Efficacy, safety and drug survival of thioguanine as maintenance treatment for inflammatory bowel disease: a retrospecti
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RESEARCH ARTICLE
Open Access
Efficacy, safety and drug survival of thioguanine as maintenance treatment for inflammatory bowel disease: a retrospective multi-centre study in the United Kingdom Ahmed B. Bayoumy1,2,3,4*† , Elsa L. S. A. van Liere1,2,3,4†, Melek Simsek5, Ben Warner2, Aathavan Loganayagam3, Jeremy D. Sanderson2, Simon Anderson2, Jonathan Nolan4, Nanne K. de Boer5, Chris J. J. Mulder1 and Azhar Ansari4
Abstract Background: Thioguanine (TG) is a thiopurine which has been used for patients with inflammatory bowel disease (IBD), who have failed azathioprine (AZA) or mercaptopurine (MP) due to adverse events or suboptimal response. Its widespread use has been hampered due to concerns about nodular regenerative hyperplasia (NRH) of the liver. The aim of this study was to investigate the long-term efficacy and safety of low-dose TG therapy in IBD patients failing AZA and MP. Methods: A retrospective multicentre study was performed in IBD patients who failed prior treatment with conventional thiopurines with or without following immunomodulation (thiopurine-allopurinol, biologicals, methotrexate, tacrolimus) and were subsequently treated with TG as rescue monotherapy between 2003 and 2019 at three hospitals in the United Kingdom. Clinical response, adverse events, laboratory results, imaging and liver biopsies were retrospectively collected. Results: A total of 193 patients (57% female and 64% Crohn’s disease) were included, with a median daily TG dose of 20 mg (range: 20–40 mg), a median treatment duration of 23 months (IQR 10–47) and a median follow-up of 36 months (IQR 22–53). The clinical response rate at 12 months was 65 and 54% remained on TG until the end of follow-up. Adverse events consisted primarily of elevated liver tests (6%), myelotoxicity (7%) and rash (5%). NRH was histologically diagnosed in two patients and two other patients (1%) developed non-cirrhotic portal hypertension. The median 6-TGN and TPMT levels were 953 pmol/8 × 105 RBC (IQR 145–1761) and 47 mu/L (IQR 34.5–96). (Continued on next page)
* Correspondence: [email protected] Ahmed B. Bayoumy and Elsa L.S.A. van Liere share first-authorship. 1 Department of Gastroenterology and Hepatology, Amsterdam UMC, VU University Medical Centre, Amsterdam, The Netherlands 2 Department of Gastroenterology, Guy’s and St Thomas’ NHS Foundation Trust, London, UK Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Common
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