As-needed (PRN) inhaled corticosteroids (ICS)/formoterol is a novel reliever therapy for patients with mild asthma, providing clinical benefits such as reducing the risks of ICS-related systemic effects in populations with short-acting β2-agonist (SABA) reliever overuse and non-adherence to ICS-based maintenance therapy.¹ With the emergence of new clinical evidence demonstrating the efficacy of PRN ICS/formoterol therapy in the management of mild asthma exacerbation, a timely review of the current recommendations by the ERS is warranted.¹ Hence, a task force set up by the ERS commenced a meta-analysis to compare the clinical efficacy of PRN ICS/formoterol against low-dose ICS maintenance treatment in treating adult and adolescent patients with mild asthma.¹ During the ERS International Congress 2023, Professor Richard Beasley from the Victoria University of Wellington, New Zealand presented the amendments for the recommendations based on the results of the meta-analysis.¹

The panel consisted of 12 experienced clinicians in treating asthma, 1 ERS early career member representative and 1 patient representative.¹ An externally commissioned methodologist conducted literature searches in October 2021 in numerous databases, which ultimately yielded 4 studies after screening 548 records from the database.¹ The panel formulated the treatment-related critical outcomes based on the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach, which included the incidence of exacerbations, emergency department (ED) visits, hospitalizations, and adverse events (AEs).¹ Other supplementary outcomes such as health-related quality of life (QoL), asthma control and systemic steroid exposure were examined as well.¹

In terms of efficacy, PRN ICS/formoterol treatment exhibited more desirable outcomes when compared to ICS maintenance treatment.¹ An 18% risk-reduction in severe exacerbations was associated with PRN ICS/formoterol treatment [Relative  risk (RR)=0.82; 95% CI: 0.64-1.04].¹ Similarly, patients who underwent PRN ICS/formoterol treatment had a relatively lower annualized rate of severe exacerbations (Rate ratio=0.86; 95% CI: 0.71-1.04) and were 30% less likely to require ED visits due to asthma worsening (RR=0.70; 95% CI: 0.44-1.09).¹ Nevertheless, hospitalization rates due to severe exacerbations remain similar between the two treatments (RR=0.92; 95% CI: 0.52-1.62).¹

In terms of QoL, the two treatments were comparable, with PRN ICS/formoterol treatment having a lower exposure to corticosteroids.¹ While the comparison in Asthma Quality of Life Questionnaire (AQLQ) scores favored ICS maintenance treatment [Mean difference (MD)=-0.1; 95% CI: -0.14 to -0.05], PRN ICS/formoterol treatment performed better in the Asthma Control Questionnaire-5 (ACQ-5) (MD=0.13; 95% CI: 0.09-0.17).¹ In addition, PRN ICS/formoterol treatment was associated with a 30% reduction in total annual systemic corticosteroid use (i.e., prednisone/year) (MD=-7.00mg; 95% CI: -14.0mg to  -0.03mg prednisone) and a >50% reduction in daily ICS exposure (MD=-154µg; 95% CI: -206.9µg to -101.1µg) compared to ICS maintenance treatment.¹ As for safety, the incidence of AEs (RR=0.98; 95% CI: 1.06-1.20) and serious AEs (RR=1.13; 95% CI: 0.83-1.54) were similar in both treatments.¹

Thus, 2 conditional recommendations were amended according to the findings of this meta-analysis (table 1).¹ For adult patients, PRN ICS/formoterol is preferred considering its benefits in lowering the incidence of severe exacerbations and reliance on systemic corticosteroids.¹ For adolescent patients, both treatments are recommended as the clinical efficacy and safety between the  2 treatments are comparable within the current limited clinical data.¹ All in all, these two statements remain aligned with the Global Strategy for Asthma Management and Prevention (GINA) international guidelines.¹

Table 1: Amendments for the ERS guidelines in asthma management

GINA: Global Strategy for Asthma Management and Prevention; ICS: Inhaled corticosteroids; SABA: Short-acting β2-agonist