Ashizawa, Keiko Nakagomi, Dai Yoshimura, Kenji Hosoda, Yoji Suzuki, Hitoshi Mochizuki, Masao Omata
AIM: The single nucleotide polymorphism (SNP) c.415C>T in exon 3 of NUDT15 affects thiopurine-induced leukopenia in Asian patients with Crohn's disease. Meanwhile, three additional genetic variants of NUDT15 were reported in patients with acute lymphoblastic leukemia. We evaluated the effects of these additional genetic variants of NUDT15 in patients with inflammatory bowel disease (IBD) treated with thiopurines. METHODS: Ninety-six Japanese patients with IBD were enrolled...
January 28, 2018: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29387964/role-of-tpmt-and-itpa-variants-in-mercaptopurine-disposition
#13
Tina Gerbek, Maria Ebbesen, Jacob Nersting, Thomas L Frandsen, Malin Lindqvist Appell, Kjeld Schmiegelow
PURPOSE: To explore the levels of thioguanine incorporated into DNA (DNA-TG), and erythrocyte levels of 6-thioguanine nucleotides (Ery-TGN) and methylated metabolites (Ery-MeMP) during 6-mercaptopurine (6MP)/Methotrexate (MTX) therapy of childhood acute lymphoblastic leukemia (ALL) and the relation to inosine triphosphatase (ITPA) and thiopurine methyltransferase (TPMT) gene variants. METHODS: Blood samples were drawn during 6MP/MTX maintenance therapy from 132 children treated for ALL at Rigshospitalet, Copenhagen...
February 1, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29385469/anti-tnf-therapeutic-drug-monitoring-in-post-operative-crohn-s-disease
#14
Emily K Wright, Michael A Kamm, Peter De Cruz, Amy L Hamilton, Fabiyola Selvaraj, Fred Princen, Alexandra Gorelik, Danny Liew, Lani Prideaux, Ian C Lawrance, Jane M Andrews, Peter A Bampton, Simon L Jakobovits, Timothy H Florin, Peter R Gibson, Henry Debinski, Finlay A Macrae, Douglas Samuel, Ian Kronborg, Graham Radford-Smith, Richard B Gearry, Warwick Selby, Sally J Bell, Steven J Brown, William R Connell
Background: Anti-TNF prevents post-operative Crohn's disease recurrence in most patients but not all. This study aimed to define the relationship between adalimumab pharmacokinetics, maintenance of remission and recurrence. Methods: As part of a study of post-operative Crohn's disease management, some patients undergoing resection received prophylactic post-operative adalimumab. In these patients, serum and faecal adalimumab concentration and serum anti-adalimumab antibodies (AAA) were measured at 6, 12 and 18 months post-operatively...
January 27, 2018: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/29384798/frequency-and-type-of-drug-related-side-effects-necessitating-treatment-discontinuation-in-the-swiss-inflammatory-bowel-disease-cohort
#15
Sébastien Godat, Nicolas Fournier, Ekaterina Safroneeva, Pascal Juillerat, Andreas Nydegger, Alex Straumann, Stephan Vavricka, Luc Biedermann, Thomas Greuter, Montserrat Fraga, Karim Abdelrahman, Dieter Hahnloser, Bernhard Sauter, Gerhard Rogler, Pierre Michetti, Alain M Schoepfer
BACKGROUND AND AIM: Systematic analyses of inflammatory bowel disease (IBD) drug-related side effects necessitating treatment cessation in large cohorts of patients with IBD are scarce. We aimed to assess the frequency and type of drug-related side effects requiring drug cessation in patients included in the Swiss IBD Cohort. PATIENTS AND METHODS: A retrospective review was performed of data from the Swiss IBD Cohort physician questionnaires documenting a treatment cessation for the following drug categories: aminosalicylates, topical and systemic steroids, thiopurines, methotrexate, tumor necrosis factor-antagonists, and calcineurin inhibitors (tacrolimus, cyclosporine)...
January 30, 2018: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29373914/genetic-polymorphism-of-thiopurine-s-methyltransferase-in-children-with-acute-lymphoblastic-leukemia-in-jordan
#16
Mervat Alsous, Al-Motassem Yousef, Mariam Abdel Jalil, Mohammed Zawiah, Shorouq Yacoub, Deema Momani, Alia Gharabli, Suha Omar, Rawad Rihani
Background and Aims: It has been demonstrated that homozygote and heterozygote mutant allele carriers for thiopurine S-methyltransferase (TPMT) are at high risk of developing myelosuppression after receiving standard doses of 6-mercaptopurine (6-MP). The aim of this study was to determine the frequency of TPMT deficient alleles in children with acute lymphoblastic leukemia (ALL) in Jordan and to compare it with other ethnic groups. Methods: We included 52 ALL childhood cases from King Hussein Cancer Research Center in Jordan...
January 27, 2018: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/29370945/-usefulness-of-thiopurine-methyltransferase-polymorphism-study-and-metabolites-measurement-for-patients-treated-by-azathioprine
#17
V Guillotin, G Galli, J-F Viallard
Azathioprine is widely used in internal medicine and frequently implicated in occurrence of adverse events. Among these adverse events the bone marrow suppression, a dose-related one, is the most serious because of is potential morbidity and mortality. Severe myelosuppression, associated with abnormal AZA metabolism, is linked to the thiopurine methyltransferase (TPMT) genetic polymorphism that results in a high variability of its activity with 89% of patients with a normal activity, 11% with an intermediate activity, and 0...
January 19, 2018: La Revue de Médecine Interne
https://www.readbyqxmd.com/read/29370346/reduced-risk-of-inflammatory-bowel-disease-associated-colorectal-neoplasia-with-use-of-thiopurines-a-systematic-review-and-meta-analysis
#18
Zhehui Zhu, Zubing Mei, Yuegui Guo, Guanghui Wang, Tingyu Wu, Ximao Cui, Zhenyu Huang, Yilian Zhu, Dongpeng Wen, Jinlve Song, Hailan He, Weimin Xu, Long Cui, Chenying Liu
Background & Aims: The association between thiopurines and colorectal neoplasia risk remains controversial in inflammatory bowel disease (IBD) patients. We performed a systematic review and meta-analysis examining this association. Methods: A comprehensive search of the PubMed, EMBASE and Cochrane Library databases was performed to identify relevant literature. Random-effects models were applied to calculate the pooled odds ratio (OR) and relative risk (RR) with corresponding 95% confidence intervals (CIs) among case-control and cohort studies, respectively...
January 23, 2018: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/29357999/recommendations-of-the-spanish-working-group-on-crohn-s-disease-and-ulcerative-colitis-geteccu-on-the-use-of-tiopurines-in-inflammatory-bowel-disease
#19
Fernando Bermejo, Mariam Aguas, María Chaparro, Eugeni Domènech, Ana Echarri, Esther Garcia-Planella, Iván Guerra, Javier P Gisbert, Antonio López-Sanromán
Thiopurines (azathioprine and mercaptopurine) are widely used in patients with inflammatory bowel disease. In this paper, we review the main indications for their use, as well as practical aspects on efficacy, safety and method of administration. They are mainly used to maintain remission in steroid-dependent disease or with ciclosporin to control a severe ulcerative colitis flare-up, as well as to prevent postoperative Crohn's disease recurrence, and also in combination therapy with biologics. About 30-40% of patients will not respond to treatment and 10-20% will not tolerate it due to adverse effects...
January 18, 2018: Gastroenterología y Hepatología
https://www.readbyqxmd.com/read/29356768/real-life-anti-tumor-necrosis-factor-experience-in-more-than-500-patients-high-co-immunosuppression-rates-but-low-rates-of-quantifying-treatment-response
#20
Victoria M Merrick, Kajal Mortier, Linda J Williams, Rafeeq Muhammed, Marcus K H Auth, Mamoun Elawad, John M E Fell, R Mark Beattie, Sabarinathan Loganathan, Franco Torrente, Mary-Anne Morris, Charles Charlton, Nick M Croft, Astor Rodrigues, Mark Furman, Babu Vadamalayan, Huw Jenkins, Veena Zamvar, Sally G Mitton, Sonny Chong, Mike Cosgrove, Anthony Akobeng, David C Wilson, Richard K Russell
OBJECTIVE: The aim of this study was to measure the effectiveness, safety, and use of anti-tumor necrosis Factor (TNF) therapy in pediatric inflammatory bowel disease in the United Kingdom (UK). METHODS: Prospective UK audit of patients newly starting anti-TNF therapy. Disease severity was assessed using Physician Global Assessment +/or the Paediatric Crohn Disease Activity Index. RESULTS: A total of 37 centers participated (23/25 specialist pediatric inflammatory bowel disease sites)...
February 2018: Journal of Pediatric Gastroenterology and Nutrition
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