Single-inhaler triple therapy improves outcomes in uncontrolled asthma

By Will Boggs MD

NEW YORK (Reuters Health) - 2/10/2019

Patients with uncontrolled asthma have improved outcomes with use of a single inhaler containing a corticosteroid (ICS), a long-acting beta2 agonist (LABA) and a long-acting muscarinic antagonist (LAMA), according to results from the TRIMARAN and TRIGGER randomized clinical trials.

"The fact that both coprimary endpoints, namely improvement in pulmonary function and the frequency of exacerbations (in the combined set of both studies), were reduced in the investigated patient population is interesting, especially as the patient population when analyzed according to the characteristics at entry into the study were indeed rather severe and more or less constituted a patient population that resembles those investigated for therapy with biologics," Dr. Johann Christian Virchow of Universitaetsmedizin Rostock, in Germany, told Reuters Health by email.

Many patients achieve good asthma control with a combination of inhaled corticosteroid plus LABA. For those who do not, a LAMA is commonly added, but this requires the use of two different inhalers of different design with different instructions and often with different dosing regimens.

Dr. Virchow and colleagues compared the single-inhaler combination of ICS (beclomethasone dipropionate), LABA (formoterol fumarate) and LAMA (glycopyrronium) versus the combination of ICS and LABA in two trials of patients with uncontrolled asthma and a history of one or more exacerbations in the previous year who had previously been treated with ICS plus LABA.

TRIMARAN enrolled 1,155 patients, and TRIGGER enrolled 1,437 patients.

The improvement in predose forced expiratory volume in 1 s (FEV1) at week 26, the coprimary endpoint, was significantly greater with triple therapy than with dual therapy in both the TRIMARAN (by 57 mL) and the TRIGGER (by 73 mL) trials.

The second coprimary endpoint, the rate of moderate and severe exacerbations over 52 weeks, was significantly reduced with triple therapy in the TRIMARAN study (by 15%, compared with dual therapy), while the 12% reduction in the TRIGGER study fell short of statistical significance, the researchers report in The Lancet, online September 30.

In the pooled analysis, the rate of severe exacerbations was 23% lower with triple therapy than with dual therapy (P=0.008).

Adverse-event rates were similar across treatment groups, and most events were mild or moderate in severity and generally not felt to be related to treatment.

"Triple therapy can improve pulmonary function and reduce exacerbations and improve asthma control in patients with asthma and should be offered to patients with moderate to severe asthma, especially in the presence of airflow obstruction despite ICS/LABA therapy and before biologics are being considered," Dr. Virchow concluded.

"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," write Dr. J. Mark FitzGerald and Dr. Mohsen Sadatsafavi of the University of British Columbia, in Vancouver, Canada, in a linked editorial. "We must continue to emphasize the importance of asthma education and inhaler technique and adherence for all patients with asthma."

"We also need to improve the characterization of the heterogeneous nature of airway diseases and in parallel target treatment for the right patient at the appropriate time," they conclude.

Chiesi Farmaceutici funded the trials and employed several authors. Dr. Virchow and others also report financial ties to the company.


Lancet 2019.

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