Tiotropium as an Add-on Treatment Option for Severe Uncontrolled Asthma in Preschool Patients

Abstract

Background

Toddlers with asthma suffer disproportionally more than school-aged children from exacerbations with emergency visits and hospital admissions despite inhaled corticosteroid (ICS) treatment. A recent trial for children ≤5 years showed tolerability of tiotropium and potential to reduce asthma-related events.

Methods

We conducted a retrospective analysis of electronic outpatient records (2017‒2019) of children <6 years treated with ICS plus long-acting β₂-agonists (LABAs) plus tiotropium as an add-on for uncontrolled severe asthma. The primary endpoint was a comparison of systemic corticosteroid (SCS) prescriptions 6 months before and after ICS/LABA/tiotropium start. Secondary endpoints included physician visits, hospitalisations and antibiotic prescriptions. We compared outcomes with children without asthma matched for age, sex, season and screening date.

Results

Compared with a mean 2.42 (95% CI: 1.75, 3.36) SCS courses per patient within 6 months prior to ICS/LABA/tiotropium, 0.74 (95% CI: 0.25, 1.08) SCS courses per patient were prescribed within 6 months after starting ICS/LABA/tiotropium (P<0.001). Physician visits dropped from 9.23 (95% CI: 7.15, 12.72) to 5.76 (95% CI: 3.10, 7.70) per patient (P<0.01). Nineteen hospitalisations were recorded 6 months before ICS/LABA/tiotropium compared with one hospitalisation after (P<0.01). A mean 1.79 antibiotic courses (95% CI: 1.22, 2.23) per patient were prescribed before ICS/LABA/tiotropium compared with 0.74 (95% CI: 0.22, 1.00) after ICS/LABA/tiotropium (P<0.001). Hospitalisation rates for patients at observation end were not statistically different from healthy controls before/after matching.

Interpretation

Our retrospective study showed that adding tiotropium to ICS/LABA is a new treatment option for patients with severe preschool asthma; however, larger confirmatory studies are needed.

Keywords:

• preschool asthma
• severe uncontrolled asthma
• tiotropium
• inhaled steroids
• long-acting β₂-agonists
• LABAs

Acknowledgements

The corresponding author confirms that he had full access to all the data in the study and had final responsibility for the decision to submit for publication. Medical writing support, furnished by Kristina Standeven, PhD of MediTechMedia, was funded by Boehringer Ingelheim. No further funding was received.

Author Contributions

All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.

Disclosure

SZ reports grants from Goethe University during the conduct of the study and reports grants and personal fees from Bene-Arzneimittel GmbH, grants from ALK Arzneimittel and personal fees from Novartis GmbH, Boehringer Ingelheim, Lofarma GmbH, IMS HEALTH GmbH & Co. OHG, GSK, Stallergen, Procter and Gamble, Allergopharma GmbH, AstraZeneca, Sanofi/Pasteur and Aimmune outside the submitted work. KB reports non-financial support from Boehringer Ingelheim for medical writing for this manuscript and reports grants, personal fees from Aimmune Therapeutics and research support from DBV technologies, and provided lectures for Bencard Allergie, HAL Allergy, Allergopharma and ALK, outside the submitted work. The authors report no other conflicts of interest in this work.