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https://www.readbyqxmd.com/read/29688409/methotrexate-for-the-treatment-of-pediatric-crohn-s-disease-a-systematic-review-and-meta-analysis
#1
Ruben J Colman, Rachel C Lawton, Marla C Dubinsky, David T Rubin
Background: Methotrexate (MTX) is an immunomodulator used for the treatment of pediatric inflammatory bowel disease (IBD). There are currently no RCTs that assess the treatment efficacy of methotrexate within the pediatric IBD patient population. This systematic review and meta-analysis assesses the efficacy of MTX therapy among the existing pediatric literature. Methods: A systematic literature search was performed using MEDLINE and the Cochrane library from inception until March 2016...
April 23, 2018: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/29688401/anal-fistulas-in-severe-perineal-crohn-s-disease-mri-assessment-in-the-determination-of-long-term-healing-rates
#2
Charlène Brochard, Amandine Landemaine, Alexandre Merlini L'Heritier, Marie Provost Dewitte, Belinda Tchoundjeu, Tanguy Rohou, Aurélien Garros, Guillaume Bouguen, Laurent Siproudhis
Background & Aims: The European Crohn's and Colitis Organization recommends magnetic resonance imaging (MRI) of anal fistulas to decide on the drug/surgery strategy. No evidence is available on the long-term impact of MRI features on fistula healing. The aim of this study was to evaluate the benefit of combined drug/surgery strategies for the treatment of perianal Crohn's fistulas based on MRI factors at referral. Methods: The clinical event (anal abscess, new fistula tract, cellulitis), therapeutic intervention (introduction/optimization of immunosuppressant/biologics, anal surgery, intestinal resection, stoma), and MRI data were prospectively recorded for patients with Crohn's disease (CD) and anal fistulas...
April 20, 2018: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/29683944/slco1b1-polymorphisms-are-associated-with-drug-intolerance-in-childhood-leukemia-maintenance-therapy
#3
İrem Eldem, Duygu Yavuz, Özge Cumaoğullari, Talia İleri, Elif Ünal İnce, Mehmet Ertem, Beyza Doğanay Erdoğan, Recep Bindak, Hilal Özdağ, N Lale Şatiroğlu-Tufan, L Zümrüt Uysal
BACKGROUND: Therapy discontinuations and toxicities occur because of significant interindividual variations in 6-mercaptopurine (6-MP) and methotrexate (MTX) response during maintenance therapy of childhood acute lymphoblastic leukemia (ALL). 6-MP/MTX intolerance in some of the patients cannot be explained by thiopurine S-methyl transferase (TPMT) gene variants. In this study, we aimed to investigate candidate pharmacogenetic determinants of 6-MP and MTX intolerance in Turkish ALL children...
April 20, 2018: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29669052/cancer-associated-chemotherapy-induces-less-ibd-exacerbations-and-a-reduction-of-ibd-medication-afterwards
#4
Özgür M Koc, Roel J W van Kampen, Adriaan A van Bodegraven
Background: The prevalence of inflammatory bowel disease (IBD) is increasing and, consequently, more IBD patients will develop cancer with need for cancer-associated chemotherapy. Physicians are therefore confronted with whether they should continue, stop, or restart IBD medication in relation with chemotherapy. The current strategy in our hospital is to discontinue immunomodulating IBD medication, comprising corticosteroids, anti-tumour necrosis factor (anti-TNF), and other immunosuppressives, before starting chemotherapy...
April 13, 2018: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/29668998/methotrexate-and-thioguanine-rescue-therapy-for-conventional-thiopurine-failing-ulcerative-colitis-patients-a-multi-center-database-study-on-tolerability-and-effectiveness
#5
Berrie Meijer, Chris J J Mulder, Gerd Bouma, Cyriel Y Ponsioen, C Janneke van der Woude, Andrea E van der Meulen, Dion S J Wintjens, Gerard Dijkstra, Frank Hoentjen, Bas Oldenburg, Adriaan A van Bodegraven, Nanne K H de Boer
Background: Patients with active ulcerative colitis (UC) failing conventional therapies are in need of rescue strategies. Due to the fact that accepted step-up therapy with biologicals is expensive and sometimes unavailable, alternative therapies are warranted. Methotrexate (MTX) and thioguanine (TG) have both been suggested as alternative maintenance strategies in conventional thiopurine failing UC patients. In this multicenter database study, we compared safety and effectiveness (drug-survival) of MTX and TG in UC patients...
April 13, 2018: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/29659353/-genetic-polymorphisms-of-thiopurine-methyltransferase-and-incidence-of-adverse-events-in-patients-with-medical-indication-of-azathioprine
#6
Manuel A Buhl, Graciela Gómez, María Victoria Collado, Elisabet M Oddo, Marina Khoury, Pablo J Azurmendi, Judith Sarano
Azathioprine is a thiopurine which has a narrow therapeutic index and marked hematological and hepatic toxicity. Thiopurine s-methyltransferase is an enzyme involved in the metabolism of thiopurines. Mutations in the gene that encodes the enzyme may augment the risk of adverse events. For that reason, pharmacogenetic determinations prior to the initiation of therapy can provide useful information for the future therapeutic strategy. Nevertheless, its utility in the local environment is not completely established...
2018: Medicina
https://www.readbyqxmd.com/read/29658768/idiopathic-portal-hypertension-with-regard-to-thiopurine-treatment
#7
Salvador Machlab, Mireia Miquel, Mercedes Vergara
Idiopathic portal hypertension (IPH) is an infrequent adverse reaction to the use of thiopurines that tends to be overlooked. Herein, we present a patient with ileocolic Crohn's disease treated with azathioprine who presented ascites, esophageal varices and splenomegaly without any signs of liver cirrhosis. A portal hemodynamics study revealed a normal portosystemic gradient compatible with presinusoidal portal hypertension. Finally, IPH was diagnosed after a liver biopsy. IPH secondary to thiopurines is due to a 6-thioguanine nucleotide (6-TGN)-dependent reaction and occurs predominantly between three months and three years after the start of treatment...
April 16, 2018: Revista Española de Enfermedades Digestivas
https://www.readbyqxmd.com/read/29655835/risk-of-serious-and-opportunistic-infections-associated-with-treatment-of-inflammatory-bowel-diseases
#8
Julien Kirchgesner, Magali Lemaitre, Fabrice Carrat, Mahmoud Zureik, Md Franck Carbonnel, Rosemary Dray-Spira
BACKGROUND & AIMS: The risk of infection associated with tumor necrosis factor antagonists (anti-TNF) and thiopurines (combination therapy) is uncertain. We assessed the risk of serious and opportunistic infections in patients with IBD treated with thiopurine monotherapy, anti-TNF monotherapy, or combination therapy in a large cohort of patients in France. METHODS: We performed a nationwide population-based study of patients (18 years or older) with a diagnosis of IBD in the French national health insurance database; we collected data from January 1, 2009 until December 31, 2014...
April 12, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29624476/immunotherapy-in-inflammatory-bowel-disease-novel-and-emerging-treatments
#9
Ignacio Catalan-Serra, Øystein Brenna
Inflammatory bowel disease (IBD) is a chronic disabling inflammatory process that affects young individuals, with growing incidence. The etiopathogenesis of IBD remains poorly understood. A combination of genetic and environmental factors triggers an inadequate immune response against the commensal intestinal flora in IBD patients. Thus, a better understanding of the immunological mechanisms involved in IBD pathogenesis is central to the development of new therapeutic options. Current pharmacological treatments used in clinical practice like thiopurines or anti-TNF are effective but can produce significant side effects and their efficacy may diminish over time...
April 6, 2018: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29623442/therapeutic-drug-monitoring-in-pediatric-inflammatory-bowel-disease
#10
REVIEW
Nicholas Carman, David R Mack, Eric I Benchimol
PURPOSE OF REVIEW: Therapeutic drug monitoring (TDM) has emerged as a useful tool to optimize the use of drug therapies in adults with inflammatory bowel disease (IBD), including both Crohn's disease (CD) and ulcerative colitis (UC), especially during the use of biological therapies, for which the pharmacokinetics and pharmacodynamics are highly variable among patients. Fewer data exist in children. This review examines the current literature on TDM in pediatric IBD. RECENT FINDINGS: Drug clearance is affected by a number of patient and disease factors...
April 5, 2018: Current Gastroenterology Reports
https://www.readbyqxmd.com/read/29618720/anti-tnf-and-thiopurine-therapy-in-pregnant-ibd-patients-does-not-significantly-alter-a-panel-of-b-cell-and-t-cell-subsets-in-1-year-old-infants
#11
Michael G Kattah, Jeffrey M Milush, Trevor Burt, Robert P McCabe, Michael I Whang, Averil Ma, Uma Mahadevan
OBJECTIVES: Infants exposed to combination therapy with anti-tumor necrosis factor (anti-TNF) agents and thiopurines may exhibit increased infections at 1 year of age compared to unexposed infants. We hypothesized that this increased risk of infection is due to abnormal development of the newborn immune system. METHODS: We immunophenotyped B-cell and T-cell subsets using multiparameter flow cytometry in 1-year-old infants whose mothers were exposed to therapeutic agents for IBD...
April 3, 2018: Clinical and Translational Gastroenterology
https://www.readbyqxmd.com/read/29618498/impact-of-thiopurines-on-the-natural-history-and-surgical-outcome-of-ulcerative-colitis-a-cohort-study
#12
Carl Eriksson, Sara Rundquist, Yang Cao, Scott Montgomery, Jonas Halfvarson
OBJECTIVE: Thiopurines are used as maintenance therapy in ulcerative colitis (UC), but whether these drugs influence the natural history of the disease is unknown. We aimed to assess the effect of thiopurines in terms of colectomy, hospital admission, progression in disease extent and anti-tumour necrosis factor (TNF) therapy within 10 years from initiation. DESIGN: Patients diagnosed with UC within the Örebro University Hospital catchment area, during 1963-2010, who initiated thiopurines (n=253) were included...
April 4, 2018: Gut
https://www.readbyqxmd.com/read/29601433/thiopurine-optimization-through-combination-with-allopurinol-in-children-with-inflammatory-bowel-diseases
#13
Mark R Serpico, Ross Maltz, Wallace Crandall, Josh Bricker, Jennifer L Dotson, Sandra C Kim, Brendan Boyle
OBJECTIVES: Thiopurines are commonly used in the maintenance of remission for children with inflammatory bowel diseases (IBD). Variation in drug metabolism may impact hepatotoxicity or therapeutic effect. We aimed to describe our center's experience with thiopurine optimization through the use of reduced thiopurine dosing in combination with allopurinol upon hepatotoxicity, drug metabolite levels and clinical outcomes in children with IBD. METHODS: Patients aged 2-21 years with IBD treated with the combination of thiopurines/allopurinol between 2008-2015 were retrospectively reviewed...
March 29, 2018: Journal of Pediatric Gastroenterology and Nutrition
https://www.readbyqxmd.com/read/29594970/lower-sustained-diphtheria-and-pertussis-antibody-concentrations-in-inflammatory-bowel-disease-patients
#14
Freddy Caldera, Sumona Saha, Arnold Wald, Christine A Garmoe, Sue McCrone, Bryant Megna, Dana Ley, Mark Reichelderfer, Mary S Hayney
BACKGROUND: Patients with inflammatory bowel disease (IBD) are often immunosuppressed, and those patients receiving anti-tumor necrosis factor α (TNF) therapy can have lower antibody responses to vaccines. Pertussis cases are at their highest levels in the post-vaccine era. There is little data regarding responses to the Tdap (tetanus, diphtheria, and acellular pertussis) vaccine in IBD patients. AIMS: The aim of this study was to compare sustained vaccine-induced Tdap antibody concentrations in a cohort of IBD patients stratified by medication regimens with healthy controls (HC) who had received an adult Tdap booster...
March 29, 2018: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/29572377/preclinical-evaluation-of-nudt15-guided-thiopurine-therapy-and-its-effects-on-toxicity-and-anti-leukemic-efficacy
#15
Rina Nishii, Takaya Moriyama, Laura J Janke, Wenjian Yang, Chase Suiter, Ting-Nien Lin, Lie Li, Kentaro Kihira, Hidemi Toyoda, Ute Hofmann, Matthias Schwab, Masatoshi Takagi, Tomohiro Morio, Atsushi Manabe, Shirley Kham, Nan Jiang, Karen R Rabin, Motohiro Kato, Katsuyoshi Koh, Allen Eng-Juh Yeoh, Hiroki Hori, Jun J Yang
Thiopurines (e.g., mercaputopruine [MP]) are highly efficacious anti-leukemic agents, but are also associated with dose-limiting toxicities. Recent studies by us and others identified inherited NUDT15 deficiency as a novel genetic cause of thiopurine toxicity, and there is a strong rationale for NUDT15 -guided dose individualization to preemptively mitigate side effects of this drug. Using CRISPR-Cas9 genome editing, we herein established a Nudt15 -/- mouse model to evaluate the effectiveness of this strategy in vivo...
March 23, 2018: Blood
https://www.readbyqxmd.com/read/29564674/interactions-between-thiopurine-metabolites-adalimumab-and-antibodies-against-adalimumab-in-previously-infliximab-treated-patients-with-inflammatory-bowel-disease
#16
Rikke B Holmstrøm, Ditte V Mogensen, Jørn Brynskov, Mark A Ainsworth, Jacob Nersting, Kjeld Schmiegelow, Casper Steenholdt
BACKGROUND: Interactions between thiopurines and infliximab presumably contribute to superior effect of infliximab-thiopurine combination therapy in patients with inflammatory bowel disease (IBD). We examined whether principal cytotoxic thiopurine metabolites influence adalimumab (ADL) and anti-ADL antibodies (Abs). METHODS: Ninety-eight IBD patients previously treated with infliximab (96%) in whom trough ADL and anti-ADL Abs had been assessed as part of their clinical care were included...
March 21, 2018: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/29562275/risk-of-serious-bacterial-infection-associated-with-tumor-necrosis-factor-alpha-inhibitors-in-children-and-young-adults-with-inflammatory-bowel-disease
#17
Wan-Ju Lee, Todd A Lee, Gregory S Calip, Katie J Suda, Leslie Briars, Glen T Schumock
Background: Prior studies evaluating the relationship between tumor necrosis factor-alpha inhibitors (TNFI) and infection were conducted in adults and had conflicting findings. We sought to examine the risk of serious infection associated with TNFIs compared with nonbiologic immunomodulators in children and young adults with inflammatory bowel disease (IBD) and to compare the risk among individual TNFIs. Methods: We conducted a cohort study using the Truven MarketScan Commercial Claims and Encounters database of patients age <30 years with a diagnosis of IBD who initiated treatment with a TNFI or immunomodulator (thiopurines or methotrexate) between 2009 and 2013...
March 19, 2018: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/29560650/an-unusual-case-of-hamartomatous-polyposis-with-malignancy-complication-in-a-patient-with-ulcerative-colitis-treated-with-golimumab
#18
A Al Khoury, C-Y Chao, S Camilleri-Broet, T Bessissow
We report an unusual case of hamartomatous polyposis with malignant complications in a patient with ulcerative colitis on golimumab and previous thiopurine therapy. This patient was evaluated for iron deficiency anemia and underwent hemicolectomy for extensive right-side predominant inflammatory pseudopolyps. Anemia persisted post-colectomy and subsequent gastroscopy showed a fungating polypoid lesion along with numerous carpet-like strawberry appearing polyps in the stomach extending from the gastro-esophageal junction to the distal part of the antrum, necessitating a gastrectomy...
October 2017: Acta Gastro-enterologica Belgica
https://www.readbyqxmd.com/read/29534852/association-between-tpmt-3c-and-decreased-thiopurine-s-methyltransferase-activity-in-patients-with-neuromyelitis-optica-spectrum-disorders-in-china
#19
Xiaoqing Gong, Shenghui Mei, Xindi Li, Xingang Li, Heng Zhou, Yonghong Liu, Anna Zhou, Li Yang, Zhigang Zhao, Xinghu Zhang
Thiopurines (TPRs) are effective drugs in treating neuromyelitis optica spectrum disorders (NMOSD) and other diseases. TPRs' toxicity is mainly imputed to thiopurine S-methyltransferase (TPMT) activity. In Chinese population, the most common and important variation of TPMT is TPMT*3C (rs1142345). This study aims to reveal the association between TPMT activity and genetic polymorphisms of TPMT in patients with NMOSD in China. An LC-MS/MS method was used to evaluate the TPMT activity by using 6-mercapthioprine as substrate in human erythrocyte hemolysate via 1 h incubation at 37 °C to form its methylated product 6-methylmercaptopurine (6-MMP)...
March 10, 2018: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/29525182/low-dose-thiopurine-with-allopurinol-co-therapy-overcomes-thiopurine-intolerance-and-allows-thiopurine-continuation-in-inflammatory-bowel-disease
#20
Abhinav Vasudevan, Lauren Beswick, Antony B Friedman, Alicia Moltzen, James Haridy, Ajay Raghunath, Miles Sparrow, Daniel van Langenberg
AIMS: To assess the utility and tolerability of thiopurine-allopurinol co-therapy in inflammatory bowel disease (IBD) patients with intolerance to thiopurine monotherapy. METHODS: A retrospective observational study assessed cases of thiopurine intolerance then switched to thiopurine allopurinol co-therapy between 2011 and 2015 at two centres. Indications for switch, dosing and subsequent clinical outcomes (including thiopurine persistence) were recorded. RESULTS: Of 767 patients on thiopurines for IBD, 89 (12%) were switched to co-therapy for intolerance...
February 10, 2018: Digestive and Liver Disease
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