POINT: Should LAMA/LABA Combination Therapy Be Used as Initial Maintenance Treatment for COPD? Yes

Cazzola, Mario; Matera, Maria Gabriella

doi:10.1016/j.chest.2018.06.022

Cited by 13 publications

(14 citation statements)

References 17 publications

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“…However, our findings suggest that patients with low exacerbation history could benefit from earlier treatment with LAMA/LABA, and support the recent argument put forward by Cazzola et al [1] that LAMA/ LABA combination therapy could have benefits as initial maintenance therapy. These findings are supported by previous studies that have consistently demonstrated LAMA/LABA combination therapy to be more effective than LAMA or LABA monotherapy in improving lung function and health status [1,6,8], and in reducing the risk of exacerbations [1,8,9].…”

Section: Discussionsupporting

confidence: 90%

“…In addition to clinical evidence advocating the benefits of dual bronchodilation [1], there is a strong rationale for using LAMA/LABA as initial maintenance treatment. Pharmacologically, the use of a LAMA/LABA combination exploits both the adrenergic and cholinergic pathways in the airway smooth muscle (ASM) to maximise bronchodilation.…”

Section: Discussionmentioning

confidence: 99%

“…Whether more patients with chronic obstructive pulmonary disease (COPD), including those with mild-to-moderate disease or fewer symptoms, could benefit from earlier treatment with longacting muscarinic antagonist (LAMA)/long-acting b 2 -agonist (LABA) combination therapy is a matter of debate [1,2]. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2020 report recommends LAMA or LABA monotherapy as initial pharmacological therapy for most patients [3].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Tiotropium/Olodaterol Delays Clinically Important Deterioration Compared with Tiotropium Monotherapy in Patients with Early COPD: a Post Hoc Analysis of the TONADO® Trials

et al. 2020

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Introduction Since chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, a composite endpoint of clinically important deterioration (CID) may provide a more holistic assessment of treatment efficacy. We compared long-acting muscarinic antagonist/long-acting β 2 -agonist combination therapy with tiotropium/olodaterol versus tiotropium alone using a composite endpoint for CID. CID was evaluated overall and in patients with low exacerbation history (at most one moderate exacerbation in the past year [not leading to hospitalisation]), Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2 patients and maintenance-naïve patients with COPD. We assessed whether early treatment optimisation is more effective with tiotropium/olodaterol versus tiotropium in delaying and reducing the risk of CID. Methods Data were analysed from 2055 patients treated with either tiotropium/olodaterol 5/5 μg or tiotropium 5 μg (delivered via Respimat ® ) in two replicate, 52-week, parallel-group, double-blind studies (TONADO ® 1/2). CID was defined as a decline of at least 0.1 L from baseline in trough forced expiratory volume in 1 s, increase from baseline of at least 4 units in St. George’s Respiratory Questionnaire score, or moderate/severe exacerbation. Time to first occurrence of one of these events was recorded as time to first CID. Results Overall, treatment with tiotropium/olodaterol significantly increased the time to, and reduced the risk of, CID versus tiotropium (median time to CID 226 versus 169 days; hazard ratio [HR] 0.76 [95% confidence interval 0.68, 0.85]; P < 0.0001). Significant reductions were also observed in patients with low exacerbation history (241 versus 170; HR 0.73 [0.64, 0.83]; P < 0.0001), GOLD 2 patients (241 versus 169; 0.72 [0.61, 0.84]; P < 0.0001) and maintenance-naïve patients (233 versus 171; 0.75 [0.62, 0.91]; P = 0.0030). Conclusion In patients with COPD, including patients with low exacerbation history, GOLD 2 patients and maintenance-naïve patients, tiotropium/olodaterol reduced the risk of CID versus tiotropium. These results demonstrate the advantages of treatment optimisation with tiotropium/olodaterol over tiotropium monotherapy. Trial Registration ClinicalTrials.gov identifier: TONADO ® 1 and 2 (NCT01431274 and NCT01431287, registered 8 September 2011). Graphic Abstract Electronic supplementary material The online version of this article (10.1007/s12325-020-01528-2) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Tiotropium/Olodaterol Delays Clinically Important Deterioration Compared with Tiotropium Monotherapy in Patients with Early COPD: a Post Hoc Analysis of the TONADO® Trials

et al. 2020

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“…The long-acting muscarinic antagonist (LAMA) is the recommended initial treatment choice for patients with mild disease and no exacerbations [ 6 ]. In case of more severe dyspnea, severe airflow obstruction, and lung hyperinflation, combining LAMA with a selective long-acting beta2-agonist (LABA) is recommended [ 7 , 8 , 9 , 10 ]. If the symptoms and exacerbations persist (more than two exacerbations per year or one hospitalization for COPD), a LAMA, a LABA, and an inhaled corticosteroid (ICS) may be prescribed [ 11 , 12 , 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

The Potential Role and Regulatory Mechanisms of MUC5AC in Chronic Obstructive Pulmonary Disease

2020

Molecules

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Chronic obstructive pulmonary disease (COPD) is associated with high morbidity and mortality globally. Studies show that airway mucus hypersecretion strongly compromises lung function, leading to frequent hospitalization and mortality, highlighting an urgent need for effective COPD treatments. MUC5AC is known to contribute to severe muco-obstructive lung diseases, worsening COPD pathogenesis. Various pathways are implicated in the aberrant MUC5AC production and secretion MUC5AC. These include signaling pathways associated with mucus-secreting cell differentiation [nuclear factor-κB (NF-κB)and IL-13-STAT6- SAM pointed domain containing E26 transformation-specific transcription factor (SPDEF), as well as epithelial sodium channel (ENaC) and cystic fibrosis transmembrane conductance regulator (CFTR)], and signaling pathways related to mucus transport and excretion-ciliary beat frequency (CBF). Various inhibitors of mucus hypersecretion are in clinical use but have had limited benefits against COPD. Thus, novel therapies targeting airway mucus hypersecretion should be developed for effective management of muco-obstructive lung disease. Here, we systematically review the mechanisms and pathogenesis of airway mucus hypersecretion, with emphasis on multi-target and multi-link intervention strategies for the elucidation of novel inhibitors of airway mucus hypersecretion.

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“…A systematic review of LABA/LAMA versus LABA, LAMA, and LABA/ICS examined 27 studies to find significantly improved respiratory outcomes with dual LAMA/LABA therapy [9]. Commencing new patients directly on LAMA/LABA combinations may improve outcomes, irrespective of GOLD stage [10][11][12]. However, there is limited evidence clarifying whether dual therapy is appropriate for the initial treatment of COPD as few studies have been conducted in patients with lapsed or no prior history of maintenance therapy.…”

Section: Introductionmentioning

confidence: 99%

Glycopyrrolate/formoterol fumarate metered dose inhaler for maintenance-naïve patients with chronic obstructive pulmonary disease: a post-hoc analysis of the randomized PINNACLE trials

Zheng

Jenkins

et al. 2020

Respir Res

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Background: Glycopyrrolate (GP)/formoterol fumarate (FF; GFF) metered dose inhaler is a fixed-dose combination dual bronchodilator for patients with chronic obstructive pulmonary disease (COPD); however, whether the efficacy in patients without current maintenance treatment is consistent with currently maintenance-treated patients is unclear. Methods: Data from patients who were not maintenance-treated at screening (NMT) (n = 1943) and patients who were maintenance-treated at screening (MT) patients (n = 3040) receiving GFF, FF, GP, or placebo were pooled from the Phase III PINNACLE studies (NCT01854645, NCT01854658, NCT02343458) for post-hoc analysis. MT patients had received long-acting bronchodilators and/or inhaled corticosteroids in the 30 days prior to screening, and/or prior to randomization. NMT patients had received short-acting bronchodilators or no treatment. Outcomes included forced expiratory volume over 1 s (FEV 1), clinically important deterioration (CID), rescue medication use, and safety. Results: GFF provided significant lung function improvements at Week 24 versus placebo, GP, and FF for NMT patients, with pre-dose trough FEV 1 treatment differences of 152 (117-188) mL, 73 (45-100) mL, and 56 (29-84) mL, respectively (least squares mean change from baseline versus comparators [95% CI]; all P < 0.0001). GFF reduced the risk of CID by 17-43% in NMT (P ≤ 0.0157) and 18-52% (P ≤ 0.0012) in MT patients compared with monotherapy and placebo, and reduced rescue medication use by 1.5 puffs/day over 24 weeks for both cohorts. Safety profiles for all cohorts were consistent with each other and the parent studies.

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POINT: Should LAMA/LABA Combination Therapy Be Used as Initial Maintenance Treatment for COPD? Yes

Cited by 13 publications

References 17 publications

Tiotropium/Olodaterol Delays Clinically Important Deterioration Compared with Tiotropium Monotherapy in Patients with Early COPD: a Post Hoc Analysis of the TONADO® Trials

Tiotropium/Olodaterol Delays Clinically Important Deterioration Compared with Tiotropium Monotherapy in Patients with Early COPD: a Post Hoc Analysis of the TONADO® Trials

The Potential Role and Regulatory Mechanisms of MUC5AC in Chronic Obstructive Pulmonary Disease

Glycopyrrolate/formoterol fumarate metered dose inhaler for maintenance-naïve patients with chronic obstructive pulmonary disease: a post-hoc analysis of the randomized PINNACLE trials

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