Effect of budesonide/formoterol maintenance and reliever therapy on asthma exacerbations

Abstract

This randomised, double-blind, 6-month study compared budesonide/formoterol for maintenance and relief with salmeterol/fluticasone and a fixed maintenance dose of budesonide/formoterol, both with terbutaline for relief. Following a 2-week run-in, 3335 symptomatic adults and adolescents (mean FEV1 73% predicted, mean inhaled corticosteroid dose 745 microg/day) received budesonide/formoterol 160/4.5 microg one inhalation bid plus additional inhalations as needed, salmeterol/fluticasone 25/125 microg two inhalations bid plus as-needed terbutaline or budesonide/formoterol 320/9 microg one inhalation bid plus as-needed terbutaline. Budesonide/formoterol for maintenance and relief prolonged the time to first severe exacerbation requiring hospitalisation, emergency room treatment or oral steroids (primary variable) vs. fixed-dose salmeterol/fluticasone and budesonide/formoterol (p=0.0034 and p=0.023 respectively; log-rank test). Exacerbation rates were 19, 16 and 12 events/100 patients/6 months for salmeterol/fluticasone, fixed-dose budesonide/formoterol and budesonide/formoterol for maintenance and relief, respectively, [rate reduction vs. fixed-dose salmeterol/fluticasone (0.61; 95% CI 0.49-0.76, p<0.001) and vs. fixed-dose budesonide/formoterol (0.72; 95% CI 0.57-0.90, p=0.0048)]. Budesonide/formoterol maintenance and relief patients used less inhaled corticosteroid vs. salmeterol/fluticasone and fixed-dose budesonide/formoterol patients. All treatments provided similar marked improvements in lung function, asthma control days and asthma-related quality of life. Budesonide/formoterol for maintenance and relief reduces asthma exacerbations and maintains similar daily asthma control at a lower overall drug load compared with fixed-dose salmeterol/fluticasone and budesonide/formoterol.

Figure 1

Patient flow. bid, twice daily; ICS, inhaled corticosteroid; SMART, Symbicort® maintenance and reliever therapy. Terbutaline dose expressed as 0.5 mg/inhalation metered dose corresponds to 0.4 mg/inhalation delivered dose

Figure 2

Time to first severe exacerbation (deterioration in asthma resulting in hospitalisation/emergency room treatment, or the need for oral steroids for ≥ 3 days). SMART, Symbicort® (budesonide/formoterol) maintenance and reliever therapy

Figure 3

Cumulative rate of (A) severe exacerbations and (B) hospitalisations/emergency room treatments caused by asthma; p-values are derived from relative rate analysis (Poisson regression analysis). SMART, Symbicort® (budesonide/formoterol) maintenance and reliever therapy

Figure 4

Mean overall (A) Asthma Quality of Life Questionnaire (standardised version) [AQLQ(S)] and (B) Asthma Control Questionnaire (ACQ) scores over the duration of the study. QoL, quality of life; SMART, Symbicort® (budesonide/formoterol) maintenance and reliever therapy

Figure 5

Range of daily mean doses of ICS/LABA reported by individual study patients. *Mean ICS doses converted to BDP equivalents based on GINA (13) guidelines. Compared with fixed-dose budesonide/formoterol treatment, 9 : 1 (ratio: 63% divided by 7%) SMART-treated patients reduced their mean daily dose by at least 160/4.5 μg than increased their dose by at least 160/4.5 μg. SMART, Symbicort® (budesonide/formoterol) maintenance and reliever therapy; BDP, beclomethasone dipropionate