Tiotropium + olodaterol shows clinically meaningful improvements in quality of life

• Published in: Respiratory medicine Vol. 109; no. 10; pp. 1312 - 1319
• Main Authors: Singh, Dave, Ferguson, Gary T, Bolitschek, Josef, Grönke, Lars, Hallmann, Christoph, Bennett, Nathan, Abrahams, Roger, Schmidt, Olaf, Bjermer, Leif
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2015; Elsevier Limited
• Subjects: Administration, Inhalation; Adrenergic beta-2 Receptor Agonists - administration & dosage; Aged; Asthma; Benzoxazines - administration & dosage; Chronic obstructive pulmonary disease; Clinical Medicine; Confidence intervals; COPD; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Forced Expiratory Volume - drug effects; Heart attacks; Humans; Hypothesis testing; Klinisk medicin; Long-acting bronchodilator; Lung diseases; Lungmedicin och allergi; Male; Medical and Health Sciences; Medicin och hälsovetenskap; Middle Aged; Muscarinic Antagonists - administration & dosage; Nebulizers and Vaporizers; Olodaterol; Pulmonary Disease, Chronic Obstructive - drug therapy; Pulmonary Disease, Chronic Obstructive - physiopathology; Pulmonary/Respiratory; Quality of Life; Questionnaires; Respiratory diseases; Respiratory Function Tests - methods; Respiratory Medicine and Allergy; Studies; Tiotropium; Tiotropium Bromide - administration & dosage; GOLD; forced vital capacity; Global initiative for chronic Obstructive Lung Disease; Transition Dyspnoea Index; MCID; LABA; TDI; AUC 0–3; long-acting muscarinic antagonist; minimum clinically important difference; St George's Respiratory Questionnaire; Long-acting bronchodilator; AE; area under the curve from 0 to 3 h; forced expiratory volume in 1 s; adverse event; LAMA; Quality of life; Tiotropium; FVC; FEV 1; SGRQ; long-acting β 2-agonist; Olodaterol; COPD; chronic obstructive pulmonary disease; AUC0–3; FEV1
• ISSN: 0954-6111; 1532-3064; 1532-3064
• DOI: 10.1016/j.rmed.2015.08.002

Abstract Background Tiotropium + olodaterol improves lung function and symptoms compared to monotherapies in chronic obstructive pulmonary disease (COPD). The OTEMTO 1 and 2 studies investigated the effects of tiotropium + olodaterol on lung function and health-related quality of life compared to placebo in patients with moderate to severe COPD. Methods In these two replicate, double-blind, parallel-group, placebo-controlled trials, patients were randomised to receive tiotropium + olodaterol 5/5 μg, 2.5/5 μg, tiotropium 5 μg or placebo for 12 weeks, via the Respimat® inhaler. Primary end points were St George's Respiratory Questionnaire (SGRQ) total score, forced expiratory volume in 1 s (FEV1 ) area under the curve from 0 to 3 h (AUC0–3 ) response and trough FEV1 response. Results In OTEMTO 1 and 2, tiotropium + olodaterol 5/5 μg improved SGRQ total score by 4.89 (95% confidence interval [CI] −6.90, −2.88) and 4.56 (95% CI −6.50, −2.63) units versus placebo (both p  < 0.0001), and 2.49 (95% CI −4.47, −0.51; p <  0.05) and 1.72 (95% CI −3.63, 0.19) units versus tiotropium 5 μg. Tiotropium + olodaterol 2.5/5 μg significantly improved SGRQ score compared to placebo. Both doses significantly improved FEV1 AUC0–3 response compared to placebo and tiotropium 5 μg. Tiotropium + olodaterol 5/5 and 2.5/5 μg also significantly improved trough FEV1 response compared to placebo (both studies) and separated from tiotropium 5 μg in OTEMTO 2. Adverse-event incidence was similar between treatment groups. Conclusion Tiotropium + olodaterol improved lung function and quality of life compared to placebo and tiotropium 5 μg. Trial registration ClinicalTrials.gov: NCT01964352 and NCT02006732.