The Comeback Delivery System

of COPD Treatment

Prof DR. dr. Faisal Yunus PhD, SpP(K), FCCP, FISR

Introduction

• Overview of Chronic Obstructive Pulmonary Disease (COPD)

• Definition: A progressive disease characterized by airflow limitation and inflammation,
often caused by long-term exposure to tobacco smoke and other pollutants
• Impact on quality of life, including breathlessness, cough, and reduced exercise capacity
• No cure, but treatment can help manage symptoms and slow disease progression
• Importance of early diagnosis and intervention to improve outcomes

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 Getting to know more about LAMA, LABA and ICS
1. LAMA (Long-acting Muscarinic Antagonists):
̶ Examples: tiotropium, aclidinium, glycopyrrolate, umeclidinium, and
indacaterol.
̶ Mechanism: They work by blocking muscarinic receptors in the airway
smooth muscle, bronchial glands, and other tissues.
̶ Benefits: Improve lung function, reduce exacerbations, and improve
quality of life for COPD patients.
̶ Delivery systems: Dry powder inhalers (DPI) or soft mist inhalers (SMI).
2. LABA (Long-acting β-agonists):
̶ Examples: formoterol, salmeterol, indacaterol, olodaterol, and vilanterol.
̶ Mechanism: They work by stimulating β2-adrenergic receptors in the
airway smooth muscle, leading to bronchodilation.
̶ Benefits: Improve lung function, reduce exacerbations, and improve
quality of life for COPD patients.
̶ Delivery systems: Dry powder inhalers (DPI), metered-dose inhalers
(MDI), or soft mist inhalers (SMI).
3. ICS (Inhaled Corticosteroids):
̶ Examples: fluticasone, budesonide, beclomethasone, and mometasone.
̶ Mechanism: They work by reducing inflammation in the airways, which
can help improve lung function and reduce exacerbations.
̶ Benefits: Improve lung function, reduce exacerbations, and improve
quality of life for COPD patients, especially in patients with eosinophilic
phenotype.
̶ Delivery systems: Dry powder inhalers (DPI), metered-dose inhalers
(MDI), or soft mist inhalers (SMI).
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4. LAMA/LABA combinations:Examples: tiotropium/olodaterol,
aclidinium/formoterol, glycopyrrolate/indacaterol, and umeclidinium/vilanterol.
• Mechanism: The combination of LAMA and LABA provides both
bronchodilation and anti-inflammatory effects, potentially improving the
overall treatment of COPD.
• Benefits: Improve lung function, reduce exacerbations, and improve
quality of life for COPD patients.
• Delivery systems: Dry powder inhalers (DPI) or soft mist inhalers (SMI).
5. ICS/LABA combinations:Examples: fluticasone/salmeterol, budesonide/formoterol,
and beclomethasone/formoterol.
• Mechanism: The combination of ICS and LABA provides both anti-
inflammatory and bronchodilatory effects, potentially improving the
overall treatment of COPD.
• Benefits: Improve lung function, reduce exacerbations, and improve
quality of life for COPD patients, especially in patients with eosinophilic
phenotype.
• Delivery systems: Dry powder inhalers (DPI), metered-dose inhalers (MDI),
or soft mist inhalers (SMI).
6. LAMA/LABA/ICS combinations:Examples: tiotropium/olodaterol/fluticasone,
aclidinium/formoterol/budesonide, and glycopyrrolate/indacaterol/beclomethasone.
• Mechanism: The combination of LAMA, LABA, and ICS provides a
comprehensive treatment approach, addressing bronchodilation, anti-
inflammatory effects, and reducing exacerbations.
• Benefits: Improve lung function, reduce exacerbations, and improve
quality of life for COPD patients, especially in patients with high
exacerbation risk.
• Delivery systems: Dry powder inhalers (DPI) or soft mist inhalers (SMI).
Clinical reasons to use LAMA for COPD patients

1. Reduced exacerbation risk: LAMA/LABA therapy has been shown to reduce the risk of moderate, severe, and overall COPD
exacerbations compared to ICS/LABA therapy1. This is particularly important for patients with a high risk of exacerbations, as it can
help prevent hospitalizations and improve quality of life.
2. Lower pneumonia hospitalization risk: In addition to reducing exacerbations, LAMA/LABA therapy has also been linked to a lowe r
risk of pneumonia hospitalizations compared to ICS/LABA therapy1. This is a significant benefit for patients with COPD, as
pneumonia is a common complication and can lead to severe complications and even death.
3. Improved lung function: LAMAs have been shown to improve lung function in patients with COPD, as indicated by increased trough
forced expiratory volume in 1 second (FEV1)3. This can lead to improved symptoms and better quality of life for patients.
4. Reduced dyspnea: LAMAs have been shown to improve dyspnea symptoms in patients with COPD, as indicated by a reduction in
the Transitional Dyspnea Index (TDI)3. This can lead to better exercise tolerance and improved quality of life.
5. Improved health-related quality of life (HRQoL): LAMAs have been shown to improve health-related quality of life in patients with
COPD, as indicated by a reduction in the St. George's Respiratory Questionnaire (SGRQ)3. This is an important outcome for
patients, as it can lead to improved overall well-being and satisfaction with treatment.
6. Cardiovascular safety: LAMAs have been found to be safe in patients with COPD, with no significant difference in the incidence of
all adverse events or cardiovascular events compared to placebo3. This is important for patients with COPD, as they often have
comorbidities that increase the risk of cardiovascular events.
7. Recommended for COPD management: LAMAs are recommended for patients with COPD in the Global Initiative for Chronic
Obstructive Lung Disease (GOLD) groups A–D3. This reflects their role as a first-line treatment option for many patients with COPD.
8. Effective in patients with asthma-COPD overlap: LAMAs have also been shown to be effective in patients with asthma-COPD
overlap, which is a common condition in clinical practice5. This highlights their versatility as a treatment option for patients with
various respiratory conditions.

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Segmentation of Single LAMA in COPD Management Based on the GOLD Guideline 2023

̶ The Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2023 guideline recommends the use
of long-acting muscarinic antagonists (LAMAs) in combination with long-acting beta-agonists (LABAs)
for the management of COPD. The GOLD guideline suggests that LAMA/LABA therapy can improve
outcomes in patients with COPD, including reduced exacerbation risk, lower pneumonia hospitalization
risk, improved lung function, reduced dyspnea, and improved health-related quality of life.
̶ The GOLD guideline also recommends the use of inhaled corticosteroids (ICS) in combination with
LABA/LAMA for patients with more severe symptoms or a history of exacerbations. The so-called
"Triple therapy" has demonstrated benefits in COPD patients in GOLD group D.In addition to
LAMA/LABA and LAMA/LABA/ICS combinations, there are also single-inhaler triple combination
therapies, such as beclometasone, formoterol, and glycopyrrolate (87 μg/5 μg/9 μg) 2 inhalations
twice per day, which have shown to produce benefits in COPD patients in GOLD group D2.
̶ The TRINITY study compared FF 6 μg, GLY 12.5 μg, and beclomethasone 100 μg to TIO and found that
the triple combination therapy resulted in a 20% reduction in the rate of improvement in pre-dose
FEV1 in COPD patients with frequent exacerbations2.
̶ The TRIBUTE study compared a single-inhaler dual bronchodilator combination of GLY/IND (43 μg/9 μg)
2 inhalations twice per day versus a single-inhaler triple combination of beclometasone, formoterol,
and glycopyrrolate (87 μg/5 μg/9 μg) 2 inhalations twice per day and found that triple therapy
significantly reduced the rate of moderate-to-severe exacerbations compared with GLY/IND without
increasing the risk of pneumonia2.
̶ Currently, there is a study comparing TIO/OLO with ICS/LABA/LAMA triple therapy, but the results are
still awaited2.

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Tiotropium in COPD Management
1. Tiotropium is a long-acting anticholinergic bronchodilator that is used for the long-term, once-
daily, maintenance treatment of bronchospasm and dyspnea associated with chronic obstructive
pulmonary disease (COPD), including chronic bronchitis and emphysema3. It is an option for
symptom control and can be used as an alternative to ipratropium or salmeterol, or in addition to
these medications3.Key benefits of tiotropium in COPD management include: Improved
pulmonary function: Tiotropium has been shown to improve pulmonary function, as indicated by
increased trough forced expiratory volume in 1 second (FEV1)1. This can lead to improved
symptoms and better quality of life for patients.
2. Reduced exacerbations: Tiotropium has been shown to reduce the number of exacerbations in
patients with COPD, including those with less severe disease (FEV1 >50% pred)2. This can help
prevent hospitalizations and improve quality of life.
3. Healthcare resource utilization (HRU): Tiotropium has been shown to reduce HRU, as indicated by
a decrease in the use of concomitant respiratory medication, antibiotics, and oral steroids, as well
as the number of unscheduled physician contacts2. This can lead to cost savings in COPD
management.
4. Improved airflow limitation: Tiotropium has been shown to ameliorate airflow limitation in
patients with moderate-to-severe COPD, reducing air trapping and exertional dyspnea5.
5. Effective in early-stage COPD: Tiotropium has also been shown to be effective in patients with
early-stage COPD, as indicated by improved airflow limitation and reduced exertional dyspnea5.

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DPI Tiotropium Position in COPD Management

The dry powder inhaler (DPI) formulation of tiotropium, has been shown to be effective in COPD
management. The key benefits of DPI tiotropium include:
1. Improved lung function: DPI tiotropium has been shown to improve lung function, as indicated by
increased trough forced expiratory volume in 1 second (FEV1).This can lead to improved
symptoms and better quality of life for patients.
2. Reduced exacerbations: DPI tiotropium has been shown to reduce the number of exacerbations in
patients with COPD, including those with less severe disease (FEV1 >50% pred). This can help
prevent hospitalizations and improve quality of life.
3. Healthcare resource utilization (HRU): DPI tiotropium has been shown to reduce HRU, as
indicated by a decrease in the use of concomitant respiratory medication, antibiotics, and oral
steroids, as well as the number of unscheduled physician contacts. This can lead to cost savings
in COPD management.
4. Improved airflow limitation: DPI tiotropium has been shown to ameliorate airflow limitation in
patients with moderate-to-severe COPD, reducing air trapping and exertional dyspnea.
5. Effective in early-stage COPD: DPI tiotropium has also been shown to be effective in patients with
early-stage COPD, as indicated by improved airflow limitation and reduced exertional dyspnea
In conclusion, DPI tiotropium is an effective treatment option for COPD patients, providing benefits in terms
of pulmonary function, exacerbation reduction, HRU, airflow limitation, and early-stage COPD management.

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Conclusion

̶ In conclusion, tiotropium is a highly effective medication for the management of COPD,

with proven benefits in terms of improving lung function, reducing dyspnea,
exacerbations, and improving health-related quality of life. The dry powder inhaler (DPI)
formulation of tiotropium, has been shown to be particularly effective, leading to its
approval in the EU (2007), US (2014), and other countries. Tiotropium has been shown to
improve lung function, reduce exacerbations, and improve quality of life in patients with
COPD, making it a valuable treatment option for patients with this chronic respiratory
condition.

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