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https://www.readbyqxmd.com/read/29147133/allopurinol-in-combination-with-thiopurine-induces-mucosal-healing-and-improves-clinical-and-metabolic-outcomes-in-ibd
#1
Brigitte Moreau, Pierre Clement, Yves Theoret, Ernest G Seidman
Background: Thiopurines, azathioprine (AZA) and 6-mercaptopurine (6-MP) are common maintenance medications for inflammatory bowel disease (IBD). Excessive methylation via thiopurine methyltransferase (TPMT) frequently causes therapeutic failure. Allopurinol reduces excessive 6-methyl-mercaptopurine (6-MMP) while enhancing 6-thioguanine (6-TGN) levels. The aim of this study was to evaluate clinical, metabolic and endoscopic impact of allopurinol in combination with low-dose thiopurine in IBD...
November 2017: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/29145599/a-role-for-thiopurine-metabolites-in-the-synergism-between-thiopurines-and-infliximab-in-inflammatory-bowel-disease
#2
Ditte V Mogensen, Jørn Brynskov, Mark A Ainsworth, Jacob Nersting, Kjeld Schmiegelow, Casper Steenholdt
Background: Interactions between principal cytotoxic thiopurine metabolites, 6-thioguanine nucleotides (6-TGN), and infliximab (IFX) and anti-IFX antibodies (Abs) may contribute to higher effectiveness of IFX-thiopurine-combination therapy than monotherapies in inflammatory bowel disease. Methods: To examine if thiopurine metabolites influenced trough IFX and anti-IFX Abs, 89 patients previously assessed for anti-IFX Abs were included. To assess if IFX influenced thiopurine metabolites, 8 patients having responded to 12 weeks of intensified IFX at a constant thiopurine dosing were included...
November 14, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/29140288/capillary-electrophoresis-hyphenated-with-mass-spectrometry-for-determination-of-inflammatory-bowel-disease-drugs-in-clinical-urine-samples
#3
Katarína Maráková, Juraj Piešťanský, Zuzana Zelinková, Peter Mikuš
Azathioprine is the main thiopurine drug used in the treatment of immune-based inflammations of gastrointestinal tract. For the purpose of therapy control and optimization, effective and reliable analytical methods for a rapid drug monitoring in biological fluids are essential. Here, we developed a separation method based on the capillary electrophoresis (CE) hyphenated with tandem mass spectrometry (MS/MS) for the simultaneous determination of azathioprine and its selected metabolites (6-thioguanine, 6-mercaptopurine, and 6-methylmercaptopurine) as well as other co-medicated drugs (mesalazine, prednisone, and allopurinol)...
November 15, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29120908/patients-beliefs-about-medicine-are-associated-with-early-thiopurine-discontinuation-in-patients-with-inflammatory-bowel-diseases
#4
Mark M T J Broekman, Marieke J H Coenen, Geert J Wanten, Corine J van Marrewijk, Wietske Kievit, Olaf H Klungel, André L M Verbeek, Dennis R Wong, Piet M Hooymans, Henk-Jan Guchelaar, Hans Scheffer, Luc J J Derijks, Marcel L Bouvy, Dirk J de Jong
BACKGROUND: Patients' beliefs about medicine may either reflect the necessity for treatment or concerns regarding the treatment. We explored the extent to which these beliefs have an effect on thiopurine metabolite levels and premature discontinuation in patients with inflammatory bowel disease (IBD). PATIENTS AND METHODS: Patients enrolled in the 'Thiopurine response Optimization by Pharmacogenetic testing in Inflammatory Bowel Disease Clinics' (TOPIC) trial were asked to complete the Beliefs about Medicine Questionnaire (BMQ) 4 weeks after thiopurine initiation...
November 8, 2017: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29114832/association-between-use-of-thiopurines-or-tumor-necrosis-factor-antagonists-alone-or-in-combination-and-risk-of-lymphoma-in-patients-with-inflammatory-bowel-disease
#5
Magali Lemaitre, Julien Kirchgesner, Annie Rudnichi, Fabrice Carrat, Mahmoud Zureik, Franck Carbonnel, Rosemary Dray-Spira
Importance: An increased risk of lymphoma has been reported among patients receiving thiopurines for inflammatory bowel disease (IBD). The risk of lymphoma associated with anti-tumor necrosis factor (TNF) agents either alone or in combination with thiopurines is uncertain. Objective: To assess the risk of lymphoma associated with thiopurines and anti-TNF agents, used alone or in combination, for the management of IBD. Design, Setting, and Participants: Nationwide cohort study based on French National Health Insurance databases...
November 7, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/29105142/the-risk-of-non-melanoma-skin-cancer-in-new-zealand-in-inflammatory-bowel-disease-patients-treated-with-thiopurines
#6
Morwan Bahi, Russell S Walmsley, Andrew R Gray, David Young, Catherine E Hobbs, Kristina Aluzaite, Michael Schultz
BACKGROUND AND AIM: New Zealand (NZ) has one of the highest rates of non-melanoma skin cancers (NMSC) in the world. Thiopurine use in Inflammatory Bowel Disease (IBD) patients has been shown to increase NMSC risk. This study aimed to investigate the possible increase of NMSC risk in thiopurine-treated IBD patients in NZ despite the high background rate. METHODS: IBD patients treated with thiopurines and healthy controls were recruited across two different latitude centers in NZ...
November 4, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29104132/clinical-and-pharmacokinetic-factors-associated-with-adalimumab-induced-mucosal-healing-in-patients-with-crohn-s-disease
#7
Kenji Watanabe, Takayuki Matsumoto, Tadakazu Hisamatsu, Hiroshi Nakase, Satoshi Motoya, Naoki Yoshimura, Tetsuya Ishida, Shingo Kato, Tomoo Nakagawa, Motohiro Esaki, Masakazu Nagahori, Toshiyuki Matsui, Yuji Naito, Takanori Kanai, Yasuo Suzuki, Masanori Nojima, Mamoru Watanabe, Toshifumi Hibi
BACKGROUND & AIMS: We previously reported results from a prospective randomized controlled trial comparing the efficacy of adalimumab monotherapy vs combination with azathioprine for patients with Crohn's disease (CD) who were naïve to biologics and thiopurines. We performed a sub-analysis of data from this study to evaluate factors associated with endoscopic response and mucosal healing in study participants. METHODS: We compared simple endoscopic scores for CD (SES-CD) in between patients with moderate to severe active CD randomly assigned groups that received adalimumab monotherapy (n=85) or adalimumab in combination with azathioprine (n=91), from June 2011 to June 2014 in Japan...
November 2, 2017: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29079905/anti-tumour-necrosis-factor-therapy-for-paediatric-crohn-s-disease-improved-benefits-through-treatment-optimisation-deeper-understanding-of-its-risks-and-reduced-costs-due-to-biosimilar-availability
#8
M A Cozijnsen, J N Samsom, L de Ridder
Antibodies directed to tumour necrosis factor-α (TNF-α) are very effective in treating paediatric Crohn's disease (CD). Over the last few years, research has provided important new insights into how to optimise this treatment's effectiveness. Research on predictors for anti-TNF treatment responsiveness has revealed potential markers, but data on their accuracy in paediatric CD patients are lagging behind. Also, new evidence has become available on the safety profile of anti-TNF antibodies that suggests the assumed increased malignancy risk seen in patients on anti-TNF and thiopurine combination treatment may be linked more to thiopurine use and not to anti-TNF treatment...
October 27, 2017: Paediatric Drugs
https://www.readbyqxmd.com/read/29077839/anti-tnf-re-induction-is-as-effective-simpler-and-cheaper-compared-with-dose-interval-shortening-for-secondary-loss-of-response-in-crohn-s-disease
#9
Ashish Srinivasan, Abhinav Vasudevan, Anne McFarlane, Miles P Sparrow, Peter R Gibson, Daniel van Langenberg
Background and Aims: The optimal duration of dose-intensified therapy following secondary loss of response (LOR) to anti-TNF therapy remains unclear. Anti-TNF re-induction involves a finite period of intensified therapy and may be a cost-effective means of re-capturing response. This study aimed to compare the efficacy, durability and cost of anti-TNF re-induction and dose interval shortening (DIS) for secondary LOR in Crohn's disease (CD). Methods: This was a retrospective observational study in CD patients who developed secondary LOR to maintenance anti-TNF therapy requiring subsequent re-induction and/or DIS...
October 25, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/29065511/novel-tetra-primer-arms-pcr-assays-for-thiopurine-intolerance-susceptibility-mutations-nudt15-c-415c-t-and-tpmt-c-719a-g-tpmt-3c-in-east-asians
#10
Chi-Chun Ho, Wai-Ying Fong, Yuen-Hon Lee, Wing-Tat Poon
Thiopurines are clinically useful in the management of diverse immunological and malignant conditions. Nevertheless, these purine analogues can cause lethal myelosuppression, which may be prevented by prospective testing for variants in the thiopurine S-methyltransferase (TPMT) and, in East Asians, Nudix hydrolase 15 (NUDT15) genes. Two single-tube, tetra-primer amplification refractory mutation system polymerase chain reaction (ARMS-PCR) assays were developed to genotype the common loss-of-function variants NUDT15 c...
October 23, 2017: Genes
https://www.readbyqxmd.com/read/29060953/-effect-of-immunomodulators-and-biologic-agents-on-malignancy-in-patients-with-inflammatory-bowel-disease
#11
REVIEW
Jee Hyun Kim, Ji Won Kim
Immunosuppressive agents and biological agents are widely used for therapy in patients with inflammatory bowel disease (IBD). However, these therapies may be associated with an increased risk of malignancy. There is evidence that exposure of the therapeutic agents such as thiopurine and anti-tumor necrosis factor for IBD is associated with an increased risk of lymphoproliferative disorders, skin cancers, or uterine cervical cancers. This article reviews the malignancies associated with the use of immunosuppressive agents and biological agents in IBD...
October 25, 2017: Korean Journal of Gastroenterology, Taehan Sohwagi Hakhoe Chi
https://www.readbyqxmd.com/read/29051993/treatment-related-sinusoidal-obstruction-syndrome-in-children-with-de-novo-acute-lymphoblastic-leukemia-during-intensification
#12
Casey L McAtee, Netta Schneller, Julienne Brackett, M Brooke Bernhardt, Eric S Schafer
PURPOSE: Sinusoidal obstruction syndrome (SOS), also known as veno-occlusive disease, has been described following treatment of acute lymphoblastic leukemia (ALL) with the anti-metabolite 6-thioguanine (6-TG). Previous studies incorporating daily 6-TG into maintenance chemotherapy demonstrated a high incidence of SOS, typically presenting after prolonged exposures to 6-TG. 6-TG continues to be used as a single, 14-day burst during intensification; however, SOS associated with brief courses of 6-TG is poorly described...
October 19, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29051981/preoperative-optimization-of-patients-with-inflammatory-bowel-disease-undergoing-gastrointestinal-surgery-a-systematic-review
#13
REVIEW
Marie Strøm Zangenberg, Nir Horesh, Uri Kopylov, Alaa El-Hussuna
PURPOSE: Surgical management of inflammatory bowel disease (IBD) is a challenging task. The aim of preoperative optimization (PO) is to decrease the risk of complications and reduce the length of postoperative stay. The aim of this study was to review and grade the available evidence, attain clear recommendations, and point out potential future research. METHODS: Studies were identified from electronic databases (PubMed, Embase, and Cochrane Library) and scanning reference lists in relevant papers...
October 19, 2017: International Journal of Colorectal Disease
https://www.readbyqxmd.com/read/29050997/transient-elastography-to-assess-liver-stiffness-in-patients-with-inflammatory-bowel-disease
#14
Berrie Meijer, Charlotte K van Everdingen, Dewkoemar Ramsoekh, Catherine Stedman, Christopher M A Frampton, Chris J J Mulder, Gerd Bouma, Nanne K H de Boer, Richard B Gearry
BACKGROUND: Liver injury during inflammatory bowel disease (IBD) is primarily diagnosed by liver biopsy, which has a small but serious risk of severe complications. The aim of this study was to assess liver stiffness, and subsequently the prevalence and associations of liver fibrosis in IBD patients with thiopurine therapy and other clinical factors, by using transient elastography (TE). METHODS: In this prospective, international two-center study, included IBD-patients underwent TE measurements...
October 6, 2017: Digestive and Liver Disease
https://www.readbyqxmd.com/read/29050991/mycophenolate-mofetil-in-autoimmune-hepatitis-patients-with-suboptimal-outcomes-to-standard-therapy-the-tapestry-study
#15
Stuart K Roberts, Ricky Lim, Simone Strasser, Amanda Nicoll, Alessia Gazzola, Joanne Mitchell, Way Siow, Tiffany Khoo, Zaki Hamarneh, Martin Weltman, Paul Gow, Natasha Janko, Edmund Tse, Gauri Mishra, En-Hsiang Cheng, Miriam Levy, Wendy Cheng, Siddarth Sood, Richard Skoien, Jonathan Mitchell, Amany Zekry, Jacob George, Gerry MacQuillan, Alan Wigg, Katherine Stuart, William Sievert, Geoffrey McCaughan
BACKGROUND AND AIMS: The outcomes of mycophenolate mofetil (MMF) as rescue therapy for AIH patients who have a suboptimal outcome to standard therapy remain unclear. We evaluated the efficacy and safety of MMF in patients who had failed or were intolerant to corticosteroids with/without azathioprine. METHODS: A retrospective study was performed of AIH patients who received MMF after an inadequate response or intolerance to standard therapy. Patients were recruited from 17 liver clinics via the Australian Liver Association Clinical Research Network...
October 16, 2017: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29049535/all-thiopurines-are-equal-but-some-thiopurines-are-more-equal-than-others
#16
Berrie Meijer, Nanne K H de Boer
No abstract text is available yet for this article.
October 12, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/29049448/all-thiopurines-are-equal-but-some-thiopurines-are-more-equal-than-others-reply
#17
Raoul Tibes, Nathalie Ertz-Archambault, Heidi Kosiorek
No abstract text is available yet for this article.
October 12, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/29040422/pharmacogenetics-a-general-review-on-progress-to-date
#18
Ann K Daly
Background: Pharmacogenetics is not a new subject area but its relevance to drug prescribing has become clearer in recent years due to developments in gene cloning and DNA genotyping and sequencing. Sources of data: There is a very extensive published literature concerned with a variety of different genes and drugs. Areas of agreement: There is general agreement that pharmacogenetic testing is essential for the safe use of drugs such as the thiopurines and abacavir...
October 11, 2017: British Medical Bulletin
https://www.readbyqxmd.com/read/29040228/analytical-pitfalls-of-therapeutic-drug-monitoring-of-thiopurines-in-patients-with-inflammatory-bowel-disease
#19
Melek Simsek, Berrie Meijer, Chris J J Mulder, Adriaan A van Bodegraven, Nanne K H de Boer
The use of thiopurines in the treatment of inflammatory bowel disease (IBD) can be optimized by the application of therapeutic drug monitoring. In this procedure, 6-thioguanine nucleotides (6-TGN) and 6-methylmercaptopurine (6-MMP) metabolites are monitored and related to therapeutic response and adverse events, respectively. Therapeutic drug monitoring of thiopurines, however, is hampered by several analytical limitations resulting in an impaired translation of metabolite levels to clinical outcome in IBD...
December 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/29035443/genetic-variants-of-pre-micrornas-a-499g-rs3746444-and-t-196a2c-rs11614913-with-ulcerative-colitis-uc-and-investigated-with-thiopurine-s-methyltransferase-tpmt-activity
#20
Farideh Ghobadi, Asad Vaisi-Raygani, Fariborz Bahrehmand, Maryam Tanhapour, Amir Kiani, Zohreh Rahimi, Tayebeh Pourmotabbed
BACKGROUND: Abnormal expression and different splicing of miRNAs are involved in several human inflammatory disorders. It has been suggested that gene variants of miRNAs may be associated with increased risk of ulcerative colitis (UC). We aimed to evaluate the association of two SNPs (miRNA-A-499G(rs3746444) and miRNA-T196a2C(rs11614913)) with the risk of UC and monitor their effect on thiopurine-S-methyltransferase (TPMT) activity in Kurdish population of Iran. METHODS: This case-control study was performed on 210 UC patients and 212 healthy individuals...
October 1, 2017: Clinical Laboratory
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