Evidence map›Paper›PMID 16543290›Full record

ArticleGut2006

Pharmacogenetics during standardised initiation of thiopurine treatment in inflammatory bowel disease.

U Hindorf, M Lindqvist, C Peterson, P Söderkvist, M Ström, H Hjortswang, A Pousette, S Almer

Open access · greenAbstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Gut, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 4 pooled it
11.6field-weighted citation impact, top 1% of its field
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

45 citing papers in PubMed, 4 syntheses or guidelines pooled it, 173 citations in OpenAlex.

  1. Pooled it
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  5. Review
  6. Article
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  11. Advances in Thiopurine Drug Delivery: The Current State-of-the-Art.European journal of drug metabolism and pharmacokinetics · 2021
    Review
  12. Article
  13. Article
  14. Review
  15. Review
  16. Article
  17. Review
  18. Article
  19. The Evolving Role of Thiopurines in Inflammatory Bowel Disease.Current treatment options in gastroenterology · 2019
    Review
  20. 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

8 authors at 3 institutions in 1 country.

U HindorfDepartment of Clinical Sciences, Division of Gastroenterology, Faculty of Medicine, Lund University, 22185 Lund, Sweden. Ulf.Hindorf@med.lu.se
M Lindqvist
C Peterson
P Söderkvist
M Ström
H Hjortswang
A Pousette
S Almer
Linköping University · SELund University · SEVrinnevisjukhuset i Norrköping · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundFirm recommendations about the way thiopurine drugs are introduced and the use of thiopurine methyltransferase (TPMT) and metabolite measurements during treatment in inflammatory bowel disease (IBD) are lacking.

aimTo evaluate pharmacokinetics and tolerance after initiation of thiopurine treatment with a fixed dosing schedule in patients with IBD. PATIENTS: 60 consecutive patients with Crohn's disease (n = 33) or ulcerative colitis (n = 27) were included in a 20 week open, prospective study.

methodsThiopurine treatment was introduced using a predefined dose escalation schedule, reaching a daily target dose at week 3 of 2.5 mg azathioprine or 1.25 mg 6-mercaptopurine per kg body weight. TPMT and ITPA genotypes, TPMT activity, TPMT gene expression, and thiopurine metabolites were determined. Clinical outcome and occurrence of adverse events were monitored.

results27 patients completed the study per protocol, while 33 were withdrawn (early protocol violation (n = 5), TPMT deficiency (n = 1), thiopurine related adverse events (n = 27)); 67% of patients with adverse events tolerated long term treatment on a lower dose (median 1.32 mg azathioprine/kg body weight). TPMT activity did not change during the 20 week course of the study but a significant decrease in TPMT gene expression was found (TPMT/huCYC ratio; p = 0.02). Patients with meTIMP concentrations >11,450 pmol/8 x 10(8) red blood cells during steady state at week 5 had an increased risk of developing myelotoxicity (odds ratio = 45.0; p = 0.015).

conclusionsAfter initiation of thiopurine treatment using a fixed dosing schedule, no general induction of TPMT enzyme activity occurred, though TPMT gene expression decreased. The development of different types of toxicity was unpredictable, but we found that measurement of meTIMP early in the steady state phase helped to identify patients at risk of developing myelotoxicity.

Indexed as

AdolescentAdultAgedAntimetabolitesAzathioprineColitis, UlcerativeCrohn DiseaseDose-Response Relationship, DrugFemaleGene ExpressionGenotypeHumansInosine TriphosphataseMaleMercaptopurineMethyltransferasesAntimetabolitesAzathioprineInosine TriphosphataseMercaptopurineMethyltransferasesPyrophosphatasesthiopurine methyltransferase

Identifiers

PMID16543290
PMCPMC1856436
OpenAlexW2144085109

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.