Long-Acting Beta2 Agonists as Steroid-Sparing Agents
Am Fam Physician. 2006 Jun 1;73(11):1935-1939.
For patients with asthma, does the addition of a long-acting beta2 agonist allow the dosage of maintenance inhaled corticosteroids to be reduced while maintaining asthma control?
For adult patients who are taking a minimum maintenance dosage of inhaled corticosteroid for asthma, adding a long-acting beta2 agonist permits reduction of the dosage of inhaled corticosteroid by 253 mcg beclomethasone equivalent per day without worsening the patient's symptoms. In patients taking higher dosages of corticosteroids, the effect of adding a long-acting beta2 agonist was even more pronounced, with a mean reduction in their maintenance inhaled corticosteroid of 600 mcg beclomethasone equivalent per day. There is no evidence of improved symptoms with combination treatment, and it is not recommended as initial treatment for asthma.
In adults and children whose asthma is not adequately controlled with inhaled corticosteroids, adding a long-acting beta2 agonist improves lung function and reduces the risk of exacerbation. Adding a long-acting beta2 agonist does not increase serious side effects or withdrawal rates when compared with inhaled steroids alone.1 Long-acting beta2 agonists alone have proven effective compared with placebo, but there are serious concerns about safety. A large study comparing salmeterol (Serevent) with placebo was stopped prematurely because of an increase in the risk of death in the active treatment group.2–4
Gibson and colleagues studied long-acting beta2 agonists as corticosteroid-sparing agents to further refine their role in the treatment of asthma. They found 10 parallel randomized controlled trials involving adult patients who required daily inhaled corticosteroids. Trial quality was good, and the power of the studies was adequate. The trials compared inhaled corticosteroids with combination treatment with reduced-dosage inhaled corticosteroids and a long-acting beta2 agonist. Patients were followed for three to 12 months. The mean reduction in the dosage of inhaled corticosteroid was 60 percent.
The researchers found no significant differences between the groups in exacerbations requiring oral steroids or in withdrawal from the study because of worsening airway inflammation. In the group that used combined treatment, forced expiratory volume in one second improved compared with baseline (weighted mean difference 0.10; 95% confidence interval, 0.07 to 0.12), there was a small but significant improvement in morning peak expiratory flow, and there were fewer days when short-acting beta2 agonists were needed. These results suggest that the beta2 agonists were not masking worsening airway inflammation.
Because adding a long-acting beta2 agonist is effective in reducing the steroid dosage in patients maintaining disease control with long-term inhaled steroids, it is reasonable to question whether combined treatment should be the initial treatment in patients with mild to moderate airway obstruction. This question was addressed by Ni Chroinin and colleagues,5 who found that in a steroid-naive population with asthma, combined therapy does not significantly reduce the rate of exacerbations over inhaled corticosteroids alone. Combined thereapy may improve lung function and symptom-free days, but it does not reduce the use of short-acting beta2 agonists. Overall, there is not sufficient evidence to recommend initiating combined therapy for patients who have never had a trial of inhaled corticosteroids, particularly given the cost of two drugs compared with one.5
Gibson PG, et al. Long-acting beta2-agonists as an inhaled corticosteroid-sparing agent for chronic asthma in adults and children. Cochrane Database Syst Rev. 2005;(4):CD005076.
1. Ni Chroinin M, Greenstone IR, Danish A, Magdolinos H, Masse V, Zhang X, et al. Long-acting beta2-agonistsversus placebo in addition to inhaled corticosteroids in children and adults with chronic asthma. Cochrane Database Syst Rev. 2005;(4):CD005535.
2. Walters EH, Walters JA, Gibson MD. Long-acting beta2-agonists for stable chronic asthma. Cochrane Database Syst Rev. 2003;(3):CD001385.
3. Lemanske RF Jr, Sorkness CA, Mauger EA, Lazarus SC, Boushey HA, Fahy JV, et al. Inhaled corticosteroid reduction and elimination in patients with persistent asthma receiving salmeterol: a randomized controlled trial. JAMA. 2001;285:2594–603.
4. Lurie P, Wolfe SM. Misleading data analyses in salmeterol (SMART) study [Letter]. Rickard KA. GlaxoSmith-Kline's reply. Lancet. 2005;366:1261–2.
5. Ni Chroinin M, Greenstone IR, Ducharme FM. Addition of inhaled long-acting beta2-agonists to inhaledsteroids as first line therapy for persistent asthma in steroid-naive adults. Cochrane Database Syst Rev. 2004;(4):CD005307.
The series coordinator for AFP is Clarissa Kripke, M.D., Department of Family and Community Medicine, University of California, San Francisco.
Copyright © 2006 by the American Academy of Family Physicians.
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