Pharmacological management to reduce exacerbations in adults with asthma: a systematic review and meta-analysis

Context  Over the last 2 decades, many new pharmacological agents have been introduced to reduce the growing morbidity associated with asthma, but the long-term effects of these agents on exacerbations are unclear. Objective  To systematically review and quantitatively synthesize the long-term effects of inhaled corticosteroids, long-acting ₂ agonists, leukotriene pathway modifiers/receptor antagonists, and anti-IgE therapies on clinical outcomes and particular clinically relevant exacerbations in adult patients with chronic asthma. Data Sources  MEDLINE, EMBASE, and Cochrane databases were searched to identify relevant randomized controlled trials and systematic reviews published from January 1, 1980, to April 30, 2004. We identified additional studies by searching bibliographies of retrieved articles and contacting experts in the field. Study Selection and Data Extraction  Included trials were double-blind, had follow-up periods of at least 3 months, and contained data on exacerbations and/or forced expiratory volume in 1 second. The effects of interventions were compared with placebo, short-acting ₂ agonists, or each other. Data Synthesis  Inhaled corticosteroids were most effective, reducing exacerbations by nearly 55% compared with placebo or short-acting ₂ agonists (relative risk RR], 0.46; 95% confidence interval CI], 0.34-0.62; P<.001 for heterogeneity). Compared with placebo, the use of long-acting ₂ agonists was associated with 25% fewer exacerbations (RR, 0.75; 95% CI, 0.64-0.88; P = .43 for heterogeneity); when added to inhaled corticosteroids, there was a 26% reduction above that achieved by steroid monotherapy (RR, 0.74; 95% CI, 0.61-0.91; P = .07 for heterogeneity). Combination therapy was associated with fewer exacerbations than was increasing the dose of inhaled corticosteroids (RR, 0.86; 95% CI, 0.76-0.96; P = .65 for heterogeneity). Compared with placebo, leukotriene modifiers/receptor antagonists reduced exacerbations by 41% (RR, 0.59; 95% CI, 0.49-0.71; P = .44 for heterogeneity) but were less effective than inhaled corticosteroids (RR, 1.72; 95% CI, 1.28-2.31; P = .91 for heterogeneity). Use of monoclonal anti-IgE antibodies with concomitant inhaled corticosteroid therapy was associated with 45% fewer exacerbations (RR, 0.55; 95% CI, 0.45-0.66; P = .15 for heterogeneity). Conclusions  Inhaled corticosteroids are the single most effective therapy for adult patients with asthma. However, for those unable or unwilling to take corticosteroids, the use of leukotriene modifiers/receptor agonists appears reasonable. Long-acting ₂ agonists may be added to corticosteroids for those who remain symptomatic despite low-dose steroid therapy. Anti-IgE therapy may be considered as adjunctive therapy for young adults with asthma who have clear evidence of allergies and elevated serum IgE levels.