Tools for Practice


#230 Less puffing, more breathing? Intermittent inhaled steroids for asthma


CLINICAL QUESTION
In patients with mild persistent asthma, is intermittent use of inhaled corticosteroids (ICS) as effective as daily use?


BOTTOM LINE
In patients with mild persistent asthma, intermittent use of ICS or ICS/LABA is similar to daily ICS in preventing exacerbations but is associated with ~5 fewer weeks per year of well-controlled asthma. Overall adverse events are similar.



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EVIDENCE
  • Focusing on two large (~4000 patients each), industry managed, randomized, double-blind, placebo-controlled trials (RCTs) in mild persistent asthma (controlled on low-dose daily ICS or uncontrolled with Short-Acting Beta-Agonist alone).1,2 Mean age ~40; ~20% had severe exacerbation in preceding year. Included patients randomized to budesonide/formoterol PRN or budesonide 200mcg BID + terbutaline PRN after a 2-4-week run-in of terbutaline only. Outcomes at 1 year (study results combined when similar outcomes reported): 
    • Patients with ≥ exacerbation: 
      • Severe exacerbations (oral steroids, hospitalization or emergency department visit with systemic corticosteroids):1,2 
        • Budesonide/formoterol PRN 7.4%, daily ICS 7.8%: not statistically different. 
      • Moderate to severe exacerbations:1 
        • Budesonide/formoterol PRN 10.3%, daily ICS 11.2%: not statistically different. 
    • Symptoms: 
      • Asthma Control Questionnaire-5 (ACQ-5): nighttime waking, symptoms on waking, activity limitation, shortness of breath, wheeze: 
        • Proportion with improvement of ≥ 0.5 points (minimally clinical important difference):1,2 
          • Budesonide/formoterol PRN 41%, daily ICS 46%, Number needed to harm (NNH)=20. 
        • Number of weeks with well controlled asthma: 
          • Budesonide/formoterol PRN 18 weeks versus 23 weeks.1 
        • Asthma Quality of Life Questionnaire: no clinically meaningful difference.1,2 
      • Adverse events: similar.1,2 
      • Total ICS exposure was ?60-70% lower with intermittent treatment.1,2 
Previous systematic review3 (6 RCTs; 1211 children and adults) of intermittent versus daily ICS (excluded ICS/LABA combination trials) found: 
  • No difference in risk of exacerbation. 
  • Fewer asthma-controlled days with intermittent versus daily ICS. 
  • For children: daily ICS resulted in ~0.5cm less growth (height) at ~1 year.3
Context: 
  • Up to 75% of asthmatics have mild asthma.4 
  • Guidelines recommend daily ICS for mild persistent asthma,5 but only ~50% adhere.6 
  • Intermittent ICS or ICS/LABA use, compared to daily ICS, results in less overall steroid use1,2 and potential cost savings.7,8 


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Author(s):

  • Michael R Kolber MD CCFP MSc
  • Nicolas Dugré PharmD MSc

1. O’Byrne PM, Mark Fitzgerald J, Bateman ED, et al. N Eng J Med. 2018; 378: 1865-76.

2. Bateman ED, Reddel HK, O’Byrne PM, et al. N Eng J Med. 2018; 378: 1877-87.


3. Chauhan BF, Chartrand C, Ducharme FM. Cochrane Database System Rev. 2013;2:CD009611.

4. Dusser D, Montani D, Chanez P, et al. Allergy. 2007; 62(6): 591-604.

5. Global initiative for asthma. https://ginasthma.org/2018-pocket-guide-for-asthma-management-and-prevention/ Last accessed: November 20, 2018.

6. Boulet LP, Vervloet D, Magar Y, et al. Clin Chest Med. 2012; 33: 405-417.

7. Alberta Health. Interactive drug benefit list. https://idbl.ab.bluecross.ca/idbl/load.do Last accessed: November 20, 2018.

8. Nickonchuk T, Lee J, Kolber M, et al. Available from: https://acfp.ca/wp-content/uploads/2018/03/ACFPPricingDoc2018.pdf. Last accessed: December 12, 2018.

Authors do not have any conflicts of interest to declare.