For most patients, asthma is not controlled as defined by guidelines; whether this is achievable has not been prospectively studied. It is also not known whether combination LABA ICS therapy is more likely to achieve this than an increased dose of ICS.
Control was achieved more rapidly and at a lower inhaled corticosteroid asthma dose with salmeterol/fluticasone than with fluticasone. This study confirms that the goal of guideline derived asthma control was achieved in most of the patients.
A 1year, randomized, stratified, double-blind, parallel group study of 3421 patients with uncontrolled asthma compared fluticasone inhaler propionate and salmeterol/fluticasone in achieving two rigorous, composite, guideline based measures of control – totally and well-controlled asthma – using measures that included the following asthma outcomes: peak expiratory flow rate (PEF), rescue medication use, symptoms, night time awakenings, exacerbations, emergency visits, and adverse events.
The definitions of control were derived from the treatment goals of the Global Initiative for Asthma/National Institutes of Health guidelines, with equal weighting given to each of the criteria. During the runin period, patients continued on their usual dose (if any) of ICS treatment and were then randomized to one of three strata based on their Asthma LABA ICS dose during the 6 months before screening: stratum 1, no ICS; stratum 2, 500 µg or less of beclomethasone dipropionate daily or equivalent; stratum 3, >500 to 1000 µg of beclomethasone dipropionate daily or equivalent.
Treatment was stepped up until total control was achieved (or a maximum of 500 µg corticosteroid twice a day was reached) for a period of 12 weeks, and patients remained on the dose at which they achieved totally controlled asthma or the maximum dose of study medication until the end of the 1year double blind treatment period. Control was assessed over an 8week period before each clinic visit at weeks 12, 24, 36 and 52. Significantly more patients in each stratum (previously corticosteroid free, low and moderatedose cortico steroid users) achieved control with salmeterol/fluticasone than with fluticasone. In phase I, totally controlled asthma was achieved in 42 and 31% of patients for salmeterol/fluticasone and fluticasone respectively in stratum 1 (odds ratio [OR] 1.71; 95% CI 1.30–2.24; P <0.001), 32 and 20% in stratum 2 (OR 2.07; 95% CI 1.56–2.76; P <0.001), and 19 and 8% in stratum 3 (OR 2.90; 95% CI 1.98–4.26; P <0.001) and 690 (41%) vs 468 (28%) at 1 year for salmeterol/fluticasone and fluticasone respectively. In each stratum, the proportion of patients achieving control at the same or a lower dose of inhaled corticosteroid was greater for those treated with salmeterol/fluticasone and control was achieved earlier. Across all strata, 68 and 76% of the patients receiving salmeterol/fluticasone and fluticasone respectively were on the highest dose at the end of treatment. Interestingly, mean annual rates of exacerbations requiring oral corticosteroids and/or hospitalization or emergency visits were low in both treatment groups and lower in the combination therapy group.
This study suggests that salmeterol/fluticasone achieves sustained control of asthma, as defined by a composite of relevant clinical goals of treatment, in more patients, more rapidly and at a lower dose of inhaled corticosteroids than fluticasone alone.
This study was mainly symptom driven and had a high degree of compliance, which may or may not reflect actual clinical practice as some patients may be reluctant to increase medication for occasional symptoms to achieve complete absence of asthma symptoms.
