title: Once- vs twice-daily budesonide/formoterol in 6- to 15-year-old patients with stable asthma.
abstract: OBJECTIVE
  To assess efficacy/tolerability of once-daily budesonide/formoterol pressurized metered-dose inhaler (pMDI) versus budesonide pMDI (primary) and twice-daily budesonide/formoterol (secondary) in children/adolescents with asthma stabilized with twice-daily budesonide/formoterol.
  
  
  METHODS
  This 12-week multicenter, double-blind randomized controlled study (www.clinicaltrials.gov identifier NCT00646321) included 521 patients aged 6 to 15 years with mild/moderate persistent asthma. Patients stabilized during a 4- to 5-week run-in with twice-daily budesonide/formoterol pMDI 40/4.5 microgx2 inhalations (160/18 microg daily) received twice-daily budesonide/formoterol pMDI 40/4.5 microgx2 inhalations (160/18 microg daily), once-daily budesonide/formoterol pMDI 80/4.5 microgx2 inhalations (160/9 microg daily; evening), or once-daily budesonide pMDI 80 microgx2 inhalations (160 microg daily; evening).
  
  
  RESULTS
  Once- or twice-daily budesonide/formoterol was more effective than budesonide for evening peak expiratory flow (primary variable) at the end of the 24-hour once-daily dosing interval (P<or=.027). Twice-daily budesonide/formoterol demonstrated better efficacy versus once-daily treatments for evening predose forced expiratory volume in 1 second (P<or=.011), versus budesonide for daytime/nighttime rescue medication (P<or=.023), and versus once-daily budesonide/formoterol for daytime rescue medication (last 12 hours of once-daily dosing) (P=.032). There were no significant between-group differences for daytime/nighttime asthma symptoms, nighttime awakenings attributed to asthma, or health-related quality of life. Fewer patients experienced asthma worsening (predefined criteria) with twice-daily budesonide/formoterol (8.2%) versus once-daily budesonide (15.5%) (P=.036) or once-daily budesonide/formoterol (19.6%) (P=.002). All treatments were well tolerated.
  
  
  CONCLUSIONS
  Once-daily budesonide/formoterol demonstrated significantly better efficacy than once-daily budesonide for most pulmonary-function variables. Twice-daily budesonide/formoterol (160/18 microg daily) maintenance therapy was generally more effective than stepping down to once-daily dosing (160/9 microg daily). Treatments were well tolerated, and there was no evident safety benefit for once- versus twice-daily dosing.
authors: Pediatric Pulmonary Medicine, Childhood Asthma Care and Education Center, 571 S Floyd St, Suite 414, Louisville, KY 40202, USA. nseid@louisville.edu
authors: Nemr S
authors: NS
authors: Eid
authors: Michael J
authors: MJ
authors: Noonan
authors: Bradley
authors: B
authors: Chipps
authors: Bhash
authors: B
authors: Parasuraman
authors: Christopher J
authors: CJ
authors: Miller
authors: Christopher D
authors: CD
authors: O'Brien
mesh_terms: D000293:Adolescent; D001249:Asthma / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000009:adverse effects*; D019819:Budesonide / Q000008:administration & dosage*; D002648:Child; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004983:Ethanolamines / Q000008:administration & dosage*; D005260:Female; D000068759:Formoterol Fumarate; D006801:Humans; D008297:Male
chemical_list: D001993:Bronchodilator Agents; D004983:Ethanolamines; D019819:Budesonide; D000068759:Formoterol Fumarate