Meeting News

Three-in-one asthma inhaler may improve lung function, reduce exacerbations

The addition of a long-acting muscarinic antagonist to inhaled corticosteroid plus long-acting beta-2 agonist therapy in a single inhaler improves lung function and reduces exacerbations among patients with uncontrolled asthma, according to data from two phase 3 studies presented at the European Respiratory Society International Congress.

The findings were also simultaneously published in The Lancet.

The TRIMARAN and TRIGGER trials, conducted from 2016 to 2018, were multicenter, international, double-blind, randomized controlled studies that enrolled patients aged 18 to 75 years with uncontrolled asthma who had at least one exacerbation during the previous year. TRIMARAN targeted patients who were on medium doses of inhaled corticosteroids plus an LABA and TRIGGER targeted patients on high doses of inhaled corticosteroids plus an LABA.

During a 2-week run-in period, patients received beclomethasone dipropionate 100 µg/formoterol fumarate 6 µg in TRIMARAN and beclomethasone dipropionate 200 µg/formoterol fumarate 6 µg in TRIGGER at two inhalations twice daily using a pressurized metered-dose inhaler. Patients in TRIMARAN were then continued on standard combined therapy at the same dose (n = 576) or switched to extrafine beclomethasone dipropionate 100 µg/formoterol fumarate 6 µg/glycopyrronium 10 µg twice daily (n = 579) via a pressurized metered-dose inhaler. Likewise, patients in TRIGGER continued on the same dose of standard combined therapy (n = 576) or switched to extrafine beclomethasone dipropionate 200 µg/formoterol fumarate 6 µg/glycopyrronium 10 µg twice daily via a pressurized metered-dose inhaler (n = 576) or switched to open-label standard combined therapy in a pressurized metered-dose inhaler plus tiotropium 2.5 µg twice daily via a soft mist inhaler (n = 288).

The addition of a long-acting muscarinic antagonist to inhaled corticosteroid plus long-acting beta-2 agonist therapy in a single inhaler improves lung function and reduces exacerbations among patients with uncontrolled asthma, according to data from two phase 3 studies presented at the European Respiratory Society International Congress.
Source: Adobe Stock

The researchers found that predose FEV1 at 26 weeks improved in the triple therapy group by 57 mL (95% CI, 15-99) in TRIMARAN and by 73 mL (95% CI, 26-120) in TRIGGER vs. standard combined therapy. This improvement in lung function was accompanied by a significant 15% reduction in the rate of moderate and severe asthma exacerbations with triple therapy vs. standard combined therapy after 52 weeks in TRIMARAN (RR = 0.85; 95% CI, 0.73-0.99). In TRIGGER, the rate of exacerbations was also reduced by 12% with triple therapy, but the finding did not reach statistical significance (RR = 0.88; 95% CI, 0.75-1.03).

Treatment-related serious adverse events occurred in four patients, including one in the triple therapy group in TRIMARAN, one in the triple therapy group in TRIGGER and two in the standard combined group in TRIGGER. Additionally, three patients in the triple therapy group in TRIMARAN, one patient in the triple therapy group in TRIGGER and one in the standard combined group in TRIGGER had adverse events leading to death, although the researchers concluded that no deaths were related to treatment.

“The patients in our studies had been using preventer inhalers combining two medicines, but they weren’t working as effectively as they do for most asthma sufferers. The effects of triple therapy might seem moderate when you look at the numbers involved, but even incremental improvements can be valuable when there are few treatment options left available,” study author Johann Christian Virchow, MD, from the Rostock University Medical Center in Germany, said in a press release.

In an accompanying editorial, J. Mark FitzGerald, MD, from The Lung Center and respiratory division at the University of British Columbia, and Mohsen Sadatsafavi, MD, PhD, from the faculty of pharmaceutical sciences at the University of British Columbia, noted that this triple therapy in a single inhaler has several benefits for patients.

“This new treatment option is to be welcomed because it provides in one inhaler a simpler treatment option for patients with asthma that is uncontrolled on a combination inhaler with a long-acting beta agonist and inhaled corticosteroids. We must continue to emphasize the importance of asthma education and inhaler technique and adherence for all patients with asthma. We also need to improve the characterization of the heterogeneous nature of airway diseases and in parallel treatment target for the right patient at the appropriate time,” they wrote. – by Melissa Foster

References:

Singh D, et al. ALERT: Abstracts Leading to Evolution in Respiratory Medicine Trials: Asthma. Presented at: European Respiratory Society International Congress; Sept. 28-Oct. 2, 2019; Madrid.

Fitzgerald JM, et al. Lancet. 2019;doi:10.1016/S0140-6736(19)32216-0.

Virchow JC, et al. Lancet. 2019;doi:10.1016/S0140-6736(19)32215-9.

Disclosures: This study was funded by Chiesi Farmaceutici. Virchow reports he has received personal fees from Chiesi Farmaceutici; he has previously lectured and received honoraria from AstraZeneca, Avontec, Bayer, Bencard, Bionorica, Boehringer Ingelheim, Chiesi, Essex/Schering-Plough, GlaxoSmithKline, Janssen-Cilag, Leti, MEDA, Merck, MSD, Mundipharma, Novartis, Nycomed/Altana, Pfizer, Revotar, Sanofi/Regeneron, Sandoz-Hexal, Stallergens, Teva, UCB/Schwarz-Pharma and Zydus/Cadila; he has participated in advisory boards and received honoraria from Avontec, Boehringer Ingelheim, Chiesi, Essex/Schering-Plough, GlaxoSmithKline, Janssen-Cilag, MEDA, MSD, Mundipharma, Novartis, Paul-Ehrlich Institut, Regeneron, Revotar, Roche, Sanofi-Aventis, Sanofi/Regeneron, Sandoz-Hexal, Teva, and UCB/Schwarz-Pharma; he has received funding for research from Deutsche Forschungsgesellschaft, Land Mecklenburg-Vorpommern, GlaxoSmithKline and MSD; and he has advised the Bemeinsame Bundesausschuss (GBA). Please see the study for all other authors’ relevant financial disclosures. FitzGerald reports he has received honoraria as a member of speaker bureaus and advisory boards for AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis and Sanofi Regeneron. Sadatsafavi reports no relevant financial disclosures.

The addition of a long-acting muscarinic antagonist to inhaled corticosteroid plus long-acting beta-2 agonist therapy in a single inhaler improves lung function and reduces exacerbations among patients with uncontrolled asthma, according to data from two phase 3 studies presented at the European Respiratory Society International Congress.

The findings were also simultaneously published in The Lancet.

The TRIMARAN and TRIGGER trials, conducted from 2016 to 2018, were multicenter, international, double-blind, randomized controlled studies that enrolled patients aged 18 to 75 years with uncontrolled asthma who had at least one exacerbation during the previous year. TRIMARAN targeted patients who were on medium doses of inhaled corticosteroids plus an LABA and TRIGGER targeted patients on high doses of inhaled corticosteroids plus an LABA.

During a 2-week run-in period, patients received beclomethasone dipropionate 100 µg/formoterol fumarate 6 µg in TRIMARAN and beclomethasone dipropionate 200 µg/formoterol fumarate 6 µg in TRIGGER at two inhalations twice daily using a pressurized metered-dose inhaler. Patients in TRIMARAN were then continued on standard combined therapy at the same dose (n = 576) or switched to extrafine beclomethasone dipropionate 100 µg/formoterol fumarate 6 µg/glycopyrronium 10 µg twice daily (n = 579) via a pressurized metered-dose inhaler. Likewise, patients in TRIGGER continued on the same dose of standard combined therapy (n = 576) or switched to extrafine beclomethasone dipropionate 200 µg/formoterol fumarate 6 µg/glycopyrronium 10 µg twice daily via a pressurized metered-dose inhaler (n = 576) or switched to open-label standard combined therapy in a pressurized metered-dose inhaler plus tiotropium 2.5 µg twice daily via a soft mist inhaler (n = 288).

The addition of a long-acting muscarinic antagonist to inhaled corticosteroid plus long-acting beta-2 agonist therapy in a single inhaler improves lung function and reduces exacerbations among patients with uncontrolled asthma, according to data from two phase 3 studies presented at the European Respiratory Society International Congress.
Source: Adobe Stock

The researchers found that predose FEV1 at 26 weeks improved in the triple therapy group by 57 mL (95% CI, 15-99) in TRIMARAN and by 73 mL (95% CI, 26-120) in TRIGGER vs. standard combined therapy. This improvement in lung function was accompanied by a significant 15% reduction in the rate of moderate and severe asthma exacerbations with triple therapy vs. standard combined therapy after 52 weeks in TRIMARAN (RR = 0.85; 95% CI, 0.73-0.99). In TRIGGER, the rate of exacerbations was also reduced by 12% with triple therapy, but the finding did not reach statistical significance (RR = 0.88; 95% CI, 0.75-1.03).

Treatment-related serious adverse events occurred in four patients, including one in the triple therapy group in TRIMARAN, one in the triple therapy group in TRIGGER and two in the standard combined group in TRIGGER. Additionally, three patients in the triple therapy group in TRIMARAN, one patient in the triple therapy group in TRIGGER and one in the standard combined group in TRIGGER had adverse events leading to death, although the researchers concluded that no deaths were related to treatment.

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“The patients in our studies had been using preventer inhalers combining two medicines, but they weren’t working as effectively as they do for most asthma sufferers. The effects of triple therapy might seem moderate when you look at the numbers involved, but even incremental improvements can be valuable when there are few treatment options left available,” study author Johann Christian Virchow, MD, from the Rostock University Medical Center in Germany, said in a press release.

In an accompanying editorial, J. Mark FitzGerald, MD, from The Lung Center and respiratory division at the University of British Columbia, and Mohsen Sadatsafavi, MD, PhD, from the faculty of pharmaceutical sciences at the University of British Columbia, noted that this triple therapy in a single inhaler has several benefits for patients.

“This new treatment option is to be welcomed because it provides in one inhaler a simpler treatment option for patients with asthma that is uncontrolled on a combination inhaler with a long-acting beta agonist and inhaled corticosteroids. We must continue to emphasize the importance of asthma education and inhaler technique and adherence for all patients with asthma. We also need to improve the characterization of the heterogeneous nature of airway diseases and in parallel treatment target for the right patient at the appropriate time,” they wrote. – by Melissa Foster

References:

Singh D, et al. ALERT: Abstracts Leading to Evolution in Respiratory Medicine Trials: Asthma. Presented at: European Respiratory Society International Congress; Sept. 28-Oct. 2, 2019; Madrid.

Fitzgerald JM, et al. Lancet. 2019;doi:10.1016/S0140-6736(19)32216-0.

Virchow JC, et al. Lancet. 2019;doi:10.1016/S0140-6736(19)32215-9.

Disclosures: This study was funded by Chiesi Farmaceutici. Virchow reports he has received personal fees from Chiesi Farmaceutici; he has previously lectured and received honoraria from AstraZeneca, Avontec, Bayer, Bencard, Bionorica, Boehringer Ingelheim, Chiesi, Essex/Schering-Plough, GlaxoSmithKline, Janssen-Cilag, Leti, MEDA, Merck, MSD, Mundipharma, Novartis, Nycomed/Altana, Pfizer, Revotar, Sanofi/Regeneron, Sandoz-Hexal, Stallergens, Teva, UCB/Schwarz-Pharma and Zydus/Cadila; he has participated in advisory boards and received honoraria from Avontec, Boehringer Ingelheim, Chiesi, Essex/Schering-Plough, GlaxoSmithKline, Janssen-Cilag, MEDA, MSD, Mundipharma, Novartis, Paul-Ehrlich Institut, Regeneron, Revotar, Roche, Sanofi-Aventis, Sanofi/Regeneron, Sandoz-Hexal, Teva, and UCB/Schwarz-Pharma; he has received funding for research from Deutsche Forschungsgesellschaft, Land Mecklenburg-Vorpommern, GlaxoSmithKline and MSD; and he has advised the Bemeinsame Bundesausschuss (GBA). Please see the study for all other authors’ relevant financial disclosures. FitzGerald reports he has received honoraria as a member of speaker bureaus and advisory boards for AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis and Sanofi Regeneron. Sadatsafavi reports no relevant financial disclosures.