Triple therapy improves asthma outcomes compared with pairs of medications

Key takeaways:

• Mometasone furoate, indacaterol acetate and glycopyrronium bromide improved lung function and reduced exacerbations more than other care.
• Patients may benefit by adding a long-acting muscarinic antagonist.

The use of an inhaled corticosteroid, long-acting beta 2 agonist and long-acting muscarinic antagonist improved asthma outcomes compared with use of just two of those medications, according to a study published in Respiratory Medicine.

The improvements were independent of baseline blood eosinophil levels, suggesting that these levels did not impact the efficacy of these medications, Konstantinos Kostikas, MD, PhD, FCCP, associate professor, respiratory medicine unit, University of Ioannina, and colleagues wrote.

The subgroup analysis of the IRIDIUM study comprised 3,065 patients with asthma aged 18 to 75 years who had been receiving medium or high doses of inhaled corticosteroids (ICS) or long-acting beta 2 agonists (LABA) for 3 months or more with a stable dose for a month or more before the screening.

These patients were randomly assigned to receive one of five treatments:

• 160 µg of mometasone furoate (MF), 150 µg of indacaterol acetate (IND) and 50 µg of glycopyrronium bromide (GLY), considered a high dose;
• 80 µg of MF, 150 µg of IND and 50 µg of GLY, considered a medium dose;
• 320 µg of MF and 150 µg of IND, considered a high dose;
• 160 µg of MF and 150 µg of IND, considered a medium dose; and
• 500 µg of fluticasone propionate (FLU) and 50 µg of salmeterol xinafoate (SAL).

Each of the groups showed improvements in trough FEV₁ from baseline regardless of their baseline eosinophil levels.

Patients in the high-dose MF/IND/GLY group with blood eosinophil levels less than 300 cells/µL had a least mean square difference (LSMD) in trough FEV₁ of 78 mL (95% CI, 36-121), whereas those with blood eosinophil levels of 300 cells/µL and higher had an LSMD of 54 mL (95% CI, 13-96) compared with their counterparts in the high-dose MF/IND group.

The high-dose MF/IND/GLY group also had greater improvements in trough FEV₁ compared with the FLU/SAL group, with LSMDs of 112 mL (95% CI, 66-157) for the patients with low eosinophil levels and 98 mL (95% CI, 52-144) for the patients with high eosinophil levels.

LSMDs for improvements in trough FEV₁ in pooled MF/IND/GLY treatment were higher than those for pooled MF/IND treatment, including 75 mL (95% CI, 40-109) for the patients with low eosinophil levels and 68 mL (95% CI, 34-102) for the patients with high eosinophil levels.

The treatment groups also all experienced reductions in exacerbation rates from baseline through 52 weeks.

Reductions in rates of moderate or severe asthma exacerbations included 23% (RR = 0.77; 95% CI, 0.57-1.04) for patients with low eosinophil levels and 10% (RR = 0.9; 95% CI, 0.67-1.22) for patients with high eosinophil levels in the high-dose MF/IND/GLY group compared with their counterparts in the high-dose MF/IND group.

These reductions also included 33% (RR = 0.67; 95% CI, 0.5-0.9) for patients with low levels of eosinophils and 41% (RR = 0.59; 95% CI, 0.44-0.8) for patients with higher levels among the MF/IND/GLY group compared with the FLU/SAL group.

Reductions in the pooled MF/IND/GLY group included 22% (RR = 0.78; 95% CI, 0.63-0.96) for low eosinophil levels and 8% (RR = 0.92; 0.75-1.13) for high eosinophil levels compared with the pooled MF/IND group as well.

Reductions in severe exacerbations included 31% (RR = 0.69; 95% CI, 0.49-0.98) for low eosinophil counts and 15% (RR = 0.85; 95% CI, 0.6-1.2) for high eosinophil counts in the high-dose MF/IND/GLY group compared with the high-dose MF/IND group.

Compared with the FLU/SAL group, high-dose MF/IND/GLY reductions included 45% (RR = 0.55; 95% CI, 0.39-0.78) for low eosinophil counts and 42% (RR = 0.58; 95% CI, 0.41-0.8) for high counts.

In pooled MF/IND/GLY totals, reductions included 21% (RR = 0.79; 95% CI, 0.62-1) with low eosinophils and 7% (RR = 0.93; 95% CI, 0.73-1.17) with high eosinophils compared with the pooled MF/IND group.

Reductions in mild, moderate and severe exacerbations overall with high-dose MF/IND/GLY included 33% (RR = 0.67; 95% CI, 0.51-0.88) for low levels of eosinophils and 10% (RR = 0.9; 95% CI, 0.69-1.18) for high levels of eosinophils compared with high-dose MF/IND.

Similarly, reductions with high-dose MF/IND/GLY included 42% (RR = 0.58; 95% CI, 0.44-0.75) for low eosinophil counts and 39% (RR = 0.61; 95% CI, 0.47-0.79) for high eosinophil counts compared with FLU/SAL.

Reductions for pooled high-dose MF/IND/GLY included 27% (RR = 0.73; 95% CI, 0.61-0.89) for low levels of eosinophils and 8% (RR = 0.92; 95% CI, 0.76-1.1) for high levels, compared with pooled MF/IND.

Considering these improvements in trough FEV₁ and asthma exacerbations with MF/IND/GLY compared with high-dose MF/IND and FLU/SAL independent of baseline blood eosinophil levels, the researchers said that these levels might not influence the efficacy of MF/IND/GLY treatment. Also, the researchers continued, patients may benefit from the addition of a long-acting muscarinic antagonist to ICS/LABA therapy.