Open-inhaler versus single-inhaler triple therapy (long-acting muscarinic antagonist, inhaled corticosteroid, and long-acting β₂-agonist) in asthma patients: a narrative review

Abstract

Objective

To review the evidence for the use of open-inhaler (inhaled corticosteroid [ICS] plus long-acting β₂-agonist [LABA] with separate add-on long-acting muscarinic antagonist [LAMA]) versus single-inhaler triple therapy (ICS/LABA/LAMA combination) and the merits of add-on LAMA to ICS/LABA in patients with uncontrolled asthma.

Data Sources

Original research articles were identified from PubMed using the search term “triple therapy asthma.” Information was also retrieved from the ClinicalTrials.gov website.

Study Selections

Articles detailing the use of add-on LAMA to ICS plus LABA (open-inhaler triple therapy), and closed triple therapy compared with ICS plus LABA dual therapy, addressing patient symptoms, exacerbations, and health-related quality of life.

Results

Open-inhaler triple therapy was associated with a significantly reduced incidence of hospitalizations and emergency department visits and a decrease in ICS dose, oral corticosteroids use, and antibiotics use. Exacerbations and acute respiratory events were also reduced. Single-inhaler triple therapy showed a greater improvement in lung function, asthma control, and health status and was noninferior to open-inhaler triple therapy for Asthma Quality of Life Questionnaire scores. Single-inhaler triple therapy may also lead to improved therapy adherence.

Conclusion

Add-on LAMA to ICS plus LABA (open- or single-inhaler triple therapy) improves the response in patients who remain symptomatic and provides a reasonable alternative to ICS dose escalation in treatment-refractory patients.

Keywords:

• Asthma
• management
• open-inhaler triple therapy
• single-inhaler triple therapy

Acknowledgements

Writing, editorial support, and formatting assistance was provided by Sandra Brasil and Shruti Muralidharan of Cactus Life Sciences (part of Cactus Communications), which was contracted and compensated by Boehringer Ingelheim Pharmaceuticals, Inc. (BIPI) for these services. BIPI was given the opportunity to review the manuscript for medical and scientific accuracy, as well as intellectual property considerations. To ensure independent interpretation of clinical study results and enable authors to fulfill their role and obligations under the ICMJE criteria, BIPI grants all external authors access to relevant clinical study data. In adherence with the BIPI Policy on Transparency and Publication of Clinical Study Data, scientific and medical researchers can request access to clinical study data after publication of the primary manuscript in a peer-reviewed journal, regulatory activities are complete, and other criteria are met. Researchers should use the https://vivli.org/ link to request access to study data and visit https://www.mystudywindow.com/msw/datasharing for further information.

Supplementary information

Additional file 1: A podcast of the review article – Podcast.

Disclosure statement

Dr. Wechsler reports grants and personal fees from Cohero Health, Novartis, and Sanofi; personal fees from Regeneron, Genentech, GlaxoSmithKline plc (GSK), Sentien, Restorbio, Equillium, and Genzyme; grants, personal fees, and nonfinancial support from Teva and AstraZeneca; and personal fees and nonfinancial support from Boehringer Ingelheim Pharmaceuticals, Inc. outside the submitted work. Dr. Wechsler also has received consulting, advisory, or speaking honoraria from Amgen, AstraZeneca, Avalo Therapeutics, Boehringer Ingelheim Pharmaceuticals, Inc., Cerecor, Cohero Health, Cytoreason, Eli Lilly, Equillium, GSK, Incyte, Kinaset, Novartis, Om Pharma, Phylaxis, Pulmatrix, Rapt Therapeutics, Regeneron, Restorbio, Roche/Genentech, Sanofi/Genzyme, Sentien, Sound Biologics, Tetherex Pharmaceuticals, Teva, and Upstream Bio. Dr. Oppenheimer reports to have served on adjudication committees/data- and safety-monitoring boards for AstraZeneca, GSK, Novartis AG, and Sanofi.

Additional information

Funding

Medical writing support was funded by Boehringer Ingelheim Pharmaceuticals, Inc.