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https://www.readbyqxmd.com/read/28731668/-azathioprine-induced-pancytopenia-case-series
#1
Cristina Martínez Faci, Ignacio Ros Arnal, José M Martínez de Zabarte Fernández, Jordi Sorribes Estorch, Mónica López Campos, Carmen Rodríguez-Vigil Iturrate
Azathioprine is an immunosuppressive drug that has shown effectiveness in inflammatory bowel disease treatment. Its metabolite, 6-mercaptopurine, is metabolized through thiopurine methyltransferase. Patients with low enzyme activity may have more frequent and severe side effects. The most common is leukopenia, and rarely pancytopenia. The thiopurine methyltransferase activity monitoring shows an individualized profile of enzymatic activity but it should not replace monitoring by performing serial blood counts...
August 1, 2017: Archivos Argentinos de Pediatría
https://www.readbyqxmd.com/read/28723860/higher-thioguanine-nucleotide-metabolite-levels-are-associated-with-better-long-term-outcomes-in-patients-with-inflammatory-bowel-diseases
#2
Andres J Yarur, Bilal Gondal, Ayal Hirsch, Britt Christensen, Russell D Cohen, David T Rubin
GOALS: The aim of this study was to assess whether sustained 6-thioguaninenucleotide (6-TGN) levels were associated with improved long-term outcomes in patients with inflammatory bowel diseases (IBD). BACKGROUND: Cross-sectional data have shown that thiopurine metabolites are correlated with clinical efficacy in patient receiving thiopurines for IBD but the role for serial measurements through treatment course is unclear. STUDY: We conducted a retrospective cohort study including patients with IBD on thiopurine monotherapy and had serial 6-TGN levels measured...
July 18, 2017: Journal of Clinical Gastroenterology
https://www.readbyqxmd.com/read/28681659/the-relationship-of-genetics-nursing-practice-and-informatics-tools-in-6-mercaptopurine-dosing-in-pediatric-oncology
#3
Wendy J Haylett
An antileukemic agent prescribed for pediatric oncology patients during the maintenance phase of therapy for acute lymphoblastic leukemia, 6-mercaptopurine (6-MP), is highly influenced by genetic variations in the thiopurine S-methyltransferase enzyme. As such, 6-MP must be dosed so that patients with 1 or 2 inactive thiopurine S-methyltransferase alleles will not incur an increased risk for myelosuppression or other toxicities. Informatics tools such as clinical decision support systems are useful for the application of this and similar pharmacogenetics information to the realm of nursing and clinical practice for safe and effective patient care...
July 1, 2017: Journal of Pediatric Oncology Nursing: Official Journal of the Association of Pediatric Oncology Nurses
https://www.readbyqxmd.com/read/28679280/assessing-medication-adherence-in-inflammatory-bowel-diseases-a-comparison-between-a-self-administered-scale-and-a-pharmacy-refill-index
#4
María Luisa de Castro, Luciano Sanromán, Alicia Martín, Montserrat Figueira, Noemi Martínez, Vicent Hernández, Victor Del Campo, Juan R Pineda, Jesús Martínez-Cadilla, Santos Pereira, José Ignacio Rodríguez Prada
BACKGROUND: Medication non-adherence in inflammatory bowel disease (IBD) has a negative impact on disease outcome. Different tools have been proposed to assess non-adherence. We aimed to compare a self-administered scale and a pharmacy refill index as a reliable measure of medication adherence and to determine what factors are related to adherence. METHODS: Consecutive non-active IBD outpatients were asked to fill in the self-reported Morisky Medication Adherence Scale (MMAS-8) and the Beliefs about Medication Questionnaire (BMQ)...
July 6, 2017: Revista Española de Enfermedades Digestivas
https://www.readbyqxmd.com/read/28678626/optimising-use-of-thiopurines-in-inflammatory-bowel-disease
#5
Robin J Dart, Peter M Irving
Thiopurines are central to inflammatory bowel disease (IBD) therapeutics, either as monotherapy or in combination with newer biologic therapies, however it is only recently that focus has increased on improving effectiveness and tolerability through optimisation. Areas covered: We review the role of thiopurines in IBD and the importance of the timing of initiation of therapy. Drug metabolism and pharmacogenetics have increasingly played a role in determining dosing and dose optimisation and we review the rationale for this in both thiopurine monotherapy and in combination with biologic agents...
July 12, 2017: Expert Review of Clinical Immunology
https://www.readbyqxmd.com/read/28670229/nudt15-fto-and-runx1-genetic-variants-and-thiopurine-intolerance-among-japanese-patients-with-inflammatory-bowel-diseases
#6
Toshiyuki Sato, Tetsuya Takagawa, Yoichi Kakuta, Akihiro Nishio, Mikio Kawai, Koji Kamikozuru, Yoko Yokoyama, Yuko Kita, Takako Miyazaki, Masaki Iimuro, Nobuyuki Hida, Kazutoshi Hori, Hiroki Ikeuchi, Shiro Nakamura
BACKGROUND/AIMS: Recent genome-wide analyses have provided strong evidence concerning adverse events caused by thiopurine drugs such as azathioprine (AZA) and 6-mercaptopurine. The strong associations identified between NUDT15 p.Arg139Cys and thiopurine-induced leukopenia and severe hair loss have been studied and confirmed over the last 2 years. However, other coding variants, including NUDT15 p.Val18_Val19insGlyVal, NUDT15 p.Val18Ile, and FTO p.Ala134Thr, and a noncoding variation in RUNX1 (rs2834826) remain to be examined in detail in this respect...
July 2017: Intestinal Research
https://www.readbyqxmd.com/read/28659275/novel-variants-in-nudt15-and-thiopurine-intolerance-in-children-with-acute-lymphoblastic-leukemia-from-diverse-ancestry
#7
Takaya Moriyama, Yung-Li Yang, Rina Nishii, Hany Ariffin, Chengcheng Liu, Ting-Nien Lin, Wenjian Yang, Dong-Tsamn Lin, Chih-Hsiang Yu, Shirley Kham, Ching-Hon Pui, William E Evans, Sima Jeha, Mary V Relling, Allen Eng-Juh Yeoh, Jun J Yang
Prolonged exposure to thiopurines (e.g., mercaptopurine [MP]) is essential for curative therapy in acute lymphoblastic leukemia (ALL) but is also associated with frequent dose-limiting hematopoietic toxicities, partly explained by inherited genetic polymorphisms in drug metabolizing enzymes (e.g., TPMT). Recently, our group and others identified germline genetic variants in NUDT15 as another major cause of thiopurine-related myelosuppression, particularly in Asians and Hispanics. Herein we described three novel NUDT15 coding variants (p...
June 28, 2017: Blood
https://www.readbyqxmd.com/read/28651549/6-methylmercaptopurine-riboside-a-thiopurine-nucleoside-with-antiviral-activity-against-canine-distemper-virus-in-vitro
#8
Otávio Valério de Carvalho, Daniele Mendes Félix, Claudia de Camargo Tozato, Juliana Lopes Rangel Fietto, Márcia Rogéria de Almeida, Gustavo Costa Bressan, Lindomar José Pena, Abelardo Silva-Júnior
BACKGROUND: Canine distemper (CD) is a widespread infectious disease that can severely impact a variety of species in the order Carnivora, as well as non-carnivore species such as non-human primates. Despite large-scale vaccination campaigns, several fatal outbreaks have been reported in wild and domestic carnivore populations. This, in association with expansion of the disease host range and the development of vaccine-escape strains, has contributed to an increased demand for therapeutic strategies synergizing with vaccine programs for effectively controlling canine distemper...
June 26, 2017: Virology Journal
https://www.readbyqxmd.com/read/28650902/itpa-activity-in-adults-and-children-treated-with-or-without-azathioprine-relationship-between-tpmt-activity-thiopurine-metabolites-and-co-medications
#9
Boulieu Roselyne, Antony Citterio-Quentin, Mustapha Moulsma, Marie-Paule Gustin
BACKGROUND: The implication of inosine triphosphate pyrophosphatase (ITPA) on thiopurine drug response variability has been investigated but little data is available on its role on thiopurine metabolites. ITPA' ability to modify the thiopurine metabolite levels currently used to optimize azathioprine (AZA) therapy in relation to TPMT activity, the aim of this study is to investigate ITPA phenotype in a large population and to evaluate the relation between ITPA and TPMT activities and thiopurine metabolites...
June 22, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28644183/more-dose-dependent-side-effects-with-mercaptopurine-over-azathioprine-in-ibd-treatment-due-to-relatively-higher-dosing
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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)...
August 2017: Inflammatory Bowel Diseases
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