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https://www.readbyqxmd.com/read/28346068/institutional-profile-university-of-florida-health-personalized-medicine-program
#1
Larisa H Cavallari, Kristin W Weitzel, Amanda R Elsey, Xinyue Liu, Scott A Mosley, Donald M Smith, Benjamin J Staley, Almut G Winterstein, Carol A Mathews, Francesco Franchi, Fabiana Rollini, Dominick J Angiolillo, Petr Starostik, Michael J Clare-Salzler, David R Nelson, Julie A Johnson
The University of Florida (UF) Health Personalized Medicine Program launched in 2012 with CYP2C19 genotyping for clopidogrel response at UF Health Shands Hospital. We have since expanded CYP2C19 genotyping to UF Health Jacksonville and established the infrastructure at UF Health to support clinical implementation for five additional gene-drug pairs: TPMT-thiopurines, IFNL3 (IL28B)-PEG IFN-α-based regimens, CYP2D6-opioids, CYP2D6/CYP2C19-antidepressants and CYP2C19-proton pump inhibitors. We are contributing to the evidence based on outcomes with genotype-guided therapy through pragmatic studies of our clinical implementations...
March 27, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28342949/use-of-thiopurines-during-conception-and-pregnancy-not-associated-with-adverse-pregancy-outcomes-or-health-of-infants-at-1-year-in-a-prospective-study
#2
Shannon L Kanis, Alison de Lima-Karagiannis, Nanne K H de Boer, C Janneke van der Woude
BACKGROUND & AIMS: Most data on the safety of thiopurine therapy for inflammatory bowel disease (IBD) during pregnancy come from retrospective studies, making it difficult to adjust for confounding factors. We performed a prospective cohort study to determine whether thiopurine use affects pregnancy outcomes or health outcomes of children. METHODS: We performed a prospective study of all women who visited the IBD preconception outpatient clinic at our tertiary health center in The Netherlands from December 2008 through May 2016...
March 22, 2017: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28333190/early-thiopurine-treatment-is-probably-beneficial-but-time-from-diagnosis-must-be-evaluated
#3
Cristina Concellón, Sara Gómez-Enjuto, Luis Fernández-Salazar
No abstract text is available yet for this article.
February 24, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28333183/machine-learning-algorithms-for-objective-remission-and-clinical-outcomes-with-thiopurines
#4
Akbar K Waljee, Kay Sauder, Anand Patel, Sandeep Segar, Boang Liu, Yiwei Zhang, Ji Zhu, Ryan W Stidham, Ulysses Balis, Peter D R Higgins
Background and Aims: Big data analytics leverage patterns in data to harvest valuable information, but are rarely implemented in clinical care. Optimising thiopurine therapy for inflammatory bowel disease [IBD] has proved difficult. Current methods using 6-thioguanine nucleotide [6-TGN] metabolites have failed in randomized controlled trials [RCTs], and have not been used to predict objective remission [OR]. Our aims were to: 1) develop machine learning algorithms [MLA] using laboratory values and age to identify patients in objective remission on thiopurines; and 2) determine whether achieving algorithm-predicted objective remission resulted in fewer clinical events per year...
March 14, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28317081/pharmacogenetic-predictors-of-treatment-related-toxicity-among-children-with-acute-lymphoblastic-leukemia
#5
REVIEW
Rochelle R Maxwell, Peter D Cole
PURPOSE OF REVIEW: The aim of this review is to summarize the most recent and most robust pharmacogenetic predictors of treatment-related toxicity (TRT) in childhood acute lymphoblastic leukemia (ALL). RECENT FINDINGS: Multiple studies have examined the toxicities of the primary chemotherapeutic agents used to treat childhood ALL in relation to host genetic factors. However, few results have been replicated independently, largely due to cohort differences in ancestry, chemotherapy treatment protocols, and definitions of toxicities...
March 20, 2017: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/28296824/multicentric-case-control-study-on-azathioprine-dose-and-pharmacokinetics-in-early-onset-pediatric-inflammatory-bowel-disease
#6
Gabriele Stocco, Stefano Martelossi, Serena Arrigo, Arrigo Barabino, Marina Aloi, Massimo Martinelli, Erasmo Miele, Daniela Knafelz, Claudio Romano, Samuele Naviglio, Diego Favretto, Eva Cuzzoni, Raffaella Franca, Giuliana Decorti, Alessandro Ventura
BACKGROUND: Early-onset inflammatory bowel disease (IBD) is generally aggressive, with a high probability of complications and need of surgery. Despite the introduction of highly effective biological drugs, treatment with azathioprine continues to be important even for early-onset IBD; however, in these patients azathioprine response seems to be reduced. This study evaluated azathioprine doses, metabolite concentrations, and their associations with patients' age in children with IBD treated at 6 tertiary pediatric referral centers...
April 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28295989/pharmacokinetics-of-two-6-mercaptopurine-liquid-formulations-in-children-with-acute-lymphoblastic-leukemia
#7
Jaszianne A Tolbert, Shasha Bai, Susan M Abdel-Rahman, Keith J August, Scott J Weir, Gregory L Kearns, Kathleen A Neville
BACKGROUND: A liquid formulation of 6-mercaptopurine (6-MP) was recently approved by the Food and Drug Administration (Purixan®) based on bioavailability (BA) data from healthy adults. We examined the pharmacokinetics (PK) and BA of 6-MP in children with acute lymphoblastic leukemia (ALL) comparing a marketed tablet, two extemporaneously prepared liquid formulations, and data from the approved liquid formulation. METHODS: Twenty-two children (6-17 years) participated in a randomized two-way, crossover study of two cohorts...
March 10, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28278299/combination-treatment-with-6-mercaptopurine-and-allopurinol-in-hepg2-and-hek293-cells-effects-on-gene-expression-levels-and-thiopurine-metabolism
#8
Sofie Haglund, Svante Vikingsson, Sven Almer, Jan Söderman
Combination treatment with low-dose thiopurine and allopurinol (AP) has successfully been used in patients with inflammatory bowel disease with a so called skewed thiopurine metabolite profile. In red blood cells in vivo, it reduces the concentration of methylated metabolites and increases the concentration of the phosphorylated ones, which is associated with improved therapeutic efficacy. This study aimed to investigate the largely unknown mechanism of AP on thiopurine metabolism in cells with an active thiopurine metabolic pathway using HepG2 and HEK293 cells...
2017: PloS One
https://www.readbyqxmd.com/read/28277331/nudt15-genotype-distributions-in-the-korean-population
#9
Hyoung-Tae Kim, Rihwa Choi, Hong-Hee Won, Yon Ho Choe, Ben Kang, Kiwuk Lee, Hong Hoe Koo, Keon Hee Yoo, Young-Ho Kim, Soo-Youn Lee
Thiopurines have a narrow therapeutic range because of frequent toxicity (i.e. marrow suppression), which is only partly explained by TPMT genetic polymorphisms, especially within Asian populations. Recent studies have identified NUDT15 variation as another important factor affecting thiopurine metabolism. In this study, a total of four NUDT15 coding variants (p.Arg139Cys, p.Arg139His, p.Val18Ile, and p.Val18_Val19insGlyVal) were genotyped in 920 Korean individuals using direct sequencing of NUDT15 for the first time in a Korean population...
March 8, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28276819/is-there-a-role-for-thioguanine-therapy-in-ibd-in-2017-and-beyond
#10
Kirstin M Taylor, Mark G Ward, Paul A Blaker, Miles P Sparrow
Conventional thiopurines are effective for the maintenance of remission of Crohn's disease and ulcerative colitis, however, up to half of patients are intolerant or unresponsive to these medications. Thioguanine is an alternative thiopurine that has shown efficacy in inflammatory bowel disease, and is particularly useful to circumvent certain side effects associated with conventional thiopurines, for example, pancreatitis. Its association with nodular regenerative hyperplasia of the liver has hindered its widespread use...
February 20, 2017: Expert Review of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28264514/excited-state-dynamics-of-the-thiopurine-prodrug-6-thioguanine-can-n9-glycosylation-affect-its-phototoxic-activity
#11
Brennan Ashwood, Steffen Jockusch, Carlos E Crespo-Hernández
6-Thioguanine, an immunosuppressant and anticancer prodrug, has been shown to induce DNA damage and cell death following exposure to UVA radiation. Its metabolite, 6-thioguanosine, plays a major role in the prodrug's overall photoreactivity. However, 6-thioguanine itself has proven to be cytotoxic following UVA irradiation, warranting further investigation into its excited-state dynamics. In this contribution, the excited-state dynamics and photochemical properties of 6-thioguanine are studied in aqueous solution following UVA excitation at 345 nm in order to provide mechanistic insight regarding its photochemical reactivity and to scrutinize whether N9-glycosylation modulates its phototoxicity in solution...
February 28, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28262261/pharmacogenetics-of-anti-cancer-drugs-state-of-the-art-and-implementation%C3%A2-%C3%A2-recommendations-of-the-french-national-network-of-pharmacogenetics
#12
Sylvie Quaranta, Fabienne Thomas
Individualized treatment is of special importance in oncology because the drugs used for chemotherapy have a very narrow therapeutic index. Pharmacogenetics may contribute substantially to clinical routine for optimizing cancer treatment to limit toxic effects while maintaining efficacy. This review presents the usefulness of pharmacogenetic tests for some key applications: dihydropyrimidine dehydrogenase (DPYD) genotyping for fluoropyrimidine (5-fluorouracil, capecitabine), UDP glucuronosylstransferase (UGT1A1) for irinotecan and thiopurine S-methyltransferase (TPMT) for thiopurine drugs...
January 30, 2017: Thérapie
https://www.readbyqxmd.com/read/28251684/influence-of-age-at-diagnosis-on-the-clinical-characteristics-of-crohn-s-disease-in-korea-results-from-the-connect-study
#13
Sung Wook Hwang, Jee Hyun Kim, Jong Pil Im, Byong Duk Ye, Hoon Sup Koo, Kyu Chan Huh, Jae Hee Cheon, You Sun Kim, Young Ho Kim, Dong Soo Han, Won Ho Kim, Joo Sung Kim
BACKGROUND AND AIM: The present study evaluated the clinical characteristics of Korean patients with Crohn's disease (CD) according to their age at diagnosis in a nationwide multicenter cohort study. METHODS: A total of 1,224 patients diagnosed with CD between 1982 and 2008 in 32 hospitals were included, and age at diagnosis was categorized as ≤ 16 (G1), 17-40 (G2), 41-59 (G3) and ≥ 60 (G4) years old. The baseline characteristics, medication, and intestinal resection were compared according to the age at diagnosis...
March 2, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28230306/suppression-of-anti-drug-antibodies-to-infliximab-or-adalimumab-with-the-addition-of-an-immunomodulator-in-patients-with-inflammatory-bowel-disease
#14
A S Strik, G R van den Brink, C Ponsioen, R Mathot, M Löwenberg, G R D'Haens
BACKGROUND: Loss of response to anti-tumour necrosis factor (TNF) therapy in patients with inflammatory bowel disease (IBD) is often caused by anti-drug antibody formation with neutralisation of drug effect. Addition of an immunomodulator has been suggested to reduce immunogenicity, leading to regained response. AIM: To investigate whether addition of an immunomodulator to anti-TNF monotherapy could lead to anti-drug antibody suppression and regained clinical response in IBD patients...
February 23, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28228435/crohn-s-disease-complicated-by-epstein-barr-virus-driven-haemophagocytic-lymphohistiocytosis-successfully-treated-with-rituximab
#15
Grace Thompson, Dominic Pepperell, Ian Lawrence, Benjamin David McGettigan
We report a case of Epstein-Barr virus (EBV)-driven haemophagocytic lymphohistiocytosis (HLH) in a man with Crohn's disease treated with 6-mercaptopurine and adalimumab therapy who was successfully treated with rituximab therapy alone. This is the first published case in an adult patient with EBV-driven HLH in the setting of thiopurine use and inflammatory bowel disease to be successfully treated with rituximab therapy alone. Here, we will discuss putative immunological mechanisms which may contribute to this potentially life-threatening complication...
February 22, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28212467/comparison-of-6-mercaptopurine-with-6-thioguanine-for-the-analysis-of-thiopurine-s-methyltransferase-activity-in-human-erythrocyte-by-lc-ms-ms
#16
Shenghui Mei, Xindi Li, Xiaoqing Gong, Xiaoyi Zhang, Xingang Li, Li Yang, Leting Zhu, Heng Zhou, Yonghong Liu, Anna Zhou, Xinghu Zhang, Zhigang Zhao
Thiopurines (TPDs) are first-line drugs in treating neuromyelitis optica spectrum disorders (NMOSD). Thiopurine S-methyltransferase activity (TPMT), a major determinant of TPDs toxicity, was suggested to be evaluated before TPDs treatment by using 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) as substrate. However, the equivalent of the two substrates in TPMT activity evaluation was unknown, and alternative substrate was required in TPMT activity evaluation in patients who were already taking 6-MP or 6-TG...
February 17, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28211629/editorial-can-we-get-more-clinical-benefit-from-thiopurine-metabolite-testing
#17
EDITORIAL
A G Fraser
No abstract text is available yet for this article.
March 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28211625/editorial-can-we-get-more-clinical-benefit-from-thiopurine-metabolite-testing-authors-reply
#18
EDITORIAL
D R Wong, P M Hooymans
No abstract text is available yet for this article.
March 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28203101/prevalence-of-clinically-actionable-genotypes-and-medication-exposure-of-older-adults-in-the-community
#19
Nilofar Daneshi, Elizabeth Holliday, Stephen Hancock, Jennifer J Schneider, Rodney J Scott, John Attia, Elizabeth A Milward
This study analyzed clinically actionable pharmacogenotypes for clopidogrel, warfarin, statins, thiopurines, and tacrolimus using microarray data for 2121 participants (55-85 years) from the Australian Hunter Community Study (HCS). At least 74% of participants (95% confidence interval [CI]: 72%-76%) had strong level evidence for at least one medium- or high-risk actionable genotype that would trigger a change in standard therapy under current international recommendations. About 14% of these participants (95% CI: 12%-16%) were taking medication potentially affected by the genotype in question...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/28193515/infliximab-not-associated-with-increased-risk-of-malignancy-or-hemophagocytic-lymphohistiocytosis-in-pediatric-patients-with-inflammatory-bowel-disease
#20
Jeffrey S Hyams, Marla C Dubinsky, Robert N Baldassano, Richard B Colletti, Salvatore Cucchiara, Johanna Escher, William Faubion, John Fell, Benjamin D Gold, Anne Griffiths, Sibylle Koletzko, Subra Kugathasan, James Markowitz, Frank M Ruemmele, Gigi Veereman, Harland Winter, Nicholas Masel, Chu Ri Shin, Kezhen L Tang, Meena Thayu
BACKGROUND AND AIMS: Immunosuppressive therapy for inflammatory bowel disease (IBD) in pediatric patients is thought to increase risk of malignancy and lymphoproliferative disorders, including hemophagocytic lymphohistiocytosis (HLH). We compared unadjusted incidence rates and of malignancy and HLH in pediatric patients with IBD exposed to infliximab compared with patients not exposed to biologics and calculated standardized incidence ratios (SIRs). METHODS: We collected and analyzed data from 5766 participants in a prospective study of long-term outcomes of pediatric patients with IBD (NCT00606346), from 2007 through 30 June 2016...
February 10, 2017: Gastroenterology
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