Addition of PRN ICS/formoterol treatment approach for patients with mild asthma: Amendments for the ERS guidelines

10 Oct 2023

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

  Recommendations Certainty of evidence
Adult patients with asthma on GINA treatment step 1 or 2 use PRN ICS/formoterol in a single inhaler without maintenance treatment instead of regular ICS maintenance treatment plus PRN SABA Low
2 Adolescent patients with asthma on GINA treatment step 1 or 2 use either PRN ICS/formoterol in a single inhaler or regular ICS maintenance treatment plus PRN SABA Low

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

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