Olodaterol for the treatment of chronic obstructive pulmonary disease: a narrative review

ABSTRACT

Introduction: Inhaled bronchodilators are the key-stone of chronic obstructive pulmonary disease (COPD) management. Olodaterol 5 µg, a long-acting β2-adrenoceptor agonist (LABA) is one such bronchodilator indicated as a once-daily maintenance therapy.

Areas covered: This article reviews the several trials that have assessed olodaterol as a COPD therapy. It covers safety and tolerability data and provides the reader with an expert opinion on its use as a treatment for COPD.

Expert opinion: Olodaterol improves lung function for 24 h and reduces rescue medication use. It may also improve dyspnea, exercise tolerance, and health-related quality of life. It is well tolerated with an acceptable cardiovascular and respiratory adverse event profile. There is some evidence that olodaterol, as well as other LABAs, can reduce exacerbation frequency, but not FEV1 decline and death.

LABAs alone are indicated in group A/B COPD subjects. Olodaterol and indacaterol are administered once-daily and may offer an adherence advantage over other LABAs with more frequent dosing schedules. Co-administration of an olodaterol/tiotropium fixed dose combination in a single inhaler device is recommended as step-up in group A/B COPD subjects not sufficiently treated by olodaterol alone or as initial therapy in those with severe exertional dyspnea.     

噻托溴铵奥达特罗吸入喷雾剂治疗慢性阻塞性肺疾病的临床效果

目的 探讨噻托溴铵奥达特罗吸入喷雾剂治疗慢性阻塞性肺疾病(COPD)的临床效果.方法 选取2019年10月至2020年9月本院58例COPD患者作为研究对象,根据随机数字表法将其分为对照组和观察组,各29例.在常规治疗的基础上,对照组给予噻托溴铵治疗,观察组给予噻托溴铵奥达特罗吸入喷雾剂治疗.比较两组的血清炎症因子水平...     

Pharmacological characterization of the interaction between tiotropium and olodaterol administered at 5:5 concentration-ratio in equine bronchi

Equine airways represent a suitable ex vivo model to study the functional impact of pharmacological treatments on human chronic obstructive pulmonary disorders, such as asthma and chronic obstructive pulmonary disease (COPD). We aimed to characterize the pharmacological interaction between the long-acting muscarinic antagonist (LAMA) tiotropium and the long-acting β₂-agonist (LABA) olodaterol in equine airways. The effect of tiotropium and olodaterol, administered alone and in combination at the ratio of concentrations reproducing ex vivo the concentration-ratio delivered by the currently available fixed-dose combination (FDC) (5:5), was investigated on the cholinergic contractile tone induced by the parasympathetic activation of equine isolated airways. The drug interaction was analysed by using the Bliss Independence and Unified Theory models. Both tiotropium and olodaterol induced a sub-maximal concentration-dependent inhibition of bronchial contractility (E_max: tiotropium 83.6 ± 14.8%, olodaterol 76.9 ± 17.9%; pEC₅₀: tiotropium 8.2 ± 0.5; olodaterol 8.3 ± 0.6). When administered at 5:5 concentration-ratio, tiotropium plus olodaterol completely inhibited the bronchial contractility (E_max 102.7 ± 8.4%; pEC₅₀ 9.0 ± 0.7). Strong synergistic interaction was detected for tiotropium/olodaterol combination (combination index 0.011). When administered at low concentrations, the drug mixture elicited up to 94.6 ± 9.5% effect that was 36.0 ± 8.1% greater than the expected additive effect. The results of this study demonstrate that the co-administration of tiotropium plus olodaterol at 5:5 concentration-ratio leads to synergistic inhibition of equine bronchial contractility when compared with either drug administered alone. These findings suggest that the currently available LABA/LABA FDC may be effective in delivering tiotropium/olodaterol combination at equipotency concentrations of each monocomponent into the lung and, thus, inducing synergistic effect in the airways.     

Olodaterol for the treatment of asthma

Introduction: Long-acting β-agonist (LABA)/inhaled corticosteroid (ICS) combinations are still the mainstay of asthma therapy but there is a pressing need to increase adherence to the prescribed treatment achievable in general by reducing the dose frequency. Consequently, there is considerable interest within the pharmaceutical industry in the discovery of once-daily β2-agonists (ultra-LABAs) to be used as a part of a combination therapy for treating asthma.

Areas covered: The authors review the preclinical and clinical development of olodaterol, a new ultra-LABA characterized by an improved selectivity for β2-adrenoceptors and a rather high intrinsic efficacy profile, in asthma. The clinical results were generated by 4 Phase 2 trials, which have enrolled 731 asthmatic patients.

Expert opinion: The available results indicate that olodaterol is able to induce an effective 24-h bronchodilation and is safe. However, one cannot formulate a solid conclusion on the best dose and/or dose frequency to be used in asthma because trials were not powered to assess the differences between doses and dose frequencies. Apparently, there is no Phase 3 trial planned or ongoing for olodaterol monotherapy in patients with asthma and also no attempt to combine olodaterol with an ICS, which is surprising.     

Adding a Second Bronchodilator in COPD: A Meta-Analysis on the Risk of Specific Cardiovascular Serious Adverse Events of Tiotropium/Olodaterol Fixed-Dose Combination

Abstract

Dual bronchodilation therapy represents the cornerstone for the treatment of COPD. A large retrospective study reports that adding a second long-acting bronchodilator in patients with COPD significantly increases the risk of heart failure. Nevertheless, retrospective studies are characterized by limitations including misdiagnosis and inaccuracy of recordkeeping. This study aimed to ascertain whether tiotropium/olodaterol (T/O) 5/5?μg fixed-dose combination (FDC) may modulate the risk of main cardiovascular outcomes in COPD patients enrolled in randomized controlled trials (RCTs). A meta-analysis (CRD42017070100) was performed by selecting RCTs reporting raw data from the ClinicalTrials.gov database concerning the impact of T/O 5/5?µg FDC vs. monocomponents on the occurrence of specific cardiovascular serious adverse events: arrhythmia, heart failure, myocardial infarction, and stroke. Data were reported as relative risk and 95% Confidence Interval, and the risk of publication bias assessed via Egger’s test. Eighty six full text articles were identified, and 10 RCTs published in 7 studies between 2015 and 2018 were included into the analysis. Data obtained from 12,690 COPD patients (44.47% T/O FDC, 55.53% monocomponents) were extracted. T/O 5/5?μg FDCs did not significantly modulate (p-value > 0.05) the risk of arrhythmia (1.02, 0.55 - 1.92), heart failure (0.88, 0.41 - 1.92), myocardial infarction (1.15, 0.70 - 1.87), and stroke (0.98, 0.44 - 2.16) vs. monocomponents. No significant publication bias affected the effect estimates of this meta-analysis. The results of this quantitative synthesis indicate that dual bronchodilation with T/O 5/5?μg FDC is characterized by an acceptable cardiovascular safety profile in COPD patients.     

Olodaterol + tiotropium bromide for the treatment of chronic obstructive pulmonary disease

A solid scientific rationale and an increasing body of clinical evidence for combining a β₂-agonist with an antimuscarinic agent in COPD fully support the opinion that patients not controlled by a single bronchodilator should be given two bronchodilators with different mechanisms of action. Tiotropium is an established choice for the management of patients with stable COPD, and olodaterol is a new effective and safe once-daily long-acting β2-agonist. The parallel bronchodilating modes of action of olodaterol and tiotropium make them an attractive combination in COPD. The large ongoing TOviTO Phase III trial program is documenting the efficacy and safety of olodaterol/tiotropium fixed dose combination delivered via the Respimat Soft Mist Inhaler as maintenance therapy in patients with moderate to very severe COPD. However, we must still know whether this fixed-dose combination will affect exacerbations and hospitalizations, and ultimately death, and also the precise estimates of its relative cardiovascular safety.     

长效支气管扩张剂盐酸奥达特罗

盐酸奥达特罗是一种新型选择性速效、长效β2-肾上腺能受体激动剂,可迅速起效且维持24h的支气管扩张作用,全身性副作用很少。由于只需每天用药1次,故能提高患者的依从性,给以气道阻塞为特征的疾病治疗提供一种新的治疗选择。本文介绍盐酸奥达特罗的药理作用、临床研究、不良反应和与其他药物联合治疗的研究情况。