Monday, March 9, 2015

Addressing unmet need in COPD: Role of dual bronchodilation



  Last Week , an awareness program  for the COPD was being tackled through Novartis by  the launching of a simple machine that would check and detect failures of airflow and  tips on how to addressed and be protected by such chronic disease that has been one of the major and prevalent problems in the Philippines and other 3rd World Countries due to pollution and other kind of substances that can be acquired through airborne .

Chronic obstructive pulmonary disease (COPD) is a major health issue worldwide. The disease is characterized by persistent airflow limitation that is usually progressive and associated with an enhanced, chronic inflammatory response in the airways or lung to noxious particles or gasses. Around 210 million people worldwide are estimated to have COPD2 and the prevalence is increasing both in developed and developing countries1.

COPD is the sixth leading cause of death in the Philippines28. The Burden of Obstructive Lung Disease (BOLD) study found that COPD prevalence in Manila was 14% while two towns in Nueva Ecija had a prevalence rate of 21%. Aside from the high prevalence rates, only 2% of these cases were diagnosed by doctors29-30.

Overall, 28.3% (17.3 million) of the Philippine population aged 15 years old and over currently smoke tobacco: 47.7 % (14.6 million) are men, and 9.0% (2.8 million) are women. The majority of deaths attributable to smoking are caused by COPD and cerebrovascular diseases31 .

Although COPD is often thought of as a disease of older age, as many as 25% of adults aged 40 years and older have mild airflow obstruction3. It is estimated that around half of people with COPD are below the age of 65 when they are likely to be at the peak of their earning power and family responsibilities1. COPD therefore puts a substantial burden on both patients and society1.

Impact of COPD symptoms and exacerbations

Airflow obstruction in COPD causes shortness of breath, coughing, wheezing, chest tightness and other symptoms. These symptoms have a destructive impact on patients’ function and quality of life4, and even simple daily activities such as walking up a short flight of stairs can become difficult as the condition gradually worsens5. Reducing the debilitating symptoms of COPD is a key goal of treatment in international guidelines6. However, a high proportion of patients experience persistent symptoms despite medical therapy with current therapies7.

Many patients with COPD experience exacerbations, a sudden worsening of symptoms most commonly caused by infections of the upper respiratory tract or tracheobronchial tree6. COPD exacerbations are linked to an accelerated decline in lung function8,9 and are associated with increased mortality and poorer quality of life for patients10,11. Because of the frequent need for hospitalization, exacerbations are a cause of increased healthcare costs12,13 and account for the greatest proportion of the total COPD burden on the healthcare system6. COPD patients typically experience one to three exacerbations each year, and between 3% and 16% of these will require hospital admission11. Up to one in ten patients with severe COPD admitted to hospital for an exacerbation will die11. Prevention of COPD exacerbations is therefore an absolute priority in COPD management6.

Bronchodilation: The cornerstone of COPD treatment

In 2013, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) updated their Strategy for the Diagnosis, Management and Prevention of COPD with the latest evidence for best practice. Pharmacological therapy is recommended to reduce COPD symptoms and exacerbations, and improve health status and exercise tolerance6. Choice of treatment is dependent on the individual patient's level of symptoms, lung function and risk of exacerbations6, however bronchodilator medications are central to the management of COPD for all (see table 1)6.

Most bronchodilators work by altering the smooth muscle tone of the lung airways, causing the passages to relax and open up. They may be used as needed or on a regular basis as maintenance treatment to prevent or reduce COPD symptoms6. Inhaled short-acting bronchodilators, which work quickly and last from four to six hours, are used as rescue medication. Inhaled long-acting bronchodilators are used regularly to open the airways and keep them open for 12 hours with twice-daily dosing, and in some cases up to 24 hours (once-daily dosing). There are two main types6:

· Long-acting beta2-agonists (LABAs) which stimulate beta2-adrenergic receptors, producing cyclic AMP which promotes muscle relaxation and therefore reduces bronchoconstriction

· Long-acting muscarinic antagonists (LAMAs) – also known as long-acting anticholinergic bronchodilators – which block the bronchoconstrictor action of acetylcholine on airway smooth muscle cells and therefore prevent muscle constriction

Table 1: Initial pharmaceutical management of COPD (adapted from GOLD 20136)

Key: SABA = Short-acting beta2-agonist SAMA = Short-acting muscarinic antagonist

LABA = Long-acting beta2-agonist LAMA = Long-acting muscarinic antagonist

ICS = Inhaled corticosteroid


Risk and symptoms

Recommended first choice treatment

(see below for more information)

Group A

Patients have lower risk of exacerbations

and lower levels of symptoms

Short- acting bronchodilators –

SABA or SAMA (as required basis)

Group B

Patients have lower risk of exacerbations

but more symptoms

Long-acting bronchodilators –


Group C

Patients have high risk of exacerbations

but experience less symptoms


Group D

Patients are at high risk of exacerbations

and experience more symptoms


Although initial treatment for COPD can reduce symptoms and exacerbations, people with the disease frequently experience a significant decline in their health status as the condition progresses14. Many patients suffer the burden of persistent symptoms despite current medical therapy7 and a need remains for improved symptom control14. Symptomatic COPD patients require a different approach to reduce the impact of the illness on their lives.

Concept of dual bronchodilation

Combining bronchodilators with different mechanisms of action may increase the degree of bronchodilation for equivalent or lesser side effects6. The GOLD strategy recommends, as an alternative choice, combined use of a LABA plus LAMA in all patients with moderate to very severe COPD (GOLD groups B-D)6. Administration of LABA plus LAMA as a once-daily dual bronchodilator simplifies treatment administration and may help improve compliance15.

The COPD Council adopted the GOLD 2014 Guideline Update recommendations and have inserted local epidemiological data to bring in Local perspective of COPD.

Introduction to indacaterol glycopyrronium

Indacaterol glycopyrronium is the first once-daily dual bronchodilator combining a LABA and a LAMA, and represents a new option for the treatment of COPD. Once daily indacaterol glycopyrronium is a maintenance bronchodilator treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD).

Once-daily indacaterol glycopyrronium has been and is still being investigated in the Phase III IGNITE clinical trial program, one of the largest clinical trial programs in COPD involving more than 10,000 patients across 52 countries including the Philippines14,16-27.

In clinical trials, indacaterol glycopyrronium was evaluated against two of the most commonly-used treatments in COPD – the LAMA, tiotropium 18 mcg, and the LABA / ICS combination, salmeterol 50 mcg / fluticasone 500 mcg (SFC). Results from the IGNITE clinical trial program showed that indacaterol glycopyrronium provided statistically significant improvements in bronchodilation versus placebo19, OL tiotropium 18 mcg and SFC 50 mcg / 500 mcg14,17,18,19.

Compared to open-label (OL) tiotropium 18 mcg, dual bronchodilation with indacaterol glycopyrronium demonstrated statistically significant improvements in breathlessness, health-related quality of life and reduced rescue medication use. Indacaterol glycopyrronium also improved breathlessness and rescue medication use compared to SFC 50 mcg / 500 mcg twice-daily in patients with no history of moderate or severe exacerbations in the last year17. The rate of all COPD exacerbations (mild, moderate and severe) was significantly improved with indacaterol glycopyrronium compared to glycopyrronium 50 mcg and OL tiotropium 18 mcg at Week 6414. Indacaterol glycopyrronium also significantly reduced the rate of moderate or severe COPD exacerbations versus glycopyrronium 50 mcg14. The rate of moderate or severe exacerbations was numerically lower in patients on indacaterol glycopyrronium versus OL tiotropium 18 mcg at Week 6414.

In clinical studies, indacaterol glycopyrronium demonstrated an acceptable safety profile with no meaningful differences between the treatment groups (placebo, indacaterol 150 mcg, glycopyrronium 50 mcg, OL tiotropium 18 mcg, SFC 50 mcg / 500 mcg in the incidence of adverse and serious adverse events14,16-18. The safety profile was characterized by typical anticholinergic and beta-adrenergic effects related to the individual components of the combination14,16-22.

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