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Efficacy of thioguanine treatment in inflammatory bowel disease: A systematic review

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World Journal of Gastroenterology 2016年第40期22卷 9012-9021页

作者： Berrie Meijer Chris JJ Mulder Godefridus J Peters Adriaan A van Bodegraven nanne kH de boer department of Gastroenterology and Hepatology VU University Medical Center department of Medical Oncology VU University Medical Center department of Gastroenterology Geriatrics Internal and Intensive Care Medicine (Co-MIK) Zuyderland Medical Center

AIM To critically assess the available literature regarding the efficacy of thioguanine treatment in inflammatory bowel disease(IBD) patients, irrespective of the(hepato-) toxicity *** A systematic literature search of the MEDLINE database using Pub Med was performed using the keywords "thioguanine", "6-TG", "thioguanine", "inflammatory bowel disease", "IBD", "Crohn's disease", "Ulcerative colitis" and "effectiveness" in order to identify relevant articles published in English starting from 2000. Reference lists of the included articles were crosschecked for missing articles. Reviewed manuscripts concerning the effectiveness of thioguanine treatment in IBD were reviewed by the authors and the data were extracted. Data were subsequently analyzed with descriptive statistics. Due to the lack of standardized outcomes, a formal meta-analysis was not *** A total of 11 applicable studies were found that involved the effectiveness of thioguanine therapy in IBD. Eight studies were conducted in a prospectivemanner, in the remaining three studies, data was collected retrospectively. In total, 353 IBD-patients(225 patients with Crohn's disease, 119 with ulcerative colitis and nine with unclassified IBD) with prior azathioprine/mercaptopurine resistance and/or intolerance(n = 321) or de novo thioguanine administration(n = 32) were included for analysis, of which 228(65%) had clinical improvement on thioguanine therapy, based on standard IBD questionnaires, biochemical parameters or global physician assessments. Short-term results were based on 268 treatment years(median follow-up 9 mo, range 3-22 mo) with a median daily dose of 20 mg(range 10-80 mg). Discontinuation, mostly due to adverse events, was reported in 72 patients(20%). CONCLUSION The efficacy of thioguanine therapy in IBD patients intolerant to conventional thiopurine therapy is observed in 65%, with short term adverse events in 20% of patients.

关键词： Thiopurines Thioguanine Inflammatory bowel disease Crohn’s disease Ulcerative colitis

On tolerability and safety of a maintenance treatment with 6-thioguanine in azathioprineor 6-mercaptopurine intolerant IBD patients

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World Journal of Gastroenterology 2005年第35期11卷 5540-5544页

作者： nanne kH de boer Luc JJ derijks Lennard PL Gilissen Daniel W Hommes Leopold GJB Engels Sybrand Y de boer Gijsbertus den Hartog Piet M Hooymans Anja BU M(?)kelburg Barend D Westerveld Anton HJ Naber Chris JJ Mulder Dirk J de Jong department of Gastroenterology and Hepatology VU University Medical Centre Amsterdam The Netherlands department of Clinical Pharmacy Maxima Medical Centre Veldhoven The Netherlands department of Gastroenterology and Hepatology Academic Hospital Maastricht The Netherlands department of Gastroenterology and Hepatology Academic Medical Centre Amsterdam The Netherlands department of Gastroenterology and Hepatology Maasland Hospital Sittard The Netherlands department of Gastroenterology and Hepatology Rijnstate Hospital Arnhem The Netherlands department of Clinical Pharmacy Maasland Hospital Sittard The Netherlands department of Gastroenterology and Hepatology Isala Clinics Location Sophia Zwolle The Netherlands department of Gastroenterology and Hepatology Radboud University Nijmegen Medical Centre The Netherlands

AIM: To determine the tolerability and safety profile of a low-dose maintenance therapy with 6-TG in azathioprine (AZA) or 6-mercaptopurine (6-MP) intolerant inflammatory bowel disease (IBD) patients over a treatment period of at least 1 ***: Database ***: Twenty out of ninety-five (21%) patients discontinued 6-TG (mean dose 24.6 mg; mean 6-TGN level 540 pmol/8×108 RBC) within 1 year. Reasons for discontinuation were GI complaints (31%), malaise (15%)and hepatotoxicity (15%). Hematological events occurred in three patients, one discontinued treatment. In the 6-TG-tolerant group, 9% (7/75) could be classified as hepatotoxicity. An abdominal ultrasound was performed in 54% of patients, one patient had ***: The majority of AZA or 6-MP-intolerant IBD patients (79%) is able to tolerate maintenance treatment with 6-TG (dosages between 0.3 and 0.4 mg/kg per d). 6-TG may still be considered as an escape maintenance immunosuppressant in this difficult to treat group of patients, taking into account potential toxicity and efficacy of other alternatives. The recently reported hepatotoxicity is worrisome and 6-TG should therefore be administered only in prospective trials.

关键词： 6-Thioguanine Azathioprine 6-Mercaptopurine Crohn's disease Ulcerative colitis Side effects Tolerance Safety

How I treat my inflammatory bowel disease-patients with thiopurines?

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World Journal of Gastrointestinal Pharmacology and Therapeutics 2016年第4期7卷 524-530页

作者： Berrie Meijer Chris JJ Mulder Adriaan A van Bodegraven nanne kH de boer department of Gastroenterology and Hepatology VU University Medical Center department of Gastroenterology GeriatricsInternal and Intensive Care Medicine (Co-MIK)Zuyderland Medical Center

Thiopurines are essential drugs to maintain remission in patients with inflammatory bowel disease(IBD).Thiopurines used in IBD are azathioprine(2.0-2.5 mg/kg),mercaptopurine(1.0-1.5 mg/kg) and thioguanine(0.2-0.3 mg/kg).However,mainly due to numerous adverse events associated with thiopurine use,almost 50% of the patients have to discontinue conventional thiopurine *** monitoring and the application of several treatment strategies,such as split-dose administration,co-administration with allopurinol or dose reduction/increase,may increase the chance of successful *** this review,we provide practical information on how thiopurines are initiated and maintained in two thiopurine research centers in The *** provide clinical information concerning safety issues,indications and management of therapy that may serve as a guide for the administration of thiopurines in IBD patients in daily practice.

关键词： Thiopurines Azathioprine Mercaptopurine Thioguanine Inflammatory bowel disease Therapeutic drug monitoring Pregnancy Metabolites

Diarrhoea in a patient with metastatic melanoma:Ipilimumab ileocolitis treated with infliximab

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World Journal of Gastrointestinal Pharmacology and Therapeutics 2013年第3期4卷 80-82页

作者： Rob ME Slangen Alfonsus JM van den Eertwegh Adriaan A van Bodegraven nanne kH de boer department of Gastroenterology and Hepatology HagaZiekenhuis2545 CH Den HaagThe Netherlands department of Medical Oncology VU University Medical Centre1007 MB AmsterdamThe Netherlands department of Gastroenterology and Hepatology VU University Medical Centre1007 MB AmsterdamThe Netherlands

Administration of ipilimumab,a cytotoxic T-lymphocyte associated antigen-4-blocking monoclonal antibody,leads to enhancement of the anti-tumor T-cell respons and as a result shows a significant survival benefit in metastatic melanoma *** patients are currently receiving this promising therapy as a secondline ***,by activation of the T-cell immune reponse,ipilimumab therapy may lead to an unwanted induction of different autoimmune *** and colitis occur in up to one third of *** we present a case of ipilimumab induced ileocolitis which was successfully treated with infliximab,an anti-tumor necrosis factor monoclonal antibody,after corticosteroid therapy *** formal trials are lacking,recently publicated series suggest that infusional therapy of infliximab is effective in ipilimumab induced ileocolitis.

关键词： Melanoma Ipilimumab Colitis Infliximab Cytotoxic T-lymphocyte associated antigen-4