PURPOSE OF THE STUDY.
To compare the clinical effectiveness and tolerability of once-daily budesonide/formoterol pressurized metered-dose inhaler (pMDI) versus budesonide pMDI in asthmatic children aged 6 to 15 years old.
Children aged 6 to 15 years with stable mild-to-moderate asthma were enrolled if they had had symptoms for ≥6 months, bronchodilator response, and forced expiratory volume in 1 second (FEV1) of 60% to 90% of that predicted at baseline.
The study was a multicenter, 12-week double-blind, parallel-group, active-controlled, randomized study. Enrolled patients had a 4- to 5-week run-in with budesonide/formoterol 80/9 μg twice per day and albuterol as needed for rescue. Patients whose asthma was stable after the run-in period were age-stratified and randomly assigned to receive budesonide pMDI 80 μg (2 inhalations daily), budesonide/formoterol 80/4.5 μg (2 inhalations once daily), or budesonide/formoterol 40/4.5 μg (2 inhalations twice daily). Primary outcome data were evening peak expiratory flow rate (PEF). PEF and predose FEV1 were recorded in an electronic diary by patients or caregivers in the morning and evening. Patients were immediately withdrawn from study if they met predefined worsening asthma symptom criteria. At the end of the study, physicians and caregivers were asked about health status and ability to manage asthma symptoms using a 5 point scale. Health-related quality of life (HRQoL) was assessed by questionnaire.
Of 719 enrolled patients, 522 were randomly assigned. The most common cause of withdrawal before randomization was worsened asthma symptoms or function. Once- and twice-daily budesonide/formoterol pMDI were superior to budesonide pMDI daily as assessed by morning PEF, morning predose FEV1, or evening PEF. Although the twice-daily budesonide/formoterol group had improved evening PEF during the study versus being unchanged in the once-daily budesonide/formoterol group, there were no statistical differences between these groups. Evening predose FEV1 increased in the twice-daily budesonide/formoterol group versus decreasing in the once-daily budesonide/formoterol group or budesonide group. Twice-daily budesonide/formoterol resulted in significantly less daytime rescue-medication use versus the once-daily medication study groups and resulted in significantly less nighttime rescue-medication use versus budesonide alone. Patients with at least 1 predefined event of worsened asthma episodes were significantly fewer in the twice-daily budesonide/formoterol group versus once-daily medication groups; however, this was seen entirely in the 6- to 11-year age group. Physician perception of ease of asthma management significantly favored the twice-daily budesonide/formoterol group, but the results of other subjective assessments of asthma control, health status, HRQoL, adverse events, and objective safety data were similar across all groups.
Once-daily dosing of budesonide-formoterol pMDI resulted in significantly higher evening PEF and most of the assessed pulmonary variables compared with once-daily budesonide pMDI. However, there were no significant differences between once-daily budesonide/formoterol and once-daily budesonide in measures for asthma control, asthma symptoms, or HRQoL measures. Twice-daily versus once-daily budesonide/formoterol resulted in improved evening predose FEV1, daytime rescue-medication use, rescue-medication–free days, and worsening asthma events. There were no differences in safety variables between the 3 treatment groups.
This study was designed by scientists employed by a pharmaceutical company and conducted by a large group of clinicians. It adds to the data regarding safety of inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) combinations in young children. In the twice-daily budesonide/formoterol group, the mean evening PEF and evening predose FEV1 continued to increase during the study, which raises the question of whether the patients achieved true baseline status at the time of randomization. A longer run-in might have lead to different results in the comparisons between twice-daily and once-daily budesonide/formoterol. The authors warned that stepping-down from twice-daily budesonide/formoterol to once-daily dosing might lead to increased asthma symptoms without a change in safety profile but did not discuss potential long-term harm from ongoing unnecessary LABA/ICS use. Current product information and national asthma guidelines should continue to be followed regarding ICS/LABA use in children, but in individual patients for whom twice-daily dosing is not feasible, once-daily dosing (with careful monitoring) might be appropriate.
- Copyright © 2011 by the American Academy of Pediatrics