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#154 Pills vs. Puffers: Leukotriene receptor antagonists for childhood asthma


CLINICAL QUESTION
#154 Are leukotriene receptor antagonists (LTRAs) effective in pediatric asthma?

BOTTOM LINE
Using leukotriene receptor antagonists instead of inhaled corticosteroids as monotherapy will lead to one more exacerbation in every 21 patients. Asadd-on to inhaled corticosteroids, leukotriene receptor antagonists are inferior to long acting beta-agonists (LABAs), and show similar outcomes to increased dosesof inhaled corticosteroids (ICS). Data is limited and not supportive of use in children ≤5 years.  


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EVIDENCE
  • Randomized Controlled Trials (RCTs) report many outcomes, particularly surrogate endpoints like FEV1. We focused on objective clinical outcomes. 
    • Three systematic reviews of RCTs: ICS superior to LTRAs for mild/moderate asthma.1-3 
      • Largest Cochrane review (19 trials, 3,333 children):1 LTRA had statistically significantly more asthma exacerbations requiring oral corticosteroids (18.8%) versus ICS (13.3%), Number Needed to Harm (NNH)=21. 
    • Three systematic reviews assess LTRA as step-up therapy to ICS (4-16 weeks).3,4,5 Exacerbation compared in one RCT each: 
      • LTRA+ICS versus ICS same dose:6  
        • 279 children, no difference. 
      • LTRA+ICS low dose versus ICS moderate dose:7  
        • 165 children, no difference.  
      • LTRA+ICS versus LABA+ICS:7 
        • 167 children, no difference.   
        • Composite endpoint (exacerbations, asthma control days and FEV1) found LTRA inferior to LABA, NNH=6. 
      • Network meta-analysis (35 RCTs) found ICS+LABA best, ICS+LTRAs, medium/high-dose ICS and low-dose ICS tied for second, LTRA alone and placebo last.8 
    • RCTs comparing LTRAs to placebo report conflicting results.9,10
Context: 
  • Children age ≤5 years are included in few RCTs and fail to show consistent benefit.11,12   
    • Guidelines state LTRA “are not advocated and/or should be avoided” until further evidence in this age group. 
  • LTRAs were the second most commonly prescribed drug in children aged 0-11 from 2007-2009 (USA).14 
  • Parental concern about ICS safety, including growth effects, may impact decision making and compliance.15 No difference between LTRA and ICS in rates of adverse events, but more patients on LTRAs withdrew from studies due to poor asthma control.1 
  • LTRAs have demonstrated some benefit in various subgroups including allergic rhinitis,16,17 exercise induced bronchospasm,18 and specific genotypes.19 Limited research suggests superior outcomes with ICS in these groups.16-19 

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Author(s):

  • Chris Novak BSc
  • Christina Korownyk MD CCFP

1. Chauhan BF, Ducharme FM. Cochrane Database Syst Rev. 2012; 5:CD002314.

2. Massingham K, Fox S, Smaldone A. J Pediatr Health Care. 2014; 28(1):51-62.

3. Castro-Rodriguez JA, Rodrigo GJ. Arch Dis Child. 2010; 95(5):365-70.

4. Chauhan BF, Ben Salah R, Ducharme FM. Cochrane Database Syst Rev. 2013; 10:CD009585.

5. Chauhan BF, Ducharme FM. Cochrane Database Syst Rev. 2014; 1:CD003137.

6. Simons FE, Villa JR, Teper AM, et al. J Pediatr. 2001; 138(5):694-8.

7. Lemanske RF, Mauger DT, Sorkness CA, et al. N Engl J Med. 2010; 362(11):975-85.

8. Zhao Y, Han S, Shang J, et al. J Asthma. 2015; 52(8):846-57.

9. Knorr B, Matz J, Bernstein JA, et al. JAMA. 1998; 279(15):1181-6.

10. Weiss KB, Gern JE, Johnston NW. Ann Allergy Asthma Immunol. 2010; 105(2):174-81.

11. Nwokoro C, Pandya H, Turner S, et al. Lancet Respir Med. 2014; 2(10):796-803.

12. Valovirta E, Boza ML, Robertson CF, et al. Ann Allergy Asthma Immunol. 2011; 106(6):518-26.

13. Ducharme FM, Dell SD, Radhakrishnan D, et al. Can Respir J. 2015; 22:135-43.

14. Gu Q, Dillon CF, Burt LI. Available at: http://www.cdc.gov/nchs/data/databriefs/db42.htm. (Last accessed September 14, 2015)

15. Chan PW, DeBruyne JA. Pediatr Int. 2000; 42(5):547-51.

16. Philip G, Nayak AS, Berger WE, et al. Curr Med Res Opin. 2004; 20(10):1549-58.

17. Wilson AM, Dempsey OJ, Sims EJ, et al. Clin Exp Allergy. 2001; 31(4):616-24.

18. Parsons JP, Hallstrand TS, Mastronarde JG, et al. Am J Respir Crit Care Med. 2013; 187(9):1016-27.

19. Nwokoro C, Pandya H, Turner S, et al. Lancet Respir Med. 2014; 2(10):796-803.

Authors do not have any conflicts of interest to declare.