Fixed-Dose MF/IND/GLY Improved Asthma Outcomes Even With Airflow Limitation

Once-daily fixed-dose mometasone furoate/indacaterol acetate/glycopyrronium bromide (MF/IND/GLY) reduced exacerbations and improved lung function in patients with asthma with and without persistent airflow limitation (PAL), according to post-hoc analysis study findings published in Respiratory Medicine.

For adults with asthma that is inadequately controlled on inhaled corticosteroid/long-acting ꞵ2-agonist (ICS/LABA) combination therapy, MF/IND/GLY is the first approved ICS/LABA/long-acting muscarinic antagonist (LAMA) maintenance therapy. In the current post-hoc analysis, investigators used data from the phase 3 IRIDIUM trial (ClinicalTrials.gov Identifier: NCT02571777) to assess the efficacy of MF/IND/GLY in patients with asthma with and without PAL.

The double-blind, double-dummy IRIDIUM trial, which included 5 treatment arms, demonstrated the efficacy of MF/IND/GLY vs other combination therapies in patients with inadequately controlled asthma. IRIDIUM participants were aged 18 to 75 years, with asthma of at least 1 year that remained symptomatic after medium- or high-dose ICS/LABA. They also had at least 1 exacerbation in the previous year and a pre-bronchodilator forced expiratory volume (FEV₁) of less than 80% of predicted.

In the post hoc analysis, PAL was defined as a pre-bronchodilator FEV₁ of less than or equal to 80% predicted and FEV₁/forced vital capacity (FVC) ratio of equal to or less than 0.7. Of the 3092 patients in the IRIDIUM study, 1981 patients met the post hoc analysis baseline criteria for the PAL subgroup, leaving 1111 patients for the non-PAL subgroup. The PAL and non-PAL subgroups had no meaningful difference in age (53.9 vs 49.3 years); however, the non-PAL subgroup included more women (69.8% vs 57.6%), more patients who never smoked (84.5% vs 77.8%), and patients with a shorter mean duration of asthma (15.84 years vs 19.38 years).

Investigators found no evidence of treatment difference between PAL and non-PAL subgroups (interaction P value for trough FEV₁, 0.42; forced expiratory flow_25%-75%, 0.08; peak expiratory flow, 0.43; moderate or severe exacerbations, 0.29; severe exacerbations, 0.35; all exacerbations, 0.12).

The published post-hoc analysis findings highlighted outcomes of patients with and without PAL in 3 of IRIDIUM’s 5 treatment arms:

• once daily high-dose MF/IND/GLY (160/150/50 μg); PAL subgroup, n=397; non-PAL subgroup, n=222;
• high-dose MF/IND (320/150 μg); PAL subgroup, n=393; non-PAL subgroup, n=225; and
• twice daily high-dose fluticasone propionate/salmeterol xinafoate (FLU/SAL) (500/50 μg); PAL subgroup, n=387; non-PAL subgroup, n=231.

In the PAL treatment subgroup, high-dose MF/IND/GLY outperformed both high-dose MF/IND and high-dose FLU/SAL. High-dose MF/IND/GLY:

• improved FEV₁ (by a mean difference of 102 mL for MF/IND and 137 mL for FLU/SAL; all P <.0001);
• reduced moderate or severe exacerbation (by 16% vs MF/IND and 32% vs FLU/SAL);
• reduced severe exacerbation (by 25% vs MF/IND and 39% vs FLU/SAL); and
• reduced all exacerbations (by 19% vs MF/IND and 38% vs FLU/SAL).

In the non-PAL subgroup, high-dose MF/IND/GLY:

• reduced moderate or severe exacerbations (by 15% vs high-dose MF/IND and 43% vs high-dose FLU/SAL);
• reduced severe exacerbations (by 15% vs high-dose MF/IND and 48% vs high-dose FLU/SAL); and
• reduced all exacerbations (by 22% vs high-dose MF/IND and 42% vs high-dose FLU/SAL).

Study limitations include a lack of assessment of safety data for the PAL or non-PAL subgroups.

“The current post hoc analysis confirms the benefits of MF/IND/GLY in the subgroup of patients with and without PAL,” the post-hoc investigators concluded.

Disclosure: This research was supported by Novartis Pharma AG. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.