Once-daily tiotropium respimat® add-on therapy has a safety profile comparable with placebo in children and adolescents

RATIONALE: Once-daily tiotropium Respimat® (tioR) as add-on to maintenance therapy is efficacious with a predictable safety profile in adults with symptomatic asthma. This pooled analysis from trials in adolescents (RubaTinA-asthma®: 12-17 years) and children (CanoTinAasthma ®: 6-11 years) with moderate persistent asthma assessed the safety of tioR versus placebo Respimat®(pboR). METHODS: Two 48-week, Phase III, randomized, double-blind, placebo- controlled, parallel-group trials. Patients received once-daily tioR 5 μg, tioR 2.5 μg, or pboR, each delivered as two puffs, as add-on to ICS (200-800 μg [RubaTinA-asthma®] or 200-400 μg [CanoTinA-asthma®] budesonide/equivalent) ± LTRA. Patients had symptomatic asthma despite stable maintenance therapy with ICS ± additional controllers for ≥4 weeks before screening. LABAs were not permitted during either trial. AEs (preferred term) were recorded throughout the trials. RESULTS: 801 patients were randomized, 798 treated. Baseline demographics and disease characteristics were similar across treatment groups; mean exposure to tioR was 330.6 days. AEs were reported by 61.7%, 63.5%, and 63.6% of patients in the tioR 5 μg, tioR 2.5 μg, and pboR groups, respectively. Proportion of patients with drug-related AEs was low (1.5%, 0.4%, and 1.1%, respectively). There were no AEs leading to discontinuation in the tioR groups (two in the pboR group). Serious AEs occurred in 1.5%, 1.9%, and 3.0%, respectively. No deaths occurred. The most commonly reported AEs were asthma (worsening), decreased PEF, and nasopharyngitis. CONCLUSIONS: The safety and tolerability of once-daily tiotropium Respimat® as add-on to maintenance therapy are similar to placebo in patients aged 6-17 years with moderate asthma, comparing well with findings in adults.