Triple-Combination Therapy Improves Lung Function in Adults with Asthma

Two studies have found that in patients with uncontrolled asthma, the addition of a long-acting muscarinic antagonist to a regimen of inhaled corticosteroid plus long-acting β₂-agonist therapy improves lung function and reduces exacerbations.

Each study compared a single-inhaler extrafine combination combination of beclometasone dipropionate (BDP; inhaled corticosteroid), formoterol fumarate (FF; long-acting β₂-agonist), and glycopyrronium (G; long-acting muscarinic antagonist) with the combination of BDP with FF.

Eligible patients were adults between 18 and 75 with uncontrolled asthma, one or more exacerbations in the previous year, and a history of treatment with an inhaled corticosteroid plus a long-lasting β₂-agonist.

TRIMARAN

In the TRIMARAN study, 1,155 patients were given either the BDP/FF/G combination or the BDP/FF combination. They were studied between February 17, 2016 and May 17, 2018. Every patient was originally treated with BDP/FF for 2 weeks, before being randomly assigned 1:1 to 52 weeks of BDP/FF/G or BDP/FF, 2 inhalations twice daily.

Patients who received the BDP/FF/G combination therapy saw reductions in the rate of moderate and severe exacerbations by 15% compared with the BDP/FF group. One patient in that group had a treatment-related serious adverse event, and 3 patients in that group had adverse events leading to death. None of the deaths were considered as related to treatment.

TRIGGER

In the TRIGGER study, 1,437 patients were randomly assigned (2:2:1) to 52 weeks of BDP/FF/G or BDP/FF, both 2 inhalations twice daily; or open-label BDP/FF, 2 inhalations twice daily plus tiotropium 2·5 µg, 2 inhalations once daily.

Compared with the other 2 groups, those receiving the BDP/FF/G combination experienced a 12% reduction in the rate of moderate and severe exacerbations. Three patients had treatment-related serious adverse events—1 in the BDP/FF/G group, and 2 in the BDP/FF group. Two patients died, 1 in the BDP/FF/G group and 1 in the BDP/FF group. Like the TRIMARAN study, none of the deaths were considered as related to treatment.

IMPLICATIONS

These 2 studies are the first to assess the efficacy and safety of single-inhaler triple therapy compared with an inhaled corticosteroid plus a long-acting β₂-agonist in adults with uncontrolled asthma.

The researchers noted that the improvement in asthma control may be somewhat attributable to a clinical trial effect, which can occur in part because of improve adherence.

Taken together, their results suggest that in adult with uncontrolled asthma treated with a medium-to-high dose of inhaled corticosteroid plus a long-acting β₂-agonist, the addition of a long-acting muscarinic antagonist in a single inhaler triple therapy can improve lung function, positively affect severe exacerbations, and can have some benefits in term of asthma symptoms and control.

REFERENCE

Virchow J, Kuna P, Paggiaro P, Papi A, et al.Single inhaler extrafine triple therapy in uncontrolled asthma (TRIMARAN and TRIGGER): two double-blind, parallel-group, randomized, controlled phase 3 trials.[online] The Lancet. Available at:https://www.thelancet.com/action/showPdf?pii=S0140-6736%2819%2932215-9[Accessed 4 Oct. 2019].