Efficacy and safety of high-dose budesonide/formoterol (Symbicort) compared with budesonide administered either concomitantly with formoterol or alone in patients with persistent symptomatic asthma.
OBJECTIVE
Budesonide/formoterol 160/4.5 microg, two inhalations bd, is an effective and well-tolerated maintenance therapy for patients not controlled on inhaled corticosteroids alone. The authors assessed the efficacy and safety of a higher dose of budesonide/formoterol in patients with persistent symptomatic asthma.


METHODS
This was a 24-week, double-blind, double-dummy randomized study. Budesonide/formoterol 320/9 microg, two inhalations bd (1280/36 microg/day), was compared with corresponding doses of budesonide during weeks 1-12 and budesonide plus formoterol via separate inhalers during weeks 1-24. Efficacy was assessed during weeks 1-12; the primary variable was morning PEF. Safety was assessed over weeks 1-24.


RESULTS
Patients (n=456; aged 12-79 years) had a mean reversibility in FEV1 of 28% and mean pre-study inhaled corticosteroid dose of 1038 microg/day. Mean morning PEF increased by 37 L/min and 36 L/min with budesonide/formoterol and budesonide plus formoterol, respectively, versus an increase of 5 L/min with budesonide (P<0.001 for both vs. budesonide). Budesonide/formoterol increased time to first mild exacerbation (P<0.005) versus budesonide. Budesonide/formoterol and budesonide plus formoterol had similar efficacy. All treatments were well tolerated and the incidence of class-related adverse events was similarly low in all groups. Changes in serum potassium and plasma cortisol were comparable across treatments.


CONCLUSIONS
High-dose budesonide/formoterol (320/9 microg, two inhalations bd) is effective and well tolerated in patients with persistent symptomatic asthma. The findings also support the safety of regular high-dose formoterol (36 microg/day).
Jenkins
Christine
C
Woolcock Institute of Medical Research, Camperdown, New South Wales, Australia. crj@med.usyd.edu.au
Kolarikova
Renata
R
Kuna
Piotr
P
Caillaud
Denis
D
Sanchis
Joaquin
J
Popp
Wolfgang
W
Pettersson
Eva
E
D000280:Administration, Inhalation; D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D019819:Budesonide / Q000008:administration & dosage* / Q000627:therapeutic use; D002648:Child; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume / Q000502:physiology; D000068759:Formoterol Fumarate; D006801:Humans; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D004983:Ethanolamines; D019819:Budesonide; D000068759:Formoterol Fumarate