Abstract Rationale KALOS and LOGOS, twin Phase 3, double-blind, double-dummy, randomized studies, compared fixed-dose triple combination inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA)/long-acting muscarinic antagonist (LAMA) (budesonide/glycopyrrolate/formoterol fumarate), delivered via a metered-dose inhaler (MDI) using Aerosphere™ co-suspension delivery technology (BGF), with ICS/LABA (budesonide/formoterol fumarate), either as the standard suspension formulation (Symbicort®; BFFS) or using Aerosphere™ co-suspension delivery technology (BFFA). KALOS and LOGOS demonstrated the superiority of BGF 36 (320/36/9.6 µg) for improving lung function and exacerbation rates versus combined comparator groups BFFA and BFFS (BFFCombined) in participants with inadequately controlled asthma. To assess whether these improvements are seen across participants with different asthma characteristics at baseline, this pre-specified exploratory analysis investigated the effect of BGF 36 versus BFFCombined by baseline airflow limitation and reversibility. Methods Participants (≥12 y) with inadequately-controlled asthma despite ICS/LABA use were randomized (pooled N = 4311) to BGF 36, BGF 18 (320/18/9.6 µg), BFFA (320/9.6 µg), or BFFS (320/9 µg) twice daily for 24 to 52 weeks. Pooled analyses across studies assessed key lung function endpoints (change from baseline in morning pre-dose trough FEV1 and FEV1 AUC0-3 over 24 weeks) and exacerbation rate assessed by baseline pre-bronchodilator FEV1 percent predicted (FEV1%) and baseline percent reversibility. Results The primary lung function endpoint (change from baseline in morning pre-dose trough FEV1) for BGF 36 versus BFFCombined was met in both KALOS and LOGOS individually (least squares mean difference in the pooled studies, 95% confidence interval CI: 76 mL 57-94; p 0.001); similar benefit was observed for FEV1 AUC0-3. The benefit of BGF 36 versus BFFCombined on lung function was observed in participants with mild/moderate airflow limitation (baseline pre-bronchodilator FEV1% 55%) and severe airflow limitation (baseline pre-bronchodilator FEV1% ≤55%; Table). Severe exacerbation rate (rate ratio 95% CI) for BGF 36 was ∼14% lower versus BFFCombined (0.86 0.76-0.97; p = 0.012). The benefit of BGF 36 versus BFFCombined on severe exacerbation rates was similar in participants with mild/moderate airflow limitation (0.87 0.74, 1.01) and severe airflow limitation (0.84 0.69, 1.02). Directionally consistent reductions in exacerbation rates were observed across both subgroups of reversibility (20%: 0.81 0.69, 0.96; ≥20%: (0.91 0.76, 1.09) although those with 20% reversibility had a greater absolute reduction in exacerbations. Conclusions The benefits of BGF 36 over dual ICS/LABA on lung function and exacerbations in asthma are observed across categories of baseline airflow limitation, and reversibility. This abstract is funded by: AstraZeneca
Patel et al. (Fri,) studied this question.
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