The risk of asthma exacerbation after stopping low-dose inhaled corticosteroids: A systematic review and meta-analysis of randomized controlled trials

Background: Current asthma guidelines suggest that patients and their providers consider decreasing or stopping controller medications when asthma is stable. Objective: We sought to estimate the risk of asthma exacerbation in patients who stop low-dose inhaled corticosteroids (ICSs) compared with those who continue ICSs in randomized controlled trials. Methods: We identified relevant trials from a systematic review of English-language and non-English-language articles using MEDLINE, EMBASE, and CENTRAL (inception to January 21, 2012). Articles were screened at the abstract and full-text level by 2 independent reviewers. We included randomized controlled trials with a stable asthma run-in period of 4 weeks or more, an intervention to stop or continue ICSs, and a follow-up period of at least 3 months. We pooled results using a random-effects meta-analysis. Results: The search strategy identified 1798 potential articles, of which 172 were reviewed at the full-text level and 7 met the criteria for inclusion. The relative risk for an asthma exacerbation in patients who stopped ICSs compared with those who continued use was 2.35 (95% CI, 1.88-2.92; P < .001; I² = 0%), as determined by using data pooled from trials with a mean follow-up of 27 weeks. The pooled absolute risk difference for an asthma exacerbation was 0.23 (95% CI, 0.16-0.30; P < .001; I² = 44%). Patients who discontinued ICSs also had a decreased FEV₁ of 130 mL (95% CI, 40-210 mL; P = .003; I² = 53%), a decreased mean morning peak expiratory flow of 18 L/min (95% CI, 6-29 L/min; P = .004; I² = 82%), and an increased mean standardized asthma symptom score of 0.43 SDs (95% CI, 0.28-0.58 SDs; P < .001; I² = 0%). Conclusion: Patients with well-controlled asthma who stop regular use of low-dose ICSs have an increased risk of an asthma exacerbation compared with those who continue ICSs.