ATLANTA, GA—In 6 to 17 year old patients with moderate persistent asthma, superior efficacy was demonstrated with adding once-daily tiotropium Respimat (tioR) to maintenance therapy of inhaled corticosteroid (ICS) ± additional controllers, according to findings of two 48-week, Phase 3 studies presented at the 2017 AAAAI Annual Meeting.
Two randomized, double-blind, placebo-controlled, parallel-group studies sought to determine the efficacy of tioR in both adolescent patients (ages 12–17 years) as well as in children (ages 6–11 years). Efficacy data obtained from the studies were then pooled and analyzed. Patients included in each study had symptomatic asthma despite stable maintenance therapy of ICS ± leukotriene receptor antagonist (LTRA).
During the treatment period, patients received two puffs of tioR 5mcg, tioR 2.5mcg, or placebo Respimat (pboR) once daily. Adolescent patients received 200–800mcg RubaTinA-asthma and children received 200–400mcg CanoTinA-asthma. Primary endpoints included the change from baseline in peak FEV1(0-3h) response at weeks 24 and 48. Secondary endpoints evaluated were trough FEV1 response, trough forced expiratory flow (FEF25–75%), ACQ/ACQ-IA responder rates, and asthma exacerbations.
The pooled full analysis set included 798 patients. Significant improvement in lung function was seen in both tioR 2.5mcg and 5mcg treatment groups. At week 24, there was a >150mL difference in peak FEV1(0-3h) response compared to placebo (P<0.0001). The adjusted mean differences vs. placebo were 168mL for tioR 5mcg (95% CI: 109, 228) and 159mL for tioR 2.5mcg (95% CI: 98, 219) at week 24; these benefits were sustained at week 48 for both tioR doses.
Additionally, there was a statistically significant >100mL difference in trough FEV1 response for both tioR doses vs. placebo (P<0.01) at week 24. The adjusted mean differences vs. placebo were 118mL for tioR 5mcg (95% CI: 58, 182; P=0.0004) and 105mL for tioR 2.5mcg (95% CI: 39, 170; P=0.0017) at week 24; these benefits were sustained at week 48 for both tioR doses.
Trough FEF25–75% was also deemed statistically significant for both tioR doses at week 24 with responses sustained at week 48 vs. placebo. Moreover, improvements in FEV1/FVC ratio vs. placebo at weeks 24 and 48 for both tioR doses were also statistically significant. ACQ responder rates were as follows: 81.0% for tioR 5mcg (P=0.0048), 78.1% for tioR 2.5mcg (P=0.0506) vs. 70.3% for placebo.
In examining asthma exacerbations, the hazard ratio (HR) calculated at week 48 for tioR 5mcg vs. placebo was 0.81 (95% CI: 0.61, 1.07; P=0.1370) and for tioR 2.5mcg vs. placebo was 0.97 (95% CI: 0.73, 1.27; P=0.8066).
Study author Christian Vogelberg of University Hospital Carl Gustav Carus and Technical University of Dresden, in Dresden, Germany, added, “The safety and tolerability of once-daily tioR 2.5mcg and 5mcg were comparable with those of placebo.” Findings from the analysis support that once-daily tiotropium Respimat add-on to ICS ± LTRA is efficacious in pediatric patients with symptomatic persistent asthma, “mirroring findings in adults.”