Abstract
Rationale: Long-term oral corticosteroid (OCS) therapy is associated with significant side effects. Reducing OCS doses causes lung function decline in OCS-dependent asthma patients, with small airways contributing significantly. A computer-controlled inhalation system (AKITA) as add-on therapy to GINA step 5 treatment (OCS) was used to deliver consistent doses of budesonide to the peripheral lungs to effectively target small airway inflammation.
Methods: Phase 2/3 randomized, four-arm parallel-group, placebo-controlled trial, conducted in 27 outpatient centers. Adult patients (18-65 years) with OCS-dependent asthma were randomly assigned (2:1:1:1) to 18-weeks, BID, double-blind add-on treatment with AICS (AKITA inhaled corticosteroid)-Bud 1 mg, AICS-Bud 0.5 mg, AICS-placebo, or add-on open-label treatment with Bud 1 mg via conventional nebulizer (CN-Bud). OCS doses were tapered until week 14 and patients were followed until week 20. Lung function parameters (including FEV1 and FEF25-75) were recorded.
Results: OCS dose could be reduced in all treatment arms. Mean [SD] FEV1 significantly improved for AICS-Bud 1 mg (239 [460] mL; p<0.001) and AICS-Bud 0.5 mg (126 [345] mL; p=0.01) but not placebo (93 [419] mL; p=0.36) or CN-Bud (137 [459] mL: p=0.18). Mean (SD) change in FEF25-75 from baseline to week 18 was +0.20 (0.60) L/sec for AICS-Bud 1 mg and 0.00 (0.40) L/sec for placebo (p=0.03).
Conclusions: AICS-Bud 1 mg significantly improved lung function, while maintaining asthma control, in patients with OCS-dependent asthma compared with placebo. This therapeutic benefit likely resulted from consistent, targeted dosing, and would substantially benefit OCS-dependent asthma patients.
- © 2014 ERS
