Review of role of roflumilast in the prevention of an exacerbation associated with the Chronic Obstructive Pulmonary Disease

Dr. Pathak Hardik, Pranami Dhiren, Barkate Hanmant V

Dr. Pathak Hardik, Pranami Dhiren, Barkate Hanmant V

Keywords: Roflumilast, Chronic Obstructive Pulmonary Disease, COPD exacerbation, Phosphodiesterase 4 inhibitor, exacerbation

Abstract

COPD (Chronic Obstructive Pulmonary Disease), is a progressive disease that is characterized by persistent airflow limitation that leads to significant breathing problems in the patient. Sudden worsening of the symptoms of COPD is called as a COPD exacerbation. Usually COPD patients are categorised as mild, moderate and severe based on the symptoms, lung function and risk of exacerbation. The severe COPD is associated with frequent exacerbations which further deteriorates lung function of the patient. COPD exacerbations lead to frequent hospitalisation and are associated with high mortality. If COPD exacerbations result in hospitalization, they carry the same mortality as a heart attack: 22% die within the following 12 months and 50% who
required ICU admission die during hospitalization. To prevent this exacerbation in COPD patients, active management with medications is necessary. Roflumilast, a selective phosphodiesterase-4 (PDE4) inhibitor, is a relatively newer option in the management of COPD. Roflumilast is used concomitantly with other available bronchodilators and also in the patients taking inhaled corticosteroids. In various clinical trials and real life studies, efficacy of roflumilast is well established in the prevention of COPD exacerbation and it also improves lung function. Because of novel mechanism of action and its efficacy in addition to current available therapy, roflumilast represents a valuable inclusion in the current armament for treating COPD patients. However, risk benefit ratio and long term safety profile of roflumilast needs further investigation particularly in the Indian patients.

References

1. Vestbo J, Hurd SS, Agustí AG, Jones PW, Vogelmeier C, Anzueto A et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease:
GOLD executive summary. Am J Respir Crit Care Med. 2013;187 (4):347–65.
2. Llordés M, Jaén A, Almagro P, Heredia JL, Morera J, Soriano JB et al. Prevalence, Risk Factors and Diagnostic Accuracy of COPD Among Smokers in Primary Care. COPD. 2015;12(4):404-12
3. WHO | Burden of COPD [Internet]. WHO. [cited 2014 Dec 12]. Available from: http://www.who.int/respiratory/copd/ burden/en/
4. Jindal SK, Aggarwal AN, Gupta D, Agarwal R, Kumar R, Kaur T et al. Indian study on epidemiology of asthma, respiratory symptoms and chronic bronchitis in adults (INSEARCH). Int J Tuberc Lung Dis. 2012;16(9):1270-7
5. Salvi S, Agrawal A. India needs a national COPD prevention and control programme. J Assoc Physicians India. 2012;60 Suppl:5–7.
6. Koul PA. Chronic obstructive pulmonary disease: Indian guidelines and the road ahead. Lung India 2013;30(3):175–7..
7. Gupta D, Agarwal R, Aggarwal AN, Maturu VN, Dhooria S, Prasad KT et al. Guidelines for diagnosis and management of chronic obstructive pulmonary disease: Joint ICS/NCCP (I) recommendations. Lung India. 2013;30(3):228–67.
8. Sanford M. Roflumilast: in chronic obstructive pulmonary disease. Drugs. 2010;70 (12):1615–27.
9. Rennard SI, Sun SX, Tourkodimitris S, Rowe P, Goehring UM, Bredenbröker D et al. Roflumilast and dyspnea in patients with moderate to very severe chronic obstructive pulmonary disease: a pooled analysis of four clinical trials. Int J Chron Obstruct Pulmon Dis. 2014;9:657–73.
10. Ho T-W, Tsai Y-J, Ruan S-Y, Huang C-T, Lai F, Yu C-J et al. In-hospital and one-year mortality and their predictors in patients hospitalized for first-ever chronic obstructive pulmonary disease exacerbations: a nationwide population-based study. PloS One. 2014;9(12):e114866.
11. Singh S, Loke YK. An overview of the benefits and drawbacks of inhaled corticosteroids in chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis. 2010;5:189–95.
12. Calverley PMA, Sanchez-Toril F, McIvor A, Teichmann P, Bredenbroeker D, Fabbri LM. Effect of 1-year treatment with roflumilast in severe chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2007;176(2):154–61.
13. Calverley PMA, Rabe KF, Goehring U-M, Kristiansen S, Fabbri LM, Martinez FJ et al. Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials.
Lancet. 2009;374(9691):685–94.
14. Hanania NA, Calverley PMA, Dransfield MT, Karpel JP, Brose M, Zhu H et al. Pooled subpopulation analyses of the effects of roflumilast on exacerbations and lung function in COPD. Respir Med. 2014;108(2):366–75.
15. Bateman E, Jardim J, Goehring U-M, Brose M, Calverley P. Effect of roflumilast on hospitalizations in COPD patients. Eur Respir J. 2012;40(Suppl 56):P2109.
16. Fabbri LM, Calverley PMA, Izquierdo-Alonso JL, Bundschuh DS, Brose M, Martinez FJ et al. Roflumilast in moderate-tosevere chronic obstructive pulmonary disease treated with longacting bronchodilators: two randomised clinical trials. Lancet. 2009; 374(9691):695–703.
17. Fabbri L, Goehring U-M, Brose M, Rabe K. Effects of roflumilast in highly symptomatic COPD patients. Eur Respir J. 2012;40(Suppl 56):P742.
18. Yan J-H, Gu W-J, Pan L. Efficacy and safety of roflumilast in patients with stable chronic obstructive pulmonary disease: a meta-analysis. Pulm Pharmacol Ther. 2014;27 (1):83–9.
19. Zheng J, Yang J, Zhou X, Zhao L, Hui F, Wang H et al. Roflumilast for the treatment of COPD in an Asian population: a randomized, double-blind, parallel-group study. Chest. 2014;145(1):44–52.
20. Wedzicha JA, Rabe KF, Martinez FJ, Bredenbröker D, Brose M, Goehring U-M et al. Efficacy of roflumilast in the COPD frequent exacerbator phenotype. Chest. 2013; 143(5):1302–11.
21. Muñoz-Esquerre M, Diez-Ferrer M, Montón C, Pomares X, López-Sánchez M, Huertas D et al. Roflumilast added to triple therapy in patients with severe COPD: A real life study. Pulm Pharmacol Ther. 2014;30C:16–21.
22. White WB, Cooke GE, Kowey PR, Calverley PMA, Bredenbröker D, Goehring U-M et al. Cardiovascular safety in patients receiving roflumilast for the treatment of COPD. Chest. 2013;144(3):758–65.
23. Yu T, Fain K, Boyd CM, Singh S, Weiss CO, Li T et al. Benefits and harms of roflumilast in moderate to severe COPD. Thorax. 2013 Dec 17;thoraxjnl – 2013–204155.
24. Gudmundsson G, Gislason T, Lindberg E, Hallin R, Ulrik CS, Brøndum E et al. Mortality in COPD patients discharged from hospital: the role of treatment and co-morbidity. Respir Res. 2006;7(1):109.