title: Application of multicategory exposure marginal structural models to investigate the association between long-acting beta-agonists and prescribing of oral corticosteroids for asthma exacerbations in the Clinical Practice Research Datalink.
abstract: OBJECTIVE
  To examine the comparative effectiveness of inhaled long-acting beta-agonist (LABA), inhaled corticosteroid (ICS), and ICS/LABA combinations.
  
  
  METHODS
  We used a retrospective cohort design of patients older than 12 years with asthma diagnosis in the Clinical Practice Research Datalink to evaluate asthma-related morbidity measured by oral corticosteroid (OCS) initiation within 12 months of initiating LABAs, ICSs, or ICSs/LABAs. Asthma severity 12 months before drug initiation (use of OCSs, asthma-related hospital or emergency department visits, and number of short-acting beta-agonist prescriptions) and during follow-up (short-acting beta-agonist prescriptions and total number of asthma drug classes) was adjusted as a time-varying variable via marginal structural models.
  
  
  RESULTS
  A total of 51,103 patients with asthma were followed for 12 months after receiving first prescription for study drugs from 1993 to 2010. About 92% initiated ICSs, 1% initiated LABAs, and 7% initiated ICSs/LABAs. Compared with ICSs, LABAs were associated with a 10% increased risk of asthma exacerbations requiring short courses of OCSs (hazard ratio [HR] 1.10; 95% confidence interval [CI] 1.07-1.18). ICS/LABA initiators were 62% less likely than ICS initiators (HR 0.38; 95% CI 0.12-0.66) and 50% less likely than LABA initiators to receive OCS prescriptions for asthma exacerbations (HR 0.50; 95% CI 0.14-0.78).
  
  
  CONCLUSIONS
  In concordance with current asthma management guidelines, inhaled LABAs should not be prescribed as monotherapy to patients with asthma. The findings suggest the presence of time-dependent confounding by asthma severity, which was accounted for by the marginal structural model.
authors.affiliation: Global Patient Safety, Eli Lilly and Company, Indianapolis, IN, USA; Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA; Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL, USA. Electronic address: ayadali@alumni.ufl.edu.
authors.forename: Ayad K
authors.initials: AK
authors.lastname: Ali
authors.affiliation: Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL, USA; Department of Epidemiology, College of Public Health and Health Professions and College of Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: Abraham G
authors.initials: AG
authors.lastname: Hartzema
authors.affiliation: Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL, USA.
authors.forename: Almut G
authors.initials: AG
authors.lastname: Winterstein
authors.affiliation: Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL, USA; Deans Office, College of Pharmacy, University of Florida, Gainesville, FL, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Segal
authors.affiliation: Department of Biostatistics, College of Public Health and Health Professions and College of Medicine, University of Florida, Gainesville, FL, USA.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Hendeles
mesh_terms: D000280:Administration, Inhalation; D000284:Administration, Oral; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage*; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage*; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D015331:Cohort Studies; D003362:Cost-Benefit Analysis / Q000379:methods*; D016208:Databases, Factual; D003692:Delayed-Action Preparations; D011307:Drug Prescriptions; D005260:Female; D005500:Follow-Up Studies; D006302:Health Services Research / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D000318:Adrenergic beta-Agonists; D018927:Anti-Asthmatic Agents; D003692:Delayed-Action Preparations
keywords: Clinical Practice Research Datalink; asthma; long-acting beta-agonists; marginal structural models