Tuberc Respir Dis.  2018 Jan;81(1):1-5. 10.4046/trd.2017.0102.

Add-on Therapy for Symptomatic Asthma despite Long-Acting Beta-Agonists/Inhaled Corticosteroid

• Dreher M
• Müller T

• KMID: 2420585
• DOI: http://doi.org/10.4046/trd.2017.0102

Abstract

Asthma, remains symptomatic despite ongoing treatment with high doses of inhaled corticosteroids (ICS) in conjunction with long-acting beta-agonists (LABA), is classified as "severe" asthma. In the course of caring for those patients diagnosed with severe asthma, stepping up from ICS/LABA to more aggressive therapeutic measures would be justified, though several aspects have to be checked in advance (including inhaler technique, adherence to therapy, and possible associated comorbidities). That accomplished, it would be advisable to step up care in accordance with the Global Initiative for Asthma (GINA) recommendations. Possible strategies include the addition of a leukotriene receptor antagonist or tiotropium (to the treatment regimen). The latter has been shown to be effective in the management of several subgroups of asthma. Oral corticosteroids have commonly been used for the treatment of patients with severe asthma in the past; however, the use of oral corticosteroids is commonly associated with corticosteroid-related adverse events and comorbidities. Therefore, according to GINA 2017 these patients should be referred to experts who specialize in the treatment of severe asthma to check further therapeutic options including biologics before starting treatment with oral corticosteroids.

Keyword

Asthma; Biological Products; Interleukin-5; Immunoglobulin E

MeSH Terms

Adrenal Cortex Hormones
Asthma*
Biological Products
Comorbidity
Humans
Immunoglobulin E
Interleukin-5
Nebulizers and Vaporizers
Receptors, Leukotriene
Tiotropium Bromide
Adrenal Cortex Hormones
Biological Products
Immunoglobulin E
Interleukin-5
Receptors, Leukotriene
Tiotropium Bromide

Reference

1. Global Initiative for Asthma. Global Strategy for asthma management and prevention, 2017 [Internet]. Bethesda: : Global Initiative for Asthma, National Heart, Lung and Blood; ;2017. cited 2017 Oct 1. Available from: http://www.ginasthma.org.

2. Chung KF, Wenzel SE, Brozek JL, Bush A, Castro M, Sterk PJ, et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J. 2014; 43:343–373.

3. Lucas AE, Smeenk FW, Smeele IJ, van Schayck CP. Overtreatment with inhaled corticosteroids and diagnostic problems in primary care patients, an exploratory study. Fam Pract. 2008; 25:86–91.

4. Aaron SD, Vandemheen KL, Boulet LP, McIvor RA, Fitzgerald JM, Hernandez P, et al. Overdiagnosis of asthma in obese and nonobese adults. CMAJ. 2008; 179:1121–1131.

5. Boulet LP, Vervloet D, Magar Y, Foster JM. Adherence: the goal to control asthma. Clin Chest Med. 2012; 33:405–417.

6. Melani AS, Bonavia M, Cilenti V, Cinti C, Lodi M, Martucci P, et al. Inhaler mishandling remains common in real life and is associated with reduced disease control. Respir Med. 2011; 105:930–938.

7. Saunders KB. Misuse of inhaled bronchodilator agents. Br J Med J. 1965; 1:1037–1038.

8. Sanchis J, Gich I, Pedersen S. Aerosol Drug Management Improvement Team (ADMIT). Systematic review of errors in inhaler use: has patient technique improved over time? Chest. 2016; 150:394–406.

9. Fink JB, Rubin BK. Problems with inhaler use: a call for improved clinician and patient education. Respir Care. 2005; 50:1360–1374.

10. Muller T, Muller A, Hubel C, Knipel V, Windisch W, Cornelissen CG, et al. Optimizing inhalation technique using web-based videos in obstructive lung diseases. Respir Med. 2017; 129:140–144.

11. Boulet LP. Influence of comorbid conditions on asthma. Eur Respir J. 2009; 33:897–906.

12. Virchow JC, Backer V, Kuna P, Prieto L, Nolte H, Villesen HH, et al. Efficacy of a house dust mite sublingual allergen immunotherapy tablet in adults with allergic asthma: a randomized clinical trial. JAMA. 2016; 315:1715–1725.

13. Powell H, Gibson PG. Inhaled corticosteroid doses in asthma: an evidence-based approach. Med J Aust. 2003; 178:223–225.

14. Vogelmeier C, Kardos P, Hofmann T, Canisius S, Scheuch G, Muellinger B, et al. Nebulised budesonide using a novel device in patients with oral steroid-dependent asthma. Eur Respir J. 2015; 45:1273–1282.

15. Chauhan BF, Ducharme FM. Anti-leukotriene agents compared to inhaled corticosteroids in the management of recurrent and/or chronic asthma in adults and children. Cochrane Database Syst Rev. 2012; (5):CD002314.

16. Virchow JC, Mehta A, Ljungblad L, Mitfessel H. MONICA Study Group. Add-on montelukast in inadequately controlled asthma patients in a 6-month open-label study: the MON-telukast In Chronic Asthma (MONICA) study. Respir Med. 2010; 104:644–651.

17. Kerstjens HA, Engel M, Dahl R, Paggiaro P, Beck E, Vandewalker M, et al. Tiotropium in asthma poorly controlled with standard combination therapy. N Engl J Med. 2012; 367:1198–1207.

18. Kerstjens HA, Moroni-Zentgraf P, Tashkin DP, Dahl R, Paggiaro P, Vandewalker M, et al. Tiotropium improves lung function, exacerbation rate, and asthma control, independent of baseline characteristics including age, degree of airway obstruction, and allergic status. Respir Med. 2016; 117:198–206.

19. Sweeney J, Patterson CC, Menzies-Gow A, Niven RM, Mansur AH, Bucknall C, et al. Comorbidity in severe asthma requiring systemic corticosteroid therapy: cross-sectional data from the Optimum Patient Care Research Database and the British Thoracic Difficult Asthma Registry. Thorax. 2016; 71:339–346.

20. Lefebvre P, Duh MS, Lafeuille MH, Gozalo L, Desai U, Robitaille MN, et al. Acute and chronic systemic corticosteroidrelated complications in patients with severe asthma. J Allergy Clin Immunol. 2015; 136:1488–1495.

21. Walsh LJ, Wong CA, Oborne J, Cooper S, Lewis SA, Pringle M, et al. Adverse effects of oral corticosteroids in relation to dose in patients with lung disease. Thorax. 2001; 56:279–284.

22. Normansell R, Walker S, Milan SJ, Walters EH, Nair P. Omalizumab for asthma in adults and children. Cochrane Database Syst Rev. 2014; (1):CD003559.

23. Pelaia G, Canonica GW, Matucci A, Paolini R, Triggiani M, Paggiaro P. Targeted therapy in severe asthma today: focus on immunoglobulin E. Drug Des Devel Ther. 2017; 11:1979–1987.

24. Celebi Sozener Z, Aydin O, Misirligil Z, Mungan D, Demirel YS, Celik GE, et al. Omalizumab in non-allergic asthma: a report of 13 cases. J Asthma. 2017; 08. 01. DOI: 10.1080/02770903.2017.1362427. [Epub].

25. Pavord ID, Korn S, Howarth P, Bleecker ER, Buhl R, Keene ON, et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet. 2012; 380:651–659.

26. Ortega HG, Liu MC, Pavord ID, Brusselle GG, FitzGerald JM, Chetta A, et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N Engl J Med. 2014; 371:1198–1207.

27. Bel EH, Wenzel SE, Thompson PJ, Prazma CM, Keene ON, Yancey SW, et al. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med. 2014; 371:1189–1197.

28. Castro M, Zangrilli J, Wechsler ME, Bateman ED, Brusselle GG, Bardin P, et al. Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from two multicentre, parallel, double-blind, randomised, placebo-controlled, phase 3 trials. Lancet Respir Med. 2015; 3:355–366.

29. Tan LD, Bratt JM, Godor D, Louie S, Kenyon NJ. Benralizumab: a unique IL-5 inhibitor for severe asthma. J Asthma Allergy. 2016; 9:71–81.

30. Bleecker ER, FitzGerald JM, Chanez P, Papi A, Weinstein SF, Barker P, et al. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2-agonists (SIROCCO): a randomised, multicentre, placebo-controlled phase 3 trial. Lancet. 2016; 388:2115–2127.

31. Nair P, Wenzel S, Rabe KF, Bourdin A, Lugogo NL, Kuna P, et al. Oral glucocorticoid-sparing effect of benralizumab in severe asthma. N Engl J Med. 2017; 376:2448–2458.

32. Shirley M. Dupilumab: first global approval. Drugs. 2017; 77:1115–1121.

33. Wenzel S, Castro M, Corren J, Maspero J, Wang L, Zhang B, et al. Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of medium-to-high-dose inhaled corticosteroids plus a long-acting beta2 agonist: a randomised double-blind placebo-controlled pivotal phase 2b dose-ranging trial. Lancet. 2016; 388:31–44.

34. Buhl R, Humbert M, Bjermer L, Chanez P, Heaney LG, Pavord I, et al. Severe eosinophilic asthma: a roadmap to consensus. Eur Respir J. 2017; 49:1700634.