Evidence map›Paper›PMID 41846507›Full record

ArticleBritish journal of clinical pharmacology2026

The decline of 6-thioguanine nucleotides is not linked to impaired efficacy or safety of thiopurines in pregnant women with inflammatory bowel disease.

Dianne G Bouwknegt, Paola Mian, Femke Groen, Denise van den Berg-Zuiddam, Andrea E van der Meulen, Femke Crouwel, Nanne K de Boer, Debbie S Deben, Dennis R Wong, Luc J J Derijks and 4 more

Abstract readMulticenter Study
In one paragraph

Article in British journal of clinical pharmacology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–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

1 citing paper in PubMed.

  1. Article
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

14 authors.

Dianne G BouwknegtDepartment of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.ORCID https://orcid.org/0000-0002-6208-2967
Paola MianDepartment of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.ORCID https://orcid.org/0000-0002-3551-1201
Femke GroenDepartment of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Denise van den Berg-ZuiddamDepartment of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden University, Leiden, the Netherlands.
Andrea E van der MeulenDepartment of Gastroenterology and Hepatology, Leiden University Medical Center, Leiden University, Leiden, the Netherlands.
Femke CrouwelDepartment of Gastroenterology and Hepatology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Nanne K de BoerDepartment of Gastroenterology and Hepatology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
Debbie S DebenDepartment of Clinical Pharmacy, Pharmacology & Toxicology, Zuyderland Medical Center, Sittard-Geleen/Heerlen, the Netherlands.ORCID https://orcid.org/0000-0002-2956-5713
Dennis R WongDepartment of Clinical Pharmacy, Pharmacology & Toxicology, Zuyderland Medical Center, Sittard-Geleen/Heerlen, the Netherlands.
Luc J J DerijksDepartment of Clinical Pharmacy and Pharmacology, Máxima Medical Center, Veldhoven, The Netherlands.
Gerard DijkstraDepartment of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Arno R BourgonjeDepartment of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
C Janneke van der WoudeDepartment of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, the Netherlands.
Marijn C VisschedijkDepartment of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.

Funding

HORIZON EUROPE Health 101095470HORIZON EUROPE Health 101136582Innovative Health Initiative 101194780Nederlandse Organisatie voor Wetenschappelijk Onderzoek 452022317
6 · The paper itself

Abstract

backgroundThiopurines are used to maintain remission in inflammatory bowel disease (IBD). These drugs are metabolized into 6-thioguanine nucleotides (6-TGN), associated with efficacy, and 6-methylmercaptopurine ribonucleotides (6-MMPR), associated with adverse drug reactions. Pregnancy has been linked to a shift in thiopurine metabolism, characterized by reduced 6-TGN and increased 6-MMPR levels. The clinical impact of these changes remains unclear. To explore the association between changes in 6-TGN and 6-MMPR levels with disease activity and toxicity markers in women with IBD during pregnancy.

methodsThis retrospective cohort study included pregnant women with IBD who used thiopurines from six Dutch hospitals (2017-2022). Linear mixed-effects models were used to model changes of 6-TGN and 6-MMPR before, during and after pregnancy, and to identify associations with markers of disease activity (faecal calprotectin) and toxicity (alanine aminotransferase [ALT], leukocytes, platelets).

resultsA total of 87 women with 100 pregnancies were included (64.4% Crohn's disease, 32.2% ulcerative colitis). A significant reduction in 6-TGN was found in the second and third trimester, but no associations with changes in faecal calprotectin were detected. There were no significant increases in 6-MMPR. Increases in 6-MMPR were associated with modest elevations in ALT, but none of the other toxicity markers. Transient thrombocytopenia and leukopenia occurred thrice, and elevated liver enzymes were observed in nine pregnancies.

conclusionsAlthough 6-TGN levels decreased during pregnancy, these fluctuations were not associated with increased disease activity or toxicity. No significant increase in 6-MMPR levels was observed. Proactive monitoring may therefore not be warranted in the pregnant population.

Indexed as

AzathioprineGuanine NucleotidesImmunosuppressive AgentsInflammatory Bowel DiseasesMercaptopurinePregnancy ComplicationsThionucleotidesAdultFecesFemaleHumansLeukocyte L1 Antigen ComplexNetherlandsPregnancyRetrospective Studies6-thioguanylic acidAzathioprineGuanine NucleotidesImmunosuppressive AgentsLeukocyte L1 Antigen ComplexMercaptopurineThionucleotides6‐thioguanine nucleotidesinflammatory bowel diseasemonitoringpregnancythiopurines

Identifiers

PMID41846507
PMCPMC13304283

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Registered trials

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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.