Triple Therapy versus Dual or Monotherapy with Long-Acting Bronchodilators for Chronic Obstructive Pulmonary Disease. A Systematic Review and Meta-analysis

Mammen, Manoj J.; Lloyd, D. R.; Kumar, Sandeep; Ahmed, Anum S.; Pai, Vandana; Kunadharaju, Rajesh; Gupta, Shilpi; Nici, Linda; Aaron, Shawn D.; Alexander, Paul

doi:10.1513/annalsats.202001-023oc

Cited by 23 publications

(22 citation statements)

References 29 publications

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“…For example, triple therapy with LAMA/LABA/ICS has been associated with an increased risk of pneumonia and higher costs compared with dual therapy with LAMA/LABA combinations [ 5 , 21 ]. Hence, escalation to triple therapy should be reserved for a specific population of patients with COPD, namely symptomatic patients with a high risk of exacerbations, in whom the treatment benefits may outweigh the risks [ 5 , 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

Effectiveness and Safety of COPD Maintenance Therapy with Tiotropium/Olodaterol versus LABA/ICS in a US Claims Database

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Montonen

Esposito³

et al. 2021

Adv Ther

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Introduction In patients with chronic obstructive pulmonary disease (COPD), treatment with long-acting muscarinic antagonist (LAMA)/long-acting β 2 -agonist (LABA) combination therapy significantly improves lung function versus LABA/inhaled corticosteroid (ICS). To investigate whether LAMA/LABA could provide better clinical outcomes than LABA/ICS, this non-interventional database study assessed the risk of COPD exacerbations, pneumonia, and escalation to triple therapy in patients with COPD initiating maintenance therapy with tiotropium/olodaterol versus any LABA/ICS combination. Methods Administrative healthcare claims and laboratory results data from the US HealthCore Integrated Research Database sm were evaluated for patients with COPD initiating tiotropium/olodaterol versus LABA/ICS treatment (January 2013–March 2019). Patients were aged at least 40 years with a diagnosis of COPD (but not asthma) at cohort entry. A Cox proportional hazard regression model was used (as-treated analysis) to assess risk of COPD exacerbation, community-acquired pneumonia, and escalation to triple therapy, both individually and as a combined risk of any one of these events. Potential imbalance of confounding factors between cohorts was handled using fine stratification, reweighting, and trimming by exposure propensity score (high-dimensional); subgroup analyses were conducted on the basis of blood eosinophil levels and exacerbation history. Results The total population consisted of 61,985 patients (tiotropium/olodaterol n = 2684; LABA/ICS n = 59,301); after reweighting, the total was 42,953 patients (tiotropium/olodaterol n = 2600; LABA/ICS n = 40,353; mean age 65 years; female 54.5%). Patients treated with tiotropium/olodaterol versus LABA/ICS experienced a reduction in the risk of COPD exacerbations (adjusted hazard ratio 0.76 [95% confidence interval 0.68, 0.85]), pneumonia (0.74 [0.57, 0.97]), escalation to triple therapy (0.22 [0.19, 0.26]), and any one of these events (0.45 [0.41, 0.49]); the combined risk was similar irrespective of baseline eosinophils and exacerbation history. Conclusions In patients with COPD, tiotropium/olodaterol was associated with a lower risk of COPD exacerbations, pneumonia, and escalation to triple therapy versus LABA/ICS, both individually and in combination; the combined risk was reduced irrespective of baseline eosinophils or exacerbation history. Trial Registration ClinicalTrials.gov identifier, NCT04138758 (registered 23 October 2019). Graphic Abstract Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-01646-5.

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Section: Introductionmentioning

confidence: 99%

Effectiveness and Safety of COPD Maintenance Therapy with Tiotropium/Olodaterol versus LABA/ICS in a US Claims Database

Quint

Montonen

Esposito³

et al. 2021

Adv Ther

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“…Until now, five systematic reviews have compared the effect of triple therapy with LAMA/LABA in patients with COPD [ 7 – 11 ]. These reviews showed that triple therapy has a risk of pneumonia but is superior to LAMA/LABA therapy due to the lower incidence of exacerbations, higher trough FEV 1 and better QOL score evaluated by GRADE.…”

Section: Discussionmentioning

confidence: 99%

“…Until now, five systematic reviews have been performed to evaluate the efficacy and safety of ICS add-on to LAMA/LABA treatment [ 7 – 11 ]. However, the included trials contain several biases, such as not using a single inhalation device [ 12 ], using different LABA between the comparison groups [ 13 ] or a short evaluation duration of only 24 weeks [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Triple versus LAMA/LABA combination therapy for patients with COPD: a systematic review and meta-analysis

et al. 2021

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Background Recently, the addition of inhaled corticosteroid (ICS) to long-acting muscarinic antagonist (LAMA) and long-acting beta-agonist (LABA) combination therapy has been recommended for patients with COPD who have severe symptoms and a history of exacerbations because it reduces the exacerbations. In addition, a reducing effect on mortality has been shown by this treatment. However, the evidence is mainly based on one large randomized controlled trial IMPACT study, and it remains unclear whether the ICS add-on treatment is beneficial or not. Recently, a large new ETHOS trial has been performed to clarify the ICS add-on effects. Therefore, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety including ETHOS trial. Methods We searched relevant randomized control trials (RCTs) and analyzed the exacerbations, quality of life (QOL), dyspnea symptom, lung function and adverse events including pneumonia and mortality, as the outcomes of interest. Results We identified a total of 6 RCTs in ICS add-on protocol (N = 13,579). ICS/LAMA/LABA treatment (triple therapy) significantly decreased the incidence of exacerbations (rate ratio 0.73, 95% CI 0.64–0.83) and improved the QOL score and trough FEV1 compared to LAMA/LABA. In addition, triple therapy significantly improved the dyspnea score (mean difference 0.33, 95% CI 0.18–0.48) and mortality (odds ratio 0.66, 95% CI 0.50–0.87). However, triple therapy showed a significantly higher incidence of pneumonia (odds ratio 1.52, 95% CI 1.16–2.00). In the ICS-withdrawal protocol including 2 RCTs, triple therapy also showed a significantly better QOL score and higher trough FEV1 than LAMA/LABA. Concerning the trough FEV1, QOL score and dyspnea score in both protocols, the differences were less than the minimal clinically important difference. Conclusion Triple therapy causes a higher incidence of pneumonia but is a more preferable treatment than LAMA/LABA due to the lower incidence of exacerbations, higher trough FEV1 and better QOL score. In addition, triple therapy is also superior to LABA/LAMA due to the lower mortality and better dyspnea score. However, these results should be only applied to patients with symptomatic moderate to severe COPD and a history of exacerbations. Clinical Trial Registration: PROSPERO; CRD42020191978.

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“…Dazu zählen Patienten mit häufigen und/oder schweren Exazerbationen unter schon bestehender Therapie in Verbindung mit erhöhten Eosinophilenzahlen im peripheren Blut. Empfehlungen der GOLD und European Respiratory Society (ERS) ebenso wie aktuelle Metaanalysen stützen diese Annahme [34][35][36][37]. Die Bedeutung einer möglichen Asthmakomponente für diese Konstellation bleibt zu klären.…”

Section: Rolle Des Zigarettenrauchensunclassified

Chronisch-obstruktive Lungenerkrankung 2021 – die richtige Therapie für den richtigen Patienten

et al. 2021

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ZusammenfassungIn den vergangenen Jahren wurden auf dem Gebiet der chronisch-obstruktiven Lungenerkrankung (COPD) große Therapiestudien publiziert, die 2020 um mehrere Post-hoc-Analysen ergänzt wurden. Die neuen Erkenntnisse flossen in das Update des Global-Initiative-for-Chronic-Obstructive-Lung-Disease(GOLD)-Report 2021 ein. Im vorliegenden Beitrag werden die aktualisierten Grundlagen und Empfehlungen zur Therapie der COPD beschrieben. Dabei wird auf die Indikationen von inhalativen Kortikosteroiden (ICS), lang wirksamen Muskarinantagonisten (LAMA) und/oder lang wirksamen β‑Mimetika (LABA) eingegangen. Die Therapie der COPD wird der des Asthma bronchiale gegenübergestellt. Diskutiert wird auch, wie sich eine gleichzeitig bestehende Asthmakomponente auf die Behandlungsstrategie bei COPD auswirkt. Ein Schwerpunkt des Beitrags liegt auf der Triple-Therapie mit LAMA, LABA und ICS. In diesem Zusammenhang werden die Studienlage und die Indikationen beschrieben. Die Bronchodilatation bleibt weiterhin die Grundlage der COPD-Therapie. Für Patienten mit gehäuften Exazerbationen bedeutet eine Triple-Therapie mit LAMA + LABA + ICS einen Mortalitätsvorteil. Weitere Analysen oder Studien sollen klären, ob dieser Effekt für spezifische Subgruppen stärker ausgeprägt ist.

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Triple Therapy versus Dual or Monotherapy with Long-Acting Bronchodilators for Chronic Obstructive Pulmonary Disease. A Systematic Review and Meta-analysis

Cited by 23 publications

References 29 publications

Effectiveness and Safety of COPD Maintenance Therapy with Tiotropium/Olodaterol versus LABA/ICS in a US Claims Database

Effectiveness and Safety of COPD Maintenance Therapy with Tiotropium/Olodaterol versus LABA/ICS in a US Claims Database

Triple versus LAMA/LABA combination therapy for patients with COPD: a systematic review and meta-analysis

Chronisch-obstruktive Lungenerkrankung 2021 – die richtige Therapie für den richtigen Patienten

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