17-PUB: Glucagon-Like Peptide 1 Receptor Agonists' Heterogeneous Treatment Effects on Asthma Exacerbations—A Causal Machine-Learning Analysis
Authors: WANG TIANSHENG , BUSE JOHN B. , PATE VIRGINIA , PRATLEY RICHARD E. , WYSS RICHARD , KVIST KAJSA , KOSOROK MICHAEL R. , KEET CORINNE , STÜRMER TIL 
Published: June 2024

While recent studies suggest GLP1RA may reduce the risk of asthma exacerbation, it is unclear which subpopulations may derive greatest benefit. To address this question, we identified GLP1RA vs sulfonylureas (SU) new user cohorts in commercially insured patients ages 18-65 from MarketScan data 10/1/2016-12/31/2020, requiring patients to have ≥ 1 inpatient or 2 outpatient encounters with asthma and without conditions necessitating the use of systemic steroids, heart failure, chronic obstructive pulmonary disease, vocal cord dysfunction, or other respiratory diseases. The outcome was acute asthma exacerbation (hospital admission or emergency department visit for asthma) ≤ 180 days after initiation. We applied hdiCF, a novel semi-automatic machine learning subgrouping algorithm which identifies subgroups with heterogeneous treatment effects by diagnostic and procedure codes and dispensed drugs in healthcare databases without requiring predefined variables. In identified subgroups, we estimated adjusted risk differences (aRD) for the effect of GLP1RA relative to SU on asthma exacerbation using inverse probability treatment weighting. Among all GLP1RA vs SU initiators (13,006 vs 8,815, # events 379 vs 94), GLP1RA was not associated with fewer asthma exacerbations with an aRD of 1.0% (0.6% to 1.3%). We identified 3 subgroups with different treatment effects, defined by the number of systematic steroid prescriptions (Rx), dyslipidemia, and the number of adrenergic inhalers Rx. Among these, only patients with 2+ systematic steroid Rx during 12-month baseline period (4,606 vs 3,192, #events 255 vs 77) had the benefit (aRD -1.9%, 95%CI=-2.8% to -1.0%). No beneficial effects were observed in the remaining 3 groups. The number of systematic steroid Rx (a proxy for asthma severity), dyslipidemia, and the number of adrenergic inhalers may help individualize prediction of the short-term benefit from GLP1RA vs SU on acute asthma exacerbation.

Disclosure
T. Wang: None. J.B. Buse: Other Relationship; Novo Nordisk. Consultant; Corcept Therapeutics. Research Support; Corcept Therapeutics, Dexcom, Inc., Insulet Corporation. Consultant; Alkahest, Anji Pharmaceuticals, Aqua Medical, Altimmune Inc., AstraZeneca, Boehringer-Ingelheim, CeQur, Eli Lilly and Company, embecta, GentiBio, Glyscend Inc., Mellitus Health, Metsera, Pendulum Therapeutics, Praetego, LLC, Stability Health, Terns Pharmaceuticals, Insulet Corporation, Vertex Pharmaceuticals Incorporated, vTv Therapeutics. Other Relationship; Medtronic. Stock/Shareholder; Glyscend Inc., Mellitus Health, Pendulum Therapeutics, Praetego, LLC, Stability Health. V. Pate: None. R.E. Pratley: Other Relationship; Bayer AG, Dompé, Endogenex, Inc., Gasherbrum Bio, Inc., Hengrui (USA) Ltd., Intas Pharmaceuticals Ltd., Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk, Novo Nordisk, Pfizer Inc., Rivus Pharmaceuticals Inc., Sun Pharmaceutical Industries Ltd. Consultant; AbbVie Inc., AstraZeneca. Other Relationship; Bayer HealthCare Pharmaceuticals, Inc., Biomea Fusion, Carmot Therapeutics, Inc., Corcept Therapeutics, Fractyl Health, Inc., Genprex. Consultant; Getz Pharma. Other Relationship; Lilly USA LLC, Sanofi. Consultant; Scholar Rock, Inc. R. Wyss: None. K. Kvist: Employee; Novo Nordisk A/S. M.R. Kosorok: None. C. Keet: Research Support; Genentech, Inc. T. Stürmer: Stock/Shareholder; Novartis AG, Novo Nordisk, Roche Pharmaceuticals.

Funding
American Diabetes Association (#4-22-PDFPM-06); NIA R01 AG056479