Objective: To compare the effectiveness of budesonide/formoterol using fixed dosing (BUD/FORM) with inhaled corticosteroid (ICS) alone or alternative ICS and long-acting beta(2)-agonist (LABA) regimens for adults with moderate/severe asthma.
Methods: BIOSIS, CENTRAL, EMBASE and MEDLINE were searched for abstracts and papers. All searching was completed in July 2006. No restriction was placed on language. Meta-analysis of randomised controlled trials (RCTs) using a fixed effects model. RCTs were included if the comparator with BUD/FORM had an equivalent daily dose of ICS at the start of the trial. The primary outcome measure was, 'treatment failure', defined as: asthma-related serious adverse event, oral glucocorticosteroid treatment, A&E visit and/or admission to hospital, withdrawal due to a need for additional asthma therapy.
Results: Of the 330 papers identified in the literature search, 15 met the inclusion criteria. The following alternative treatments were found: ICS alone (BUD), BUD/FORM adjustable maintenance dose (BUD/FORM-AMD), and salmeterol/fluticasone in a single inhaler (SALM/FP). Meta-analysis of treatment failure demonstrated a 50% increase with BUD versus BUD/FORM (Relative Risk [RR] 1.50, 95% confidence interval [95% CI]: 1.12-2.02, p = 0.007; 2 RCTs); a trend in favour of a reduction with BUD/FORM-AMD versus BUD/FORM (RR 0.88, 95% CI: 0.77-1.02, p = 0.09; 11 RCTs); and no evidence of a difference with SALM/FP versus BUD/FORM (RR 0.99, 95% CI: 0.83-1.16, p = 0.86; 3 RCTs). Significant heterogeneity was not detected in the primary analyses. Secondary analyses demonstrated the following significant differences: hospitalisations/A&E visits (49% increased risk with SALM/FP vs. BUD/FORM, RR 1.49, 95% CI: 1.07-2.08, p = 0.02, and 28% reduced risk with BUD/FORM-AMD vs. BUD/FORM, RR 0.72, 95% CI: 0.52-0.99, p = 0.04); and use of oral steroids (51% increase in risk with BUD vs. BUD/FORM, RR 1.51, 95% CI: 1.10-2.09, p = 0.01, and 19% reduced risk with BUD/FORM-AMD vs. BUD/FORM, RR 0.81, 95% CI: 0.70-0.95, p = 0.01).
Conclusions: Fixed-dose BUD/FORM is an effective treatment option for adult patients with moderate/severe asthma when compared to BUD and SALM/FP, with adjustable maintenance dosing demonstrating important advantages over fixed dosing in relation to exacerbation prevention and reduced treatment load.