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 β2 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 β2 agonists, or each other.
Data Synthesis Inhaled corticosteroids were most effective, reducing exacerbations
by nearly 55% compared with placebo or short-acting β2 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 β2 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 β2 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.