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Thiopurine

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https://www.readbyqxmd.com/read/27875356/corticosteroids-and-thiopurines-but-not-tumor-necrosis-factor-antagonists-are-associated-with-cytomegalovirus-reactivation-in-inflammatory-bowel-disease-a-systematic-review-and-meta-analysis
#1
Tushar Shukla, Siddharth Singh, Parul Tandon, Jeffrey D McCurdy
BACKGROUND: The association between cytomegalovirus (CMV) reactivation and individual immunosuppressive agents in inflammatory bowel disease (IBD) has not been clearly defined. Therefore, we performed a systematic review and meta-analysis to assess this association. METHODS: Multiple electronic databases were searched systematically through July 2015 for observational studies reporting CMV reactivation (based on serum-based or tissue-based tests) in IBD patients stratified by medication exposure...
November 21, 2016: Journal of Clinical Gastroenterology
https://www.readbyqxmd.com/read/27867685/how-i-treat-my-inflammatory-bowel-disease-patients-with-thiopurines
#2
REVIEW
Berrie Meijer, Chris Jj Mulder, Adriaan A van Bodegraven, Nanne K H de Boer
Thiopurines are essential drugs to maintain remission in patients with inflammatory bowel disease (IBD). Thiopurines used in IBD are azathioprine (2.0-2.5 mg/kg), mercaptopurine (1.0-1.5 mg/kg) and thioguanine (0.2-0.3 mg/kg). However, mainly due to numerous adverse events associated with thiopurine use, almost 50% of the patients have to discontinue conventional thiopurine treatment. Extensive monitoring and the application of several treatment strategies, such as split-dose administration, co-administration with allopurinol or dose reduction/increase, may increase the chance of successful therapy...
November 6, 2016: World Journal of Gastrointestinal Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27862102/addition-of-an-immunomodulator-can-reverse-antibody-formation-and-loss-of-response-in-patients-treated-with-adalimumab
#3
B Ungar, U Kopylov, T Engel, M Yavzori, E Fudim, O Picard, A Lang, N Williet, S Paul, Y Chowers, A Bar-Gil Shitrit, R Eliakim, S Ben-Horin, X Roblin
BACKGROUND: Anti-adalimumab antibodies (AAA) are associated with loss of clinical response (LOR). Addition of an immunomodulator has been shown to reverse immunogenicity and regain response with infliximab monotherapy. Similar data on adalimumab are lacking. AIM: To study the impact of immunomodulator addition on the emergence of AAA and LOR among adalimumab therapy patients. METHODS: The databases of three tertiary medical centres were reviewed to identify patients who developed AAA during adalimumab monotherapy with resultant LOR, and received an immunomodulator as a salvage combination therapy...
November 16, 2016: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27859568/6-methylmercaptopurine-induced-leukocytopenia-during-thiopurine-therapy-in-ibd-patients
#4
Berrie Meijer, Joany E Kreijne, Sofia A W van Moorsel, Luc J J Derijks, Gerd Bouma, Chris J J Mulder, Dennis R Wong, C Janneke van der Woude, Adriaan A van Bodegraven, Nanne K H de Boer
BACKGROUND: Thiopurines have a favorable benefit-risk ratio in the treatment of inflammatory bowel disease (IBD). A feared adverse event of thiopurine therapy is myelotoxicity, mostly occurring due to toxic concentrations of the pharmacologically active metabolites 6-thioguaninenucleotides. In oncology, myelosuppression has also been associated with elevated 6-methylmercaptopurine (6-MMP). In this case-series, we provide a detailed overview of 6-MMP-induced myelotoxicity in IBD patients...
November 16, 2016: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/27853898/rate-and-predictors-of-mucosal-healing-in-ulcerative-colitis-treated-with-thiopurines-results-of-a-multicentric-cohort-study
#5
Caroline Prieux-Klotz, Stéphane Nahon, Aurelien Amiot, Leila Sinayoko, Carole Galéano-Cassaz, Stanislas Chaussade, Romain Coriat, Pierre Lahmek, Vered Abitbol
BACKGROUND AND AIMS: Mucosal healing (MH) with thiopurines has been poorly investigated in ulcerative colitis (UC). We aimed to assess MH rate in UC patients treated with thiopurine monotherapy. PATIENTS AND METHODS: We retrospectively collected all UC patients treated with thiopurines more than 6 months who have undergone colonoscopy at baseline and after at least 6 months of treatment. Patients were recruited from January 2005 to May 2015 through a personal database and/or standardized hospital inpatient diagnostic dataset...
November 16, 2016: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/27833392/efficacy-of-thioguanine-treatment-in-inflammatory-bowel-disease-a-systematic-review
#6
Berrie Meijer, Chris Jj Mulder, Godefridus J Peters, Adriaan A van Bodegraven, Nanne Kh de Boer
AIM: To critically assess the available literature regarding the efficacy of thioguanine treatment in inflammatory bowel disease (IBD) patients, irrespective of the (hepato-) toxicity profile. METHODS: A systematic literature search of the MEDLINE database using PubMed was performed using the keywords "thioguanine", "6-TG", "thioguanine", "inflammatory bowel disease", "IBD", "Crohn's disease", "Ulcerative colitis" and "effectiveness" in order to identify relevant articles published in English starting from 2000...
October 28, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27809554/mercaptopurine-and-inflammatory-bowel-disease-the-other-thiopurine
#7
Fernando Bermejo San José, Alicia Algaba, Sergio López Durán, Iván Guerra, Marta Aicart, María Hernández-Tejero, Elena Garrido, María de Lucas, Daniel Bonillo, Antonio López Sanromán
BACKGROUND: Data about use and effectiveness of mercaptopurine in inflammatory bowel disease are relatively limited. AIMS: To assess the possible therapeutic indications, efficacy and safety of mercaptopurine as an alternative to azathioprine in inflammatory bowel disease. METHODS: Retrospective observational study in patients treated with mercaptopurine in a total cohort of 1,574 patients with inflammatory bowel disease. RESULTS: One hundred and fifty-two patients received mercaptopurine, 15...
November 4, 2016: Revista Española de Enfermedades Digestivas
https://www.readbyqxmd.com/read/27787512/weight-and-body-composition-compartments-do-not-predict-therapeutic-thiopurine-metabolite-levels-in-inflammatory-bowel-disease
#8
Darcy Q Holt, Boyd Jg Strauss, Gregory T Moore
OBJECTIVES: Thiopurine drugs are the most commonly used steroid-sparing therapies in moderate-to-severe inflammatory bowel disease (IBD). Their complex metabolism and their narrow therapeutic windows means that optimal dosing is difficult. However, weight-based dosing is the norm. Similar antimetabolites are dosed by body composition parameters. In IBD, treatment response and toxicity has been shown to correlate with thiopurine metabolite levels. We sought to determine whether weight or body composition parameters predicted therapeutic 6-thioguanine nucleotide (6TGN) or toxic 6-methylmercaptopurine (6MMP) levels...
October 27, 2016: Clinical and Translational Gastroenterology
https://www.readbyqxmd.com/read/27781286/therapeutic-management-of-inflammatory-bowel-disease-in-real-life-practice-in-the-current-era-of-anti-tnf-agents-analysis-of-the-french-administrative-health-databases-2009-2014
#9
J Kirchgesner, M Lemaitre, A Rudnichi, A Racine, M Zureik, F Carbonnel, R Dray-Spira
BACKGROUND: Management of inflammatory bowel disease (IBD) has evolved in the last decade. AIM: To assess IBD therapeutic management, including treatment withdrawal and early treatment use in the current era of anti-TNF agents (anti-TNFs). METHODS: All patients affiliated to the French national health insurance diagnosed with IBD were included from 2009 to 2013 and followed up until 31 December 2014. Medication uses, treatment sequences after introduction of thiopurine or anti-TNF monotherapies or both (combination therapy), surgical procedures and hospitalisations were assessed...
January 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27781203/real-life-treatment-paradigms-show-adalimumab-is-cost-effective-for-the-management-of-ulcerative-colitis
#10
Candace L Beilman, Nguyen Xuan Thanh, Victoria Ung, Christopher Ma, Karen Wong, Karen I Kroeker, Thomas Lee, Haili Wang, Arto Ohinmaa, Phil Jacobs, Brendan P Halloran, Richard N Fedorak
Background. Adalimumab is effective for the maintenance of remission in patients with moderate-to-severe ulcerative colitis (UC). Currently, biologic therapies are used in cases where patients fail conventional medical therapies. If biologic therapies are not available, patients often choose to remain in an unwell state rather than undergo colectomy. Objective. The aim of the study was to evaluate the cost-effectiveness of adalimumab in patients with UC where adalimumab was readily available compared to not available...
2016: Canadian Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/27770805/a-disease-spectrum-for-itpa-variation-advances-in-biochemical-and-clinical-research
#11
Nicholas E Burgis
Human ITPase (encoded by the ITPA gene) is a protective enzyme which acts to exclude noncanonical (deoxy)nucleoside triphosphates ((d)NTPs) such as (deoxy)inosine 5'-triphosphate ((d)ITP), from (d)NTP pools. Until the last few years, the importance of ITPase in human health and disease has been enigmatic. In 2009, an article was published demonstrating that ITPase deficiency in mice is lethal. All homozygous null offspring died before weaning as a result of cardiomyopathy due to a defect in the maintenance of quality ATP pools...
October 22, 2016: Journal of Biomedical Science
https://www.readbyqxmd.com/read/27770449/polymorphic-variation-in-tpmt-is-the-principal-determinant-of-tpmt-phenotype-a-meta-analysis-of-three-genome-wide-association-studies
#12
Riin Tamm, Reedik Mägi, Roman Tremmel, Stefan Winter, Evelin Mihailov, Alenka Smid, Anja Möricke, Kathrin Klein, Martin Schrappe, Martin Stanulla, Richard Houlston, Richard Weinshilboum, Irena Mlinarič Raščan, Andres Metspalu, Lili Milani, Matthias Schwab, Elke Schaeffeler
Thiopurine-related hematotoxicity in paediatric acute lymphoblastic leukemia (ALL) and inflammatory bowel diseases has been linked to genetically defined variability in thiopurine S-methyltransferase (TPMT) activity. While gene testing of TPMT is being clinically implemented, it is unclear if additional genetic variation influences TPMT activity with consequences for thiopurine-related toxicity. To examine this possibility, we performed a genome-wide association study (GWAS) of red blood cell TPMT activity in 844 Estonian individuals and 245 paediatric ALL-cases...
October 22, 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27766449/a-case-of-thiopurine-induced-acute-myocarditis-in-a-patient-with-ulcerative-colitis
#13
Anastasiya Latushko, Leyla J Ghazi
No abstract text is available yet for this article.
October 20, 2016: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/27739352/preterm-birth-in-women-with-inflammatory-bowel-disease-the-association-with-disease-activity-and-drug-treatment
#14
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
https://www.readbyqxmd.com/read/27720912/can-thiopurines-prevent-formation-of-antibodies-against-tumor-necrosis-factor-antagonists-after-failure-of-these-therapies
#15
Ray K Boyapati, Gwo-Tzer Ho, Jack Satsangi
No abstract text is available yet for this article.
October 5, 2016: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/27720019/pharmacogenomics-and-adverse-drug-reactions-primetime-and-not-ready-for-primetime-tests
#16
David A Khan
Adverse drug reactions (ADRs) are a relatively common cause of morbidity and mortality. Many factors can contribute to ADRs, including genetics. The degree to which genetics contributes to ADRs is not entirely clear and varies by drug, as well as the type of ADR. Pharmacogenetics and, more recently, pharmacogenomics have been applied to the field of ADRs for both predictable ADRs and hypersensitivity drug reactions. Evaluations for glucose-6-phosphate dehydrogenase and thiopurine S-methyltransferase are commonplace clinical tests to reduce hematologic problems associated with drugs, such as dapsone and azathioprine, respectively...
October 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27703193/genes-implicated-in-thiopurine-induced-toxicity-comparing-tpmt-enzyme-activity-with-clinical-phenotype-and-exome-data-in-a-paediatric-ibd-cohort
#17
Tracy Coelho, Gaia Andreoletti, James J Ashton, Akshay Batra, Nadeem Ahmad Afzal, Yifang Gao, Anthony P Williams, Robert M Beattie, Sarah Ennis
The aim of our study was to assess the utility of next generation sequencing (NGS) for predicting toxicity and clinical response to thiopurine drugs in paediatric patients with inflammatory bowel disease. Exome data for 100 patients were assessed against biochemically measured TPMT enzyme activity, clinical response and adverse effects. The TPMT gene and a panel of 15 other genes implicated in thiopurine toxicity were analysed using a gene based statistical test (SKAT-O test). Nine patients out of 100 (Crohn's disease- 67, ulcerative colitis- 23 and IBDU-10) had known TPMT mutations associated with deficient enzyme activity...
October 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27699641/recent-trends-and-future-directions-for-the-medical-treatment-of-ulcerative-colitis
#18
Makoto Naganuma, Shinta Mizuno, Kosaku Nanki, Shinya Sugimoto, Takanori Kanai
Recently, several medical treatments for ulcerative colitis (UC) have been developed, including 5-aminosalicylic acids (5-ASAs), corticosteroids, thiopurine, calcineurin inhibitors, and anti-tumor necrosis factor (TNF) α treatments. Treatment options including calcineurin inhibitors and anti-TNF treatment for refractory UC are discussed in this article. Furthermore, upcoming treatments are introduced, such as golimumab, vedolizumab, AJM300, tofacitinib. Budesonide foamwill be used as one treatment option in patients with distal colitis...
October 3, 2016: Clinical Journal of Gastroenterology
https://www.readbyqxmd.com/read/27689330/interconnections-between-apoptotic-and-autophagic-pathways-during-thiopurine-induced-toxicity-in-cancer-cells-the-role-of-reactive-oxygen-species
#19
Wiem Chaabane, Malin Lindqvist Appell
Thiopurines (azathioprine, 6-mercaptopurine and 6-thioguanine) are a class of genotoxic drugs extensively used in the treatment of various illnesses including leukemia. Their underlying molecular mechanism of action involves the activation of apoptosis and autophagy but remains widely unclear. Here we present evidence that autophagy induction by thiopurines is a survival mechanism that antagonizes apoptosis and is involved in degrading damaged mitochondria through mitophagy. On the other hand, apoptosis is the main cell death mechanism by thiopurines as its inhibition prohibited cell death...
September 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/27686002/randomized-clinical-trial-a-pilot-study-comparing-efficacy-of-low-dose-azathioprine-and-allopurinol-to-azathioprine-on-clinical-outcomes-in-inflammatory-bowel-disease
#20
Marianne Kiszka-Kanowitz, Klaus Theede, Anette Mertz-Nielsen
BACKGROUND: Treating inflammatory bowel diseases (IBD) using thiopurines is effective; however, a high rate of adverse effects and lack of efficacy limit its use. Retrospective studies have suggested that treatment with low-dose thiopurines in combination with allopurinol is associated with higher remission rates and lower incidence of adverse events. AIM: To compare the rates of clinical remission and the rates of adverse events in IBD patients treated with either standard treatment with azathioprine or low-dose azathioprine in combination with allopurinol...
December 2016: Scandinavian Journal of Gastroenterology
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