Inhaled anticholinergic bronchodilator tiotropium as an add-on therapy has the potential to reduce exacerbations.
Preschoolers with persistent asthmatic symptoms despite being on medication might be able to tolerate additional treatment with tiotropium, a drug routinely used for chronic obstructive pulmonary disease (COPD) and other respiratory diseases in adults and older children, according to a new study.
Tiotropium is an inhaled anticholinergic bronchodilator approved by the US Food and Drug Administration (FDA) for long-term use in asthma and COPD patients. Typically, tiotropium is reserved for patients who have uncontrolled symptoms despite combination therapy with inhaled glucocorticoids and long-acting beta-adrenoceptor agonists (LABA), study co-author Elianne Vrijlandt, MD, PhD, professor at the University of Groningen, the Netherlands told MD Magazine.
“Recent studies in children and adolescents between 6 and 18 show that tiotropium add-on therapy has a safety and tolerability profile comparable with placebo, irrespective of asthma severity,” Vrijlandt said. “Our small study is the first to assess the safety and efficacy of tiotropium in children aged 1-5 years with persistent asthma symptoms.”
The 12-week trial was conducted at 32 hospitals, clinics and research units in 11 countries throughout Asia, Europe and North America. To be eligible for the study, children had to be between ages 1 and 5, have at least a six-month history of sustained asthmatic symptoms, and a need for inhaled corticosteroids.
Between July 26, 2012 and December 4, 2014, 101 subjects were randomly assigned to 3 treatment groups: 36 received 2.5 mg tiotropium; 32 received 5 mg tiotropium; and 34 received placebo as an add-on to inhaled corticosteroids with or without additional controller medication. Tiotropium was administered through the Respimat inhaler once daily. Safety outcomes were measured as the change in weekly mean combined daytime asthma symptom score from baseline to week 12.
There was not a significant difference in adjusted weekly mean combined daytime asthma symptoms scores between the three groups. Adjusted mean difference between the tiotropium 2.5 mg group and the placebo group was -0.080 (95 CI; -0.312 to 0.152) and the difference between the tiotropium 5 mg group and the placebo group was -0.048 (-0.292 to 0.195). The placebo group reported more adverse events (29%) than in the tiotropium groups (14% of 2.5 mg group; 6% of the 5 mg group).
There were 3 serious adverse events in the placebo group, though none of them resulted in a discontinuation of treatment or fatalities.
“This is consistent with previous findings in older populations, including children between 6-12 years,” Vrijlandt said. “Although the mean daytime asthma symptom scores were not significantly different between groups, tiotropium showed the potential to reduce asthma exacerbation risk compared with placebo.”
Currently, tiotropium is not widely used among young children for asthma treatment. This study introduces much needed preliminary evidence to support the use of this medication in young children.
“The findings are limited by the small sample size and descriptive statistical analysis,” Vrijlandt said. “More well powered trials are needed. But the implication is that tiotropium might be considered to be used as a step-up medication, after beta-two agonists and inhaled corticosteroids.”
The study, "Safety and efficacy of tiotropium in children aged 1—5 years with persistent asthmatic symptoms: a randomised, double-blind, placebo-controlled trial," was published online in The Lancet Respiratory Medicine.
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