Rostock, Germany—If two is good, three might be better. That was the assumption of a new study looking at treatment of adults with severe asthma that is not controlled with standard treatment. The report in The Lancet suggests that those patients could benefit from using a single inhaler combining three, instead of two, therapies.

Results of the phase III randomized, controlled trials involving more than 2,500 patients across 17 countries, led by researchers from Rostock University Medical Center in Germany, also were presented at the European Respiratory Society Conference 2019.

The authors decried the use of multiple inhalers—which could include devices with different designs, different instructions, and different dosing regimens, such as the number of inhalations per day—and suggested that those protocols could hinder treatment adherence.

Researchers reported on two studies that compared the single-inhaler extrafine combination of beclometasone dipropionate (BDP; inhaled corticosteroid), formoterol fumarate (FF; long-acting beta-2 agonist), and glycopyrronium (G; long-acting muscarinic antagonist) with the combination of BDP plus FF.

The two parallel-group, double-blind, randomized, active-controlled, phase III trials (Triple in Asthma With Uncontrolled Patients on Medium Strength of ICS + LABA [TRIMARAN] and Triple in Asthma High Strength Versus ICS/LABA HS and Tiotropium [TRIGGER]) involved participants from as many as 221 secondary-and tertiary-care sites, as well as specialized investigative units.

Eligible patients were adults with uncontrolled asthma, a history of one or more exacerbations in the previous year, and previous treatment an with inhaled corticosteroid—TRIMARAN: medium dose; TRIGGER: high dose—in addition to a long-acting beta-2 agonist.

Endpoints for both trials (BDP/FF/G vs. BDP/FF) were predose forced expiratory volume in 1 s (FEV1) at week 26 and rate of moderate and severe exacerbations over 52 weeks.

In TRIMARAN, between February 17, 2016, and May 17, 2018, patients were given either BDP/FF/G or BDP/FF. In TRIGGER, between April 6, 2016, and May 28, 2018, 1,437 patients were given BDP/FF/G, BDP/FF, or BDP/FF plus tiotropium.

Results indicate that, compared with the BDP/FF group, Week 26 predose FEV 1 improved in the BDP/FF/G group by 57 mL (95% CI, 15-99; P = .0080) in TRIMARAN and by 73 mL (26-120; P = .0025) in TRIGGER. Identified were reductions in the rate of moderate and severe exacerbations of 15% (rate ratio 0.85, 95% CI, 0.73-0.99; P = .033) in TRIMARAN and 12% (0.88, 0.75-1.03; P = .11) in TRIGGER.

“In uncontrolled asthma, addition of a long-acting muscarinic antagonist to inhaled corticosteroid plus long-acting beta-2-agonist therapy improves lung function and reduces exacerbations,” the authors concluded.

“The patients in our studies had been using preventer inhalers combining two medicines but they weren’t working as effectively as they do for most asthma sufferers. The effects of triple therapy might seem moderate when you look at the numbers involved, but even incremental improvements can be valuable when there are few treatment options left available,” explained lead researcher J. Christian Virchow, MD, from the Rostock University Medical Center.

In a linked commentary from the University of British Columbia, Canadian authors noted, “This new treatment option is to be welcomed because it provides in one inhaler a simpler treatment option for patients with asthma that is uncontrolled on a combination inhaler with a long acting beta agonist and inhaled corticosteroids.”

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