Single-Inhaler Triple Therapy Improves Asthma Attacks, Lung Function

Dr. J. Christian Virchow

New trial results from a pair of phase 3 controlled trials showed triple-combination, single-inhaler therapy is associated with significant improvements to lung function and the rate of severe asthma attacks in prescribed patients.

The findings from the TRIMARAN and TRIGGER trials, presented at the European Respiratory Society (ERS) 2019 Congress in Madrid, found positive results with 100 mcg inhaled corticosteroid (ICS)/ 6 mcg long-acting beta2 agonist (LABA)/10 mcg long-acting muscarinic antagonist (LAMA) and 200 mcg ICS/6 mcg LABA/10 mcg LAMA in patients with severe, uncontrolled asthma.

TRIMARAN included 579 patients treated with the medium strength-dose triple therapy, in comparison to 576 patients administered control medium-dose ICS/LABA. In TRIGGER, 573 patients on double-dose ICS/LABA/LAMA were compared to 576 patients on double-dose ICS/LABA—of which another 50% (n = 288) patients were on 2.5 mcg LAMA in a separate inhaler.

Investigators assessed for outcomes of lung function and the rate of moderate to severe asthma attacks—the former being gauged via forced expiratory volume (FEV₁). They found that patients in both studies reported FEV₁ improvements of 57 mL in TRIMARAN versus control (185 mL vs 127 mL improvement from baseline), and 73 mL in TRIGGER (229 mL vs 157 mL improvement from baseline).

Triple-therapy treated patients in the TRIMARAN group reported a 15% reduction in moderate and severe asthma attacks, from 2.16 mean exacerbations per patient per year, to 1.83. However, there was no statistically significant difference in exacerbation reduction in treated patients in the TRIGGER study.

The findings from the 17-country, 2500-plus patient study program complements previous assessment into ICS/LABA/LAMA triple therapy for asthma exacerbation and symptoms. That said, those trials observed the treatment in 2 separate inhalers—the TRIMARAN and TRIGGER studies are novel in their single-inhaler observation.

“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,” study author J. Christian Virchow, a professor at the Rostock University Medical Centre in Germany, said in a statement. “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.”

It’s the belief of Virchow and colleagues that the reported asthma symptom control improvements in treated patients were due to improved prescription adherence with a single inhaler device.

Dr. Mark Fitzgerald, from the University of British Columbia, expressed optimism for the simplified asthma treatment option.

“We must continue to emphasize the importance of asthma education and inhaler technique and adherence for all patients with asthma,” Fitzgerald said. “We need to continue to improve characterization of the heterogeneous nature of airway diseases and in parallel employ targeted treatments for the right patient at the appropriate time.”

The study, “Single inhaler extrafine triple therapy in uncontrolled asthma (TRIMARAN and TRIGGER): two double-blind, parallel-group, randomised, controlled phase 3 trials,” was published online in The Lancet.