Tiotropium in Children and Adolescents With Asthma

To perform a systematic review of published data to evaluate the efficacy and safety of tiotropium, a long-acting muscarinic antagonist (LAMA), as an add-on therapy in children and adolescents with uncontrolled asthma currently on inhaled corticosteroid (ICS) maintenance therapy with or without other controller medications.

The systematic review included randomized controlled trials (RCTs) of patients aged 1 to 17 years treated with once daily tiotropium (5µg, 2.5µg, or 1.25 µg administered via slow/soft mist inhaler Respimat) as add on therapy to ICS for 12 or 48 weeks compared with placebo.

The study included a search of PubMed through June 12, 2018, for randomized controlled trials (RCTs) meeting study population criteria with outcomes being evaluation of lung function parameters and adverse events. Articles that met inclusion criteria were reviewed and analyzed with discrepancies about inclusion resolved by consensus.

After review and analysis, 7 RCTs were included in this systematic review consisting of 1902 children and adolescents (3 trials with ages 12 to 17, n = 895; 3 trials with ages 6 to 11, n = 905; and 1 trial with ages 1 to 5, n = 102). All 6 RCTs of ages 6–17 demonstrated that once daily tiotropium as add-on maintenance therapy improved lung function parameters when compared with placebo. The one trial with ages 1–5 showed that although change in mean daytime asthma score did not significantly differ across treatment groups, more children in the placebo group versus tiotropium group had asthma exacerbations reported as adverse events. Overall, tiotropium was well tolerated with the most commonly reported adverse events in the treatment group being asthma exacerbations, decreased peak expiratory flow rate, nasopharyngitis, viral respiratory tract infections, and respiratory tract infections.

This systematic review found that add-on tiotropium maintenance therapy is safe and efficacious for children and adolescents with moderate to severe asthma, supporting the expanded indication by the U.S. Food and Drug Administration (approved dose = 2.5 µg), European Medicine Agency (approved dose = 5 µg), and recommendations from Global Initiative for Asthma (GINA) for children 6 years or older.

This systematic review parallels findings in adult studies about the safety and efficacy of the long acting muscarinic antagonist tiotropium in treating asthma. There continues to be lacking evidence in safety and efficacy in children less than 6 years of age given only 1 RCT has been performed and in the long-term safety profile of tiotropium in children of all ages. However, for children aged 6–11 and adolescents 12–17 with uncontrolled asthma despite ICS with or without additional controller therapies, tiotropium may be considered.