Evidence map›Paper›PMID 33118191›Full record

ArticleBritish journal of clinical pharmacology2021

Influence of allopurinol on thiopurine associated toxicity: A retrospective population-based cohort study.

Jeroen P A Houwen, Antoine C G Egberts, Anthonius de Boer, Erik M van Maarseveen, Roderick H J Houwen, Arief Lalmohamed

Open access · hybridAbstract read
In one paragraph

Article in British journal of clinical pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 2 pooled it
0.5field-weighted citation impact, top 28% 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

4 citing papers in PubMed, 2 syntheses or guidelines pooled it, 8 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Review
  4. 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

6 authors at 2 institutions in 1 country.

Jeroen P A HouwenDepartment of Clinical Pharmacy, University Medical Center Utrecht, Utrecht, Netherlands.ORCID 0000-0001-5521-2519
Antoine C G EgbertsDepartment of Clinical Pharmacy, University Medical Center Utrecht, Utrecht, Netherlands.ORCID 0000-0003-1758-7779
Anthonius de BoerUtrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands.ORCID 0000-0002-9485-8037
Erik M van MaarseveenDepartment of Clinical Pharmacy, University Medical Center Utrecht, Utrecht, Netherlands.ORCID 0000-0003-2163-0311
Roderick H J HouwenDepartment of Paediatric Gastroenterology, University Medical Center Utrecht, Utrecht, Netherlands.ORCID 0000-0001-6124-7937
Arief LalmohamedDepartment of Clinical Pharmacy, University Medical Center Utrecht, Utrecht, Netherlands.ORCID 0000-0002-3149-3501
Utrecht University · NLUniversity Medical Center Utrecht · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsThiopurines are important for treating inflammatory bowel disease, but are often discontinued due to adverse effects. Concomitant use of allopurinol might lower the risk of these unwanted effects, but large studies in the general population are lacking. The aims of this study were to evaluate rates of hepatotoxicity, myelotoxicity, pancreas toxicity and therapy persistence in adult thiopurine users with or without allopurinol.

methodsA retrospective population-based cohort study was conducted within current thiopurine users (Clinical Practice Research Datalink). Among these patients, co-use of allopurinol was compared to non-use. Hazard ratios (HRs) for hepatotoxicity, myelotoxicity and pancreatitis were derived using time-dependent Cox proportional hazards models, and were adjusted for potential confounders. Persistence of thiopurine use was evaluated using Log-rank statistics.

resultsPatients using thiopurines (n = 37 360) were identified of which 1077 were concomitantly taking allopurinol. A 58% decreased risk of hepatotoxicity was observed in those concomitantly taking allopurinol (HR 0.42; 95% CI 0.30-0.60; NNT 46). Rate of myelotoxicity (HR 0.96; 95% CI 0.89-1.03) was not influenced. Risk of pancreatitis was increased (HR 3.00; 95% CI 1.01-8.93; NNH 337), but was only seen in those with active gout (suggesting confounding by indication). Finally, allopurinol co-users were able to maintain thiopurine therapy over twice as long as those not on allopurinol (3.9 years vs. 1.8 years, P < 0.0001).

conclusionIn thiopurine users, allopurinol is associated with a 58% reduced risk of hepatotoxicity. In addition, thiopurine persistence was prolonged by 2.1 years in allopurinol users. These data support the use of allopurinol in individuals requiring thiopurine therapy.

Indexed as

AllopurinolInflammatory Bowel DiseasesAdultAzathioprineCohort StudiesDrug Therapy, CombinationHumansImmunosuppressive AgentsMercaptopurineRetrospective StudiesTreatment OutcomeAllopurinolAzathioprineImmunosuppressive AgentsMercaptopurineallopurinolhepatotoxicitymyelotoxicitypancreas toxicitythiopurines

Identifiers

PMID33118191
PMCPMC8246992
OpenAlexW3096756485

What OpenQuestion holds

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LicenceCC BY-NC
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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.