Tuberc Respir Dis.  2007 Oct;63(4):337-345.

The Efficacy of Added Montelukast in Persistent Asthmatics Who Were Not Completely Controlled on Inhaled Corticosteroids and Inhaled Long-acting beta2-agonists

• Choi JH
• Park HS
• Lee KH
• Shim JJ
• Uh ST
• Lee SP
• Lee YC
• Choi WI
• Kim JI
• Lee JH
• Lee MG
• Jung KS

Abstract

BACKGROUNDS: Although glucocorticoids are one of the most potent anti-inflammatory agents, they have limited effect on cysteinyl leukotriene biosynthesis. In addition, the response to inhaled corticosteroids (ICS) and inhaled long-acting beta2-agonists (LABA) combination therapy in moderate to severe persistent asthmatics varies. Additional therapy with leukotriene receptor antagonists (LTRA) in patients with moderate to severe asthma suboptimally controlled with ICS and LABA combination therapy would be complementary to asthma control.
METHODS
One hundred and ninety eight asthmatics entered a 2 month, open-label descriptive study. Patients suffering from persistent asthma and suboptimally controlled on a combination therapy of fluticasone/salmeterol or budesonide/ formoterol were given montelukast 10 mg daily as an add-on therapy. The level of asthma control was assessed using the Asthma Control Questionnaire (ACQ) including FEV(1) % predicted at the baseline and after a 2-month treatment with montelukast. A global evaluation of the treatment was also made by the patients and physicians.
RESULTS
The mean ACQ score decreased significantly on montelukast (11.5+/-5.4 at baseline vs. 6.7+/-5.0), with a significant improvement in all individual symptom scores (p<0.01). The FEV(1) % predicted values did not show any significant change. 59.9% of patients and 59.4% of physicians reported global improvement in their asthma (kappa=0.85).
CONCLUSION
These results suggest that the addition of montelukast in patients with persistent asthma that is suboptimally contolled by combination therapy of ICS and LABA might confer complementary effects on asthma control.

Keyword

Asthma control; Inhaled glucocorticosteroid; Long-acting inhaled beta2-agonist; Montelukast

MeSH Terms

Adrenal Cortex Hormones*
Anti-Inflammatory Agents
Asthma
Glucocorticoids
Humans
Leukotriene Antagonists
Surveys and Questionnaires
Formoterol Fumarate
Adrenal Cortex Hormones
Anti-Inflammatory Agents
Glucocorticoids
Leukotriene Antagonists

Figure

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  Figure 1 Mean individual symptom scores of the ACQ in patients before and after addition of montelukast to fixed association(FA) of ICS plus LABA.

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  Figure 2 Global evaluation of asthma symptoms at visit 2.

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  Figure 3 Global evaluation of rhinitis symptoms at visit 2.

Reference

1. Busse WW, O'Byrne PM, Holgate ST. Adkinson NF, Yunginger JW, Busse WW, Bochner BS, Holgate ST, Simons FE, editors. Chapter 66. Asthma pathogenesis. Middleton's allergy. Principles and practices. 2003. 6th ed. Philadelphia: Mosby, Inc.;1175–1207.

2. Global strategy for asthma management and prevention (Revised 2006). Global initiative for asthma (GINA). Available from: http://ginasthma.org.

3. Szefler SJ, Martin RJ, King TS, Boushey HA, Cherniack RM, Chinchilli VM, et al. Significant variability in response to inhaled corticosteroids for persistent asthma. J Allergy Clin Immunol. 2002. 109:410–418.

4. Schleimer RP, Spahn JD, Covar R, Szefler SJ. Adkinson NF, Yunginger JW, Busse WW, Bochner BS, Holgate ST, Simons FE, editors. Chapter 52. Glucocorticoids. Middleton's allergy. Principles and practices. 2003. 6th ed. Philadelphia: Mosby, Inc.;870–913.

5. Salvi SS, Krishna MT, Sampson AP, Holgate ST. The anti-inflammatory effects of leukotriene-modifying drugs and their use in asthma. Chest. 2001. 119:1533–1546.

6. Lewis RA, Austen KF, Soberman RJ. Leukotrienes and other products of the 5-lipoxygenase pathway. N Engl J Med. 1990. 323:645–655.

7. Henderson WR Jr. The role of leukotrienes in inflammation. Ann Intern Med. 1994. 121:684–697.

8. Lipworth BJ. Leulkotriene-receptor antagonists. Lancet. 1999. 353:57–62.

9. Drazen JM, Israel E, O'Byrne PM. Treatment of asthma with drugs modifying the leukotriene pathway. N Engl J Med. 1999. 340:197–206.

10. Barnes NC, Miller CJ. Effect of leukotriene receptor antagonists therapy on the risk of asthma exacerbations in patients with mild to moderate asthma: an integrated analysis of zafirlukast trials. Thorax. 2000. 55:478–483.

11. Currie GP, Lee DK, Haggart K, Bates CE, Lipworth BJ. Effects of montelukast on surrogate inflammatory markers in corticosteroid treated asthmatics. Am J Respir Crit Care Med. 2003. 167:1232–1238.

12. Dupont L, Potvin E, Korn D, Lachman A, Dramaix M, Gusman J, et al. Improving asthma control in patients suboptimally controlled on inhaled steroids and long-acting β2-agonists: addition of montelukast in an open-label pilot study. Curr Med Res Opin. 2005. 21:863–869.

13. Juniper EF, O'Byrne PM, Guyatt GH, Ferrie PJ, King DR. Development and validation of a questionnaire to measure asthma control. Eur Respir J. 1999. 14:902–907.

14. Bateman ED, Boushey HA, Bousquet J, Busse WW, Clark TJ, Pauwels RA, et al. Can guideline-defined asthma control be achieved? The gaining optimal asthma control study. Am J Respir Crit Care Med. 2004. 170:836–844.

15. Malonne H, Lachman A, Van den Brande P. Impact of montelukast on symptoms in mild-to-moderate persistent asthma and exercise-induced asthma: results of the asthma survey. Curr Med Res Opin. 2002. 18:512–519.

16. Bjermer L, Bisgaard H, Bousquet J, Fabbri LM, Greening AP, Haahtela T, et al. Motelukast and fluticasone compared with salmeterol and fluticasone in protecting against asthma exacerbation in adults: one year, double blind, randomized, comparative trial. BMJ. 2003. 327:891.

17. Ducharme FM, Lasserson TJ, Cates CJ. Long-acting beta2-agonists versus anti-leukotrienes as add-on therapy to inhaled corticosteroids for chronic asthma. Cochrane Database Syst Rev. 2006. 18:CD003137.

18. Deykin A, Wechsler ME, Boushey HA, Chinchilli VM, Kunselman SJ, Craig TJ, et al. Combination therapy with a long acting β-agonist and a leukotriene antagonist in moderate asthma. Am J Respir Crit Care Med. 2007. 175:228–234.

19. Philip G, Nayak AS, Berger WE, Leynadier F, Vrijens F, Dass SB, et al. The effect of montelukast on rhinitis symptoms in patients with asthma and seasonal allergic rhinitis. Curr Med Res Opin. 2004. 20:1549–1558.