Tiotropium Plus Olodaterol Provides Improvements In Sgrq And Dyspnea Compared With Monotherapy Components In Patients With Copd: Results From Four Randomized, Double-Blind Studies

SESSION TITLE: COPD Posters V SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, October 28, 2015 at 01:30 PM - 02:30 PM PURPOSE: To evaluate the effects of tiotropium (T) + olodaterol (O) on health status (St. George's Respiratory Questionnaire [SGRQ]) and dyspnea (Transition Dyspnea Index [TDI]) in patients with chronic obstructive pulmonary disease (COPD). METHODS: Two sets of replicate, double-blind, parallel-group studies (52-week TONADO 1 and 2 [NCT01431274; NCT01431287] and 12-week OTEMTO 1 and 2 [NCT01964352; NCT02006732]) compared the efficacy of T+O 5/5 μg and T+O 2.5/5 μg with T 5 or 2.5 μg, O 5 μg, and placebo (OTEMTO only), all delivered once daily (QD) via Respimat®. This analysis presents the effects on SGRQ total score and TDI focal score, and responder analyses, focusing on T+O 5/5 μg. RESULTS: 5162 patients were treated in TONADO and 1621 in OTEMTO. Common mean for SGRQ was 43.51 in TONADO and 42.57 in OTEMTO, while baseline dyspnea index was 6.54 for both study sets. SGRQ total scores were significantly lower with T+O 5/5 μg versus T 5 μg and O 5 μg in TONADO (36.67 versus 37.91 and 38.37; both p<0.05) and with T+O 5/5 μg versus T 5 μg and placebo in OTEMTO (37.60 versus 39.69 and 42.27; both p<0.005). Percentage of responders (decrease from baseline ≥4.0 units) was higher with T+O 5/5 μg versus T 5 μg and O 5 μg in TONADO (57.5% versus 48.7% and 44.8%, respectively) and with T+O 5/5 μg versus T 5 μg or placebo in OTEMTO (52.4% versus 41.4% and 31.9%). Odds ratios (ORs) were significant (p<0.005) across both trial sets for all comparisons of T+O 5/5 μg versus monotherapy/placebo. TDI focal score significantly improved with T+O 5/5 μg versus T 5 μg or O 5 μg after 24 weeks (TONADO; adjusted mean 1.98 versus 1.63 and 1.56, respectively; both p<0.01), and versus T 5 μg or placebo after 12 weeks (OTEMTO; 1.73 versus 1.14 and 0.11, respectively; both p<0.005). A higher percentage of TDI responders (score ≥1.0 unit) was seen with T+O 5/5 μg (54.9%) versus T 5 μg (50.6%; OR 1.19; p=0.0546) and O 5 μg in TONADO (48.2%; OR 1.31; p<0.01) and for T+O 5/5 μg versus T 5 μg and placebo in OTEMTO (53.9% versus 41.0% and 26.2%; ORs 1.68 and 3.30, respectively; both p<0.001). CONCLUSIONS: T+O 5/5 μg QD provided greater improvements in both SGRQ and dyspnea than those achieved with either monotherapy in patients with COPD. CLINICAL IMPLICATIONS: Treatment with T+O provides additional benefits in effects beyond lung function compared to monotherapy with either component in COPD. Funding: Boehringer Ingelheim. Editorial assistance: Complete HealthVizion. DISCLOSURE: Gary Ferguson: Grant monies (from industry related sources): Boehringer Ingelheim, Novartis, Pearl Therapeutics, AstraZeneca, Sunovian, Forest/Almirall, Consultant fee, speaker bureau, advisory committee, etc.: Boehringer Ingelheim, Novartis, Sunovian, AstraZeneca, Pearl Therapeutics, Fiduciary position (of any organization, association, society, etc, other than ACCP: GlaxoSmithKline Emmanuelle Clerisme-Beaty: Employee: Boehringer Ingelheim Lars Groenke: Employee: Boehringer Ingelheim Florian Voss: Employee: Boehringer Ingelheim Lawrence Korducki: Employee: Boehringer Ingelheim Nathan Bennett: Employee: Boehringer Ingelheim Roger Abrahams: Grant monies (from industry related sources): Boehringer Ingelheim, GSK, AstraZeneca Tiotripium+Olodaterol 5/5ug has been submitted to European and US regulatory authorities; currently awaiting approval decision