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Thiopurine

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https://www.readbyqxmd.com/read/28644183/more-dose-dependent-side-effects-with-mercaptopurine-over-azathioprine-in-ibd-treatment-due-to-relatively-higher-dosing
#1
Mark M T J Broekman, Marieke J H Coenen, Corine J van Marrewijk, Geert J A Wanten, Dennis R Wong, Andre L M Verbeek, Olaf H Klungel, Piet M Hooymans, Henk-Jan Guchelaar, Hans Scheffer, Luc J J Derijks, Dirk J de Jong
BACKGROUND: There are substantial global differences in the preference for mercaptopurine (MP) or its prodrug azathioprine (AZA) as first-choice thiopurine to treat inflammatory bowel diseases. Studies comparing both agents are scarce. Our aim was to compare AZA and MP in thiopurine-naive patients with inflammatory bowel disease for the frequency of side effects and efficacy. METHODS: Post hoc analysis of the "Thiopurine response Optimization by Pharmacogenetic testing in Inflammatory bowel disease Clinics" (TOPIC) trial, in which thiopurine-naive patients with inflammatory bowel disease with an indication for a thiopurine were randomized for a genotype-based dose versus standard of care...
June 20, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28627831/whole-blood-thiopurine-s-methyltransferase-genotype-and-phenotype-concordance-in-iranian-kurdish-ulcerative-colitis-uc-patients
#2
Fariborz Bahrehmand, Asad Vaisi-Raygani, Amir Kiani, Homayoun Bashiri, Mahdi Zobeiri, Maryam Tanhapour, Tayebeh Pourmotabbed
BACKGROUND: Thiopurine methyl transferase (TPMT), a drug-metabolizing enzyme, catalyzes methylation and consequently, the metabolism of thiopurine compounds used for treatment of inflammatory bowel disease (IBD). Individuals who are homozygous recessive or have extremely low TPMT activity need to avoid thiopurines because of concern for significant leukopenia. The aim of this research was to determine TPMT phenotypes and genotypes in IBD patients to predict the risk of thiopurine toxicity before treatment...
May 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28623449/differential-effects-of-thiopurine-methyltransferase-tpmt-and-multidrug-resistance-associated-protein-gene-4-mrp4-on-mercaptopurine-toxicity
#3
Chengcheng Liu, Laura J Janke, Jun J Yang, William E Evans, John D Schuetz, Mary V Relling
PURPOSE: Mercaptopurine plays a pivotal role in treatment of acute lymphoblastic leukemia (ALL) and autoimmune diseases, and inter-individual variability in mercaptopurine tolerance can influence treatment outcome. Thiopurine methyltransferase (TPMT) and multi-drug resistant Protein 4 (MRP4) have both been associated with mercaptopurine toxicity in clinical studies, but their relative contributions remain unclear. METHODS: We studied the metabolism of and tolerance to mercaptopurine in murine knockout models of Tpmt, Mrp4, and both genes simultaneously...
June 16, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28618062/examining-maintenance-care-following-infliximab-salvage-therapy-for-acute-severe-ulcerative-colitis
#4
Dean Seah, Matthew C Choy, Alexandra Gorelik, William R Connell, Miles P Sparrow, Daniel van Langenberg, Geoffrey Hebbard, Gregory Moore, Peter De Cruz
BACKGROUND AND AIMS: Data supporting the optimal maintenance drug therapy & strategy to monitor ongoing response following successful infliximab (IFX) induction, for acute severe ulcerative colitis (ASUC), are limited. We aimed to evaluate maintenance & monitoring strategies employed in patients post IFX induction therapy. METHODS: Patients in 6 Australian tertiary centres treated with IFX for steroid-refractory ASUC between April 2014 & May 2015 were identified via hospital IBD & pharmacy databases...
June 15, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28617756/optimizing-thiopurine-therapy-in-inflammatory-bowel-disease-among-2-real-life-intercept-cohorts-effect-of-allopurinol-comedication
#5
Berrie Meijer, Margien L Seinen, Remco van Egmond, Gerd Bouma, Chris J J Mulder, Adriaan A van Bodegraven, Nanne K H de Boer
BACKGROUND: Thiopurines (azathioprine and mercaptopurine) are frequently used immunosuppressive drugs to maintain remission in patients with inflammatory bowel disease. Half of the conventional thiopurine-derivative users have to discontinue treatment within 5 years, mainly because of intolerable adverse events. Over recent years, different strategies to optimize thiopurine treatment were suggested, yet, studies describing the clinical effectiveness of these strategies remain scarce. The aims of this study were to compare tolerability and sustained clinical benefit of conventional thiopurine derivatives therapy among two 5-year real-life intercept cohorts and to assess the clinical value of specifically allopurinol cotherapy...
June 14, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28617055/new-treatment-strategies-for-ulcerative-colitis
#6
Julian Panés, Ignacio Alfaro
Therapeutic strategies in ulcerative colitis are evolving. A personalized and optimal use of available drugs and the integration of new drug classes are the cornerstones underpinning the new treatment paradigms. Areas covered: A structured literature search in Medline and PubMed, Cochrane meta-analyses, and abstracts of international congresses has been performed to review therapeutic approaches to ulcerative colitis. The primary therapeutic objective of therapy is to achieve clinical remission since persistence of active disease, even if mild, leads to a significant reduction in quality of life...
June 21, 2017: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/28617029/medium-to-long-term-efficacy-and-safety-of-oral-tacrolimus-in-moderate-to-severe-steroid-refractory-ulcerative-colitis
#7
Raúl Vicente Olmedo Martín, Víctor Amo Trillo, Rocío González Grande, Miguel Jiménez Pérez
BACKGROUND: Oral tacrolimus is an effective drug that induces clinical remission in patients with moderate to severe ulcerative colitis refractory to steroids. However, there is little data with regard to its medium to long-term efficacy and safety. The aim of this study was to assess the medium to long-term efficacy and safety of oral tacrolimus in this challenging clinical situation. METHODS: This was a retrospective observational review of the clinical charts of 34 patients with moderate to severe ulcerative colitis refractory to steroids treated with oral tacrolimus at our hospital (July 2001-July 2016)...
June 15, 2017: Revista Española de Enfermedades Digestivas
https://www.readbyqxmd.com/read/28597827/inflammatory-bowel-disease-in-childhood-and-adolescence
#8
Jan Däbritz, Patrick Gerner, Axel Enninger, Martin Claßen, Michael Radke
BACKGROUND: The incidence of inflammatory bowel disease (IBD) in childhood and adolescence is 5-11 cases per 100 000 persons per year, corresponding to a new diagnosis of IBD in 800-1470 patients in Germany each year. METHODS: This review is based on pertinent publications retrieved by a selective search in PubMed, including guidelines from Germany and abroad. RESULTS: Children and adolescents with IBD often have extensive involvement and an aggressive course of disease...
May 12, 2017: Deutsches Ärzteblatt International
https://www.readbyqxmd.com/read/28596686/clinical-course-of-ulcerative-colitis-patients-who-develop-acute-pancreatitis
#9
Jong Wook Kim, Sung Wook Hwang, Sang Hyoung Park, Tae Jun Song, Myung-Hwan Kim, Ho-Su Lee, Byong Duk Ye, Dong-Hoon Yang, Kyung-Jo Kim, Jeong-Sik Byeon, Seung-Jae Myung, Suk-Kyun Yang
AIM: To investigate the clinical course of ulcerative colitis (UC) patients who develop acute pancreatitis. METHODS: We analyzed 3307 UC patients from the inflammatory bowel disease registry at Asan Medical Center from June 1989 to May 2015. The clinical course of UC patients who developed acute pancreatitis was compared with that of non-pancreatitis UC patients. RESULTS: Among 51 patients who developed acute pancreatitis, 13 (0.40%) had autoimmune, 10 (0...
May 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28588888/thioguanine-in-inflammatory-bowel-disease-long-term-efficacy-and-safety
#10
Mark G Ward, Kamal V Patel, Viraj C Kariyawasam, Rishi Goel, Ben Warner, Tim R Elliott, Paul A Blaker, Peter M Irving, Anthony M Marinaki, Jeremy D Sanderson
BACKGROUND: Thioguanine (TG) is efficacious in inflammatory bowel disease (IBD), but its toxicity, particularly nodular regenerative hyperplasia (NRH) of the liver, has limited its use. We assessed the long-term clinical outcomes and safety of TG in patients whom were intolerant or refractory to conventional immunomodulators. METHODS: This is a retrospective, single-centre study of IBD patients treated with TG from 2001-2013. Response was defined as clinical remission (Harvey-Bradshaw Index < 5 for Crohn's disease (CD), Simple Clinical Colitis Activity Index < 4 for ulcerative colitis (UC)) without corticosteroids or, if receiving anti-tumour-necrosis-factor (anti-TNF) therapy, absence of dose escalation...
June 2017: United European Gastroenterology Journal
https://www.readbyqxmd.com/read/28570429/incidence-of-and-predictors-for-early-discontinuation-of-biological-therapies-in-veteran-patients-with-inflammatory-bowel-disease
#11
Linda A Feagins, Akbar Waljee, Jason K Hou, Phillip Gu, Steven Kanjo, Vivek Rudrapatna, Daisha J Cipher, Shail Govani, Jill Gaidos
BACKGROUND: Biological therapies are effective for inducing and maintaining remission in inflammatory bowel disease (IBD), but patients often require changes in biological agents over the course of their illness. We sought to evaluate the rate of and reasons for discontinuing biological agents and to identify risk factors for their discontinuation. METHODS: We performed a retrospective cohort study across 4 VA hospital systems (Dallas, TX; Houston, TX; Ann Arbor, MI; Richmond, VA)...
May 24, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28570428/combined-detection-of-nudt15-variants-could-highly-predict-thiopurine-induced-leukopenia-in-chinese-patients-with-inflammatory-bowel-disease-a-multicenter-analysis
#12
Kang Chao, Xueding Wang, Qian Cao, Jiaming Qian, Kaichun Wu, Xia Zhu, Hong Yang, Jie Liang, Lang Lin, Zicheng Huang, Yu Zhang, Yibiao Huang, Yinghao Sun, Xianmin Xue, Min Huang, Pinjin Hu, Ping Lan, Xiang Gao
BACKGROUND: NUDT15 c.415C>T was a novel genetic marker confirmed in our center for thiopurine-induced leukopenia in Chinese inflammatory bowel disease (IBD). For validation, a large cohort study is needed. Meanwhile, the newly discovered NUDT15 coding variants (c.36_37insGGAGTC and c.52 G>A) have not been studied in patients with IBD. We aimed to further confirm the influence of 3 NUDT15 variants (c.415C>T, c.36_37insGGAGTC, and c.52G>A) on thiopurine-induced leukopenia in Chinese patients with IBD...
May 24, 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28566883/thiopurine-use-associated-with-reduced-b-and-natural-killer-cells-in-inflammatory-bowel-disease
#13
James D Lord, Donna M Shows
AIM: To identify which blood and mucosal lymphocyte populations are specifically depleted by thiopurine use in vivo. METHODS: The thiopurines azathioprine and 6-mercaptopurine have been a mainstay of inflammatory bowel disease (IBD) therapy for decades, but their mechanism of action in vivo remains obscure. Although thiopurines are lymphotoxic at high doses, and have been reported to cause T cell apoptosis in vitro, their ability to control IBD at lower doses suggests that they may selectively deplete particular lymphocyte populations...
May 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28566182/nudt15-p-r139c-variant-is-common-and-strongly-associated-with-azathioprine-induced-early-leukopenia-and-severe-alopecia-in-korean-patients-with-various-neurological-diseases
#14
Sun-Young Kim, Jin-Hong Shin, Jin-Sung Park, Sa-Yoon Kang, Tai-Seung Nam, Jong Kuk Kim, Ki-Jong Park, So-Young Huh, Ji Seon Oh, Boram Kang, Dae-Seong Kim
Azathioprine (AZA)-induced leukopenia is a relatively common complication in Korean patients. In addition to variation in TPMT (thiopurine S-methyltransferase), the NUDT15 p.R139C variant was recently identified to have a strong association with AZA-induced leukopenia. We investigated these associations in Korean patients undergoing AZA treatment with various neurological diseases. Among 84 enrolled patients, 20 (23.8%; 7 early, 13 late) exhibited leukopenia. The NUDT15 p.R139C variant was associated with leukopenia (OR: 11...
July 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28554266/tolerability-profile-of-thiopurines-in-inflammatory-bowel-disease-a-prospective-experience
#15
Fabio Salvatore Macaluso, Sara Renna, Marcello Maida, Mariangela Dimarco, Chiara Sapienza, Marco Affronti, Emanuele Orlando, Giulia Rizzuto, Rosalba Orlando, Marco Ventimiglia, Mario Cottone, Ambrogio Orlando
OBJECTIVES: The occurrence of thiopurine-related adverse events (AEs) may complicate the management of patients with inflammatory bowel disease (IBD). We aimed to evaluate the tolerability of thiopurines in a current IBD setting. MATERIALS AND METHODS: All consecutive patients who started a treatment with azathioprine (AZA) from January 2010 to March 2016 were entered in a prospectively maintained database, and the AEs which led to the permanent discontinuation of the drug were reported...
May 29, 2017: Scandinavian Journal of Gastroenterology
https://www.readbyqxmd.com/read/28552060/thiopurine-s-methyltransferase-as-a-pharmacogenetic-biomarker-significance-of-testing-and-review-of-major-methods
#16
Chingiz Asadov, Gunay Aliyeva, Kamala Mustafayeva
Thiopurine S-methyltransferase (TPMT) enzyme metabolizes thiopurine drugs which are widely used in various disciplines as well as in leukemias. Individual enzyme activity varies depending on the genetic polymorphisms of TPMT gene located at chromosome 6. Up to 14% of population is known to have a decreased enzyme activity, and if treated with standard doses of thiopurines, these individuals are at the high risk of severe adverse drug reactions (ADR) as myelosuppression, gastrointestinal intolerance, pancreatitis and hypersensitivity...
May 28, 2017: Cardiovascular & Hematological Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/28534520/extracolonic-cancer-in-inflammatory-bowel-disease-data-from-the-geteccu-eneida-registry
#17
María Chaparro, M Ramas, J M Benítez, A López-García, A Juan, J Guardiola, M Mínguez, X Calvet, L Márquez, L I Fernández Salazar, L Bujanda, C García, Y Zabana, R Lorente, J Barrio, E Hinojosa, M Iborra, M Domínguez Cajal, M Van Domselaar, M F García-Sepulcre, F Gomollón, M Piqueras, G Alcaín, V García-Sánchez, J Panés, E Domènech, E García-Esquinas, F Rodríguez-Artalejo, J P Gisbert
OBJECTIVES: The objective of this study was (a) To know the prevalence and distribution of extracolonic cancer (EC) in patients with inflammatory bowel disease (IBD); (b) To estimate the incidence rate of EC; (c) To evaluate the association between EC and treatment with immunosuppressants and anti-tumor necrosis factor (TNF) agents. METHODS: This was an observational cohort study. INCLUSION CRITERIA: IBD and inclusion in the ENEIDA Project (a prospectively maintained registry) from GETECCU...
May 23, 2017: American Journal of Gastroenterology
https://www.readbyqxmd.com/read/28533920/inflammatory-bowel-disease-efficient-remission-maintenance-is-crucial-for-cost-containment
#18
REVIEW
Giovanni C Actis, Rinaldo Pellicano
The inflammatory bowel diseases (IBD) are chronic incurable inflammatory disorders of the gut. Some 10% run a downhill course, requiring emergency medical support and often surgery; another small subset are monogenic, and, threatening pediatric patients, are the challenge of these days. The majority of the IBDs, however, are polygenic low-penetrance diseases, running a lifetime waxing-and-waning course. The prevalent trend is towards a slow worsening and steady cost increase. Each and all drugs of the available arsenal exhibit strengths and weaknesses: Mesalamines are chiefly effectively for mild-moderate colitis, and do not work in Crohn's; steroids do not control some 40% of the ulcerative colitis cases, and are not indicated for Crohn's; thiopurines are effective in the maintenance of the IBDs but do not prevent relapses on withdrawal; biologics are still being used empirically (not monitored) causing further increase of their cost over that of hospitalization...
May 6, 2017: World Journal of Gastrointestinal Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28525791/determination-of-thiopurine-s-methyltransferase-activity-by-hydrophilic-interaction-liquid-chromatography-hyphenated-with-mass-spectrometry
#19
Daniel Pecher, Svetlana Dokupilová, Zuzana Zelinková, Maikel Peppelenbosch, Veronika Mikušová, Peter Mikuš
Thiopurine S-methyltransferase (TPMT) plays an important role in the metabolism of thiopurines used in the therapy of inflammatory bowel diseases (IBD). In this work a new progressive method for the determination of TPMT activity in red blood cells lysates was developed. Analysis was carried out by means of hydrophilic interaction liquid chromatography (HILIC) hyphenated with mass spectrometry (MS). In comparison with reversed-phase high-performance liquid chromatography (RP-HPLC), that has been typically applied in determination of TPMT activity, the HILIC significantly improved the analytical signal provided by MS, shortened analysis time, and improved chromatographic resolution...
May 10, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28523321/autoimmune-hepatitis-with-sclerosing-cholangitis-in-a-patient-with-thiopurine-methyltransferase-deficiency-case-presentation
#20
Sorin Claudiu Man, Cristina Nicoleta Schnell, Valentina Sas, Anca Dana Buzoianu, Dan Gheban
The association between two autoimmune diseases is known in the literature as overlap syndrome. We present the case of an 18-year-old boy, diagnosed at the age of 13 with an overlap syndrome between type I autoimmune hepatitis and sclerosing cholangitis. The response to immunosuppressant therapy was hampered by azathioprine-induced toxicity causing severe pancytopenia, as a result of thiopurine methyltransferase enzyme genetic deficiency. Treatment was replaced by mycophenolate mofetil. Although the relapse rate was reduced, the disease progressed to cirrhosis...
2017: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
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