The Role of ICS-Containing Rescue Therapy Versus SABA Alone in Asthma Management Today

Abstract

The Global Initiative for Asthma (GINA) recommends that short-acting β₂-agonist (SABA) monotherapy should no longer be prescribed, and that as-needed combination inhaled corticosteroids (ICS)-formoterol is the preferred reliever therapy in adults and adolescents with mild asthma. These recommendations are based on the risks of SABA monotherapy, the evidence that ICS-formoterol reliever therapy markedly decreases the occurrence of severe asthma exacerbations compared with SABA reliever therapy alone, and because ICS-formoterol reliever therapy has a favorable risk/benefit profile compared with maintenance ICS plus SABA reliever therapy. Data supporting the use of combination ICS-albuterol reliever therapy in mild asthma are more limited, but there are studies that inform its use in this population. In this review, we compare, using a pros and cons format, the (1) long-term safety and efficacy of ICS-formoterol reliever therapy versus SABA reliever therapy alone, (2) long-term safety and efficacy of ICS-albuterol reliever therapy versus SABA reliever therapy alone, (3) immediate bronchodilator effects of ICS-formoterol versus SABA alone, and (4) clinical and regulatory factors that may inform reliever therapy prescription decisions. By presenting the evidence of these reliever inhaler options, we hope to inform the reader while also calling for necessary future effectiveness and implementation research.

Keywords: Albuterol; Asthma; ICS-albuterol; ICS-formoterol; Mild asthma.

Figure 1:

Inhaled corticosteroid-formoterol reliever vs. SABA reliever at different treatment steps. The relative risk of severe exacerbations from randomised controlled trials of inhaled corticosteroid-formoterol vs. short-acting beta₂-agonist reliever therapy is shown for Global Initiative of Asthma Step 1–5 (although this article focuses on comparing SABA alone to ICS-containing reliever therapy in mild asthma). The risk with 95% confidence intervals is presented for each study, based on data summarized by Beasley et al. *The treatment steps refer to the randomised reliever-based regimen, as defined by the Global Initiative of Asthma (GINA) 2018 criteria. Abbreviations used: short-acting beta₂-agonist (SABA), inhaled corticosteroid-formoterol (ICD/F), low dose (LD), medium dose (MD), high dose (HD), and maintenance and reliever therapy (MART).

Figure 2:

Ranking plot of the efficacy of 5 therapeutic regimens in preventing the risk of severe exacerbation in mild-to-moderate asthma. Therapeutic regimens were plotted on the X-axis according to surface under the cumulative ranking curve (SUCRA), where 1 represents the treatment considered to be the best and 0 the treatment considered to be the worst. The treatments were plotted on the Y-axis according to the rank probability of best therapy, where a score of 1 is assigned to the best therapeutic strategy and 5 to the worst. Abbreviations used: Low-dose (LD), single maintenance and reliever therapy (SMART), inhaled corticosteroid (ICS), and long-acting beta agonist (LABA). Reproduced with written permission of the ERS from Rogliani et al.

Figure 3:

Kaplan-Meier estimates of the time to first severe exacerbation based on reliever inhaler therapy regimen are shown side-by-side for inhaled corticosteroid [ICS]-formoterol and ICS-albuterol vs. short-acting beta-agonist (SABA) reliever regimens. In Panel A, results from the Novel Symbicort Turbuhaler Asthma Reliever Therapy [Novel START]) are shown for the time to first severe asthma exacerbation by randomized inhaler regimen with budesonide-formoterol reliever therapy only demarcated in blue, budesonide maintenance and albuterol reliever therapy in red, and albuterol reliever therapy only in black. In Panel B, time to first severe asthma exacerbation comparing beclomethasone-albuterol to other inhaler regimens is shown. Tick marks demarcate the first asthma exacerbation for a patient. As-needed combination therapy consisted of twice daily placebo plus reliever beclomethasone-albuterol 250–100μg in a single inhaler, regular beclomethasone therapy consisted of beclomethasone 250μg twice daily plus reliever albuterol 100μg, regular combination therapy consisted of beclomethasone-albuterol 250–100μg twice daily plus reliever albuterol 100μg, and as-needed albuterol therapy consisted of twice daily placebo plus reliever albuterol 100μg. Please note the different scales on the y axes in the Figures. Figures reproduced with written permission of the NEJM from Beasley et al and Papi et al.