Triple Therapy with Mometasone/Indacaterol/Glycopyrronium or Doubling the ICS/LABA Dose in GINA Step 4: IRIDIUM Analyses

Richard N van Zyl-Smit; Huib A M Kerstjens; Jorge Maspero; Ana-Maria Tanase; David Lawrence; Karen Mezzi; Peter D'Andrea; Kenneth R Chapman

doi:10.1007/s41030-023-00234-y

Triple Therapy with Mometasone/Indacaterol/Glycopyrronium or Doubling the ICS/LABA Dose in GINA Step 4: IRIDIUM Analyses

Pulm Ther. 2023 Sep;9(3):395-409. doi: 10.1007/s41030-023-00234-y. Epub 2023 Aug 1.

Authors

Richard N van Zyl-Smit¹, Huib A M Kerstjens², Jorge Maspero³, Ana-Maria Tanase⁴, David Lawrence⁴, Karen Mezzi⁴, Peter D'Andrea⁵, Kenneth R Chapman⁶

Affiliations

¹ Division of Pulmonology and UCT Lung Institute, University of Cape Town, Cape Town, South Africa.
² Department of Pulmonology, University of Groningen, University Medical Center Groningen, and Groningen Research Institute for Asthma and COPD, Groningen, The Netherlands.
³ Allergy and Respiratory Research Unit, Fundación CIDEA, Buenos Aires, Argentina.
⁴ Novartis Pharma AG, Basel, Switzerland.
⁵ Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
⁶ Division of Respiratory Medicine, Department of Medicine, University of Toronto, Toronto, ON, Canada. [email protected].

Abstract

Introduction: GINA guidelines recommend increasing the dose of inhaled corticosteroids (ICS) as a step-up option for patients with inadequately controlled asthma at GINA step 4 [inadequately controlled asthma on medium-dose ICS/long-acting beta-2 agonist (LABA)]. The aim of this study was to compare the efficacy and safety of long-acting muscarinic antagonists (LAMA) add-on to medium-dose ICS/LABA in patients at GINA 2022 step 4.

Methods: This post hoc analysis of the IRIDIUM study evaluated the change from baseline in trough forced expiratory volume (FEV₁ ) in patients receiving medium-dose MF/IND/GLY versus high-dose MF/IND and high-dose FLU/SAL at Week 26. Other outcomes included improvement in lung functions [peak expiratory flow (PEF), forced vital capacity (FVC), forced expiratory flow between 25% and 75% of the FVC (FEF)_25-75%)], asthma control [Asthma Control Questionnaire (ACQ-7)], responder analysis (≥ 0.5 unit improvement in ACQ-7), and reduction in asthma exacerbations at Weeks 26 and 52.

Results: A total of 1930 patients were included in this analysis. Medium-dose MF/IND/GLY improved trough FEV₁ versus high-dose MF/IND (Δ 41 mL; 95% CI - 7-90) and high-dose FLU/SAL (Δ 88 mL; 95% CI 39-137) at Week 26 which were sustained until Week 52. Exacerbation rates were 16% lower with medium-dose MF/IND/GLY versus high-dose MF/IND for all (mild, moderate, and severe) exacerbations and 21-30% lower versus high-dose FLU/SAL for all (mild, moderate, and severe), moderate or severe, and severe exacerbations over 52 weeks. Further improvements in other lung functions were observed with medium-dose MF/IND/GLY. No new safety signals were identified.

Conclusion: Medium-dose MF/IND/GLY improved lung function and reduced asthma exacerbations compared to high-dose ICS/LABA and may be an undervalued option in patients at GINA 2022 step 4.

Trial registration: ClinicalTrials.gov Identifier: NCT02571777.

Keywords: Asthma exacerbations; GINA step 4; Glycopyrronium; ICS/LABA; IRIDIUM; Inadequately controlled asthma; LAMA add-on; Lung function.

Associated data

ClinicalTrials.gov/NCT02571777