One time a day mometasone/indacaterol fixed-dose combination versus two times a day fluticasone/salmeterol in patients with inadequately controlled asthma: pooled analysis from PALLADIUM and IRIDIUM studies

Kenneth Chapman, Richard van Zyl-Smit, Jorge Maspero, Huib A M Kerstjens, Yasuhiro Gon, Motoi Hosoe, Ana-Maria Tanase, Abhijit Pethe, Xu Shu, Peter D'Andrea, Kenneth Chapman, Richard van Zyl-Smit, Jorge Maspero, Huib A M Kerstjens, Yasuhiro Gon, Motoi Hosoe, Ana-Maria Tanase, Abhijit Pethe, Xu Shu, Peter D'Andrea

Abstract

Background: Despite currently available standard-of-care inhaled corticosteroid (ICS)/long-acting β2-agonist therapies, a substantial proportion of patients with asthma remain inadequately controlled. This pooled analysis evaluated efficacy and safety of mometasone furoate/indacaterol acetate (MF/IND) versus fluticasone propionate/salmeterol xinafoate (FLU/SAL) in patients with inadequately controlled asthma.

Methods: This analysis included patients from PALLADIUM (NCT02554786) and IRIDIUM (NCT02571777) studies who received high-dose MF/IND (320/150 µg) or medium-dose MF/IND (160/150 µg) one time a day or high-dose FLU/SAL (500/50 µg) two times a day for 52 weeks. Reduction in asthma exacerbations, improvement in lung function, asthma control, and safety were evaluated for 52 weeks.

Results: In total, 3154 patients (high-dose MF/IND, n=1054; medium-dose MF/IND, n=1044; high-dose FLU/SAL, n=1056) were included. High-dose MF/IND showed 26%, 22% and 19% reductions in rate of severe, moderate or severe, and all (mild, moderate and severe) exacerbations versus high-dose FLU/SAL, respectively, over 52 weeks (all, p<0.05). High-dose MF/IND improved trough FEV1 versus high-dose FLU/SAL at weeks 26 (Δ, 43 mL, p=0.001) and 52 (Δ, 51 mL, p<0.001). Reductions in asthma exacerbation rate and improvement in trough FEV1 with medium-dose MF/IND were comparable with high-dose FLU/SAL over 52 weeks. All treatments improved Asthma Control Questionnaire-7 score from baseline to 52 weeks with no difference between treatments. Safety was comparable between high-dose MF/IND and high-dose FLU/SAL.

Conclusions: One time a day, single-inhaler, high-dose MF/IND reduced asthma exacerbations and improved lung function versus two times a day, high-dose FLU/SAL in patients with inadequately controlled asthma. Similarly, improved outcomes were seen with one time a day, medium-dose MF/IND and two times a day, high-dose FLU/SAL, but at a lower ICS dose.

Keywords: asthma; asthma in primary care; asthma pharmacology.

Conflict of interest statement

Competing interests: Authors received no compensation related to development of the manuscript. KC reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Grifols, Novartis, Regeneron, Sanofi, and Takeda, grants from Vertex, and personal fees from CSL Behring, Inhibrx, and Kamada, all outside of the submitted work. RvZ-S reports receiving personal fees from Aspen–GlaxoSmithKline, Pfizer, Roche, AstraZeneca, Novartis, Merck Sharp & Dohme, and Cipla, outside of the submitted work. JM reports grants and personal fees from Novartis, during the conduct of the study, grants and personal fees from Sanofi, and personal fees from AstraZeneca and ImmunoTek. HAMK reports grants and fees for consultancy or advisory board participation from Novartis, during the conduct of the study; and grants and fees for consultancy or advisory board participation from GlaxoSmithKline and Boehringer Ingelheim, and a grant from Chiesi, outside of the submitted work. All were paid to his institution. YG reports receiving personal fees from Novartis, GlaxoSmithKline, AstraZeneca, and Boehringer Ingelheim, outside the submitted work. MH and A-MT are employees of Novartis Pharma. AP, XS, and PD are employees of Novartis Pharmaceuticals.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Annualised rate of asthma exacerbations over 52 weeks with: (A) high-dose MF/IND one time a day and (B) medium-dose MF/IND one time a day compared with high-dose FLU/SAL two times a day in patients with inadequately controlled asthma. Data presented as annualised rate (95% CI); error bars represent CI values. Participants received high-dose MF/IND (320/150 µg) one time a day; or medium-dose MF/IND (160/150 µg) one time a day; or high-dose FLU/SAL (500/50 µg) two times a day. n, number of patients analysed. FLU/SAL, fluticasone propionate/salmeterol xinafoate; MF/IND, mometasone furoate/indacaterol acetate; RR, rate ratio.
Figure 2
Figure 2
Improvements in trough FEV1 at weeks 26 and 52 with (A) high-dose MF/IND one time a day and (B) medium-dose MF/IND one time a day compared with high-dose FLU/SAL two times a day in patients with inadequately controlled asthma. Data presented as LS mean±SE, error bars represent SE values. Participants received high-dose MF/IND (320/150 µg) one time a day; or medium-dose MF/IND (160/150 µg) one time a day; or high-dose FLU/SAL (500/50 µg) two times a day. n, number of patients analysed. Δ, LS mean treatment difference; FEV1, forced expiratory volume in 1 s; FLU/SAL, fluticasone propionate/salmeterol xinafoate; LS, least square; MF/IND, mometasone furoate/indacaterol acetate.
Figure 3
Figure 3
Change in (A) morning and (B) evening peak expiratory flow (PEF) rate from baseline to week 52 with high-dose MF/IND one time a day compared with high-dose FLU/SAL two times a day in patients with inadequately controlled asthma. Data presented as LS mean. Participants received high-dose MF/IND (320/150 µg) one time a day; or high-dose FLU/SAL (500/50 µg) two times a day. Δ, LS mean treatment difference; FLU/SAL, fluticasone propionate/salmeterol xinafoate; LS, least square; MF/IND, mometasone furoate/indacaterol acetate.
Figure 4
Figure 4
(A) Treatment difference in ACQ-7 score. (B) Proportion of patients achieving MCID in ACQ-7 score, and (C) proportion of patients achieving ACQ-7 score

References

    1. Global Initiative for Asthma . Global strategy for asthma management and prevention, 2019. Available: [Accessed 25 Jun 2020].
    1. Canadian Agency for Drugs and Technologies in Health (CADTH) . Long-acting beta(2)-agonist and inhaled corticosteroid combination therapy for adult persistent asthma: systematic review of clinical outcomes and economic evaluation. CADTH Technol Overv 2010;1:e0120
    1. Averell CM, Stanford RH, Laliberté F, et al. . Medication adherence in patients with asthma using once-daily versus twice-daily ICS/LABAs. J Asthma 2021;58:102–11. 10.1080/02770903.2019.1663429
    1. Dal Negro RW, Bonadiman L, Turco P. Fluticasone furoate/Vilanterol 92/22 μg once-a-day vs Beclomethasone dipropionate/Formoterol 100/6 μg b.I.D.: a 12-month comparison of outcomes in mild-to-moderate asthma. Multidiscip Respir Med 2018;13:18. 10.1186/s40248-018-0131-x
    1. Scichilone N, Braido F, Lavorini F, et al. . Routine use of budesonide/formoterol fixed dose combination in elderly asthmatic patients: practical considerations. Drugs Aging 2017;34:321–30. 10.1007/s40266-017-0449-7
    1. McKeage K, Keam SJ. Salmeterol/Fluticasone propionate. Drugs 2009;69:1799–828. 10.2165/11202210-000000000-00000
    1. Huchon G, Magnussen H, Chuchalin A, et al. . Lung function and asthma control with beclomethasone and formoterol in a single inhaler. Respir Med 2009;103:41–9. 10.1016/j.rmed.2008.09.002
    1. Woodcock A, Vestbo J, Bakerly ND, et al. . Effectiveness of fluticasone furoate plus vilanterol on asthma control in clinical practice: an open-label, parallel group, randomised controlled trial. Lancet 2017;390:2247–55. 10.1016/S0140-6736(17)32397-8
    1. Buhl R, Heaney LG, Loefroth E, et al. . One-year follow up of asthmatic patients newly initiated on treatment with medium- or high-dose inhaled corticosteroid-long-acting β2-agonist in UK primary care settings. Respir Med 2020;162:105859. 10.1016/j.rmed.2019.105859
    1. Schatz M, Meckley LM, Kim M, et al. . Asthma exacerbation rates in adults are unchanged over a 5-year period despite high-intensity therapy. J Allergy Clin Immunol Pract 2014;2:570–4. 10.1016/j.jaip.2014.05.002
    1. van Zyl-Smit RN, Krüll M, Gessner C, et al. . Once-Daily mometasone plus indacaterol versus mometasone or twice-daily fluticasone plus salmeterol in patients with inadequately controlled asthma (PALLADIUM): a randomised, double-blind, triple-dummy, controlled phase 3 study. Lancet Respir Med 2020;8:987–99. 10.1016/S2213-2600(20)30178-8
    1. Kerstjens HAM, Maspero J, Chapman KR, et al. . 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. Lancet Respir Med 2020;8:1000–12. 10.1016/S2213-2600(20)30190-9
    1. Juniper EF, Bousquet J, Abetz L, et al. . Identifying 'well-controlled' and 'not well-controlled' asthma using the Asthma Control Questionnaire. Respir Med 2006;100:616–21. 10.1016/j.rmed.2005.08.012
    1. Juniper EF, O'Byrne PM, Guyatt GH, et al. . Development and validation of a questionnaire to measure asthma control. Eur Respir J 1999;14:902–7. 10.1034/j.1399-3003.1999.14d29.x
    1. Jia CE, Zhang HP, Lv Y, et al. . The asthma control test and asthma control questionnaire for assessing asthma control: systematic review and meta-analysis. J Allergy Clin Immunol 2013;131:695–703. 10.1016/j.jaci.2012.08.023
    1. Barnes PJ, Casale TB, Dahl R, et al. . The asthma control questionnaire as a clinical trial endpoint: past experience and recommendations for future use. Allergy 2014;69:1119–40. 10.1111/all.12415
    1. Seong G, Lee J, Song J. Comparison of clinical efficacy between morning and evening dosing of once-daily inhaled corticosteroids in patients with asthma: a systemic review and meta-analysis [Abstract]. Am J Respir Crit Care Med 2018;197:P4833.
    1. Kempsford RD, Oliver A, Bal J, et al. . The efficacy of once-daily fluticasone furoate/vilanterol in asthma is comparable with morning or evening dosing. Respir Med 2013;107:1873–80. 10.1016/j.rmed.2013.07.002
    1. Jacques L, Bakerly ND, New JP, et al. . Effectiveness of fluticasone furoate/vilanterol versus fluticasone propionate/salmeterol on asthma control in the Salford lung study. J Asthma 2019;56:748–57. 10.1080/02770903.2018.1490751
    1. Kuna P. Treatment comparison of Budesonide/Formoterol with Salmeterol/Fluticasone propionate in adults aged ≥16 years with asthma. Clin Drug Investig 2010;30:565–79. 10.2165/11533450-000000000-00000
    1. Woodcock A, Bleecker ER, Lötvall J, et al. . Efficacy and safety of fluticasone furoate/vilanterol compared with fluticasone propionate/salmeterol combination in adult and adolescent patients with persistent asthma: a randomized trial. Chest 2013;144:1222–9. 10.1378/chest.13-0178
    1. Papi A, Paggiaro P, Nicolini G, et al. . Beclomethasone/formoterol vs fluticasone/salmeterol inhaled combination in moderate to severe asthma. Allergy 2007;62:1182–8. 10.1111/j.1398-9995.2007.01493.x
    1. Bernstein D, Andersen L, Forth R, et al. . Once-daily fluticasone furoate/vilanterol versus twice-daily fluticasone propionate/salmeterol in patients with asthma well controlled on ICS/LABA. J Asthma 2018;55:984–93. 10.1080/02770903.2017.1386214
    1. Bernstein DI, Hébert J, Cheema A, et al. . Efficacy and onset of action of mometasone furoate/formoterol and fluticasone propionate/salmeterol combination treatment in subjects with persistent asthma. Allergy Asthma Clin Immunol 2011;7:21–30. 10.1186/1710-1492-7-21

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