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Open Access Adding tiotropium or long-acting β2-agonists to inhaled corticosteroids: Asthma-related exacerbation risk and healthcare resource utilization

This article is Open Access under the terms of the Creative Commons CC BY-NC-ND licence.


Based on current clinical guidelines, long-acting β2-agonists (LABA) are frequently prescribed before long-acting muscarinic antagonists (LAMA) as an add-on to inhaled corticosteroids (ICS) in uncontrolled asthma. However, there is insufficient real-world evidence that supports this therapeutic approach.


The objective was to compare asthma exacerbations and healthcare resource utilization in patients with asthma using the LAMA tiotropium bromide (Tio) or a LABA as an add-on to ICS (ICS + Tio or ICS/LABA) in a real-world setting.


This retrospective, observational study included patients aged ≥12 years with asthma diagnoses identified in a U.S. longitudinal claims database (October 2015 to August 2020). The ICS + Tio and ICS/LABA cohorts were 1:2 propensity score matched for baseline variables. Outcomes were compared in the postmatched cohorts, and the risk of exacerbation was evaluated by using Kaplan-Meier curves.


After propensity score matching, there were 633 and 1266 patients in the ICS + Tio and ICS/LABA cohorts, respectively. The proportion of patients who experienced a severe or a moderate-or-severe exacerbation during follow-up was similar between the ICS + Tio versus ICS/LABA cohorts (4% versus 3%, p = 0.472, and 50% versus 45%, p = 0.050, respectively). The mean time to first severe (ICS + Tio 43.8 days versus ICS/LABA 49.4 days, p = 0.758) and moderate-or-severe exacerbation (ICS + Tio 65.8 days versus ICS/LABA 58.9 days, p = 0.474) was not statistically different between cohorts. The treatments had no effect on the risk of severe exacerbation, although it was 36% lower in ICS + Tio users than in ICS/LABA users (hazard ratio 0.64 [95% confidence interval, 0.22‐1.84]). All-cause and asthma-related average monthly healthcare resource utilization were comparable between the treatments for hospitalizations and emergency department visits but were significantly greater in the ICS + Tio cohort than in the ICS/LABA cohort for asthma-related outpatient visits (p < 0.0001).


This study provides real-world evidence that ICS + Tio may be a valid alternative when ICS/LABA cannot be used as first-line treatment for asthma maintenance therapy.

Keywords: HCRU; ICS; asthma; asthma control; bronchodilator; inhaled anticholinergic agent; long-acting beta2-agonist; long-acting muscarinic antagonist; observational study:; tiotropium bromide

Document Type: Research Article

Affiliations: 1: From the Section of Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston, Texas; 2: Allergy and Asthma Center and Alpert Medical School of Brown University, East Providence, Rhode Island; 3: Clinical Development and Medical Affairs, Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut; 4: eMAX Health, White Plains, New York; 5: eMAX Health, Delray Beach, Florida; and 6: Division of Allergy and Immunology, Advocate Health Care, Chicago, Illinois

Publication date: November 15, 2023

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  • Allergy and Asthma Proceedings is a peer reviewed publication dedicated to distributing timely scientific research regarding advancements in the knowledge and practice of allergy, asthma and immunology. Its primary readership consists of allergists and pulmonologists.

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    The journal is indexed in Thomson Reuters Web of Science and Science Citation Index Expanded, plus the National Library of Medicine's PubMed service.
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