On-demand Inhaled Corticosteroid and Fast-onset Beta-2 Agonist Combination Therapy Versus Conventional Treatment for Mild to Moderate Asthma: A Non-inferiority, Network Meta-analysis

The aim of this study was to assess the non-inferiority of on-demand (OD) inhaled corticosteroid (ICS) and fast-onset beta-2 agonist (FOBA) combination therapy. Although the guidelines recommend regular inhalation of ICS and long-acting beta-2 agonist (LABA), we investigated whether OD-ICS/FOBA is as effective as regular inhalation. A network meta-analysis of randomized controlled trials was conducted to inspect the non-inferiority of OD-ICS/FOBA efficacy compared with conventional best practice, i.e. regular low – to medium-dose ICS with or without LABA, plus OD short-acting beta-2 agonist (REG-ICS+OD-SABA or REG-ICS/LABA+OD-SABA) in patients with mild to moderate asthma. PubMed, the Cochrane library database, and Scopus were searched to identify relevant articles. Outcome measures were the incidence of asthma exacerbation or aggravation. A network meta-analysis was performed to estimate risk ratios (RRs) with 95% confidence intervals (CIs) and the probability of being the best treatment for the outcome. Four randomized controlled trials of treatment for mild to moderate asthma met the criteria and were included in the study. We could not demonstrate non-inferiority of OD-ICS/FOBA to REG-ICS+OD-SABA (RR, 1.17; 95% CI, 0.61 to 2.26) or to REG-ICS/LABA+OD-SABA (RR, 1.47; 95% CI, 0.79 to 2.71) for mild to moderate asthma. The probability of being the best treatment to reduce asthma exacerbation or aggravation was 10.5% for OD-ICS/FOBA, 10.3% for REG-ICS+OD-SABA, and 79.3% for REG-ICS/LABA+OD-SABA. Surface under the cumulative ranking (SUCRA) curves were 0.4, 0.2 and 0.9 for OD-ICS/FOBA, REG-ICS+OD-SABA, and REG-ICS/LABA+OD-SABA, respectively. Although non-inferiority of OD-ICS/FOBA to conventional best practice was not shown, SUCRA was higher for OD-ICS/FOBA than for REG-ICS+OD-SABA. From these results, we propose that OD-ICS/FOBA can be an effective alternative to REG-ICS+OD-SABA to reduce asthma exacerbation or aggravation in patients with mild to moderate asthma