Effect of extrafine medium strength (MS) ICS-containing triple therapy on exacerbations in asthmatics with persistent airflow limitation: A post-hoc analysis of the TRIMARAN study

Abstract

Introduction: Persistent airflow limitation (PAL) may predict a positive clinical response to add-on long-acting muscarinic antagonist (LAMA) in patients with asthma taking inhaled corticosteroids and long-acting β2-receptor agonists (ICS/LABA).

Aims and Objectives: We evaluated the effect of extrafine MS beclometasone dipropionate/formoterol fumarate/glycopyrronium bromide (BDP/FF/GB) on asthma exacerbations in a subset of patients with PAL.

Methods: TRIMARAN was a phase III multinational, randomized, parallel group trial comparing 52-week treatment with (BDP/FF/GB) 400/24/50 µg/d to BDP/FF 400/24 µg/d delivered via a pressurized metered dose inhaler (pMDI) in adult patients with uncontrolled asthma on medium dose ICS/LABA and a history of exacerbation in the past year. PAL was defined as an FEV1 ≤80% of predicted normal and FEV1/FVC ≤0.7 after 400 μg salbutamol pMDI.

Results: 1155 subjects were randomized and 658 (57.0%) met the PAL criteria on BDP/FF/GB (n=331) and BDP/FF (n=327), respectively. Treatment of this subgroup with BDP/FF/GB compared to BDP/FF resulted in a 15.2% and 37.7% reduction in the annual rates of moderate-severe and severe asthma exacerbations respectively, (RR [95% CI] = 0.848 [0.694, 1.036], p=0.106; 0.623 [0.430; 0.902], p=0.012), vs. 15.4% (p=0.033) and 26.3% (p=0.040) reduction in the entire study population.

Conclusions: In patients with asthma uncontrolled on medium dose ICS/LABA, PAL did not influence the efficacy of extrafine MS BDP/FF/GB in reducing moderate-severe exacerbations and was associated with a greater reduction in annual severe exacerbation rates.