A Proposed Revision of the Stepwise Treatment Algorithm in Asthma

To the Editor:The stepwise approach to the pharmacologic treatment of asthma is a core foundation of asthma guidelines (1).Through this approach, treatment intensity is increased in discrete steps to obtain symptom control and reduce exacerbation risk and is decreased after a period of prolonged control.The stepwise approach is usually shown by an algorithm, as illustrated in the 2020 Global Initiative for Asthma (GINA) strategy update (Figure 1).Here, we review the 2020 GINA stepwise algorithm and suggest alternative evidence-based algorithms that address potential problems with the currently recommended approach.Currently at each step, the GINA algorithm aligns treatment recommendations based on inhaled corticosteroid (ICS)/formoterol reliever therapy with those of the traditional short-acting b 2 -agonist (SABA) reliever therapy.This assumes that the efficacy of treatment incorporating ICS/formoterol reliever therapy at each step aligns more closely with the corresponding alternative treatment incorporating a SABA reliever at the same step, rather than at adjacent higher or lower steps, which is not the case (2-4).This is illustrated by the recent systematic review and network meta-analysis that reported that the relative risk of a severe exacerbation with low-dose ICS/formoterol maintenance and reliever therapy at GINA step 3 compared with lowdose ICS/long-acting b 2 -agonist (LABA) plus SABA therapy (GINA step 3), medium-dose ICS/LABA plus SABA (GINA step 4), and highdose ICS/LABA plus SABA (GINA step 5) was 0.55 (95% confidence interval [CI], 0.47-0.64),0.71 (95% CI, 0.56-0.91),and 0.78 (95% CI, 0.51-1.21)respectively (3).Thus, low-dose ICS/formoterol maintenance and reliever therapy at GINA step 3 aligns most closely in terms of efficacy with high-dose ICS/LABA plus SABA therapy at GINA step 5 and then progressively aligns to a lesser extent with medium-dose ICS/LABA plus SABA therapy at GINA step 4 and then with low-dose ICS/LABA plus SABA therapy at GINA step 3.This ranking of efficacy is thus discordant with the current algorithm.This structural problem could be resolved by separating the instructions for the stepwise approach incorporating ICS/formoterol reliever therapy from those incorporating SABA reliever therapy by using two separate algorithms, as was undertaken in the New Zealand asthma guidelines in 2020 (5).This avoids the problem of step misalignment and the potential inadvertent mixing of the two approaches.It is possible to simplify the