Indacaterol: a comprehensive review

Abstract

At present there is no cure for chronic obstructive pulmonary disease (COPD). However, some nonpharmacologic treatments, such as rehabilitation and lung volume reduction surgery, as well as pharmacologic intervention, can relieve some of the patient's symptoms and improve quality of life, while also reducing the rate of exacerbations and hospitalizations. There needs to be a paradigm shift away from the unjustified nihilistic approach to COPD towards considering it a preventable and treatable disease. After patients quit smoking and start to lead healthier lifestyles, long-acting bronchodilators, such as long-acting beta-adrenergic agents (LABA) and long-acting antimuscarinic agents (LAMA), are recommended as the cornerstone of treatment for COPD, either as monotherapy or in combination. COPD is characterized by a reduced maximum expiratory flow and slow forced emptying of the lungs, which progress over time and are not completely reversible. In this condition, gas gets trapped in the lungs and pulmonary hyperinflation occurs. LABA and LAMA improve airway patency and deflate the lungs. Indacaterol is the first once-daily LABA approved for treatment of COPD, and is administered by inhalation through the Breezhaler® device. The speed of bronchodilation is similar to that with salbutamol (ie, about five minutes) and longer (ie, 24 hours) than that with traditional LABA, with the same 12-hour effect as salmeterol and formoterol, both of which require twice-daily administration. This is why indacaterol has been called the "ultra-LABA". On the one hand, the fast onset of action provides immediate relief of symptoms, and on the other, its constant 24-hour bronchodilation provides "pharmacologic stenting" which facilitates lung emptying, thereby decreasing trapped gas and pulmonary hyperinflation. Once-daily administration of a fast and long-acting bronchodilator can improve patient adherence with therapy, which is known to be a major problem for many medical treatments. Dose-finding trials have shown that 75 μg is the minimum dose needed to achieve clinically important improvement. However, indacaterol 150 μg and 300 μg achieve an even greater improvement in lung function and patient-oriented outcomes. Further, these two doses of indacaterol significantly reduce pulmonary hyperinflation, thereby improving exercise tolerance and ability to perform day-to-day activities. It is more effective on lung volumes at the 300 μg dose than formoterol, and better than salmeterol and tiotropium at the 150 μg dose, at least in the acute setting. It is noteworthy that few studies document these results in patients with COPD and moderate airflow obstruction. These are exactly the kind of patients our research should be concentrating on, in view of the accelerated decay in forced expiratory volume in one second at this stage of the disease. Finally, all the relevant studies show that indacaterol is consistently well tolerated by patients with COPD at every stage, and that it has a high safety profile.

Keywords: chronic obstructive pulmonary disease; indacaterol.

Figure 1

Schematic illustration showing that the natural history of chronic obstructive pulmonary disease is characterized by a progressive increase in gas trapping measured as a progressive increase in residual volume. Note: A lesser increase in TLC leads to progressive decline in VC, imposing a reduction in FEV₁.© 2010 European Respiratory Society. Reproduced with permission of the European Respiratory Society Eur Respir J March 2010 35:676-680; doi: 10.1183/09031936.00120609. Abbreviations: FEV₁, forced expiratory volume in one second; FRC, functional residual capacity; IC, inspiratory capacity; TLC, total lung capacity; VC, vital capacity; RV, residual volume; L, liters.

Figure 2

Effect of active treatments (differences compared with placebo) on trough FEV₁ at week 26. Notes: Data are least squares means with 95% confidence intervals. ^aP < 0.001 versus placebo. The broken line indicates the minimum clinically important difference.© 2012 Elsevier Limited. Reproduced with permission from Decramer et al. Abbreviation: FEV₁, forced expiratory volume in one second.

Figure 3

Range of average rate of decline of FEV₁ in patients with chronic obstructive pulmonary disease according to severity of airflow obstruction. Notes: The dashed segment of the line highlights any stage or part of it where consistent information is still lacking. Control data from the UPLIFT study were not considered in the analysis.© 2012 Dove Medical Press. Reproduced with permission from Tantucci C, Modina D. Lung function decline in COPD. Int J Chron Obstruc Pulmon Dis. 2012;7:95–99. Abbreviation: FEV₁, forced expiratory volume in one second.

Figure 4

Comparison of effects of indacaterol and formoterol on FEV₁ and inspiratory capacity as percent change in unadjusted mean values from predose. Notes: Error bars omitted for clarity. n = 30 from each treatment. Black squares, indacaterol FEV₁; black circles, indacaterol inspiratory capacity; empty squares, formoterol FEV₁; empty circles, formoterol inspiratory capacity.From © 2009 Elsevier Limited. Reproduced with permission from Beier et al. Abbreviation: FEV₁, forced expiratory volume in one second.

Figure 5

Changes in FRC, TLC, and RV at hour 4 after administration. Notes: FRC was decreased compared with predose by 305+100mL with indacaterol (p=0.01*), and by 236+88 with tiotropium (p=0.053); TLC by 152+114mL with indacaterol (p=0.208), and by 28+85mL with tiotropium (p=0.806); and RV by 395+125mL with indacaterol (p=0.004**), and by 301+106mL with tiotropium (p=0.029***). Data are expressed as the mean+standard error of the mean. Black and gray bars are indacaterol and tiotropim, respectively.© 2012 Elsevier Limited. Reproduced with permission from Rossi et al. Abbreviations: FRC, functional residual capacity; TLC, total lung capacity; RV, residual volume.