In adolescents and adults with sub-optimal control on low dose ICS monotherapy, the combination of LABA and ICS is modestly more effective in reducing the risk of exacerbations requiring oral corticosteroids than a higher dose of ICS. Combination therapy also led to modestly greater improvement in lung function, symptoms and use of rescue ß2 agonists and to fewer withdrawals due to poor asthma control than with a higher dose of inhaled corticosteroids. Apart from an increased rate of tremor and less oral candidiasis with combination therapy, the two options appear relatively safe in adults although adverse effects associated with long-term ICS treatment were seldom monitored. In children, combination therapy did not lead to a significant reduction, but rather a trend towards an increased risk, of oral steroid-treated exacerbations and hospital admissions. These trends raised concern about the safety of combination therapy in view of modest improvement in children under the age of 12 years.
Concurrent use of salmeterol with inhaled corticosteroids is more effective than inhaled corticosteroid dose increases.
This randomized, double-blind, parallel, multi-center study was designed to determine whether the addition of salmeterol to existing inhaled corticosteroid therapy provides greater therapeutic benefit than doubling the dose of inhaled corticosteroids in symptomatic patients with asthma. A total of 514 adults were randomized to either beclomethasone 168 micrograms plus salmeterol 42 micrograms twice daily or beclomethasone 336 micrograms twice daily for 24 weeks. Both treatments resulted in significantly improved symptom control and increased pulmonary function. However, beclomethasone plus salmeterol provided greater improvements than doubling the dose of beclomethasone (p < or = 0.05) in FEV1 and in daily-recorded measurements of morning (38 L/minute versus 20 L/minute after treatment with higher dose beclomethasone) and evening peak expiratory flow, asthma symptom scores, symptom-free days, supplemental albuterol use, and days and nights not requiring albuterol. There were no significant differences between treatment groups in the number of patients with abnormal response to corticotropin stimulation at Treatment Week 24. No treatment differences in asthma exacerbation and adverse event frequency rates were seen. Beclomethasone 168 micrograms plus salmeterol 42 micrograms administered twice daily was superior to beclomethasone 336 micrograms taken twice daily in patients symptomatic on beclomethasone 168 micrograms, with no added safety risks.