An independent in-depth analysis proposing adjusted Global Initiative on Asthma Step 1-2 treatment suggestions

The Global Initiative on Asthma (GINA) strategy included major changes for the treatment of mild asthma in the 2020 version that are even taken to the next level in 2021, leaving a preferred track with only rescue therapy with inhaled corticosteroid and formoterol (ICS-FORM) for steps 1-2 in 12+ years old. It has been questioned how solid the evidence behind these recommendations is. We decided to independently conduct an in-depth analysis of published evidence based on a comprehensive evaluation of original articles and related appendices and publications, including quality of evidence and risk of bias per article. We first defined the major asthma treatment goals and proceeded to review how these were met in publications referenced in the main asthma guidelines. For patients with GINA (2021) Step 1 characteristics, the analysis supports GINA's decision to avoid SABA monotherapy and to prefer ICS-FORM rescue with an alternative ICS rescue every time a SABA is used for ≥12 years, even though evidence is extrapolated from step 2 patients. For 6- to 11-year-olds, we propose to consider ICS-FORM rescue as an alternative, as its use has been approved in this age group, be it not as rescue medication. For patients with GINA 2021 Step 2 characteristics, our proposal slightly differs from GINA 2021. We propose to continue avoiding the separate use of SABA, using ICS rescue whenever a fast-acting bronchodilator is taken (even with ICS maintenance). Also, the superiority of ICS-FORM rescue over classical step 2 treatment is not uniform and year-long experience is lacking. Consequently, for now, both treatment options seem equal: ICS-FORM rescue or ICS maintenance with SABA (+ICS) rescue. For 6- to 11-year-olds, ICS rescue every time a SABA is used has the advantage of lower total ICS dose; as alternative we suggest ICS-FORM rescue. The best treatment option depends on patient characteristics and treatment goals. Recommendations should be reviewed as soon as new evidence becomes available.