NEW YORK (Reuters Health) – Children with mild to moderate asthma have better pulmonary function and require less rescue medication if they take budesonide/formoterol (BUD/FM; Symbicort) twice a day instead of once a day, a large U.S. trial has shown.
The 95-center trial involved 521 children, ages 6 to 15. All of the children had first been stabilized during a 4- to 5-week run-in period. In that phase, each child took two inhalations of BUD/FM, 40/4.5 mcg, via pressurized metered-dose inhaler (for a total of 160/18mcg daily).
For the next phase, the authors randomized the children to three regimens: -Twice daily BUD/FM, 40/4.5 mcg x 2 inhalations (160/18 mcg/day)-Once daily BUD/FM, 80/4.5 mcg x 2 inhalations (160/9 mcg/day in the evening) -Once-daily BUD only, 80 mcg x 2 inhalations (160 mcg/day in the evening).
Twice-daily budesonide/formoterol produced significantly better results for all pulmonary-function variables, lead author Dr. Nemr S. Eid from the University of Louisville, Kentucky, and colleagues report in the August 16th online issue of Pediatrics.
Both regimens that used budesonide in combination with the long-acting beta2-adrenergic agonist (LABA) formoterol were more effective than budesonide alone for evening peak expiratory flow (trough levels, p = 0.027 for both).
Evening predose forced expiratory volume in 1 second (FEV1) improved from baseline with twice-daily BUD/FM (+ 0.02 L) and decreased with the two once-daily strategies(-0.04 L with BUD/FM and -0.07 L with BUD only; p= 0.011 for both).
Children in each group could use albuterol for rescue. The twice-daily group needed significantly less albuterol and had more rescue-medication-free days compared to the other groups.
Significantly fewer patients withdrew because of worsening asthma (on the basis of predefined criteria) in the twice daily group compared to the other two (p = 0.036).
The BUD/FM twice-daily group also had the lowest rate of patients developing at least one worsening asthma event, but the difference was only significant for children ages 6 to 11.
Once daily treatment was no safer than the twice-daily strategy, the authors said.
LABAs such as salmeterol and formoterol are controversial, particularly in children. Studies indicate that LABA monotherapy increases mortality, though the risk is lower when LABAs are combined with inhaled corticosteroids. The U.S. Food and Drug Administration advises that LABAs not be used alone in children. (See Reuters Health reports of Jan 6 and Jun 2, 2010.)
The FDA also advises that once asthma control is achieved and maintained, step down therapy to wean patients from the LABA should begin if possible.
This trial was supported by Astra-Zeneca LP, Wilmington, Delaware, which markets the BUD/FM pressurized metered-dose inhaler as Symbicort. Astra-Zeneca also employs three of the paper’s seven authors and has financial arrangements with the other four.
Once- vs Twice-Daily Budesonide/Formoterol in 6- to 15-Year-Old Patients With Stable Asthma