title: The effect of budesonide/formoterol maintenance and reliever therapy on the risk of severe asthma exacerbations following episodes of high reliever use: an exploratory analysis of two randomised, controlled studies with comparisons to standard therapy.
abstract: BACKGROUND
  Divergent strategies have emerged for the management of severe asthma. One strategy utilises high and fixed doses of maintenance treatment, usually inhaled corticosteroid/long-acting β2-agonist (ICS/LABA), supplemented by a short-acting β2-agonist (SABA) as needed. Alternatively, budesonide/formoterol is used as both maintenance and reliever therapy. The latter is superior to fixed-dose treatment in reducing severe exacerbations while achieving similar or better asthma control in other regards. Exacerbations may be reduced by the use of budesonide/formoterol as reliever medication during periods of unstable asthma. We examined the risk of a severe exacerbation in the period after a single day with high reliever use.
  
  
  METHODS
  Episodes of high reliever use were quantified and exacerbations occurring post-index day with these episodes were examined post hoc in two double-blind studies comparing the efficacy and safety of budesonide/formoterol maintenance and reliever therapy (Symbicort SMART™, Turbuhaler®) 160/4.5 μg twice daily plus as needed with similar or higher maintenance doses of ICS/LABA plus SABA or formoterol.
  
  
  RESULTS
  Budesonide/formoterol maintenance and reliever therapy significantly reduced the risk of episodes of high reliever use (>6 inhalations/day) vs. all alternative ICS/LABA regimens. With conventional fixed-dose treatment the need for exacerbation treatment within 21 days ranged from 6.0-10.1% of days post-index for all regimens compared with 2.5-3.4% of days with budesonide/formoterol maintenance and reliever therapy.
  
  
  CONCLUSIONS
  Budesonide/formoterol maintenance and reliever therapy reduces the incidence of high reliever episodes and the exacerbation burden immediately following these episodes vs. alternative ICS/LABA plus SABA regimens at up to double the maintenance dose of ICS.
  
  
  BACKGROUND
  These studies do not have registration numbers as they were conducted before clinical trial registration was required.
authors: Mainz University Hospital, Langenbeckstrasse 1, Mainz, D-55131, Germany. Roland.Buhl@unimedizin-mainz.de
authors: Roland
authors: R
authors: Buhl
authors: Piotr
authors: P
authors: Kuna
authors: Matthew J
authors: MJ
authors: Peters
authors: Tomas L G
authors: TL
authors: Andersson
authors: Ian P
authors: IP
authors: Naya
authors: Stefan
authors: S
authors: Peterson
authors: Klaus F
authors: KF
authors: Rabe
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage* / Q000009:adverse effects; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000009:adverse effects; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy* / Q000453:epidemiology; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects; D019819:Budesonide / Q000008:administration & dosage* / Q000009:adverse effects; D000069502:Budesonide, Formoterol Fumarate Drug Combination; D018450:Disease Progression; D004311:Double-Blind Method; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000008:administration & dosage* / Q000009:adverse effects; D000068759:Formoterol Fumarate; D006801:Humans; D012307:Risk Factors; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D001993:Bronchodilator Agents; D000069502:Budesonide, Formoterol Fumarate Drug Combination; D004338:Drug Combinations; D004983:Ethanolamines; D019819:Budesonide; D000068759:Formoterol Fumarate