Long-Acting Muscarinic Antagonist as an Alternative to Inhaled Corticosteroids in Type 2-Low Mild Asthma: A Randomized Crossover Non-inferiority Trial.

BACKGROUND

Type 2 (T2)-low asthma is often less responsive to ICS; however, optimal controller strategies for this phenotype remain inadequately defined.

OBJECTIVE

To evaluate whether long-acting muscarinic antagonists (LAMA) are non-inferior to ICS in patients with T2-low mild asthma.

METHODS

In this multicenter, pragmatic, randomized, open-label, crossover trial, adults with T2-low mild asthma (blood eosinophils <300/μL and either FeNO <25 part per billion or sputum eosinophils <3%) were randomized 1:1 to 6 months of ICS followed by 6 months of LAMA, or vice versa. The primary outcome was a composite treatment-success end point. Non-inferiority was established if the lower bound of the 95% CI for the success rate difference was greater than -10 percentage points.

RESULTS

Among 150 randomized patients, 89 completed both phases (per-protocol population). Treatment success was 7.9 percentage points higher with LAMA (95% CI, -2.9 to 18.8; P < .001), consistent with two intention-to-treat analyses (risk differences, 4.1-4.2 percentage points). In another intention-to-treat analysis in which all uncompleted phases were considered to be failures, non-inferiority was not established (-3.3 percentage points; 95% CI, -11.3 to 4.5), although it was supported under a non-responder imputation approach for missing data (one-sided P = .020). The favorable effect was more pronounced in patients aged less than 65 years. Exacerbation rates did not differ significantly, and symptom control and lung function remained stable across both phases.

CONCLUSION

In patients with T2-low mild asthma, LAMA monotherapy may be non-inferior to ICS and may be considered an alternative controller option for selected patients.