Normalisation of airflow limitation in asthma: Post‐hoc analyses of TRIMARAN and TRIGGER

Abstract

Background In asthma, persistent airflow limitation (PAL) is associated with poorer control, lung function decline and exacerbations. Using post‐hoc analyses we evaluated: the relationship between post‐salbutamol PAL at screening, airflow limitation (AL) during 52 weeks treatment with extrafine beclometasone dipropionate/formoterol fumarate/glycopyrronium (BDP/FF/G) versus BDP/FF and the risk of moderate/severe asthma exacerbations. Methods TRIMARAN and TRIGGER were double‐blind studies comparing BDP/FF/G with BDP/FF (TRIMARAN medium‐dose ICS; TRIGGER high‐dose) in adults with uncontrolled asthma. Patients were subgrouped according to post‐salbutamol PAL status at screening, and AL over the 52‐week treatment period. Results Most patients with post‐salbutamol PAL at screening had AL at all on‐treatment visits (TRIMARAN 62.8%; TRIGGER 66.8%). A significantly higher proportion of patients had normalised airflow on ≥1 follow‐up visit when receiving BDP/FF/G than BDP/FF (TRIMARAN 44.1 vs. 33.1% [p = 0.003]; TRIGGER 40.1 vs. 26.0% [p < 0.001]). In patients with post‐salbutamol PAL at screening and normalised AL at ≥1 follow‐up visit, exacerbation rates were 15% (p = 0.105) and 19% (p = 0.039) lower in TRIMARAN and TRIGGER versus those with AL on all visits. There was a trend to lower exacerbation rates in patients receiving BDP/FF/G than BDP/FF, particularly in patients in whom AL was normalised. Conclusion In these analyses, AL in asthma was associated with an increased exacerbation incidence. Inhaled triple therapy with extrafine BDP/FF/G was more likely to normalise airflow, and was associated with a trend to a lower exacerbation rate than BDP/FF, particularly in the subgroup of patients in whom treatment was associated with airflow normalisation. ClinicalTrials.gov: TRIMARAN, NCT02676076; TRIGGER, NCT02676089.

Open and Closed Triple Inhaler Therapy in Patients with Uncontrolled Asthma

“…The patients under triple inhaler treatment (open or closed) in the TRIMARAN and TRIGGER studies demonstrated a significant reduction in the rate of moderate and severe exacerbations compared to those on ICS + LABA alone, by 15% and 12%, respectively, with no significant differences between the open and closed treatment combinations [ 30 ]. These reductions, however, showed a significant seasonal variation, as they were greater in winter, when the reduction in the rate of moderate and severe exacerbations with triple inhaler treatment was 20.3% compared to ICS + LABA alone, while in the other seasons of the year the corresponding reductions varied between 8.6% and 12.0% [ 46 ]. Furthermore, patients with higher reversibility in post-bronchodilator forced expiratory volume in 1 s (post-FEV 1 ) (>400 mL) experienced greater exacerbation reduction benefit.…”

“…Lung function is another key aspect of asthma, as it might mirror disease control. In contrast to asthma symptoms and exacerbation control, the addition of a LAMA to the dual therapy of ICS + LABA in patients with asthma that remains uncontrolled leads to a clearly beneficial effect on lung function [ 46 ]. For this reason, patients on LAMA + ICS + LABA usually presented with worse lung function during the initial clinical assessment [ 10 ].…”

“…Papi 2022 [46] Post-hoc analyses of TRIMARAN and TRIGGER 1155 asthma patients in TRIMARAN and1437 in TRIGGER.…”

Improving asthma outcomes: Clinicians’ perspectives on peripheral airways

“…Fixed airflow obstruction occurs in up to a third of people with asthma, even in those labeled as “mild asthma.” 3 It can be debilitating and is complex in pathophysiology in which peripheral airway dysfunction is fundamental. 3 , 4 , 5 Although long-acting muscarinic antagonists are particularly beneficial when there is fixed airflow obstruction, 6 , 7 suggesting parallels with smoking-related obstructive disease, treatments that are disease-modifying or curative remain greatly needed. Arguably, the key to finding treatments and managing this major problem will be in the peripheral airways.…”