Lung function Improvement and Asthma Exacerbation Reduction with Indacaterol/Glycopyrronium/Mometasone Furoate in Uncontrolled Asthma: IRIDIUM Study

Aim:A novel once-daily (o.d.) fixed-dose combination of indacaterol (IND, long-acting β2-agonist [LABA]), glycopyrronium (GLY, long-acting muscarinic antagonist) and mometasone furoate (MF, inhaled corticosteroid [ICS]) is under development for maintenance treatment of asthma. As a part of a pre-specified and post-hoc analysis, the IRIDIUM study (NCT02571777) evaluated the efficacy of IND/GLY/MF medium-dose o.d. (via Breezhaler®) on lung function (trough forced expiratory volume in one second [FEV1]) and asthma exacerbations compared with salmeterol/fluticasone (Sal/Flu) twice daily (b.i.d.) (via Diskus®) and IND/MF o.d. (via Breezhaler®) in patients with uncontrolled asthma. Methods:This was a Phase-III, multicentre, 52-week, randomised, double-blind, parallel-group, double-dummy, active-controlled study. Patients aged ≥18 – ≤75 years with asthma, pre-bronchodilator FEV1% predicted <80%, an Asthma Control Questionnaire (ACQ-7) score ≥1.5, who experienced ≥1 severe asthma exacerbation requiring systemic corticosteroids in the previous year, and symptomatic at screening despite treatment with medium-/high-dose LABA/ICS were included. Data for patients randomised to receive IND/GLY/MF medium-dose (150/50/80 µg) o.d. or IND/MF high-dose (150/320 μg) o.d. or Sal/Flu high-dose (50/500 μg) b.i.d. for 52-weeks are presented. Trough FEV1 (Weeks 26 and 52) and the rate of asthma exacerbations (moderate/severe, severe, and all [mild, moderate and severe]) over 52-weeks with IND/GLY/MF versus Sal/Flu and IND/MF were evaluated. Safety was also assessed.Results:Significant improvements in trough FEV1 at Weeks 26 and 52 were observed with IND/GLY/MF medium-dose o.d. versus Sal/Flu high-dose b.i.d. (p<0.001) (Figure 1a). Over 52 weeks, IND/GLY/MF medium-dose o.d. showed greater reductions in the rates of moderate/severe (19%; p=0.041), and all exacerbations (30%; p<0.001) compared with Sal/Flu high-dose b.i.d., while there was a non-significant reduction in severe exacerbations (16%, p=0.117) (Figure 1b). At Week 26, trough FEV1 significantly improved with IND/GLY/MF medium-dose o.d. versus IND/MF high-dose o.d. with a mean treatment difference of 44 mL (95% CI: 10 to 79, p=0.012) and at Week 52, the two treatments were comparable with a mean treatment difference of 27 mL (95% CI: −8 to 62, p=0.128). Over 52 weeks, the rates of moderate/severe, severe and all exacerbations were comparable between IND/GLY/MF medium-dose o.d. and IND/MF high-dose o.d. (all p>0.05). All treatments were well tolerated with favourable safety profiles.Conclusions:Once-daily IND/GLY/MF medium-dose resulted in a significant improvement in lung function and a reduction in moderate/severe and all exacerbations versus twice-daily Sal/Flu high-dose, while reducing the steroid load. Once-daily IND/GLY/MF medium dose also improved lung function versus once-daily IND/MF high-dose in patients with uncontrolled asthma. Implementation Science/Service Development Research Ideas on Respiratory Conditions and Tobacco Dependency Abstract Declaration of Interest Study funded by Novartis Pharma AG. References and Clinical Trial Registry Information Clinicaltrials.gov:NCT02571777