Evidence map›Paper›PMID 24237037›Full record

Trial reportAlimentary pharmacology & therapeutics2014

Randomised clinical trial: individualised vs. weight-based dosing of azathioprine in Crohn's disease.

T Dassopoulos, M C Dubinsky, J L Bentsen, C F Martin, J A Galanko, E G Seidman, R S Sandler, S B Hanauer

Registry-linked trialOpen access · bronzeAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Alimentary pharmacology & therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00113503 (A Multi-site Trial of Azathioprine Dosing in Crohn's Disease), which is not on this map. Cited by 33 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed, 1 pooled it
6.5field-weighted citation impact, top 3% 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.

NCT00113503 phase2terminatednot on this map

A Multi-site Trial of Azathioprine Dosing in Crohn's Disease

TypeinterventionalSponsorNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)Ran2005 to 2007Enrolled50ConditionsCrohn's DiseaseArmsAzathioprine weight-based dose, Azathioprine individualised dose
3 · Its place in the literature

Who cites it

33 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Review
  5. Observational
  6. Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. Review
  13. Review
  14. The Evolving Role of Thiopurines in Inflammatory Bowel Disease.Current treatment options in gastroenterology · 2019
    Review
  15. Article
  16. Review
  17. The Evolving Role of Thiopurines in Inflammatory Bowel Disease.Current treatment options in gastroenterology · 2019
    Review
  18. Article
  19. Review
  20. External Validation of a Thiopurine Monitoring Algorithm on the SONIC Clinical Trial Dataset.Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association · 2018
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 5 institutions in 2 countries.

T DassopoulosDepartment of Medicine, Johns Hopkins University, Baltimore, MD, USA.
M C Dubinsky
J L Bentsen
C F Martin
J A Galanko
E G Seidman
R S Sandler
S B Hanauer
University of North Carolina at Chapel Hill · USUniversity of Chicago · USCedars-Sinai Medical Center · USJohns Hopkins University · USMcGill University · CA

Funding

PILOT AND FEASIBILITY STUDIESP30DK034987 · NIDDK · UNIV OF NORTH CAROLINA CHAPEL HILL · PI ROBERT S. SANDLER · 1985 to 2026
$30.5M
Multi-site Trial of Azathioprine Dosing in Crohn DiseaseU01DK060083 · NIDDK · UNIVERSITY OF CHICAGO · PI HANAUER, STEPHEN B. · 2004 to 2004
$744k
NIDDK NIH HHS P30 DK034987NIDDK NIH HHS P30DK34987NIDDK NIH HHS U01 DK060083NIDDK NIH HHS U01 DK60083
6 · The paper itself

Abstract

backgroundAzathioprine (AZA), a pro-drug metabolised to the active metabolites 6-tioguanine nucleotides (6TGN), is a steroid-sparing therapy for Crohn's disease (CD).

aimTo investigate whether AZA therapy is optimised by individualised dosing based on thiopurine methyltransferase (TPMT) activity and 6TGN concentrations.

methodsThis multicentre, double-blind, randomised controlled trial compared the efficacy and safety of weight-based vs. individualised AZA dosing in inducing and maintaining remission in adults and children with steroid-treated CD. The primary outcome was clinical remission (CR) at 16 weeks. In the weight-based arm, subjects received 2.5 mg/kg/day. In the individualised dosing arm, the initial AZA dose was 1.0 mg/kg/day (if intermediate TPMT) or 2.5 mg/kg/day (if normal TPMT). Starting at week 5, the dose was adjusted to target 6TGN concentrations of 250-400 pmol/8 × 10(8) red blood cells (RBC), or to a maximal dose of 4 mg/kg/day.

resultsAfter randomising 50 subjects, the trial was stopped prematurely due to insufficient enrolment. In intention-to-treat analysis, CR rates at week 16 were 40% in the individualised arm vs. 16% in the weight-based arm (P = 0.11). In per-protocol (PP) analysis, week 16 CR rates were 60% in the individualised arm and 25% in the weight-based arm (P = 0.12). At week 16, median 6TGN concentrations in PP remitters and nonremitters were 216 and 149 pmol/8 × 10(8) RBC respectively (P = 0.07).

conclusionsDespite trends favouring individualised over weight-based AZA dosing, there were no statistically significant differences in efficacy, likely due to low statistical power and inability to achieve the target 6TGN concentrations in the individualised arm. [Clinicaltrials.Gov Identifier Nct00113503].

Indexed as

AdolescentAdultAzathioprineBody WeightChildCrohn DiseaseDouble-Blind MethodFemaleHumansImmunosuppressive AgentsMaleProdrugsThioguanineTreatment OutcomeYoung AdultAzathioprineImmunosuppressive AgentsProdrugsThioguanine

Identifiers

PMID24237037
PMCPMC3918445
OpenAlexW2007879037

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Registered trials

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.