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. This analysis assessed the effect of BGF versus BFFCombined on severe exacerbation rate, time to first severe exacerbation and number needed to treat (NNT) for severe exacerbation rate in pooled KALOS and LOGOS. 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. There was no inclusion requirement for severe exacerbation history. Pooled analyses across studies assessed severe exacerbation rate and time to first severe asthma exacerbation. Results Severe exacerbation rates (incidence rate ratio 95% confidence interval; CI) for BGF 36 were 10% lower versus BFFA (0.90 0.78-1.03), 18% lower versus BFFS (0.82 0.71-0.94), and 14% lower versus combined BFFCombined (0.86 0.76-0.97). For BGF 18, severe exacerbation rates were approximately 12% lower versus BFFA (0.88 0.75-1.03), 20% lower versus BFFS (0.80 0.69-0.94), and 16% lower versus BFFCombined (0.84 0.73-0.97). BGF delayed time to first severe exacerbation versus BFFCombined (hazard ratio 95% CI; BGF 36: 0.84 0.75-0.95; BGF 18: 0.86 0.75-0.99). The NNT (95% CI) for severe exacerbation rate was 11 (6-45) for BGF 36 versus BFFCombined, 16 (7-not calculable; NC) for BGF 36 versus BFFA, and 8 (5-26) for BGF 36 versus BFFS; for BGF 18, the NNT was 10 (6-48) versus BFFCombined, 14 (6-NC) versus BFFA and 8 (5-26) versus BFFS. Conclusions BGF reduced severe exacerbations versus ICS/LABA, highlighting the benefits of BGF as a single combination inhaler treatment option in asthma. These data support BGF as a treatment option for patients with inadequately controlled asthma, including patients without a recent exacerbation history who are receiving ICS/LABA, to reduce the risk of severe exacerbations. This abstract is funded by: AstraZeneca
Patel et al. (Fri,) studied this question.