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Original Article
- IBD
- Long-term efficacy and tolerability of dose-adjusted thiopurine treatment in maintaining remission in inflammatory bowel disease patients with NUDT15 heterozygosity
- Takato Maeda, Hirotake Sakuraba, Hiroto Hiraga, Shukuko Yoshida, Yoichi Kakuta, Hidezumi Kikuchi, Shogo Kawaguchi, Keisuke Hasui, Tetsuya Tatsuta, Daisuke Chinda, Tatsuya Mikami, Shinsaku Fukuda
- Intest Res 2022;20(1):90-100. Published online January 22, 2021
- DOI: https://doi.org/10.5217/ir.2020.00133
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Abstract
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Supplementary Material
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ePub - Background/Aims
Thiopurines are key drugs for inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD). Recently, NUDT15 polymorphism (R139C, c.415C > T) has been shown to be associated with thiopurineinduced adverse events in Asian populations. In patients with the C/T genotype, low-dose thiopurine treatment is recommended, but its long-term efficacy and tolerability remain unclear. This study aimed to uncover the long-term efficacy and appropriate dosage of thiopurine for IBD patients with the C/T genotype.
Methods
A total of 210 patients with IBD (103 UC and 107 CD) determined to have NUDT15 R139C variants were enrolled. Clinical data were retrospectively reviewed from medical records.
Results
Of 46 patients (21.9%) with the C/T genotype, 30 patients (65.2%) were treated with thiopurines. Three of whom (10.0%) discontinued thiopurine treatment due to adverse events and 27 of whom continued. The median maintenance dosage of 6-mercaptopurine was 0.25 mg/kg/day (range, 0.19–0.36 mg/kg/day), and 6-thioguanine nucleotides level was 230 (104–298) pmol/8 × 108 red blood cells. Cumulative thiopurine continuation rates for 120 months for patients with the C/C and C/T genotypes were not significantly different (P= 0.895). Cumulative non-relapse rates in the patients with UC treated with thiopurine monotherapy and surgery-free rates in CD patients treated with combination therapy (thiopurines and anti-tumor necrosis factor-α agents) for maintenance remission were not significantly different at 60 months (C/C vs. C/T, P= 0.339 and P= 0.422, respectively).
Conclusions
Low-dose thiopurine treatment is an effective and acceptable treatment for patients with C/T genotype. -
Citations
Citations to this article as recorded by
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- 9,213 View
- 390 Download
- 8 Web of Science
- 9 Crossref
Review
- Inflammatory bowel diseases
- NUDT15 gene variants and thiopurine-induced leukopenia in patients with inflammatory bowel disease
- Katsuyoshi Matsuoka
- Intest Res 2020;18(3):275-281. Published online June 3, 2020
- DOI: https://doi.org/10.5217/ir.2020.00002
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Abstract
PDFPubReaderePub
- Thiopurine has been used to maintain remission and to reduce antidrug antibody formation in monoclonal antibody therapy in patients with inflammatory bowel disease (IBD). The use of thiopurine is limited by side effects such as leukopenia. Thiopurine S-methyltransferase (TPMT) variants are associated with thiopurine-induced leukopenia in Westerners, but the frequency of the risk alleles is low in Asians. Recently, a variant in the nudix hydrolase 15 (NUDT15) gene (R139C, c.415C > T) was reported to be associated with early severe leukopenia in Asians. NUDT15 is an enzyme that converts 6-thio-(deoxy)guanosine triphosphate (6-T(d)GTP) to 6-thio-(deoxy)guanosine monophosphate (6-T(d)GMTP). The R139C variant impairs the stability of the protein and increases incorporation of 6-TGTP and 6-TdGTP into RNA and DNA, respectively, resulting in leukopenia. The frequency of C/C, C/T, and T/T are approximately 80%, 20%, and 1%, respectively in East Asians. Early leukopenia occurred in less than 3% of patients with C/C and in around 20% of those with C/T, whereas it occurred in almost all patients with T/T. Patients homozygous for this variant also develop severe hair loss. The measurement of NUDT15 R139C can increase the safety of thiopurine dramatically and is a successful example of personalized medicine in the field of IBD.
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Citations
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Original Articles
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NUDT15 ,FTO , andRUNX1 genetic variants and thiopurine intolerance among Japanese patients with inflammatory bowel diseases - Toshiyuki Sato, Tetsuya Takagawa, Yoichi Kakuta, Akihiro Nishio, Mikio Kawai, Koji Kamikozuru, Yoko Yokoyama, Yuko Kita, Takako Miyazaki, Masaki Iimuro, Nobuyuki Hida, Kazutoshi Hori, Hiroki Ikeuchi, Shiro Nakamura
- Intest Res 2017;15(3):328-337. Published online June 12, 2017
- DOI: https://doi.org/10.5217/ir.2017.15.3.328
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Abstract
PDFPubReaderePub
<b>Background/Aims</b><br/> Recent genome-wide analyses have provided strong evidence concerning adverse events caused by thiopurine drugs such as azathioprine (AZA) and 6-mercaptopurine. The strong associations identified between
NUDT15 p.Arg139Cys and thiopurine-induced leukopenia and severe hair loss have been studied and confirmed over the last 2 years. However, other coding variants, includingNUDT15 p.Val18_Val19insGlyVal,NUDT15 p.Val18Ile, andFTO p.Ala134Thr, and a noncoding variation inRUNX1 (rs2834826) remain to be examined in detail in this respect. Therefore, we investigated the correlation between these adverse events and the 5 recently identified variants mentioned above among Japanese patients with inflammatory bowel diseases (IBD).Methods One hundred sixty thiopurine-treated patients with IBD were enrolled. Genotyping was performed using TaqMan SNP Genotyping Assays or Sanger sequencing.
Results None of the 5 variants were associated with gastrointestinal intolerance to AZA. However,
NUDT15 p.Arg139Cys was significantly associated with the interval between initiation and discontinuation of AZA among patients with gastrointestinal intolerance. This variant was strongly associated with early (<8 weeks) and late (≥8 weeks) leukopenia and severe hair loss. Moreover, it correlated with the interval between initiation of thiopurine therapy and leukopenia occurrence, and average thiopurine dose.NUDT15 p.Val18_Val19insGlyVal,NUDT15 p.Val18Ile,FTO p.Ala134Thr, andRUNX1 rs2834826 exhibited no significant relationship with the adverse events examined.Conclusions Of the 5 variants investigated,
NUDT15 p.Arg139Cys had the strongest impact on thiopurine-induced leukopenia and severe hair loss; therefore, its genotyping should be prioritized over that of other variants in efforts to predict these adverse events in Japanese patients with IBD.-
Citations
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Sara van Gennep, Kadère Konté, Berrie Meijer, Martijn W. Heymans, Geert R. D’Haens, Mark Löwenberg, Nanne K. H. de Boer
Alimentary Pharmacology & Therapeutics.2019; 50(5): 484. CrossRef - Mycophenolate mofetil and prednisolone for cerebral sinus venous thrombosis with Behcet's disease
Shintaro Terashita, Tomomi Tanaka, Hiromichi Taneichi, Yuichi Adachi, Masaaki Mori
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Frontiers in Neurology.2019;[Epub] CrossRef - Pharmacogenetics of thiopurines for inflammatory bowel disease in East Asia: prospects for clinical application of NUDT15 genotyping
Yoichi Kakuta, Yoshitaka Kinouchi, Tooru Shimosegawa
Journal of Gastroenterology.2018; 53(2): 172. CrossRef - NUDT15 codon 139 is the best pharmacogenetic marker for predicting thiopurine-induced severe adverse events in Japanese patients with inflammatory bowel disease: a multicenter study
Yoichi Kakuta, Yosuke Kawai, Daisuke Okamoto, Tetsuya Takagawa, Kentaro Ikeya, Hirotake Sakuraba, Atsushi Nishida, Shoko Nakagawa, Miki Miura, Takahiko Toyonaga, Kei Onodera, Masaru Shinozaki, Yoh Ishiguro, Shinta Mizuno, Masahiro Takahara, Shunichi Yanai
Journal of Gastroenterology.2018; 53(9): 1065. CrossRef - Severe thiopurine‐induced leukocytopenia and hair loss in Japanese patients with defective NUDT15 variant: Retrospective case–control study
Mari Kishibe, Hiroyoshi Nozaki, Mizue Fujii, Shin Iinuma, Sawa Ohtsubo, Satomi Igawa, Kyoko Kanno, Masaru Honma, Kan Kishibe, Kensaku Okamoto, Akemi Ishida‐Yamamoto
The Journal of Dermatology.2018; 45(10): 1160. CrossRef - Diagnostic accuracy of NUDT15 gene variants for thiopurine-induced leukopenia: a systematic review and meta-analysis
Sarah Cargnin, Armando A. Genazzani, Pier Luigi Canonico, Salvatore Terrazzino
Pharmacological Research.2018; 135: 102. CrossRef - A single‐center experience with methotrexate in the treatment of Chinese Crohn’s disease patients
Tian Rong Wang, Yu Qi Qiao, Duo Wu Zou, Zhi Hua Ran
Journal of Digestive Diseases.2018; 19(12): 753. CrossRef
- A case of rapidly progressive hair loss due to azathioprine, and the prevalence of NUDT15 variants among Japanese patients with autoimmune blistering diseases: A single‐center retrospective observational study
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- Pregnancy outcome in women with inflammatory bowel disease treated with anti-tumor necrosis factor and/or thiopurine therapy: a multicenter study from Japan
- Shunsuke Komoto, Satoshi Motoya, Yuji Nishiwaki, Toshiyuki Matsui, Reiko Kunisaki, Katsuyoshi Matsuoka, Naoki Yoshimura, Takashi Kagaya, Makoto Naganuma, Nobuyuki Hida, Mamoru Watanabe, Toshifumi Hibi, Yasuo Suzuki, Soichiro Miura, Ryota Hokari
- Intest Res 2016;14(2):139-145. Published online April 27, 2016
- DOI: https://doi.org/10.5217/ir.2016.14.2.139
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Abstract
PDFPubReaderePub
<b>Background/Aims</b><br/> Anti-tumor necrosis factor drugs (anti-TNF) and thiopurines are important treatment options in patients with inflammatory bowel disease (IBD), including during pregnancy. However, there are limited data on the benefit/risk profile of anti-TNF and thiopurines during pregnancy in Asia. The aim of this study was to analyze pregnancy outcomes of female Japanese IBD patients treated with anti-TNF and/or thiopurines.
Methods This cross-sectional study assessed pregnancy outcomes in 72 women with IBD. Pregnancy outcomes were compared among 31 pregnancies without exposure to infliximab (IFX), adalimumab (ADA), or thiopurines; 24 pregnancies with exposure to anti-TNF treatment (23 IFX, 1 ADA); 7 pregnancies with exposure to thiopurines alone; and 10 pregnancies with exposure to both IFX and thiopurines.
Results Thirty-five of the 41 pregnancies (85.3%) that were exposed to anti-TNF treatment and/or thiopurines resulted in live births after a median gestational period of 38 weeks. Of the 35 live births, 3 involved premature deliveries; 7, low birth weight; and 1, a congenital abnormality. There were 6 spontaneous abortions in pregnancies that were exposed to anti-TNF treatment (17.7%). Pregnancy outcomes among the 4 groups were similar, except for the rate of spontaneous abortions (
P =0.037).Conclusions Exposure to anti-TNF treatment or thiopurines during pregnancy was not related to a higher incidence of adverse pregnancy outcomes in Japanese IBD patients except for spontaneous abortion.
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Navid Najarpour, Elham Rajaei, Karim Mowla, Alireza Ghanbaran
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Wei Huang, Xinxing Zhang, Li Zhang, Xiaosong Dai, Heping Chen, Qin Xie
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Navid Najarpour, Elham Rajaei, Karim Mowla, Alireza Ghanbaran
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Yu Chen, Guolin Zhang, Yuewen Yang, Shuangshuang Zhang, Haozheng Jiang, Kang Tian, Arenbaoligao, Dapeng Chen
Biomedicine & Pharmacotherapy.2023; 157: 114081. CrossRef - Saudi consensus guidance for the management of inflammatory bowel disease during pregnancy
Nahla A. Azzam, Abdulelah Almutairdi, Hajer Y. Almudaiheem, Turki AlAmeel, Shakir A. Bakkari, Othman R. Alharbi, Khalidah A. Alenzi, Maha A. AlMolaiki, Bedor A. Al-Omari, Rayan G. Albarakati, Ahmed H. Al-Jedai, Omar I. Saadah, Majid A. Almadi, Badr Al-Baw
Saudi Journal of Gastroenterology.2023;[Epub] CrossRef - Biologics for Inflammatory Bowel Disease and Their Safety in Pregnancy: A Systematic Review and Meta-analysis
Ole Haagen Nielsen, John Mark Gubatan, Carsten Bogh Juhl, Sarah Elizabeth Streett, Cynthia Maxwell
Clinical Gastroenterology and Hepatology.2022; 20(1): 74. CrossRef - British Society for Rheumatology guideline on prescribing drugs in pregnancy and breastfeeding: immunomodulatory anti-rheumatic drugs and corticosteroids
Mark D Russell, Mrinalini Dey, Julia Flint, Philippa Davie, Alexander Allen, Amy Crossley, Margreta Frishman, Mary Gayed, Kenneth Hodson, Munther Khamashta, Louise Moore, Sonia Panchal, Madeleine Piper, Clare Reid, Katherine Saxby, Karen Schreiber, Naz Se
Rheumatology.2022;[Epub] CrossRef - Association between Thiopurines Use and Pregnancy Outcomes in Female Patients with Inflammatory Bowel Disease: A Meta-Analysis
Yang Zhang, Dandan Li, Heng Guo, Weina Wang, Xingang Li, Su Shen
Current Pharmaceutical Design.2021; 27(19): 2317. CrossRef - Exposure to Infliximab During Pregnancy: Post-Marketing Experience
Anja Geldhof, Jennifer Slater, Michael Clark, Urmila Chandran, Danielle Coppola
Drug Safety.2020; 43(2): 147. CrossRef - The use of biological disease-modifying antirheumatic drugs for inflammatory arthritis in Korea: results of a Korean Expert Consensus
Eun-Jung Park, Hyungjin Kim, Seung Min Jung, Yoon-Kyoung Sung, Han Joo Baek, Jisoo Lee
The Korean Journal of Internal Medicine.2020; 35(1): 41. CrossRef - The Use of Biological Disease-modifying Antirheumatic Drugs for Inflammatory Arthritis in Korea: Results of a Korean Expert Consensus
Eun-Jung Park, Hyungjin Kim, Seung Min Jung, Yoon-Kyoung Sung, Han Joo Baek, Jisoo Lee
Journal of Rheumatic Diseases.2020; 27(1): 4. CrossRef - Maternal and neonatal outcomes associated with biologic exposure before and during pregnancy in women with inflammatory systemic diseases: a systematic review and meta-analysis of observational studies
Nicole W Tsao, Nevena Rebic, Larry D Lynd, Mary A De Vera
Rheumatology.2020; 59(8): 1808. CrossRef - Intrauterine Exposure to Biologics in Inflammatory Autoimmune Diseases: A Systematic Review
N. Ghalandari, R. J. E. M. Dolhain, J. M. W. Hazes, E. P. van Puijenbroek, M. Kapur, H. J. M. J. Crijns
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Rohan D'Souza, Danielle Wuebbolt, Katarina Andrejevic, Rizwana Ashraf, Vanessa Nguyen, Nusrat Zaffar, Dalia Rotstein, Ahraaz Wyne
Frontiers in Neurology.2020;[Epub] CrossRef - Relationship between the Clinical Course of Ulcerative Colitis during Pregnancy and the Outcomes of Pregnancy: A Retrospective Evaluation
Ayumi Ito, Bunei Iizuka, Teppei Omori, Shinichi Nakamura, Katsutoshi Tokushige
Internal Medicine.2018; 57(2): 159. CrossRef - The use of biologics and small molecules in pregnant patients with rheumatic diseases
Maria Gerosa, Lorenza Maria Argolini, Carolina Artusi, Cecilia Beatrice Chighizola
Expert Review of Clinical Pharmacology.2018; 11(10): 987. CrossRef - Long-term clinical outcome after infliximab discontinuation in patients with inflammatory bowel disease
Ji Min Lee, Yoon Jae Kim, Kang-Moon Lee, Hyuk Yoon, Bo-In Lee, Dae Bum Kim, Donghoon Kang
Scandinavian Journal of Gastroenterology.2018; 53(10-11): 1280. CrossRef - Impact of inflammatory bowel disease activity and thiopurine therapy on birth weight: A meta-analysis
Begoña Gonzalez-Suarez, Shreyashee Sengupta, Alan C Moss
World Journal of Gastroenterology.2017; 23(45): 8082. CrossRef - Maternal and fetal outcomes in pregnant Japanese women with inflammatory bowel disease: our experience with a series of 23 cases
Naoki Minami, Minoru Matsuura, Yorimitsu Koshikawa, Satoshi Yamada, Yusuke Honzawa, Shuji Yamamoto, Hiroshi Nakase
Intestinal Research.2017; 15(1): 90. CrossRef - Concerns in pregnancy and childbirth of women with inflammatory bowel disease
Sung-Ae Jung
Intestinal Research.2016; 14(2): 107. CrossRef - Common Adverse Effects of Anti-TNF Agents on Gestation
Zacharias Fasoulakis, Panagiotis Antsaklis, Nikolaos Galanopoulos, Emmanuel Kontomanolis
Obstetrics and Gynecology International.2016; 2016: 1. CrossRef
- Ulcerative Colitis in Pregnancy: A Japanese Multicenter Cohort Study Focusing on Their Mutual Influence
- 8,642 View
- 82 Download
- 26 Web of Science
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- Efficacy of Thiopurines in Biologic-Naive Japanese Patients With Crohn's Disease: A Single-Center Experience
- Takuya Yoshino, Minoru Matsuura, Naoki Minami, Satoshi Yamada, Yusuke Honzawa, Masamichi Kimura, Yorimitsu Koshikawa, Ali Madian, Takahiko Toyonaga, Hiroshi Nakase
- Intest Res 2015;13(3):266-273. Published online June 9, 2015
- DOI: https://doi.org/10.5217/ir.2015.13.3.266
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Abstract
PDFPubReader
<b>Background/Aims</b><br/> Early use of biologics in patients with Crohn's disease (CD) improves quality of life. However, the effects of the early use of immunomodulators on long-term outcomes remain unclear. This study aimed to evaluate the effects of immunomodulators in patients with CD.
Methods Between January 2004 and December 2011, 47 biologic-naive CD patients treated with thiopurines alone for remission maintenance were analyzed. The patients were classified into 2 groups depending on the presence or absence of digestive complications. We evaluated the efficacy of and predictive factors for thiopurine use for remission maintenance.
Results The cumulative relapse rates at 24 and 60 months were 13.7% and 35.4%, respectively. Regarding patient characteristics, there was a significant difference in patient history of surgery between the non-relapse and relapse groups (
P =0.021). The cumulative relapse rate was lower in patients without a history of surgery than in those with such a history (27.2% and 52.9% at 60.0 months, respectively). Multivariate analysis suggested that the prevalence of stricturing and penetrating complications is an independent factor for relapse. The cumulative relapse rate in patients without a history of surgery was significantly lower in the non-stricturing and non-penetrating group than in the stricturing and penetrating group (11.8% at 85.0 months vs. 58.5% at 69.0 months;P =0.036).Conclusions Thiopurine use might be beneficial for the long-term maintenance of remission in biologic-naive Crohn's disease patients without digestive complications and a history of surgery.
-
Citations
Citations to this article as recorded by- Thiopurines Have Sustained Long-term Effectiveness in Patients with Inflammatory Bowel Disease, Which is Independent of Disease Duration at Initiation: A Propensity Score Matched Analysis
Mukesh Kumar Ranjan, Peeyush Kumar, Sudheer Kumar Vuyyuru, Bhaskar Kante, Sandeep K Mundhra, Rithvik Golla, Shubi Virmani, Raju Sharma, Peush Sahni, Prasenjit Das, Mani Kalaivani, Ashish Datt Upadhyay, Govind Makharia, Saurabh Kedia, Vineet Ahuja
Journal of Crohn's and Colitis.2024; 18(2): 192. CrossRef - Efficacy of drug and endoscopic treatment of Crohn's disease strictures: A systematic review
Julien D Schulberg, Emily K Wright, Bronte A Holt, Helen E Wilding, Amy L Hamilton, Alyson L Ross, Michael A Kamm
Journal of Gastroenterology and Hepatology.2021; 36(2): 344. CrossRef - Short-term tolerability and effectiveness of methotrexate monotherapy in adult patients with Crohn’s disease: a retrospective study
Hee Seung Hong, Kyuwon Kim, Kyunghwan Oh, Jae Yong Lee, Seung Wook Hong, Jin Hwa Park, Sung Wook Hwang, Dong-Hoon Yang, Byong Duk Ye, Jeong-Sik Byeon, Seung-Jae Myung, Suk-Kyun Yang, Sang Hyoung Park
Therapeutic Advances in Gastroenterology.2021;[Epub] CrossRef - NUDT15,FTO, andRUNX1genetic variants and thiopurine intolerance among Japanese patients with inflammatory bowel diseases
Toshiyuki Sato, Tetsuya Takagawa, Yoichi Kakuta, Akihiro Nishio, Mikio Kawai, Koji Kamikozuru, Yoko Yokoyama, Yuko Kita, Takako Miyazaki, Masaki Iimuro, Nobuyuki Hida, Kazutoshi Hori, Hiroki Ikeuchi, Shiro Nakamura
Intestinal Research.2017; 15(3): 328. CrossRef - Importance of Patients’ Knowledge of Their Prescribed Medication in Improving Treatment Adherence in Inflammatory Bowel Disease
Chung Hyun Tae, Sung-Ae Jung, Hye Sung Moon, Jung-A Seo, Hye Kyung Song, Chang Mo Moon, Seong-Eun Kim, Ki-Nam Shim, Hye-Kyung Jung
Journal of Clinical Gastroenterology.2016; 50(2): 157. CrossRef
- Thiopurines Have Sustained Long-term Effectiveness in Patients with Inflammatory Bowel Disease, Which is Independent of Disease Duration at Initiation: A Propensity Score Matched Analysis
- 6,671 View
- 49 Download
- 5 Web of Science
- 5 Crossref
- Efficacy and Safety of Long-Term Thiopurine Maintenance Treatment in Japanese Patients With Ulcerative Colitis
- Satoshi Yamada, Takuya Yoshino, Minoru Matsuura, Masamichi Kimura, Yorimitsu Koshikawa, Naoki Minami, Takahiko Toyonaga, Yusuke Honzawa, Hiroshi Nakase
- Intest Res 2015;13(3):250-258. Published online June 9, 2015
- DOI: https://doi.org/10.5217/ir.2015.13.3.250
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Abstract
PDFSupplementary MaterialPubReader
<b>Background/Aims</b><br/> The long-term clinical outcomes of patients with bio-naive ulcerative colitis (UC) who maintain remission with thiopurine are unclear. The aim of this study was to assess the long-term efficacy and safety of maintenance treatment with thiopurine in UC patients.
Methods This was a retrospective observational cohort analysis conducted at a single center. Between December 1998 and August 2013, 59 of 87 patients with bio-naive UC who achieved remission after induction with treatments other than biologics were enrolled. Remission maintenance with thiopurine was defined as no concomitant treatment needed other than 5-aminosalicylate without relapse. We assessed the remission-maintenance rate, mucosal healing rate, colectomy-free rate, and treatment safety in UC patients who received thiopurine as maintenance treatment.
Results The 84-month cumulative remission-maintenance and colectomy-free survival rates in the UC patients who were receiving maintenance treatment with thiopurine and 5-aminosalicylate were 43.9% and 88.0%, respectively. Of the 38 patients who underwent colonoscopy during thiopurine maintenance treatment, 23 (60.5%) achieved mucosal healing. Of the 59 patients who achieved clinical remission with thiopurine, 6 patients (10.2%) discontinued the thiopurine therapy because of adverse events.
Conclusions Our study demonstrates the long-term efficacy and safety of thiopurine treatment in patients with bio-naive UC.
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Citations
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Xi Chen, Xiaohua Tang, Sixuan Chen, Yang Ye, Fei Mao
Frontiers in Immunology.2026;[Epub] CrossRef - Thiopurines Have Sustained Long-term Effectiveness in Patients with Inflammatory Bowel Disease, Which is Independent of Disease Duration at Initiation: A Propensity Score Matched Analysis
Mukesh Kumar Ranjan, Peeyush Kumar, Sudheer Kumar Vuyyuru, Bhaskar Kante, Sandeep K Mundhra, Rithvik Golla, Shubi Virmani, Raju Sharma, Peush Sahni, Prasenjit Das, Mani Kalaivani, Ashish Datt Upadhyay, Govind Makharia, Saurabh Kedia, Vineet Ahuja
Journal of Crohn's and Colitis.2024; 18(2): 192. CrossRef - Potential benefits of immunomodulator use with vedolizumab for maintenance of remission in ulcerative colitis
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Journal of Gastroenterology and Hepatology.2022; 37(1): 81. CrossRef - Real-World Long-Term Remission Maintenance for 10 Years With Thiopurines in Ulcerative Colitis
Satohiro Matsumoto, Hirosato Mashima
Crohn's & Colitis 360.2021;[Epub] CrossRef - Treatment of Inflammatory Bowel Disease: A Comprehensive Review
Zhaobei Cai, Shu Wang, Jiannan Li
Frontiers in Medicine.2021;[Epub] CrossRef - Optimizing the Use of Current Treatments and Emerging Therapeutic Approaches to Achieve Therapeutic Success in Patients with Inflammatory Bowel Disease
Hiroshi Nakase
Gut and Liver.2020; 14(1): 7. CrossRef - The Leading Edge of the Treatment of Inflammatory Bowel Disease
Hiroshi Nakase
Nihon Naika Gakkai Zasshi.2020; 109(6): 1145. CrossRef -
Predictive Role of
NUDT15
Variants on Thiopurine-Induced Myelotoxicity in Asian Inflammatory Bowel Disease Patients
Natalia Sutiman, Sylvia Chen, Khoon Lin Ling, Sai Wei Chuah, Wai Fook Leong, Vinayak Nadiger, Madeline Tjai, Chris San Choon Kong, Brian John Schwender, Webber Chan, Hang Hock Shim, Wee Chian Lim, Chiea Chuen Khor, Yin Bun Cheung, Balram Chowbay
Pharmacogenomics.2018; 19(1): 31. CrossRef - NUDT15,FTO, andRUNX1genetic variants and thiopurine intolerance among Japanese patients with inflammatory bowel diseases
Toshiyuki Sato, Tetsuya Takagawa, Yoichi Kakuta, Akihiro Nishio, Mikio Kawai, Koji Kamikozuru, Yoko Yokoyama, Yuko Kita, Takako Miyazaki, Masaki Iimuro, Nobuyuki Hida, Kazutoshi Hori, Hiroki Ikeuchi, Shiro Nakamura
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Yoon Jee Lee, Jae Hee Cheon, Jae Hyun Kim, SunHo Yoo, Hyun Jung Lee, Soo Jung Park, Sung Pil Hong, Tae Il Kim, Won Ho Kim
Yonsei Medical Journal.2017; 58(1): 144. CrossRef - Rate and Predictors of Mucosal Healing in Ulcerative Colitis Treated with Thiopurines: Results of a Multicentric Cohort Study
Caroline Prieux-Klotz, Stéphane Nahon, Aurelien Amiot, Leila Sinayoko, Carole Galéano-Cassaz, Stanislas Chaussade, Romain Coriat, Pierre Lahmek, Vered Abitbol
Digestive Diseases and Sciences.2017; 62(2): 473. CrossRef - Effect of mucosal healing (Mayo 0) on clinical relapse in patients with ulcerative colitis in clinical remission
Jae Hyun Kim, Jae Hee Cheon, Yehyun Park, Hyun Jung Lee, Soo Jung Park, Tae Il Kim, Won Ho Kim
Scandinavian Journal of Gastroenterology.2016; 51(9): 1069. CrossRef - Is Long-Term Therapy With Thiopurines Effective for Maintaining Remission in Patients With Moderate-To-Severe Ulcerative Colitis?
Seong Ran Jeon, Won Ho Kim
Intestinal Research.2015; 13(3): 191. CrossRef
- cGAS-STING signaling: a therapeutic target in inflammatory bowel disease and related colorectal cancer
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Statement
- Use of Thiopurines in Inflammatory Bowel Disease: A Consensus Statement by the Korean Association for the Study of Intestinal Diseases (KASID)
- Kang-Moon Lee, You Sun Kim, Geom Seog Seo, Tae Oh Kim, Suk-Kyun Yang, IBD Study Group of the Korean Association for the Study of Intestinal Diseases
- Intest Res 2015;13(3):193-207. Published online June 9, 2015
- DOI: https://doi.org/10.5217/ir.2015.13.3.193
-
Abstract
PDFPubReader
<b>Background/Aims</b><br/> For decades, thiopurines have been the mainstay of inflammatory bowel disease (IBD) treatment and will play an important role in the future. However, complex metabolism and various side effects limit the use of these potent drugs in clinical practice. The Korean Association for the Study of Intestinal Diseases developed a set of consensus statements with the aim of guiding clinicians on the appropriate use of thiopurines in the management of IBD.
Methods Sixteen statements were initially drafted by five committee members. The quality of evidence and classification of recommendation were assessed according to the Grading of Recommendations Assessment, Development and Evaluation system. The statements were then circulated to IBD experts in Korea for review, feedback, and then finalized and accepted by voting at the consensus meeting.
Results The consensus statements comprised four parts: (1) pre-treatment evaluation and management strategy, including value of thiopurine S-methyltransferase screening, dosing schedule, and novel biomarkers for predicting thiopurine-induced leukopenia; (2) treatment with thiopurines with regards to optimal duration of thiopurine treatment and long-term outcomes of combination therapy with anti-tumor necrosis factors; (3) safety of thiopurines, especially during pregnancy and lactation; and (4) monitoring side effects or efficacy of therapy using biomarkers.
Conclusions Thiopurines are an effective treatment option for patients with IBD. Management decisions should be individualized according to the risk of relapse and adverse events.
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Journal of Gastroenterology and Hepatology.2022; 37(8): 1544. CrossRef - NUDT15Genotyping in Thiopurine Drug Therapy
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Laboratory Medicine Online.2022; 12(4): 217. CrossRef - Association of genetic variants in TPMT, ITPA, and NUDT15 with azathioprine-induced myelosuppression in southwest china patients with autoimmune hepatitis
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Scientific Reports.2021;[Epub] CrossRef - Treatment of inflammatory bowel diseases: focusing on 5-aminosalicylates and immunomodulators
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Journal of the Korean Medical Association.2021; 64(9): 596. CrossRef - Randomised clinical trial: dose optimising strategy by NUDT15 genotyping reduces leucopenia during thiopurine treatment of Crohn's disease
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Alimentary Pharmacology & Therapeutics.2021; 54(9): 1124. CrossRef - NUDT15: A bench to bedside success story
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Clinical Biochemistry.2021; 92: 1. CrossRef - Meta-Analysis of NUDT15 Genetic Polymorphism on Thiopurine-Induced Myelosuppression in Asian Populations
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Frontiers in Pharmacology.2021;[Epub] CrossRef - Pharmacogenetics-based personalized treatment in patients with inflammatory bowel disease: A review
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Precision and Future Medicine.2021; 5(4): 151. CrossRef - Sexual Dysfunction and Fertility Problems in Men with Inflammatory Bowel Disease
Yong Eun Park, Tae Oh Kim
The World Journal of Men's Health.2020; 38(3): 285. CrossRef - Genotype-based Treatment With Thiopurine Reduces Incidence of Myelosuppression in Patients With Inflammatory Bowel Diseases
Ji Young Chang, Soo Jung Park, Eun Suk Jung, Sung-Ae Jung, Chang Mo Moon, Jaeyoung Chun, Jae Jun Park, Eun Sun Kim, Yehyun Park, Tae-Il Kim, Won Ho Kim, Jae Hee Cheon
Clinical Gastroenterology and Hepatology.2020; 18(9): 2010. CrossRef - Optimizing the Use of Current Treatments and Emerging Therapeutic Approaches to Achieve Therapeutic Success in Patients with Inflammatory Bowel Disease
Hiroshi Nakase
Gut and Liver.2020; 14(1): 7. CrossRef - Adjustment of azathioprine dose should be based on a lower 6‐TGN target level to avoid leucopenia in NUDT15 intermediate metabolisers
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Alimentary Pharmacology & Therapeutics.2020; 52(3): 459. CrossRef - NUDT15 genotyping during azathioprine treatment in patients with inflammatory bowel disease: implications for a dose-optimization strategy
Ye Xu, Yu-Qi Qiao, Han-Yang Li, Mi Zhou, Chen-Wen Cai, Jun Shen, Zhi-Hua Ran
Gastroenterology Report.2020; 8(6): 437. CrossRef -
Complete remission of refractory pemphigus vulgaris in a Chinese patient with mutated
NUDT15
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Dermatologic Therapy.2020;[Epub] CrossRef - Prevention of thiopurine-induced early leukopenia in a Korean pediatric patient with Crohn’s disease who turned out to possess homozygous mutations in NUDT15 R139C
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Yeungnam University Journal of Medicine.2020; 37(4): 332. CrossRef - NUDT15 C415T variant compared with TPMT genotyping in predicting azathioprine‐induced leucopenia: prospective analysis of 1014 inflammatory bowel disease patients in India
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Alimentary Pharmacology & Therapeutics.2020; 52(11-12): 1683. CrossRef - Improving the quality of care for inflammatory bowel disease
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Intestinal Research.2019; 17(1): 45. CrossRef - NUDT15 Polymorphism Confer Increased Susceptibility to Thiopurine-Induced Leukopenia in Patients With Autoimmune Hepatitis and Related Cirrhosis
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Frontiers in Pharmacology.2019;[Epub] CrossRef - Thiopurine Therapy in Patients With Inflammatory Bowel Disease: A Focus on Metabolism and Pharmacogenetics
Ji Young Chang, Jae Hee Cheon
Digestive Diseases and Sciences.2019; 64(9): 2395. CrossRef - Nucleoside diphosphate-linked moiety X-type motif 15 R139C genotypes impact 6-thioguanine nucleotide cut-off levels to predict thiopurine-induced leukopenia in Crohn’s disease patients
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World Journal of Gastroenterology.2019; 25(38): 5850. CrossRef - How to Optimally Use Currently Available Drugs in a Therapeutic Algorithm?
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The Korean Journal of Gastroenterology.2018; 71(2): 74. CrossRef - Diagnostic accuracy of NUDT15 gene variants for thiopurine-induced leukopenia: a systematic review and meta-analysis
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Pharmacological Research.2018; 135: 102. CrossRef - Treatment of Autoimmune Bullous Disorders in Pregnancy
Carolyn J. Kushner, Josef Symon S. Concha, Victoria P. Werth
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Intestinal Research.2018; 16(2): 216. CrossRef - Asian Organization for Crohn's and Colitis and Asia Pacific Association of Gastroenterology consensus on tuberculosis infection in patients with inflammatory bowel disease receiving anti-tumor necrosis factor treatment. Part 1: risk assessment
Dong Il Park, Tadakazu Hisamatsu, Minhu Chen, Siew Chien Ng, Choon Jin Ooi, Shu Chen Wei, Rupa Banerjee, Ida Normiha Hilmi, Yoon Tae Jeen, Dong Soo Han, Hyo Jong Kim, Zhihua Ran, Kaichun Wu, Jiaming Qian, Pin-Jin Hu, Katsuyoshi Matsuoka, Akira Andoh, Yasu
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World Journal of Gastroenterology.2018; 24(8): 941. CrossRef - NUDT15 R139C Variants Increase the Risk of Azathioprine-Induced Leukopenia in Chinese Autoimmune Patients
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Frontiers in Pharmacology.2018;[Epub] CrossRef - Pharmacotherapy of ulcerative colitis – current status and emerging trends
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Journal of Basic and Clinical Physiology and Pharmacology.2018; 29(6): 581. CrossRef - Asian Organization for Crohn's and Colitis and Asian Pacific Association of Gastroenterology consensus on tuberculosis infection in patients with inflammatory bowel disease receiving anti‐tumor necrosis factor treatment. Part 1: Risk assessment
Dong II Park, Tadakazu Hisamatsu, Minhu Chen, Siew Chien Ng, Choon Jin Ooi, Shu Chen Wei, Rupa Banerjee, Ida Normiha Hilmi, Yoon Tae Jeen, Dong Soo Han, Hyo Jong Kim, Zhihua Ran, Kaichun Wu, Jiaming Qian, Pin‐Jin Hu, Katsuyoshi Matsuoka, Akira Andoh, Yasu
Journal of Gastroenterology and Hepatology.2018; 33(1): 20. CrossRef - Postoperative course of Crohn disease according to timing of bowel resection
Ji Min Lee, Kang-Moon Lee, Joo Sung Kim, You Sun Kim, Jae Hee Cheon, Byong Duk Ye, Young-Ho Kim, Dong Soo Han, Chang Kyun Lee, Hyun-Ju Park
Medicine.2018; 97(16): e0459. CrossRef - Revisiting the Role of Thiopurines in Inflammatory Bowel Disease Through Pharmacogenomics and Use of Novel Methods for Therapeutic Drug Monitoring
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Frontiers in Pharmacology.2018;[Epub] CrossRef - Changing treatment paradigms for the management of inflammatory bowel disease
Jong Pil Im, Byong Duk Ye, You Sun Kim, Joo Sung Kim
The Korean Journal of Internal Medicine.2018; 33(1): 28. CrossRef - NUDT15,FTO, andRUNX1genetic variants and thiopurine intolerance among Japanese patients with inflammatory bowel diseases
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Intestinal Research.2017; 15(3): 328. CrossRef - Second Korean Guideline for the Management of Ulcerative Colitis
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Intestinal Research.2017; 15(2): 147. CrossRef - Second Korean guidelines for the management of ulcerative colitis
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Intestinal Research.2017; 15(1): 7. CrossRef - Combined Detection of NUDT15 Variants Could Highly Predict Thiopurine-induced Leukopenia in Chinese Patients with Inflammatory Bowel Disease
Kang Chao, Xueding Wang, Qian Cao, Jiaming Qian, Kaichun Wu, Xia Zhu, Hong Yang, Jie Liang, Lang Lin, Zicheng Huang, Yu Zhang, Yibiao Huang, Yinghao Sun, Xianmin Xue, Min Huang, Pinjin Hu, Ping Lan, Xiang Gao
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World Journal of Gastroenterology.2017; 23(35): 6385. CrossRef - Is the Therapeutic Drug Monitoring of Anti-TNF Agents Necessary in Korean Inflammatory Bowel Disease Patients?
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Gut and Liver.2017; 11(1): 3. CrossRef - Second Korean Guidelines for the Management of Crohn's Disease
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Intestinal Research.2017; 15(1): 38. CrossRef - Long-Term Outcomes of Infliximab Treatment in 582 Korean Patients with Crohn’s Disease: A Hospital-Based Cohort Study
Sang Hyoung Park, Sung Wook Hwang, Min Seob Kwak, Wan Soo Kim, Jeong-Mi Lee, Ho-Su Lee, Dong-Hoon Yang, Kyung-Jo Kim, Byong Duk Ye, Jeong-Sik Byeon, Seung-Jae Myung, Yong Sik Yoon, Chang Sik Yu, Jin-Ho Kim, Suk-Kyun Yang
Digestive Diseases and Sciences.2016; 61(7): 2060. CrossRef - Measurement of red blood cell 6-thioguanine nucleotide is beneficial in azathioprine maintenance therapy of Chinese Crohn’s disease patients
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Scandinavian Journal of Gastroenterology.2016; 51(9): 1093. CrossRef - NUDT15 polymorphisms are better than thiopurine S‐methyltransferase as predictor of risk for thiopurine‐induced leukopenia in Chinese patients with Crohn's disease
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Alimentary Pharmacology & Therapeutics.2016; 44(9): 967. CrossRef - Influences ofXDHgenotype by gene–gene interactions with SUCLA2 for thiopurine-induced leukopenia in Korean patients with Crohn’s disease
Soo-Kyung Park, Myunghee Hong, Byong Duk Ye, Kyung-Jo Kim, Sang Hyoung Park, Dong-Hoon Yang, Sung-Wook Hwang, Min Seob Kwak, Ho-Su Lee, Kyuyoung Song, Suk-Kyun Yang
Scandinavian Journal of Gastroenterology.2016; 51(6): 684. CrossRef - Change in the diagnosis of inflammatory bowel disease: a hospital-based cohort study from Korea
Ho-Su Lee, Jaewon Choe, Hyo Jeong Lee, Sung Wook Hwang, Sang Hyoung Park, Dong-Hoon Yang, Kyung-Jo Kim, Byong Duk Ye, Jeong-Sik Byeon, Seung-Jae Myung, Yong Sik Yoon, Chang Sik Yu, Jin-Ho Kim, Suk-Kyun Yang
Intestinal Research.2016; 14(3): 258. CrossRef - Six Cases of Lung Injury Following Anti-tumour Necrosis Factor Therapy for Inflammatory Bowel Disease
Ho-Su Lee, Kyung-Wook Jo, Tae Sun Shim, Jin Woo Song, Hyo Jeong Lee, Sung Wook Hwang, Sang Hyoung Park, Dong-Hoon Yang, Kyung-Jo Kim, Byong Duk Ye, Jeong-Sik Byeon, Seung-Jae Myung, Jin-Ho Kim, Suk-Kyun Yang
Journal of Crohn's and Colitis.2015; 9(11): 1053. CrossRef
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