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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
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
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
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
Erik Munnig-Schmidt, Mei Zhang, Chris J Mulder, Murray L Barclay
Background: The thiopurines azathioprine and mercaptopurine remain pivotal maintenance treatments in inflammatory bowel disease (IBD); however, up to 15%-20% of patients preferentially produce the hepatotoxic metabolite 6-methylmercaptopurine (6MMP) at the expense of the therapeutic 6-thioguanine nucleotides (6TGN). This metabolic shunting usually begins within 3 months of therapy. We noted patients developing shunting many months or years after starting treatment and aimed to determine how often this late shunting occurs and whether this could be explained by patient factors or concomitant medications...
March 7, 2018: Inflammatory Bowel Diseases
Nabeel Khan, Chinmay Trivedi, Yash Shah, Dhruvan Patel, James Lewis, Yu-Xiao Yang
Aim: There is a paucity of data on the clinical course and the factors affecting the clinical course of herpes zoster (HZ) in inflammatory bowel disease (IBD). Our aim was to determine the impact of anti-TNF therapy and other factors on the clinical course of HZ in IBD patients. Methods: We conducted a retrospective cohort study among a cohort of nation-wide Veterans Affairs patients with IBD who developed incident HZ. The exposed group consisted of eligible study patients who were actively exposed to anti-TNF alone or anti-TNF plus thiopurines at the time of HZ onset...
March 7, 2018: Inflammatory Bowel Diseases
Yiping Zhu, Dandan Yin, Yali Su, Xuyang Xia, Takaya Moriyama, Rina Nishii, Fei Liao, Shouyue Zhang, Xia Guo, Qianqian Hou, Yuan Ai, Xueyan Zhou, Shuwen Sun, Duyu Zhang, Yan Zhang, Chao Lin, Yiqi Deng, Xiaoxi Lu, Yuelan Wang, Zhigui Ma, Heyao Wang, Bo Liu, Li Yang, Wei Zhang, Jun J Yang, Yang Shu, Ju Gao, Heng Xu
No abstract text is available yet for this article.
March 8, 2018: Haematologica
Ziad Bakouny, Fares Yared, Elie El Rassy, Rita Jabbour, Rachel Hallit, Nathalie Khoury, Khalil Honein, Joseph Bou Jaoude
INTRODUCTION: There is a lack of studies on the optimal anti-tumor necrosis factor (anti-TNF) agent for postoperative prophylaxis of Crohn's disease (CD) recurrence. Therefore, we conducted a network meta-analysis (NMA) of prospective trials to compare the efficacy of anti-TNF agents in the prevention of postoperative endoscopic and clinical recurrence of CD following ileocolonic resection. METHODS: We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and recent American gastroenterology association (AGA) meeting abstracts through August 2017...
March 6, 2018: Journal of Clinical Gastroenterology
Hlaing H Maw, Xingzhong Zeng, Scot Campbell, Mitchell E Taub, Aaron M Teitelbaum
BI 187004, an 11β-hydroxysteroid dehydrogenase 1 (HSD) inhibitor, was administered once daily for 14 days to eight patients with type 2 diabetes mellitus. N-methylation was identified as a major biotransformation pathway. In four patients treated with BI 187004, the plasma exposure of an N-methylbenzimidazole metabolite (M1) was 7 fold higher than the remaining four patients, indicating a substantial degree of metabolic variation. To identify the methyltransferase enzyme(s) responsible for N-methylation, BI 187004 was incubated with human liver microsomes (HLM), human kidney microsomes (HKM), and their respective cytosolic preparations in the presence and absence of isoform-selective chemical inhibitors...
March 7, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Eugeni Domènech, Julián Panés, Joaquín Hinojosa, Vito Annese, Fernando Magro, Giacomo Carlo Sturniolo, Fabrizio Bossa, Francisco Fernández, Benito González-Conde, Valle García-Sánchez, Axel Dignass, José Manuel Herrera, José Luis Cabriada, Jordi Guardiola, Maurizio Vecchi, Francisco Portela, Daniel Ginard
Background and Aims: Steroid-dependency occurs in up to 30% of patients with ulcerative colitis (UC). In this setting, few drugs have demonstrated efficacy in inducing steroid-free remission. The aim was to evaluate the efficacy and safety of adding granulocyte/monocyte apheresis (GMA) to oral prednisone in patients with steroid-dependent UC. Methods: Randomized, multicentre, open trial comparing 7 weekly sessions of GMA plus oral prednisone (40mg/day and tapering) to prednisone alone in patients with active, steroid-dependent UC (Mayo score 4-10 and inability to withdraw corticosteroids in 3 months or relapse within the first 3 months after discontinuation)...
February 27, 2018: Journal of Crohn's & Colitis
Matthew James Lee, Steven R Brown, Nicola S Fearnhead, Ailsa Hart, Alan J Lobo
Objective: Fistulating perianal Crohn's disease represents a significant challenge to both clinicians and patients. This survey set out to describe current practice and variation in the medical management of this condition. Design: A survey was designed by an expert group of gastroenterologists and surgeons with an inflammatory bowel disease (IBD) interest. The questionnaire aimed to capture opinions from consultant gastroenterologists with a UK practice on the management of acutely symptomatic fistula, assessment of a new fistula presentation, medical management strategies and surgical intervention...
January 2018: Frontline Gastroenterology
Ben Warner, Emma Johnston, Monica Arenas-Hernandez, Anthony Marinaki, Peter Irving, Jeremy Sanderson
Thiopurines are often the mainstay of treatment for many patients with inflammatory bowel disease. As such, a general understanding of the evidence behind their use and of their metabolism is extremely useful in clinical practice. This review gives a practical overview of thiopurine metabolism, the importance of thiopurine S-methyltransferase testing prior to the start of therapy and the monitoring of thioguanine nucleotide levels while on treatment, guiding a personalised approach to optimising thiopurine therapy...
January 2018: Frontline Gastroenterology
Swarup A V Shah, Minal U Paradkar, Devendra C Desai, Tester F Ashavaid
BACKGROUND: Thiopurine methyltransferase (TPMT) gene variants have achieved limited success in predicting the outcome of thiopurine therapy, which shows wide inter-individual variations. The literature indicates a strong association between the NUDT15 gene variant and thiopurine-induced toxicity in Asian patients. The present study intends to explore the role of the NUDT15 variant (C415T) in Indian patients on thiopurine therapy. METHODS: NUDT15 and TPMT genotyping were performed using amplification-refractory mutation system-polymerase chain reaction (ARMS-PCR) and the restriction fragment length polymorphism (RFLP) technique...
March 28, 2018: Drug Metabolism and Personalized Therapy
A B Friedman, S J Brown, P Bampton, M L Barclay, A Chung, F A Macrae, J McKenzie, J Reynolds, P R Gibson, S B Hanauer, M P Sparrow
BACKGROUND: Thiopurine hypermethylation towards 6-methylmercaptopurine (6MMP) instead of 6-thioguanine nucleotides (6TGN) is associated with inefficacy in patients with IBD. Allopurinol reverses such hypermethylation. AIMS: To prospectively determine efficacy of allopurinol-thiopurine combination and to compare 2 doses of allopurinol. DESIGN: In a multicentre, double-blind trial, patients with clinically active or steroid-dependent IBD and thiopurine shunting were randomised to 50 or 100 mg/d allopurinol and 25% of their screening thiopurine dose, which was subsequently optimised, aiming for 6TGN of 260-500 pmol/8x108 RBCs...
February 21, 2018: Alimentary Pharmacology & Therapeutics
Steven Bots, Krisztina Gecse, Murray Barclay, Geert D'Haens
Whether to use biologic treatment for inflammatory bowel disease as monotherapy or in combination with immunosuppressives has been a matter of debate in the last 2 decades. Combination therapy was not superior in any of the registration trials for Crohn's disease and ulcerative colitis for TNF antagonists, vedolizumab, or ustekinumab. It needs to be mentioned, though, that none of these trials were powered to detect such differences, and that many patients entered the trial after having failed conventional immunosuppressives...
February 15, 2018: Inflammatory Bowel Diseases
Hanna M J L Hazenberg, Nanne K H de Boer, Chris J J Mulder, Stijn H Mom, Ad A van Bodegraven, Greetje J Tack Md PhD
In this review the risk of breast, ovarian, and endometrial cancer and cervical and vulvovaginal (pre)malignant abnormalities in patients with inflammatory bowel disease (IBD) with or without immune suppressive treatment will be discussed. So far, this has not been studied thoroughly and large studies taking into account diverse potential confounding factors are lacking. IBD per se has not been associated with development of cervical cancer, yet patients with Crohn's disease who smoke, have a younger age at diagnosis or who use(d) thiopurines might be more at risk...
February 15, 2018: Inflammatory Bowel Diseases
M Chaparro, A Verreth, T Lobaton, E Gravito-Soares, M Julsgaard, E Savarino, F Magro, I Avni Biron, P Lopez-Serrano, M J Casanova, M Gompertz, S Vitor, M Arroyo, D Pugliese, Y Zabana, R Vicente, M Aguas, A Bar-Gil Shitrit, A Gutierrez, G A Doherty, L Fernandez-Salazar, J Martínez Cadilla, J M Huguet, A O'Toole, E Stasi, N Manceñido Marcos, A Villoria, K Karmiris, J F Rahier, C Rodriguez, M Diz-Lois Palomares, G Fiorino, J M Benitez, M Principi, T Naftali, C Taxonera, G Mantzaris, L Sebkova, B Iade, D Lissner, I Ferrer Bradley, A Lopez-San Roman, I Marin-Jimenez, O Merino, M Sierra, M Van Domselaar, F Caprioli, I Guerra, P Peixe, M Piqueras, I Rodriguez-Lago, Y Ber, K van Hoeve, P Torres, M Gravito-Soares, D Rudbeck-Resdal, O Bartolo, A Peixoto, G Martin, A Armuzzi, A Garre, M G Donday, F J Martín de Carpi, J P Gisbert
OBJECTIVES: The long-term safety of exposure to anti-tumor necrosis factor (anti-TNFα) drugs during pregnancy has received little attention. We aimed to compare the relative risk of severe infections in children of mothers with inflammatory bowel disease (IBD) who were exposed to anti-TNFα drugs in utero with that of children who were not exposed to the drugs. METHODS: Retrospective multicenter cohort study. Exposed cohort: children from mothers with IBD receiving anti-TNFα medication (with or without thiopurines) at any time during pregnancy or during the 3 months before conception...
February 20, 2018: American Journal of Gastroenterology
Eun Mi Song, Nayoung Kim, Sun-Ho Lee, Kiju Chang, Sung Wook Hwang, Sang Hyoung Park, Dong-Hoon Yang, Jeong-Sik Byeon, Seung-Jae Myung, Suk-Kyun Yang, Byong Duk Ye
OBJECTIVES: This study aimed to evaluate the clinical characteristics and clinical course of Asian elderly-onset Crohn's disease (EOCD) patients in a large well-defined cohort of South Korean IBD patients. MATERIALS AND METHODS: From the Asan inflammatory bowel disease registry, we identified 29 EOCD patients (diagnosed with CD in age of 60 years or over) out of 2989 CD patients (1.0%). After excluding two patients with unclear data, 27 EOCD were matched with 108 young-onset CD (YOCD) and 108 middle age-onset CD (MOCD) for the interval from symptom onset to diagnosis (±3 years) and follow-up duration (±3 years)...
February 19, 2018: Scandinavian Journal of Gastroenterology
Antonio Di Sario, Paola Sassaroli, Luigi Daretti, Giulia Annulli, Laura Schiada, Giorgia Falcioni, Emanuele Bendia, Simone Antuono, Antonio Benedetti
BACKGROUND: Up to 80% of Crohn`s disease (CD) patients require at least one surgical intervention in their lifetime and up to 70% of these patients develop postoperative endoscopic recurrence within 1 year. The most important predictors of early postoperative recurrence are represented by smoking, prior intestinal surgery, penetrating disease and perianal location. Genetic factors, gut microbiota structure and immunological alterations may be involved in the pathogenesis of postoperative recurrence of CD, although their specific roles have to be determined yet...
February 16, 2018: Current Pharmaceutical Biotechnology
Nikki A Evensen, P Pallavi Madhusoodhan, Julia Meyer, Jason Saliba, Ashfiyah Chowdhury, David J Araten, Jacob Nersting, Teena Bhatla, Tiffaney L Vincent, David Teachey, Stephen P Hunger, Jun Yang, Kjeld Schmiegelow, William L Carroll
Survival of children with relapsed acute lymphoblastic leukemia is poor and understanding mechanisms underlying resistance is essential in developing new therapy. Relapse-specific heterozygous deletions in MSH6, a crucial part of DNA Mismatch Repair, are frequently detected. Our aim was to determine whether MSH6 deletion results in a hypermutator phenotype associated with generation of secondary mutations involved in drug resistance or leads to a failure to initiate apoptosis directly in response to chemotherapeutic agents...
February 15, 2018: Haematologica
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