P230 Once-daily Tiotropium Respimat(R) Improves Lung Function In Patients With Severe Symptomatic Asthma Independent Of Leukotriene Modifier Use

Abstract

RATIONALE: Once-daily tiotropium Respimat®, a long-acting anticholinergic bronchodilator, has been shown in a Phase III program to improve lung function and reduce severe exacerbation risk in severe asthma patients who remain symptomatic despite using ICS+LABA. Use of pre-trial leukotriene receptor antagonists (LTRAs) was not restricted; we analyzed whether pre-screening LTRA use affected tiotropium Respimat® efficacy. METHODS: In two Phase III, replicate, randomized, double-blind, placebo-controlled, parallel-group trials (NCT00772538/NCT00776984), symptomatic patients received high-dose ICS+LABA and once-daily tiotropium Respimat® 5 mg or placebo. LTRAs were permitted during run-in and treatment. Co-primary endpoints were peak and trough FEV1 response (difference from baseline) at 24 weeks. Subgroups were defined by pre-screening LTRA use: “Yes”/“No”. RESULTS: Of 912 randomized patients 205 reported pre-screening LTRA use 200 reported use during the treatment period, and 187 had efficacy data at week 24. Baseline characteristics were comparable between groups. Mean BMI in LTRA “Yes”/“No” groups: 27.8 kg/m2 and 28.3 kg/m2, respectively. Mean % predicted FEV1 at baseline: 56% in both groups. Lung function responses improved independent of LTRA use: peak FEV1 was 99±50 mL (p=0.049) in the LTRA “Yes” group, and 113±28 mL (p<0.001) in the LTRA “No” group (peak FEV1 improvements independent of concomitant LTRA use [interaction p-value=0.6742]). Trough FEV1 (difference from placebo) was 90±46 mL (p=0.052) in the LTRA “Yes” group and 93±25 mL (p<0.001) in the LTRA “No” group (trough FEV1 improvements independent of concomitant LTRA use [interaction p-value=0.5218]). CONCLUSIONS: Once-daily tiotropium Respimat® added to ICS+LABA improves lung function in patients with severe symptomatic asthma, independent of initial LTRA use.