Tiotropium as a 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 add-on for uncontrolled severe asthma. Primary endpoint was 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 and screening date. Findings: 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 in nine patients 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: Tiotropium is a potential add-on for preschool patients with uncontrolled severe asthma; however, larger confirmatory studies are needed. Funding Statement: Medical writing assistance, provided by Kristina Standeven PhD, is funded by Boehringer Ingelheim. Declaration of Interests: SZ reports grants and personal fees from bene-Arzneimittel GmbH, grants from ALK Arzneimittel, 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. Ethics Approval Statement: Ethics approval was obtained from the ethics committee of the J.W. Goethe University in Frankfurt (application number 149/19).