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Allergy, Asthma & Clinical Immunology

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Open Access 01-12-2014 | Research

Effectiveness of montelukast administered as monotherapy or in combination with inhaled corticosteroid in pediatric patients with uncontrolled asthma: a prospective cohort study

Authors: Denis Bérubé, Michel Djandji, John S Sampalis, Allan Becker

Published in: Allergy, Asthma & Clinical Immunology | Issue 1/2014

Abstract

Background

Asthma is the most common chronic disease of childhood and a leading cause of childhood morbidity. The aim of the current study was to assess the effectiveness of montelukast administered as monotherapy or in combination with current inhaled corticosteroids (ICS) in pediatric patients with uncontrolled asthma as per the Canadian Asthma Consensus Guidelines.

Methods

Twelve-week, multicentre, open-label, observational study. Primary effectiveness outcome was the proportion of patients achieving asthma control (Asthma Control Questionnaire (ACQ) score ≤0.75) at weeks 4 and 12.

Results

A total of 328 patients with uncontrolled asthma (ACQ > 0.75) were enrolled with mean ± SD age of 6.9 ± 3.4 years. Among these, 76 (23.2%) were treated with montelukast monotherapy and 252 (76.8%) with montelukast combined with ICS. By 4 weeks of treatment 61.3% and 52.9% of the patients in the monotherapy and combination group, respectively, achieved asthma control. These proportions increased to 75.0% and 70.9%, respectively, at 12 weeks. Within the monotherapy group, clinically significant improvements in the ACQ score (mean ± SD of 1.67 ± 0.69, 0.71 ± 0.70 and 0.50 ± 0.52 at baseline, 4 and 12 weeks, respectively; p < 0.001) and the PACQLQ score (mean ± SD of 5.34 ± 1.14, 6.32 ± 0.89 and 6.51 ± 0.85 at baseline, 4 and 12 weeks, respectively; p < 0.001) were observed. In the combination group, the mean ± SD ACQ score significantly improved from 2.02 ± 0.83 at baseline to 0.90 ± 0.86 at 4 weeks and 0.64 ± 0.86 at 12 weeks (p < 0.001), while the PACQLQ score improved from 4.42 ± 1.35 at baseline to 5.76 ± 1.30 at 4 weeks and 6.21 ± 1.03 at 12 weeks (p < 0.001). After a 12-week montelukast add-on therapy, 22.6% of patients reduced their ICS dosage. Similar results were observed among preschool- and school-aged patients.

Conclusions

Montelukast as monotherapy or in combination with ICS represents an effective treatment strategy for achieving asthma control in pediatric patients and improving caregivers’ quality of life.

Trial registration

This study is registered at ClinicalTrial.gov: NCT00832455.

Available only for authorised users

Akinbami LJ, Schoendorf KC: Trends in childhood asthma: prevalence, health care utilization, and mortality. Pediatrics. 2002, 110 (2 Pt 1): 315-322.CrossRefPubMed

Bateman ED, Hurd SS, Barnes PJ, Bousquest J, Drazen JM, Fitzgerald M, Gibson P, Ohta K, Byrne P, Pedersen SE, Pizzichini E, Sullivan SD, Wenzel SE, Zar J: Global strategy for asthma management and prevention: GINA executive summary. Eur Respir J. 2008, 31 (1): 143-178. 10.1183/09031936.00138707.CrossRefPubMed

Garner R, Kohen D: Changes in the prevalence of asthma among Canadian children. Health Rep Stat Can Catalogue 82–003. 2008, 19: 1-7.

Millar WJ, Gerry BH: Childhood asthma. Health Rep Stat Can Catalogue 82–003. 1998, 10: 9-21.

Global strategy for asthma management and prevention. Global Initiative for Asthma (GINA), 2009. http://www.ginasthma.org (Version current at May 05, 2010)

Becker A, Lemière C, Bérubé D, Boulet LP, Ducharme FM, Fitzgerald M, Kovesi T: Summary of recommendations from the Canadian asthma consensus guidelines, 2003. CMAJ. 2005, 173 (Suppl 6): S3-S11.PubMedCentralPubMed

Becker A, Bérubé D, Chad Z, Dolovich M, Ducharme F, D’Urzo T, Ernst P, Ferguson A, Gillespie C, Kapur S, Kovesi T, Lyttle B, Mazer B, Montgomery M, Pedersen S, Pianosi P, Reisman JJ, Sears M, Simons E, Spier S, Thivierge R, Watson W, Zimmerman B: Canadian pediatric asthma consensus guidelines, 2003 (updated to December 2004): introduction. CMAJ. 2005, 173 (Suppl 6): S12-S14.PubMedCentralCrossRefPubMed

Global strategy for the diagnosis and management of asthma in children 5 years and younger. Global Initiative for Asthma (GINA), 2009. http://www.ginasthma.org (Version current at May 05, 2010)

Zeiger RS, Szefler SJ, Phillips BR, Schatz M, Martinez FD, Chinchilli VM, Lemanske RF, Strunk RC, Larsen G, Spahn JD, Bacharier LB, Bloomberg GR, Guilbert TW, Heldt G, Morgan WJ, Moss MH, Sorkness CA, Taussig LM: Response profiles to fluticasone and montelukast in mild-to-moderate persistent childhood asthma. J Allergy Clin Immunol. 2006, 117 (1): 45-52. 10.1016/j.jaci.2005.10.012.CrossRefPubMed

10.

Szefler SJ, Phillips BR, Martinez FD, Chinchilli VM, Lemanske RF, Strunk RC, Zeiger RS, Larsen G, Spahn JD, Bacharier LB, Bloomberg GR, Guilbert TW, Heldt G, Morgan WJ, Moss MH, Sorkness CA, Taussig LM: Characterization of within-subject responses to fluticasone and montelukast in childhood asthma. J Allergy Clin Immunol. 2005, 115 (2): 233-242. 10.1016/j.jaci.2004.11.014.CrossRefPubMed

11.

Wahn U, Dass SB: Review of recent results of montelukast use as a monotherapy in children with mild asthma. Clin Ther. 2008, 30: 1026-1035.CrossRefPubMed

12.

National Asthma Education and Prevention Program: National Asthma Education and Prevention Program. Expert panel report: guidelines for the diagnosis and management of asthma update on selected topics--2002. J Allergy Clin Immunol. 2002, 110 (5): S141-S219. 10.1016/S0091-6749(02)80002-1.CrossRef

13.

Knorr B, Franchi LM, Bisgaard H, Vermeulen JH, LeSouef P, Santanello N, Michele TM, Reiss TF, Ngyen HH, Bratton DL: Montelukast, a leukotriene receptor antagonist, for the treatment of persistent asthma in children aged 2 to 5 years. Pediatrics. 2001, 108 (3): E48-E58. 10.1542/peds.108.3.e48.CrossRefPubMed

14.

Knorr B, Matz J, Bernstein JA, Nguyen H, Seidenberg BC, Reiss TF, Becker A: Montelukast for chronic asthma in 6- to 14-year-old children: a randomized, double-blind trial. Pediatric Montelukast Study Group. JAMA. 1998, 279 (15): 1181-1186. 10.1001/jama.279.15.1181.CrossRefPubMed

15.

Juniper EF, Bousquet J, Abetz L, Bateman ED, GOAL Committee: Identifying ‘well-controlled’ and ‘not well-controlled’ asthma using the asthma control questionnaire. Respir Med. 2006, 100 (4): 616-621. 10.1016/j.rmed.2005.08.012.CrossRefPubMed

16.

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 (4): 902-907. 10.1034/j.1399-3003.1999.14d29.x.CrossRefPubMed

17.

Juniper EF, Guyatt GH, Feeny DH, Ferrie PJ, Griffith LE, Townsend M: Measuring quality of life in the parents of children with asthma. Qual Life Res. 1996, 5 (1): 27-34. 10.1007/BF00435966.CrossRefPubMed

18.

Global strategy for asthma management and prevention. Global Initiative for Asthma (GINA), 2006. http://www.ginasthma.com/Guidelineitem.asp?l1=2&l2=1&intId=1388. 2010

19.

International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH): Medical dictionary for regulatory activities terminology. MedDRA Version 90. 2006

20.

Phillips C, McDonald T: Trends in medication use for asthma among children. Curr Opin Allergy Clin Immunol. 2008, 8 (3): 232-237. 10.1097/ACI.0b013e3282fe9d2f.CrossRefPubMed

21.

Bisgaard H, Zielen S, Garcia-Garcia ML, Johnston SL, Gilles L, Menten J, Tozzi CA, Polos P: Montelukast reduces asthma exacerbations in 2- to 5-year-old children with intermittent asthma. Am J Respir Crit Care Med. 2005, 171 (4): 315-322. 10.1164/rccm.200407-894OC.CrossRefPubMed

22.

Muijsers RB, Noble S: Montelukast: a review of its therapeutic potential in asthma in children 2 to 14 years of age. Paediatr Drugs. 2002, 4 (2): 123-139. 10.2165/00128072-200204020-00005.CrossRefPubMed

23.

Bukstein DA, Luskin AT, Bernstein A: “Real-world” effectiveness of daily controller medicine in children with mild persistent asthma. Ann Allergy Asthma Immunol. 2003, 90 (5): 543-549. 10.1016/S1081-1206(10)61848-0.CrossRefPubMed

24.

Garcia Garcia ML, Wahn U, Gilles L, Swern A, Tozzi CA, Polos P: Montelukast, compared with fluticasone, for control of asthma among 6- to 14-year-old patients with mild asthma: the MOSAIC study. Pediatrics. 2005, 116 (2): 360-369. 10.1542/peds.2004-1172.CrossRefPubMed

25.

Joos S, Miksch A, Szecsenyi J, Wieseler B, Grouven U, Kaiser T, Schneider A: Montelukast as add-on therapy to inhaled corticosteroids in the treatment of mild to moderate asthma: a systematic review. Thorax. 2008, 63 (5): 453-462. 10.1136/thx.2007.081596.CrossRefPubMed

26.

Kondo N, Katsunuma T, Odajima Y, Morikawa A: A randomized open-label comparative study of montelukast versus theophylline added to inhaled corticosteroid in asthmatic children. Allergol Int. 2006, 55 (3): 287-293. 10.2332/allergolint.55.287.CrossRefPubMed

27.

Phipatanakul W, Greene C, Downes SJ, Cronin B, Eller TJ, Schneider LC, Irani AM: Montelukast improves asthma control in asthmatic children maintained on inhaled corticosteroids. Ann Allergy Asthma Immunol. 2003, 91 (1): 49-54. 10.1016/S1081-1206(10)62058-3.CrossRefPubMed

28.

Williams B, Noonan G, Reiss TF, Knorr B, Guerra J, White R, Matz J: Long-term asthma control with oral montelukast and inhaled beclomethasone for adults and children 6 years and older. Clin Exp Allergy. 2001, 31 (6): 845-854. 10.1046/j.1365-2222.2001.01085.x.CrossRefPubMed

29.

Holbrook JT, Wise RA, Gold BD, Blake K, Brown ED, Castro M, Dozor AJ, Lima JJ, Mastronarde JG, Sockrider MM, Teague WG: Lansoprazole for children with poorly controlled asthma: a randomized controlled trial9. JAMA. 2012, 307 (4): 373-381.PubMedCentralCrossRefPubMed

30.

Kersten ET, van Leeuwen JC, Brand PL, Duiverman EJ, de Jongh FH, Thio BJ, Driessen JMM: Effect of an intranasal corticosteroid on exercise induced bronchoconstriction in asthmatic children2. Pediatr Pulmonol. 2012, 47 (1): 27-35. 10.1002/ppul.21511.CrossRefPubMed

31.

Dean BB, Calimlim BM, Kindermann SL, Khandker RK, Tinkelman D: The impact of uncontrolled asthma on absenteeism and health-related quality of life. J Asthma. 2009, 46 (9): 861-866. 10.3109/02770900903184237.CrossRefPubMed

32.

Halterman JS, Yoos HL, Conn KM, Callahan PM, Montes G, Neely TL, Szilagyi PG: The impact of childhood asthma on parental quality of life. J Asthma. 2004, 41 (6): 645-653. 10.1081/JAS-200026410.CrossRefPubMed

33.

Löfdahl CG, Reiss TF, Leff JA, Israel E, Noonan MJ, Finn AF, Seidenberg BC, Capizzi T, Kundu S, Godard P: Randomised, placebo controlled trial of effect of a leukotriene receptor antagonist, montelukast, on tapering inhaled corticosteroids in asthmatic patients. BMJ. 1999, 319 (7202): 87-90. 10.1136/bmj.319.7202.87.PubMedCentralCrossRefPubMed

34.

Riccioni G, Vecchia RD, Castronuovo M, Ilio CD, D’Orazio N: Tapering dose of inhaled budesonide in subjects with mild-to-moderate persistent asthma treated with montelukast: a 16-week single-blind randomized study. Ann Clin Lab Sci. 2005, 35 (3): 285-289.PubMed

35.

Strunk RC, Bacharier LB, Phillips BR, Szefler SJ, Zeiger RS, Chinchilli VM, Martinez FD, Lemanske RF, Taussig LM, Mauger DT, Morgan WJ, Sorkness CA, Paul IM, Guilbert T, Krawiec M, Covar R, Larsen G: Azithromycin or montelukast as inhaled corticosteroid-sparing agents in moderate-to-severe childhood asthma study. J Allergy Clin Immunol. 2008, 122 (6): 1138-1144. 10.1016/j.jaci.2008.09.028.PubMedCentralCrossRefPubMed

36.

Tamesis GP, Covar RA: Long-term effects of asthma medications in children. Curr Opin Allergy Clin Immunol. 2008, 8 (2): 163-167. 10.1097/ACI.0b013e3282f50e9d.CrossRefPubMed

37.

Jartti T: Inhaled corticosteroids or montelukast as the preferred primary long-term treatment for pediatric asthma?. Eur J Pediatr. 2008, 167 (7): 731-736. 10.1007/s00431-007-0644-3.CrossRefPubMed

38.

Bisgaard H: Leukotriene modifiers in pediatric asthma management. Pediatrics. 2001, 107 (2): 381-390. 10.1542/peds.107.2.381.CrossRefPubMed

39.

Malmstorm K, Rodriguez-Gomez G, Guerra J, Villaran C, Pineiro A, Wei LX, Seidengerg BC, Reiss TF: Oral montelukast, inhaled beclomethasone, and placebo for chronic asthma. A randomized, controlled trial. Montelukast/Beclomethasone Study Group. Ann Intern Med. 1999, 130 (6): 487-495. 10.7326/0003-4819-130-6-199903160-00005.CrossRef

40.

Szefler SJ, Martin RJ, King TS, Boushey HA, Cherniack RM, Chinchilli VM, Craig TJ, Dolovich M, Drazen JM, Fagan JK, Fahy JV, Fish JE, Ford JG, Israel E, Kiley J, Kraft M, Lazarus SC, Lemanske RF, Mauger E, Peters SP, Sorkness CA: Significant variability in response to inhaled corticosteroids for persistent asthma. J Allergy Clin Immunol. 2002, 109 (3): 410-418. 10.1067/mai.2002.122635.CrossRefPubMed

41.

Meyer KA, Arduino JM, Santanello NC, Knorr BA, Bisgaard H: Response to montelukast among subgroups of children aged 2 to 14 years with asthma. J Allergy Clin Immunol. 2003, 111 (4): 757-762. 10.1067/mai.2003.1391.CrossRefPubMed

42.

Bateman ED, Reddel HK, Eriksson G, Peterson S, Ostlund O, Sears MR, Jenkins C, Humbert M, Buhl R, Harrison TW, Quirce S, O’Byrne PO: Overall asthma control: the relationship between current control and future risk 14. J Allergy Clin Immunol. 2010, 125 (3): 600-608. 10.1016/j.jaci.2009.11.033. 608CrossRefPubMed

43.

van den Nieuwenhof L, Schermer T, Eysink P, Halet E, van Weel C, Bindels P, Bottema B: Can the asthma control questionnaire be used to differentiate between patients with controlled and uncontrolled asthma symptoms? A pilot study. Fam Pract. 2006, 23 (6): 674-681. 10.1093/fampra/cml041.CrossRefPubMed

44.

Stocks J, Sly PD, Tepper RS, Morgan WJ: Infant Respiratory Function Testing. 1996, New York, NY: Wiley-Liss, Inc.

45.

Juniper EF, O’Byrne PM, Roberts JN: Measuring asthma control in group studies: do we need airway calibre and rescue beta2-agonist use?. Respir Med. 2001, 95 (5): 319-323. 10.1053/rmed.2001.1034.CrossRefPubMed

Title: Effectiveness of montelukast administered as monotherapy or in combination with inhaled corticosteroid in pediatric patients with uncontrolled asthma: a prospective cohort study
Authors: Denis Bérubé
Michel Djandji
John S Sampalis
Allan Becker
Publication date: 01-12-2014
Publisher: BioMed Central
Published in: Allergy, Asthma & Clinical Immunology / Issue 1/2014
Electronic ISSN: 1710-1492
DOI: https://doi.org/10.1186/1710-1492-10-21

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Effectiveness of montelukast administered as monotherapy or in combination with inhaled corticosteroid in pediatric patients with uncontrolled asthma: a prospective cohort study

Abstract

Background

Methods

Results

Conclusions

Trial registration

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Trial registration

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