Evidence map›Paper›PMID 40717037›Full record

ArticlePharmacoepidemiology and drug safety2025

Glucagon-like Peptide-1 Receptor Agonists in Asthma Exacerbations: An Application of High-Dimensional Iterative Causal Forest to Identify Subgroups.

Tiansheng Wang, Jeanny H Wang, Alan C Kinlaw, Richard Wyss, Virginia Pate, Zhuoyue Gou, John B Buse, Corinne A Keet, Michael R Kosorok, Til Stürmer

Abstract read
In one paragraph

Article in Pharmacoepidemiology and drug safety, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
  2. 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

10 authors.

Tiansheng WangDepartment of Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, North Carolina, USA.ORCID https://orcid.org/0000-0002-0980-8896
Jeanny H WangDepartment of Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, North Carolina, USA.
Alan C KinlawDepartment of Pharmaceutical Outcomes and Policy, University of North Carolina Eshelman School of Pharmacy, Chapel Hill, North Carolina, USA.ORCID https://orcid.org/0000-0002-4279-8685
Richard WyssDivision of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Virginia PateDepartment of Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, North Carolina, USA.ORCID https://orcid.org/0000-0002-2141-8882
Zhuoyue GouDepartment of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, New Jersey, USA.
John B BuseDepartment of Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.ORCID https://orcid.org/0000-0002-9723-3876
Corinne A KeetDepartment of Pediatrics, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.ORCID https://orcid.org/0000-0002-6585-239X
Michael R KosorokDepartment of Biostatistics, University of North Carolina Gillings School of Global Public Health, Chapel Hill, North Carolina, USA.ORCID https://orcid.org/0000-0002-6070-9738
Til StürmerDepartment of Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, North Carolina, USA.ORCID https://orcid.org/0000-0002-9204-7177

Funding

North Carolina Translational and Clinical Sciences Institute (NC TraCS)UM1TR004406 · NCATS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI NICHOLAS J SHAHEEN · 2023 to 2026
$37.5M
Biostatstics for Research in Environmental HealthT32ES007018 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Stephanie Engel, Rebecca Fry · 1985 to 2026
$31.3M
Pilot & Feasibility ProgramP30DK124723 · NIDDK · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI P Darrell Neufer · 2020 to 2026
$11.0M
Propensity scores and preventive drug use in the elderlyR01AG056479 · NIA · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Til Sturmer · 2017 to 2026
$5.0M
Applying causal inference methods to improve estimation of the real-world benefits and harms of lung cancer screening - NCI Diversity SupplementR01CA277756 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Louise Henderson, Jennifer Lund · 2023 to 2026
$1.5M
American Diabetes Association #4-22-PDFPM-06NCATS NIH HHS UM1 TR004406NCI NIH HHS R01 CA277756NIA NIH HHS R01 AG056479NIDDK NIH HHS P30 DK124723NIEHS NIH HHS T32 ES007018The National Institute of Diabetes and Digestive and Kidney Diseases P30DK124723The National Institute of Environmental Health Sciences T32ES007018The National Institute on Aging R01AG056479The North Carolina Translational and Clinical Sciences Institute, UM1TR004406
6 · The paper itself

Abstract

backgroundGlucagon-like Peptide-1 Receptor Agonists (GLP1RA) may reduce asthma exacerbation (AE) risk, but it is unclear which populations benefit most. Recent pharmacoepidemiologic studies have employed iterative causal forest (iCF), a machine learning (ML) algorithm, to identify subgroups with heterogeneous treatment effects (HTEs). While iCF does not rely on prior knowledge of treatment-variable interactions, it may be constrained by missing or poorly defined variables in pharmacoepidemiologic studies.

methodsWe applied the high-dimensional iterative causal forest (hdiCF)-a causal ML algorithm requiring predefined variables-to MarketScan 2016-2020 claims data to identify populations with asthma that might benefit most from GLP1RA in reducing AE risk. We built a GLP1RA vs. sulfonylurea new-user cohort with ≥ 1 inpatient or two outpatient asthma encounters, excluding patients with nonasthma indications for systemic steroids. The outcome was acute AE (hospital admission or emergency department visit for asthma), assessed over 6 months using 599 high-dimensional features from inpatient/outpatient services and pharmacy claims.

resultsIn the overall population, GLP1RA decreased AE risk relative to sulfonylurea: aRD -1.4% (-2.0%, -0.8%). hdiCF identified three subgroups based on the quantity of systemic steroid prescription fills (0, 1, and ≥ 2): patients with ≥ 2 prescriptions (GLP1RA: 34 events/1367 individuals; sulfonylurea: 53/1013) benefited most from GLP1RA: aRD -3.8% (-5.3%, -2.2%).

conclusionsThis study demonstrates how automated feature identification can pinpoint clinically relevant subgroups with HTEs. The quantity of systemic steroid prescriptions, as a proxy for severe asthma, may guide personalized predictions of GLP1RA's short-term benefits on acute AE.

Indexed as

AsthmaGlucagon-Like Peptide-1 Receptor AgonistsAdolescentAdultAgedAlgorithmsCohort StudiesDisease ProgressionFemaleHospitalizationHumansMachine LearningMaleMiddle AgedPharmacoepidemiologySulfonylurea CompoundsGlucagon-Like Peptide-1 Receptor AgonistsSulfonylurea Compoundsasthma exacerbationGLP‐1 receptor agonistheterogeneous treatment effecthigh‐dimensional iterative causal forestmachine learningprecision medicinereal‐world data

Identifiers

PMID40717037
PMCPMC12831167

What Socratic holds

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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 Socratic graph.