Evidence map›Paper›PMID 38589597›Full record

ArticleJournal of gastroenterology2024

Real-world NUDT15 genotyping and thiopurine treatment optimization in inflammatory bowel disease: a multicenter study.

Motoki Makuuchi, Yoichi Kakuta, Junji Umeno, Toshimitsu Fujii, Tetsuya Takagawa, Takashi Ibuka, Miki Miura, Yu Sasaki, Sakuma Takahashi, Hiroshi Nakase and 40 more

Abstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of gastroenterology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Guideline
  2. Review
  3. Article
  4. Article
  5. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

50 authors.

Motoki Makuuchi *Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aoba, Sendai, 980-8574, Japan.
Yoichi Kakuta *Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aoba, Sendai, 980-8574, Japan. ykakuta@med.tohoku.ac.jp.ORCID 0000-0002-7042-009X
Junji UmenoDepartment of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Toshimitsu FujiiDepartment of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan.
Tetsuya TakagawaCenter for Clinical Research and Education/Center for Inflammatory Bowel Disease, Hyogo Medical University, Nishinomiya, Japan.
Takashi IbukaDepartment of Gastroenterology, Gifu University Graduate School of Medicine, Gifu, Japan.
Miki MiuraDepartment of Gastroenterology and Hepatology, Kyorin University School of Medicine, Tokyo, Japan.
Yu SasakiDepartment of Gastroenterology, Faculty of Medicine, Yamagata University, Yamagata, Japan.
Sakuma TakahashiDepartment of Gastroenterology, Kagawa Prefectural Central Hospital, Takamatsu, Japan.
Hiroshi NakaseDepartment of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan.
Hiroki KiyoharaDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
Keiichi TominagaDepartment of Gastroenterology, Dokkyo Medical University, Tochigi, Japan.
Yosuke ShimodairaDepartment of Gastroenterology and Neurology, Akita University, Akita, Japan.
Sakiko HiraokaDepartment of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Nobuhiro UenoDivision of General Medicine, Asahikawa Medical University Hospital, Asahikawa, Japan.
Shunichi YanaiDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Iwate Medical University, Morioka, Japan.
Takeo YoshiharaDepartment of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan.
Kazuki KakimotoSecond Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Osaka, Japan.
Katsuyoshi MatsuokaDivision of Gastroenterology and Hepatology, Department of Internal Medicine, Toho University Sakura Medical Center, Chiba, Japan.
Ryohei HayashiDepartment of Gastroenterology, Hiroshima University Hospital, Hiroshima, Japan.
Sohachi NanjoThird Department of Internal Medicine, Graduate School of Medicine, University of Toyama, Toyama, Japan.
Itaru IwamaDivision of Gastroenterology and Hepatology, Saitama Children's Medical Center, Saitama, Japan.
Yoh IshiguroDivision of Clinical Research, Hirosaki General Medical Center, NHO, Hirosaki, Japan.
Hirofumi ChibaDepartment of Gastroenterology, Iwate Prefectural Isawa Hospital, Oshu, Japan.
Katsuya EndoDivision of Gastroenterology, Tohoku Medical and Pharmaceutical University School of Medicine, Sendai, Japan.
Takashi KagayaDepartment of Gastroenterology, NHO Kanazawa Medical Center, Kanazawa, Japan.
Tomohiro FukudaCenter for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan.
Yasuhisa SakataDivision of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, Japan.
Takahiro KudoDepartment of Pediatrics, Juntendo University Faculty of Medicine, Tokyo, Japan.
Tomohisa TakagiDepartment of Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Kenichi TakahashiDepartment of Colorectal Surgery, Tohoku Rosai Hospital, Sendai, Japan.
Makoto NaganumaThird Department of Internal Medicine, Kansai Medical University, Hirakata, Japan.
Masaru ShinozakiSaitama Gastroenterology Clinic, Saitama, Japan.
Noriyuki OgataDigestive Disease Center, Showa University Northern Yokohama Hospital, Yokohama, Japan.
Hiroki TanakaSapporo IBD Clinic, Sapporo, Japan.
Kazuyuki NarimatsuDepartment of Internal Medicine, National Defense Medical College, Tokorozawa, Japan.
Haruka MiyazakiDivision of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Takashi IshigeDepartment of Pediatrics, Gunma University Graduate School of Medicine, Maebashi, Japan.
Motoyuki OnoderaOsaki Citizen Hospital, Osaki, Japan.
Yu HashimotoDepartment of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Maebashi, Japan.
Hiroshi NagaiDivision of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aoba, Sendai, 980-8574, Japan.
Yusuke ShimoyamaDivision of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aoba, Sendai, 980-8574, Japan.
Takeo NaitoDivision of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aoba, Sendai, 980-8574, Japan.
Rintaro MoroiDivision of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aoba, Sendai, 980-8574, Japan.
Hisashi ShigaDivision of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aoba, Sendai, 980-8574, Japan.
Post-MENDEL study group
Yoshitaka KinouchiStudent Healthcare Center, Institute for Excellence in Higher Education, Tohoku University, Sendai, Japan.
Akira AndohDivision of Gastroenterology and Hematology, Department of Medicine, Shiga University of Medical Science, Otsu, Japan.
Tadakazu HisamatsuDepartment of Gastroenterology and Hepatology, Kyorin University School of Medicine, Tokyo, Japan.
Atsushi MasamuneDivision of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo, Aoba, Sendai, 980-8574, Japan.

Funding

Japan Agency for Medical Research and Development JP20ek0410056Japan Agency for Medical Research and Development JP22ek0410091Japan Society for the Promotion of Science 21K07955Japan Society for the Promotion of Science 22K08024
6 · The paper itself

Abstract

backgroundThis study evaluated the effectiveness of NUDT15 codon 139 genotyping in optimizing thiopurine treatment for inflammatory bowel disease (IBD) in Japan, using real-world data, and aimed to establish genotype-based treatment strategies.

methodsA retrospective analysis of 4628 IBD patients who underwent NUDT15 codon 139 genotyping was conducted. This study assessed the purpose of the genotyping test and subsequent prescriptions following the obtained results. Outcomes were compared between the Genotyping group (thiopurine with genotyping test) and Non-genotyping group (thiopurine without genotyping test). Risk factors for adverse events (AEs) were analyzed by genotype and prior genotyping status.

resultsGenotyping test for medical purposes showed no significant difference in thiopurine induction rates between Arg/Arg and Arg/Cys genotypes, but nine Arg/Cys patients opted out of thiopurine treatment. In the Genotyping group, Arg/Arg patients received higher initial doses than the Non-genotyping group, while Arg/Cys patients received lower ones (median 25 mg/day). Fewer AEs occurred in the Genotyping group because of their lower incidence in Arg/Cys cases. Starting with < 25 mg/day of AZA reduced AEs in Arg/Cys patients, while Arg/Arg patients had better retention rates when maintaining ≥ 75 mg AZA. Nausea and liver injury correlated with thiopurine formulation but not dosage. pH-dependent mesalamine reduced leukopenia risk in mesalamine users.

conclusionsNUDT15 codon 139 genotyping effectively reduces thiopurine-induced AEs and improves treatment retention rates in IBD patients after genotype-based dose adjustments. This study provides data-driven treatment strategies based on genotype and identifies risk factors for specific AEs, contributing to a refined thiopurine treatment approach.

Indexed as

AzathioprineGenotypeInflammatory Bowel DiseasesMercaptopurinePyrophosphatasesAdolescentAdultAgedCodonFemaleHumansImmunosuppressive AgentsJapanMaleMiddle AgedNudix HydrolasesAzathioprineCodonImmunosuppressive AgentsMercaptopurineNudix HydrolasesNUDT15 protein, humanPyrophosphatases6-mercaptopurineAdverse eventAzathioprineNUDT15Thiopurine

Identifiers

PMID38589597
PMCPMC11128409

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.