β-Blockers in COPD

Background Cardiovascular disease is a frequent comorbidity in patients with COPD. Many physicians, particularly pulmonologists, are reluctant to use β-adrenoceptor blocking agents (β-blockers) in patients with COPD, despite their proven effectiveness in preventing cardiovascular events. Methods The large (5,162 patients) phase III TONADO 1 and 2 studies assessed lung function and patient-reported outcomes in patients with moderate to very severe COPD receiving long-acting bronchodilator treatment across 1 year. This post hoc analysis characterized lung-function changes, patient-reported outcomes, and safety in the subgroup of patients receiving β-blockers in the studies. Results In total, …

P254 Once-daily Tiotropium And Olodaterol Fixed-dose Combination Via The Respimat(R) Improves Outcomes Versus Mono-components In Copd In Two 1-year Studies

Introduction Tiotropium (T), a once-daily long-acting muscarinic antagonist, is a well-established first-line maintenance treatment in chronic obstructive pulmonary disease (COPD); olodaterol (O) is a once-daily long-acting β 2 -agonist that has recently gained approval in several countries. Two Phase III replicate pivotal studies assessed the efficacy and safety of fixed-dose combinations of T and O (T+O) delivered via Respimat ® Soft Mist™ inhaler in patients with GOLD 2–4 COPD. Methods Two 52-week, double-blind, parallel-group studies randomised 5162 patients to O 5 µg, T 2.5 µg, T 5 µg, T+O 2.5/5 µg or T+O 5/5 µg. Primary efficacy end points were trough forced expiratory volume in 1 sec…

P296 Effect of tiotropium/olodaterol therapy on copd exacerbations in the tonado® studies

Rationale The lung-function efficacy, symptomatic benefits and safety of combined tiotropium (T), a long-acting muscarinic antagonist, and olodaterol (O), a long-acting β 2 -agonist, for the treatment of COPD, was established in the year-long TONADO ® studies (NCT01431274; NCT01431287). It is unknown if these benefits of T/O translate into a reduction in COPD exacerbation rate. Methods Two replicate, randomised, double-blind, parallel-group trials assessed T/O 2.5/5 μg and T/O 5/5 μg compared to the monocomponents T 5 μg, T 2.5 μg and O 5 µg (all delivered via Respimat ® inhaler) in patients with moderate to very severe COPD. Primary end points included lung function (forced expiratory volu…

Tiotropium and olodaterol fixed-dose combination versus mono-components in COPD (GOLD 2-4).

Efficacy and safety of tiotropium+olodaterol fixed-dose combination (FDC) compared with the mono-components was evaluated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in two replicate, randomised, double-blind, parallel-group, multicentre, phase III trials. Patients received tiotropium+olodaterol FDC 2.5/5 μg or 5/5 μg, tiotropium 2.5 μg or 5 μg, or olodaterol 5 μg delivered once-daily via Respimat inhaler over 52 weeks. Primary end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0–3) response, trough FEV1 response and St George's Respiratory Questionnaire (SGRQ) total score at 24 weeks. In total, 5162 patien…

Impact of grouping patients by 2017 GOLD strategy assessment criteria: a post hoc analysis of the TONADO and OTEMTO trials

Introduction: Compared to the 2014 scheme, the 2017 GOLD COPD strategy uses only symptoms and exacerbation history to group patients, and no longer gives reference to the severity of airflow limitation. Aims: This post hoc analysis of TONADO and OTEMTO data aims to determine the impact of updated assessment criteria on patient classification and characteristics within these groups. Methods: TONADO (NCT01431274/NCT01431287; N=5162) and OTEMTO (NCT01964352/NCT02006732; N=1621) Phase III trials investigated efficacy and safety of tiotropium+olodatorol fixed-dose combination in COPD patients. In this analysis, patients were classed as GOLD A–D by the 2017 or 2014 criteria. In TONADO the mMRC Dy…

The impact of grouping patients by the 2017 GOLD COPD strategy on response to therapy: post hoc results from the TONADO tiotropium+olodaterol trials

Introduction: In the 2017 GOLD COPD strategy the classification of patients by assessment of symptoms and history of exacerbation is used to guide treatment choices. The previous strategy also included lung function. Aims and objectives: To investigate the effect of the 2017 classification on an analysis of the efficacy of tiotropium+olodaterol (T+O) in GOLD stage A/B patients with COPD. Methods: Patients from the Phase III, replicate 52-week TONADO studies (NCT01431274, NCT01431287), who received T+O or the mono-components, were classed as GOLD A/B or C/D by the 2017 strategy (using exacerbation history) or 2014 strategy (using lung function and exacerbation history). Since mMRC Dyspnoea S…

<p>Efficacy and safety of tiotropium + olodaterol maintenance treatment in patients with COPD in the TONADO<sup>®</sup> and OTEMTO<sup>®</sup> studies: a subgroup analysis by age</p>

BACKGROUND Increasing age is associated with poor prognosis in patients with COPD. OBJECTIVE This analysis from the replicate Phase III OTEMTO® and TONADO® studies examined the efficacy and safety of tiotropium, a long-acting anticholinergic, combined with olodaterol, a long-acting β2-agonist, compared to monotherapies and placebo in patients with COPD aged 40 years to <65 years, 65 years to <75 years, 75 years to <85 years, and ≥85 years. METHODS In these double-blind, parallel-group, active-controlled, multicenter, randomized studies, patients received tiotropium + olodaterol 2.5/5 μg or 5/5 μg, tiotropium 5 μg or 2.5 μg (TONADO only), olodaterol 5 μg (TONADO only), or placebo (OTEMTO onl…

S61 Analysis of the efficacy and safety of the combination of tiotropium + olodaterol in patients with COPD by previous usage of inhaled corticosteroids: Abstract S61 Table 1

Rationale Tiotropium (T), a long-acting muscarinic antagonist, and olodaterol (O), a long-acting β 2 -agonist (both administered once daily), have been studied as a once-daily combination. Two Phase III studies have demonstrated that T+O significantly improved lung function and symptoms over T and O monotherapy treatments in patients with moderate to very severe chronic obstructive pulmonary disease (COPD). 1 During these studies, patients were allowed to continue existing treatment with inhaled corticosteroids (ICS); this analysis was conducted to determine the effects of study treatment in patients receiving or not receiving ICS as reported at baseline. Methods A total of 5162 patients we…

Determining SGRQ and TDI responder rates across the duration of clinical trials: Results from tiotropium + olodaterol in COPD

Introduction: Patient-reported outcomes (PROs) are important in COPD for understanding patients’ symptoms and experience of the disease. Responder rates at specific timepoints are frequently used to analyse clinically important improvements in PROs. Alternatively, responders can be defined using average PRO improvement vs. baseline over the whole study period or the last two timepoints, as recently discussed by the FDA. Aims and objectives: To compare three techniques for determining responder rates of St. George’s Respiratory Questionnaire (SGRQ) and transition dyspnoea index (TDI). Methods: Two double-blind, replicate, Phase III, 52-week TONADO trials compared tiotropium + olodaterol (T+O…

Benefits of Tiotropium + Olodaterol Over Tiotropium at Delaying Clinically Significant Events in Patients with COPD Classified as GOLD B

P256 Safety Of Once-daily Tiotropium And Olodaterol Fixed-dose Combination Via The Respimat In Chronic Obstructive Pulmonary Disease In Two 1-year Studies

Introduction The fixed-dose combination (FDC) of tiotropium (T), a once-daily long-acting muscarinic antagonist, and olodaterol (O), a once-daily long-acting β 2 -agonist, is currently being evaluated in chronic obstructive pulmonary disease (COPD). Two 52-week, Phase III replicate pivotal studies were conducted to assess the efficacy and safety of FDCs of T and O (T+O) delivered via Respimat® Soft Mist™ inhaler in patients (pts) with GOLD Stage 2–4 COPD. Pooled safety data from the two studies are presented here. Methods These were double-blind, randomised, parallel-group studies with 5 arms: O 5 µg, T 2.5 µg, T 5 µg, T+O 2.5/5 µg, T+O 5/5 µg. Key inclusion criteria were: age ≥40 years, di…

P121 Characteristics of COPD patients with and without maintenance treatment at baseline, by GOLD stage: TONADO: Abstract P121 Table 1

Rationale The efficacy and safety of the once-daily combination of tiotropium (T), a long-acting muscarinic antagonist (LAMA), and olodaterol (O), a long-acting β 2 -agonist (LABA), for the treatment of chronic obstructive pulmonary disease (COPD) has been established. We investigated whether there was a difference in the characteristics of COPD patients with and without baseline maintenance treatment. Methods Two replicate, randomised, 52-week, double-blind, parallel-group, Phase III trials (NCT01431274; NCT01431287; n = 5162) assessed the efficacy and safety of once-daily treatment with T+O (2.5/5 μg; 5/5 μg; Respimat® inhaler) compared to the individual components. Baseline characteristi…

P125 Tiotropium plus olodaterol combination therapy provides lung-function benefits when compared to tiotropium alone, irrespective of prior treatment with a long-acting bronchodilator: post hoc analyses of two 1-year studies: Abstract P125 Table 1

Rationale Tiotropium plus olodaterol (T+O) is a novel once-daily combination of the long-acting muscarinic antagonist (LAMA) tiotropium (T) and the recently approved long-acting β 2 -agonist (LABA) olodaterol, for use as maintenance treatment in chronic obstructive pulmonary disease (COPD). These post hoc analyses of data from the two pivotal 1-year TONADO studies determined whether treatment with a long-acting bronchodilator (LABD) prior to randomisation affected the lung-function benefits of T+O 5/5 µg (via Respimat®) compared to T 5 µg (via Respimat®). Methods In the studies, 2124 patients had not received prior LABD treatment (T+O n = 426; T n = 454) and 3038 patients had (T+O n = 603, …

P123 Inhaled corticosteroid plus long-acting β2-agonist therapy is overused in the treatment of patients with chronic obstructive pulmonary disease: post hoc analyses of two 1-year studies: Abstract P123 Table 1

Rationale Inhaled corticosteroid (ICS) plus long-acting β2-agonist (LABA) therapy is indicated for different patient groups with chronic obstructive pulmonary disease (COPD) in the USA and Europe. In the previous version of the Global initiative for chronic Obstructive Lung Disease (GOLD) recommendations, the use of ICS plus LABA therapy was restricted to patients with severe and very severe lung-function impairment and frequent exacerbations, with overtreatment in milder patient populations well documented. The current GOLD document recommends the use of ICS plus LABA maintenance therapy for patients in categories C and D. Methods We present post hoc analyses from the two pivotal 1-year TO…

P294 Benefits of tiotropium/olodaterol over tiotropium at delaying clinically significant events in patients with copd classified as gold B

Rationale The once-daily combination of tiotropium (T), a long-acting muscarinic antagonist, and olodaterol (O), a long-acting β 2 -agonist, has demonstrated efficacy and safety in COPD. Two large clinical studies (TONADO ® 1 + 2) have also demonstrated the benefits of T/O compared to the monocomponents in patients with moderate to very severe COPD. This post hoc analysis investigated whether T/O is more effective than T at delaying clinically significant events in patients with GOLD stage B COPD. Methods A total of 5162 patients were randomised to O 5 µg, T 2.5 µg, T 5 µg, T/O 2.5/5 µg or T/O 5/5 µg (delivered via Respimat ® inhaler) in two 52-week, parallel-group, double-blind studies (NC…

Tiotropium + olodaterol in patients with moderate to severe COPD with chronic bronchitis and/or emphysema

Introduction: Chronic bronchitis and emphysema are two COPD phenotypes that can affect pharmacologic treatment decisions. Aims: Tiotropium (T) + olodaterol (O) was established for COPD treatment in two large Phase III trials. This post hoc analysis assessed the effect of T+O on lung function, symptoms and health-related quality of life (QoL) in patients (pts) with investigator-defined bronchitis and/or emphysema. Methods: TONADO ® 1+2 were replicate, randomised, double-blind, parallel-group trials. Pts with GOLD 2–4 COPD were randomised to once-daily T+O 2.5/5 or 5/5 µg, T 2.5 or 5 µg, or O 5 µg via Respimat ® inhaler. 1 End points included forced expiratory volume in 1 second (FEV 1 ) area…