Extrafine triple therapy and asthma exacerbation seasonality: TRIMARAN and TRIGGER post-hoc analyses

Background: Previous studies have shown seasonal variation in asthma exacerbations, peaking over the winter months. A single-inhaler triple therapy containing extrafine formulations of the inhaled corticosteroid (ICS) beclomethasone dipropionate (BDP), long-acting β2-agonist (LABA) formoterol fumarate (FF) and long-acting muscarinic antagonist (LAMA) glycopyrronium (G) is in development for asthma. Objective: To evaluate whether calendar season impacted the relative effect of BDP/FF/G versus BDP/FF on moderate-and-severe asthma exacerbations. Methods: TRIMARAN and TRIGGER were double-blind 52-week studies comparing BDP/FF/G with BDP/FF (TRIMARAN medium-dose ICS; TRIGGER high-dose) in adults with uncontrolled asthma (Asthma Control Questionnaire-7 ≥1.5), pre-bronchodilator FEV1 <80% predicted, history of ≥1 asthma exacerbation, who had been receiving ICS/LABA for ≥4 weeks prior to entry. Moderate and severe asthma exacerbations were captured throughout each study. In these post-hoc analyses, the annual moderate-and-severe exacerbation rate was calculated for each month, with rate ratios determined from events grouped by season. Results: In patients who received BDP/FF alone, there was a marked seasonal effect on the occurrence of asthma exacerbations, with the rate highest in the winter months. However, the addition of the LAMA component to BDP/FF reduced this seasonal variation, especially during the winter, such that the relative effect of BDP/FF/G versus BDP/FF was greatest in the winter (significant 20.3% reduction [p=0.0008]). Reductions in the other seasons ranged between 8.6 and 12.0%. Conclusions: These post-hoc analyses indicate that inhaled triple therapy with extrafine BDP/FF/G reduces seasonal peaks in moderate-and-severe exacerbations, and confirm the overall utility of adding LAMA to ICS/LABA in the management of asthma.