Benralizumab efficacy and safety in severe asthma: A randomized trial in Asia.

BACKGROUND: Benralizumab is indicated as add-on therapy in patients with uncontrolled, severe eosinophilic asthma; it has not yet been evaluated in a large Asian population with asthma in a clinical trial. OBJECTIVE: To evaluate the efficacy and safety of benralizumab in patients with severe asthma in Asia. METHODS: MIRACLE (NCT03186209) was a randomized, Phase 3 study in China, South Korea, and the Philippines. Patients aged 12-75 years with severe asthma receiving medium-to-high-dose inhaled corticosteroid/long-acting ß2-agonists, stratified (2:1) by baseline blood eosinophil count (bEOS) (≥300/µL; <300/µL), were randomized (1:1) to benralizumab 30 mg or placebo. Endpoints included annual asthma exacerbation rate (AAER; primary endpoint), change from baseline at Week 48 in pre-bronchodilator (BD) forced expiratory volume in 1 second (pre-BD FEV1) and total asthma symptom score (TASS). Safety was evaluated ≤ Week 56. RESULTS: Of 695 patients randomized, 473 had baseline bEOS ≥300/µL (benralizumab n = 236; placebo n = 237). In this population, benralizumab significantly reduced AAER by 74% (rate ratio 0.26 [95% CI 0.19, 0.36], p < 0.0001) and significantly improved pre-BD FEV1 (least squares difference [LSD] 0.25 L [95% CI 0.17, 0.34], p < 0.0001) and TASS (LSD -0.25 [-0.45, -0.05], p = 0.0126) versus placebo. In patients with baseline bEOS <300/µL, there were numerical improvements in AAER, pre-BD FEV1, and TASS with benralizumab versus placebo. The frequency of adverse events was similar for benralizumab (76%) and placebo (80%) in the overall population. CONCLUSIONS: MIRACLE data reinforces the efficacy and safety of benralizumab for severe eosinophilic asthma in an Asian population, consistent with the global Phase 3 results.

Budesonide/formoterol via Turbuhaler® versus formoterol via Turbuhaler® in patients with moderate to severe chronic obstructive pulmonary disease: phase III multinational study results.

BACKGROUND AND OBJECTIVE: The efficacy and tolerability of budesonide/formoterol versus formoterol in patients with moderate to severe chronic obstructive pulmonary disease (COPD) was evaluated. METHODS: In this randomized, double-blind, parallel-group, phase III study (NCT01069289), patients with moderate to severe COPD for ≥2 years received either budesonide/formoterol 160/4.5 µg two inhalations twice daily via Turbuhaler® or formoterol 4.5 µg two inhalations twice daily via Turbuhaler® for 12 weeks. Salbutamol was available as reliever medication. Primary outcome variable: change from baseline to average during treatment in pre-dose forced expiratory volume in 1 s (FEV1 ). RESULTS: One thousand two hundred ninety-three patients were randomized (budesonide/formoterol n = 636; formoterol n = 657). Both budesonide/formoterol and formoterol increased pre-dose FEV1 versus baseline (improvements of 4.6% and 1.5% over baseline, respectively), with the increase from baseline being significantly greater with budesonide/formoterol versus formoterol (budesonide/formoterol:formoterol ratio 1.032; 95% confidence interval: 1.013-1.052; P = 0.0011). The budesonide/formoterol group had a significantly prolonged time to first exacerbation versus the formoterol group (hazard ratio: 0.679; 95% confidence interval: 0.507-0.909; P = 0.0094) and significantly greater improvements in many secondary outcome measures. Both treatments were well tolerated; the incidence and type of adverse events were similar: most commonly reported (budesonide/formoterol vs formoterol): COPD (8.0% vs 9.4%) and nasopharyngitis (5.5% vs 4.9%). CONCLUSIONS: Budesonide/formoterol 160/4.5 µg two inhalations twice daily was effective and well tolerated in patients with moderate to severe COPD, offering benefits over formoterol alone in terms of improved lung function and reduced risk of exacerbation.

Airway pathogens detected in stable and exacerbated COPD in patients in Asia-Pacific.

Background: The burden of chronic obstructive pulmonary disease (COPD) in the Asia-Pacific region is projected to increase. Data from other regions show bacterial and viral infections can trigger acute exacerbations of COPD (AECOPD). Methods: This 1-year prospective epidemiological study (ClinicalTrials.gov identifier: NCT03151395) of patients with moderate to very severe COPD in Hong Kong, the Philippines, South Korea and Taiwan assessed the prevalence in sputum samples (by culture and PCR) of bacterial and viral pathogens during stable COPD and AECOPD. The odds of experiencing an exacerbation was evaluated for pathogen presence, acquisition and apparition. Health-related quality of life (HRQOL) was assessed. Results: 197 patients provided 983 sputum samples, with 226 provided during exacerbation episodes. The mean yearly AECOPD incidence rate was 1.27 per patient. The most prevalent bacteria by PCR at exacerbation were Haemophilus influenzae (Hi) and Moraxella catarrhalis (Mcat); Mcat prevalence was higher at exacerbation than at stable state. Virus prevalence was low, other than for human rhinovirus (HRV) (8.1%, stable state; 16.6%, exacerbation). The odds ratio (95% CI) for an exacerbation (versus stable state) was statistically significant for the presence, acquisition and apparition of Hi (2.20, 1.26-3.89; 2.43, 1.11-5.35; 2.32, 1.20-4.46, respectively), Mcat (2.24, 1.30-3.88; 5.47, 2.16-13.86; 3.45, 1.71-6.98, respectively) and HRV (2.12, 1.15-3.91; 2.22, 1.09-4.54; 2.09, 1.11-3.91, respectively). HRQOL deteriorated according to the number of exacerbations experienced. Conclusion: In patients with COPD in the Asia-Pacific region, the presence of Hi, Mcat or HRV in sputum samples significantly increased the odds of an exacerbation, providing further evidence of potential roles in triggering AECOPD.