Once-daily, single-inhaler mometasone–indacaterol–glycopyrronium versus mometasone–indacaterol or twice-daily fluticasone–salmeterol in patients with inadequately controlled asthma (IRIDIUM): a randomised, double-blind, controlled phase 3 study

Kerstjens, Huib A. M.; Máspero, Jorge; Chapman, Kenneth R.; Zyl-Smit, Richard van; Hosoe, Motoi; Tanase, Ana-Maria; Lavecchia, Catherine; Pethe, Abhijit; Xu, Shunqing; D’Andrea, Peter

doi:10.1016/s2213-2600(20)30190-9

Cited by 112 publications

(192 citation statements)

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“…This is a post hoc analysis of data from the IRIDIUM study 14 in patients from Asian countries (Japan, China, Philippines, Vietnam and Thailand). IRIDIUM was a 52-week, randomised, double-blind, double-dummy, parallel-group, active-controlled study ( ClinicalTrials.…”

Section: Methodsmentioning

confidence: 99%

“…9 10 Similar to the Global Initiative for Asthma report, 5 the Japanese asthma guidelines 6 and Korean asthma guidelines 7 also recommend treatment with add-on long-acting muscarinic antagonist (LAMA, tiotropium) in patients with uncontrolled asthma with LABA/ICS therapy. The addition of LAMA to LABA/ICS has demonstrated improvement in lung function, asthma control and exacerbation reduction, with fewer non-serious adverse events, overall, [11][12][13][14] as well as in the Asian population 15 with uncontrolled asthma.…”

Section: Why Read On?mentioning

confidence: 99%

“…In the IRIDIUM study 14 particularly, one time per day fixed-dose combination of indacaterol acetate/glycopyrronium bromide/mometasone furoate (IND/GLY/ MF) demonstrated improvements in lung function and reductions in asthma exacerbations with comparable asthma control versus IND/MF one time per day and salmeterol xinafoate/fluticasone propionate (SAL/FLU) two times per day in patients with asthma inadequately controlled with LABA/ICS medium-and high-dose. In a study including healthy subjects, there were no ethnic differences (Asian vs Caucasian patients) found in the pharmacokinetics of IND, GLY and MF.…”

Section: Why Read On?mentioning

confidence: 99%

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Efficacy of one time per day, single-inhaler indacaterol/glycopyrronium/mometasone in patients with inadequately controlled asthma: post hoc analysis of IRIDIUM study in Asian population

et al. 2021

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Background and objectiveThe 52-week IRIDIUM study demonstrated the efficacy of indacaterol acetate/glycopyrronium bromide/mometasone furoate (IND/GLY/MF) versus IND/MF and salmeterol xinafoate/fluticasone propionate (SAL/FLU) in patients with symptomatic asthma, despite long-acting β2-agonist/inhaled corticosteroids (LABA/ICS) medium-dose or high-dose, predicted forced expiratory volume in 1 s (FEV1) <80% and at least one exacerbation in the previous year. Here, we present data from a post hoc analysis of the IRIDIUM study in the Asian subpopulation.MethodsThis post hoc analysis evaluated improvements in lung function, asthma control and reduction in asthma exacerbations with IND/GLY/MF medium- (150/50/80 µg) and high-dose (150/50/160 µg) versus IND/MF medium- (150/160 µg) and high-dose (150/320 µg), all one time per day and SAL/FLU high-dose (50/500 µg) two times per day, in Asian patients from the IRIDIUM study.ResultsIn total, 258 patients (IND/GLY/MF medium-dose, 52; IND/GLY/MF high-dose, 52; IND/MF medium-dose, 51; IND/MF high-dose, 51; SAL/FLU high-dose, 52) were included. IND/GLY/MF medium- and high-dose showed greater improvement in trough FEV1 at week 26 versus respective doses of IND/MF (Δ, 100 mL and 101 mL; both p<0.05, respectively), and SAL/FLU high-dose (Δ, 125 mL; p=0.0189, and 136 mL; p=0.0118, respectively), which were maintained over 52 weeks. Both doses of IND/GLY/MF showed greater improvement in morning and evening peak expiratory flow versus respective doses of IND/MF and SAL/FLU high-dose at week 52. The changes in Asthma Control Questionnaire-7 scores from baseline were comparable in all treatment groups. IND/GLY/MF medium- and high-dose showed greater reductions in severe (34%, 69%), moderate or severe (18%, 54%) and all exacerbations (21%, 34%) compared with SAL/FLU high-dose over 52 weeks.ConclusionOne time per day, single-inhaler IND/GLY/MF improved lung function, reduced asthma exacerbations and provided comparable asthma control versus IND/MF and SAL/FLU in Asian patients with inadequately controlled asthma despite LABA/ICS. The results of this analysis were consistent with the overall population in the IRIDIUM study.

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Section: Methodsmentioning

confidence: 99%

Section: Why Read On?mentioning

confidence: 99%

Section: Why Read On?mentioning

confidence: 99%

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Efficacy of one time per day, single-inhaler indacaterol/glycopyrronium/mometasone in patients with inadequately controlled asthma: post hoc analysis of IRIDIUM study in Asian population

et al. 2021

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“…The observed differences were small in magnitude and were not considered clinically relevant in view of the observed exposure variability, challenges with characterizing C max for inhaled drugs and the available safety data at doses higher than proposed doses of IND [25], GLY [26] and MF [27] as part of IND/GLY/MF. In the Phase 3 clinical study for IND/GLY/MF in asthma patients [28], while the study was not powered to demonstrate differences by subgroups, there were no observed differences in clinical efficacy or safety profile according to recorded ethnicity. In addition, during the development of IND/GLY/MF in Japan, 52 weeks treatment of IND/GLY/MF was well tolerated in Japanese patients with inadequately controlled asthma [29].…”

Section: Table 4 Summary Of the Exploratory Analysis Of Plasma Mf Pk mentioning

confidence: 99%

Pharmacokinetics of indacaterol, glycopyrronium and mometasone furoate administered as an inhaled fixed-dose combination in Japanese and Caucasian healthy subjects

et al. 2021

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Background A once-daily (o.d.) fixed-dose combination of indacaterol acetate (IND), glycopyrronium bromide (GLY), and mometasone furoate (MF) delivered via the Breezhaler® device (IND/GLY/MF) is being developed for treatment of asthma. This study compared steady-state pharmacokinetics of IND, GLY and MF between Japanese and Caucasian male subjects after multiple inhalations of IND/GLY/MF o.d. Methods This was a single-center, open-label, 2-treatment crossover study with a 21-day washout period. Japanese and Caucasian subjects received IND/GLY/MF 150/50/80 μg (inhaled corticosteroid [ICS] medium-dose) or 150/50/160 μg o.d. (ICS high-dose) for 14 days in each period. Pharmacokinetics were characterized up to 24 h post-dose on Days 1 and 14. Results In total, 16 Japanese (median age 31 years [range 20–40 years], mean weight 68.3 kg) and 17 Caucasian subjects (median age 27 years [range 21–43 years], mean weight 75.0 kg) were randomized. Geometric mean ratios (Japanese/Caucasian) [90% confidence interval (CI)] for Cmax for IND, GLY and MF at the high ICS dose on Day 14 were 1.31 [1.13, 1.51] 1.38 [1.13, 1.69] and 1.07 [0.969, 1.18], respectively. Geometric mean ratios (Japanese/Caucasian) [90% CI] for AUC0–24h on Day 14 for IND, GLY and MF at the high ICS dose were 1.17 [1.01, 1.35], 1.05 [0.920, 1.20] and 1.15 [1.05, 1.27] respectively. Similar trends were noted for all components for the medium ICS dose treatment. IND/GLY/MF was safe and well tolerated; no AEs suspected to be study drug-related were observed. Conclusion Pharmacokinetics of IND, GLY and MF (high and medium dose) when delivered as a fixed-dose combination were comparable between Japanese and Caucasian subjects. The IND/GLY/MF combination at the administrated doses was safe and well tolerated in both ethnic groups. Trial registration Japan Registry of Clinical Trial: jRCT2031200227, retrospectively registered on 04, December, 2020.

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“…published, showing that different ICS/LABA/LAMA combinations can improve lung function and symptoms in patients with moderate or severe asthma who remain uncontrolled with ICS/LABA. [68][69][70] High ICS doses would be only prescribed in "T2-high" patients who have failed prior therapeutic attempts. Consequently, biologic therapy would be restricted to those asthmatics who remain uncontrolled with high-dose ICS triple therapy if they express biomarkers indicative of "T2-high" inflammatory response.…”

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confidence: 99%

Phenotype-Guided Asthma Therapy: An Alternative Approach to Guidelines

Llano

Rivas

Cid

et al. 2021

JAA

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Despite recent advances in therapy, a substantial proportion of asthmatics remain not well controlled. The classical stepwise approach to pharmacological therapy in adult asthma recommends that treatment is progressively stepped up by increasing the inhaled corticosteroid (ICS) dose or by adding another controller medication-to achieve symptom control and reduce the risk of exacerbations, and stepped down after a period of control. In general, asthma guideline recommendations do not reflect that there are significant differences between ICS in terms of potency. Moreover, they do not consider efficacy and safety separately, incorrectly assuming that "low" and "high" dose categories inevitably correspond with low and high risk of systemic effects. Another point of criticism is the fact that guidelines do not take into account the inflammatory profile of the patient, although substantial groups of patients with mild and moderate asthma have little evidence of "T2high" inflammation, and by extension are likely to show a poor response to ICS treatment. On the other hand, the latest version of the Global Initiative for Asthma (GINA) equally recommends regular ICS and ICS/formoterol as needed to prevent exacerbations in step 2 patients, without taking into consideration that the therapeutic objectives (exacerbations, symptoms) may differ between individual patients and that different goals may warrant distinct treatment strategies. In this review, we bring to the table several controversial issues concerning asthma treatment and suggest an alternative proposal that takes into consideration the potential side effects of high ICS doses, the patient's inflammatory profile and the therapeutic goals to be achieved.

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Once-daily, single-inhaler mometasone–indacaterol–glycopyrronium versus mometasone–indacaterol or twice-daily fluticasone–salmeterol in patients with inadequately controlled asthma (IRIDIUM): a randomised, double-blind, controlled phase 3 study

Abstract: Once-daily, single-inhaler mometasone-indacaterol-glycopyrronium versus mometasoneindacaterol or twice-daily fluticasone-salmeterol in patients with inadequately controlled asthma (IRIDIUM) IRIDIUM trial investigators; Kerstjens, Huib A

Cited by 112 publications

References 27 publications

Efficacy of one time per day, single-inhaler indacaterol/glycopyrronium/mometasone in patients with inadequately controlled asthma: post hoc analysis of IRIDIUM study in Asian population

Efficacy of one time per day, single-inhaler indacaterol/glycopyrronium/mometasone in patients with inadequately controlled asthma: post hoc analysis of IRIDIUM study in Asian population

Pharmacokinetics of indacaterol, glycopyrronium and mometasone furoate administered as an inhaled fixed-dose combination in Japanese and Caucasian healthy subjects

Phenotype-Guided Asthma Therapy: An Alternative Approach to Guidelines

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