Optimal Bronchodilation for COPD Patients: Are All Long-Acting β2-Agonist/Long-Acting Muscarinic Antagonists the Same?

Abstract Background In chronic obstructive pulmonary disease (COPD) patients, combination treatment with long-acting muscarinic antagonist (LAMA) and long-acting β2 agonist (LABA) increases forced expiratory volume in one second and reduces symptoms compared to monotherapy. In Japan, three different once-daily fixed-dose combinations (FDCs) have been prescribed since 2015, although a direct comparison of these FDCs has never been performed. The objective of the present study was to compare the effectiveness, preference, and safety of three LAMA/LABA FDCs—glycopyrronium/indacaterol (Gly/Ind), umeclidinium/vilanterol (Ume/Vil), and tiotropium/olodaterol (Tio/Olo)—in patients with COPD. Methods We enrolled 75 COPD outpatients (male:female ratio, 69:6; 77.4 ± 6.9 years). A prospective, randomized, crossover study was conducted on three groups using three FDCs: Gly/Ind; Ume/Vil; and Tio/Olo. Each medication was administered for 4 weeks before crossover (total 12 weeks). After each FDC administration, a respiratory function test and questionnaire survey were conducted. A comparative questionnaire survey of all three LAMA/LABA FDCs was conducted after 12 weeks (following administration of final FDC). Results No significant differences in COPD Assessment Test or modified Medical Research Council dyspnea questionnaire were reported in the surveys completed after each FDC administration; no significant differences in spirometric items were observed. In the final comparative questionnaire survey, patients reported better actual feeling of being able to inhale following Gly/Ind administration compared with Tio/Olo, although no significant differences in adverse events or other evaluations were reported. Conclusions The three LAMA/LABA FDCs administered to COPD patients show similar effects and safety, although some minor individual preference was reported. Trial registration This study retrospectively registered with the University Hospital Medical Information Network Clinical Trials Registry (number UMIN000041342, registered on August 6, 2020).

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Efficacy of an inhaled corticosteroid/long-acting β2-agonist combination in symptomatic COPD patients in GOLD groups B and D

European Respiratory Journal ◽

10.1183/09031936.00047115 ◽

2015 ◽

Vol 46 (1) ◽

pp. 255-258

Author(s):

Antonio Anzueto ◽

Christine R. Jenkins ◽

Barry J. Make ◽

Magnus Lindberg ◽

Peter M. Calverley ◽

...

Keyword(s):

Inhaled Corticosteroid ◽

Copd Patients ◽

Long Acting ◽

Β2 Agonist

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COPD patients prescribed inhaled corticosteroid in general practice: Based on disease characteristics according to guidelines?

Chronic Respiratory Disease ◽

10.1177/1479973119867949 ◽

2019 ◽

Vol 16 ◽

pp. 147997311986794 ◽

Cited By ~ 2

Author(s):

Osman Savran ◽

Nina Godtfredsen ◽

Torben Sørensen ◽

Christian Jensen ◽

Charlotte Suppli Ulrik

Keyword(s):

Primary Care ◽

General Practice ◽

Symptom Severity ◽

Airflow Limitation ◽

Disease Characteristics ◽

Copd Patients ◽

Co Morbidity ◽

Long Acting ◽

Blood Eosinophils ◽

Β2 Agonist

In a primary care setting, our aim was to investigate characteristics of patients classified as having chronic obstructive pulmonary disease (COPD) and currently being prescribed inhaled corticosteroids (ICSs). The electronic patient record system in each participating general practice was searched for patients coded as COPD (ICPC, Second Edition code R95) and treated with ICS (ACT code R03AK and R03BA, that is, ICS in combination with a long-acting β2-agonist) or ICS as monotherapy. Data, if available, on demographics, smoking habits, spirometry, COPD medication, symptom score, blood eosinophils, co-morbidity and exacerbation history were retrieved from the medical records for all identified cases. Of all patients registered in the 138 participating general practices, 12.560 (3%) were coded as COPD, of whom 32% were prescribed ICS. The final study sample comprised 2.289 COPD patients currently prescribed ICS (98% also prescribed long-acting β2-agonist), with 24% being coded as both COPD and asthma. Post-bronchodilator spirometry was available in 79% (mean forced expiratory volume in 1 second 60% pred (standard deviation (SD) 23.3)), symptom severity score in 53% (mean Medical Research Council score 2.7 (SD 1.1)) and 56% of the COPD patients had had no exacerbation in the previous year (and 45% not within the 2 previous years). Blood eosinophils were measured in 67% of the patients. Information on severity of airflow limitation was missing in 15% of the patients, and the combined information on symptom severity and exacerbation history was missing in in 46%. Most of the patients (74%) were managed only by their general practitioner. Although only one-third of the COPD patients were prescribed ICSs, our findings from this study of a large cohort of patients prescribed ICSs for COPD in general practice suggest that more detailed assessment of diagnosis and disease characteristics is likely to improve the risk–benefit ratio of maintenance therapy with ICSs in COPD patients managed in primary care.

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Effect of pulmonary rehabilitation with assistive use of short-acting β2 agonist in COPD patients using long-acting bronchodilators

Physiotherapy Theory and Practice ◽

10.1080/09593985.2019.1641866 ◽

2019 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Yasuhiko Tsujimura ◽

Tetsuo Hiramatsu ◽

Eiji Kojima ◽

Kazuyuki Tabira

Keyword(s):

Pulmonary Rehabilitation ◽

Short Acting ◽

Copd Patients ◽

Long Acting ◽

Β2 Agonist

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Inhaled long-acting muscarinic antagonists in asthma – A narrative review

European Journal of Internal Medicine ◽

10.1016/j.ejim.2021.01.027 ◽

2021 ◽

Vol 85 ◽

pp. 14-22

Author(s):

Alberto Papi ◽

Leonardo M Fabbri ◽

Huib A.M. Kerstjens ◽

Paola Rogliani ◽

Henrik Watz ◽

...

Keyword(s):

Narrative Review ◽

Muscarinic Antagonists ◽

Long Acting

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Cost-effectiveness of the fixed-dose combination tiotropium/olodaterol versus tiotropium monotherapy or a fixed-dose combination of long-acting β2-agonist/inhaled corticosteroid for COPD in Finland, Sweden and the Netherlands: a model-based study

BMJ Open ◽

10.1136/bmjopen-2021-049675 ◽

2021 ◽

Vol 11 (8) ◽

pp. e049675

Author(s):

Martine Hoogendoorn ◽

Isaac Corro Ramos ◽

Stéphane Soulard ◽

Jennifer Cook ◽

Erkki Soini ◽

...

Keyword(s):

Cost Effectiveness ◽

The Netherlands ◽

Cost Effective ◽

Fixed Dose Combination ◽

Fixed Dose ◽

Inhaled Corticosteroid ◽

Dose Combination ◽

Long Acting ◽

Β2 Agonist ◽

Country Specific

ObjectivesChronic obstructive pulmonary disease (COPD) guidelines advocate treatment with combinations of long-acting bronchodilators for patients with COPD who have persistent symptoms or continue to have exacerbations while using a single bronchodilator. This study assessed the cost-utility of the fixed dose combination of the bronchodilators tiotropium and olodaterol versus two comparators, tiotropium monotherapy and long-acting β2 agonist/inhaled corticosteroid (LABA/ICS) combinations, in three European countries: Finland, Sweden and the Netherlands.MethodsA previously published COPD patient-level discrete event simulation model was updated with most recent evidence to estimate lifetime quality-adjusted life years (QALYs) and costs for COPD patients receiving either tiotropium/olodaterol, tiotropium monotherapy or LABA/ICS. Treatment efficacy covered impact on trough forced expiratory volume in 1 s (FEV1), total and severe exacerbations and pneumonias. The unit costs of medication, maintenance treatment, exacerbations and pneumonias were obtained for each country. The country-specific analyses adhered to the Finnish, Swedish and Dutch pharmacoeconomic guidelines, respectively.ResultsTreatment with tiotropium/olodaterol gained QALYs ranging from 0.09 (Finland and Sweden) to 0.11 (the Netherlands) versus tiotropium and 0.23 (Finland and Sweden) to 0.28 (the Netherlands) versus LABA/ICS. The Finnish payer’s incremental cost-effectiveness ratio (ICER) of tiotropium/olodaterol was €11 000/QALY versus tiotropium and dominant versus LABA/ICS. The Swedish ICERs were €6200/QALY and dominant, respectively (societal perspective). The Dutch ICERs were €14 400 and €9200, respectively (societal perspective). The probability that tiotropium/olodaterol was cost-effective compared with tiotropium at the country-specific (unofficial) threshold values for the maximum willingness to pay for a QALY was 84% for Finland, 98% for Sweden and 99% for the Netherlands. Compared with LABA/ICS, this probability was 100% for all three countries.ConclusionsBased on the simulations, tiotropium/olodaterol is a cost-effective treatment option versus tiotropium or LABA/ICS in all three countries. In both Finland and Sweden, tiotropium/olodaterol is more effective and cost saving (ie, dominant) in comparison with LABA/ICS.

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