Integrating Efficacy and Effectiveness Evidence from Randomized Controlled Trials and Real-World Studies of Inhaled Corticosteroid/Long-Acting β2-Agonist Therapies in Moderate Asthma

Inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) combinations are a cornerstone of moderate asthma management that have been approved to treat asthma on the basis of results from randomized controlled trials (RCTs). However, efficacy observed in RCTs does not necessarily translate directly into effectiveness, partly because of lower adherence or persistence and less intensive follow-up structures in routine clinical practice. This has driven interest in real-world evidence (RWE) studies and pragmatic RCTs as sources of evidence complementary to conventional RCTs. We aimed to assess how considering multiple study types could enhance our understanding of ICS/LABA therapy in asthma management. We undertook a targeted literature search of PubMed/MEDLINE of RCTs (conventional and pragmatic) and RWE studies evaluating ICS/LABA therapies in patients with moderate asthma through a structured screening approach. Twenty two publications were selected for descriptive comparison. Similar results for ICS/LABA therapies were reported across studies, supporting the generalizability of conventional RCT findings to routine clinical practice. Reported severe exacerbation rates per patient per year (PPPY) were approximately 0.14–0.31 PPPY in conventional RCTs, 0.12–0.47 PPPY in pragmatic RCTs, and overall exacerbation rates 0.07–0.18 in RWE studies, with lower rates reported for ICS/LABA interventions than comparator. Across studies, approximately half of patients reported improvements in asthma control following ICS/LABA treatment. Conventional RCTs reported high treatment persistence and generally higher treatment adherence than pragmatic RCTs or RWE studies; however, the perceived impacts of adherence on treatment effects were mixed between studies. Where reported, lung function data indicated improvements following ICS/LABA treatment, although RWE data were limited. Our findings support the view that conventional RCTs, pragmatic RCTs, and RWE studies represent complementary components of a unified evidence continuum that should be considered together to optimize patient care. Integrating evidence across this continuum provides a more comprehensive understanding of ICS/LABA therapy and may better inform personalized treatment decisions in asthma. Asthma that is moderately severe is typically treated with a combination of medications that suppress inflammation (called inhaled corticosteroids) and relax muscles around the airway (long-acting β2-agonists). Large-scale studies called randomized controlled trials have shown that several of these treatment combinations are safe and effective. Traditional, conventional randomized controlled trials have strict entry criteria and are tightly supervised; therefore, they may not exactly represent the population and experience of patients with asthma in the “real world” seen in clinical practice. Studies aiming to include patients with asthma who more closely represent real-world asthma populations have been carried out to add to the findings from conventional randomized controlled trials. In this review article, we looked in the databases PubMed and MEDLINE for published articles describing these different types of studies and selected 22 relevant studies in moderate asthma. Overall, the rates of worsening symptoms of asthma called exacerbations were similar across all types of studies (approximately 0.1 per year for a typical patient), and the rates were lower with combined inhaled corticosteroids and long-acting β2-agonists than other treatment options. Control of asthma symptoms also improved, suggesting that findings from conventional randomized controlled trials apply to the wider real-world asthma population. Patients most often took their medication as directed in conventional randomized controlled trials. Overall, these findings support the view that randomized trials and “real-world” studies together provide a broad understanding of inhaled corticosteroids and long-acting β2-agonists, which may be useful for deciding on the most suitable treatment for individual patients with asthma.