title: Increased Dose of Inhaled Corticosteroid versus Add-On Long-acting β-Agonist for Step-Up Therapy in Asthma.
abstract: BACKGROUND
  Guidelines advocate adding long-acting β-agonist (LABA) to inhaled corticosteroid as the preferred step-up therapy to increasing inhaled corticosteroid dose for patients with uncontrolled asthma on inhaled corticosteroid monotherapy. However, less than 5% of patients with asthma qualify for the randomized controlled trials on which guidelines are based. Thus, real-world data are needed to complement the results of randomized trials with narrow entry criteria.
  
  
  OBJECTIVE
  To compare the effectiveness of stepping up asthma therapy with an increased dose of various types of inhaled corticosteroid as compared with add-on LABA.
  
  
  METHODS
  We performed a historical matched cohort study using large primary care databases to compare asthma step-up therapy with small- and standard size-particle inhaled corticosteroid versus added LABA for patients 12-80 years old. As outcomes, we examined a composite of asthma control and rates of severe exacerbations.
  
  
  RESULTS
  The odds of asthma control and rates of severe exacerbations over one outcome year were comparable with increased inhaled corticosteroid dose versus added LABA. The adjusted odds ratios (95% confidence interval) for achieving asthma control with increased inhaled corticosteroid dose versus inhaled corticosteroid/LABA were 0.99 (0.88-1.12) for small-particle inhaled corticosteroid (n = 3,036 per cohort) and 0.85 (0.67-1.07) for standard size-particle inhaled corticosteroid (n = 809 per cohort). The adjusted rate ratios (95% confidence interval) for severe exacerbations, compared with inhaled corticosteroid/LABA combination inhaler, were 1.04 (0.91-1.20) and 1.18 (0.92-1.54), respectively. The results were not affected by smoking status.
  
  
  CONCLUSIONS
  When applied to a broad primary care population, antiinflammatory therapy using increased doses of small- or standard size-particle inhaled corticosteroid is as effective as adding LABA, as measured by outcomes important to both patients and providers. Real-world populations and outcomes need to be taken into consideration when formulating treatment recommendations.
authors.affiliation: 1 Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Elliot
authors.initials: E
authors.lastname: Israel
authors.affiliation: 2 Cochin Hospital Group, Assistance Publique-Hôpitaux de Paris, University of Paris Descartes, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Roche
authors.affiliation: 3 National Jewish Health and University of Colorado Denver, Denver, Colorado.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Martin
authors.affiliation: 4 Washington Hospital Center and George Washington University School of Medicine, Washington, DC.
authors.forename: Gene
authors.initials: G
authors.lastname: Colice
authors.affiliation: 5 Cipla Europe NV, Antwerp, Belgium.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Dorinsky
authors.affiliation: 6 Department of Pulmonary Medicine and Tuberculosis, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Dirkje S
authors.initials: DS
authors.lastname: Postma
authors.affiliation: 7 Cincinnati Children's Hospital and Medical Center, Cincinnati, Ohio.
authors.forename: Theresa W
authors.initials: TW
authors.lastname: Guilbert
authors.affiliation: 8 Emma Children's Hospital Academisch Medisch Centrum, Amsterdam, The Netherlands; and.
authors.forename: Willem M C
authors.initials: WM
authors.lastname: van Aalderen
authors.affiliation: 9 Blizard Institute, Queen Mary University of London.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Grigg
authors.affiliation: 10 Research in Real-Life, Ltd, Cambridge, and.
authors.forename: Elizabeth V
authors.initials: EV
authors.lastname: Hillyer
authors.affiliation: 10 Research in Real-Life, Ltd, Cambridge, and.
authors.forename: Anne
authors.initials: A
authors.lastname: Burden
authors.affiliation: 10 Research in Real-Life, Ltd, Cambridge, and.
authors.forename: Julie
authors.initials: J
authors.lastname: von Ziegenweidt
authors.affiliation: 10 Research in Real-Life, Ltd, Cambridge, and.
authors.forename: Victoria
authors.initials: V
authors.lastname: Thomas
authors.affiliation: 10 Research in Real-Life, Ltd, Cambridge, and.|11 Academic Primary Care, University of Aberdeen, Aberdeen, United Kingdom.
authors.forename: David B
authors.initials: DB
authors.lastname: Price
mesh_terms: D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage / Q000009:adverse effects; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000009:adverse effects; D001249:Asthma / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D015331:Cohort Studies; D057186:Comparative Effectiveness Research; D016208:Databases, Factual; D003692:Delayed-Action Preparations; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D018927:Anti-Asthmatic Agents; D003692:Delayed-Action Preparations; D005938:Glucocorticoids
keywords: adrenergic β2-agonists; antiasthmatic agents; bronchodilator agents; disease exacerbation; glucocorticoids