Tapering of inhaled corticosteroids in stable T2-low asthma: a randomized trial of symptom- and biomarker trajectories.

OBJECTIVE

To investigate whether tapering of inhaled corticosteroids (ICSs) is non-inferior to standard of care (SoC) in asthma patients with a stable type 2 (T2)-low inflammatory profile, generally considered less responsive to ICS therapy, and to describe symptom and biomarker trajectories during tapering.

METHODS

This randomized, controlled, open-label multicenter trial conducted across specialist centers between 2022 and 2024 recruited adult asthma patients with persistently low T2 biomarkers, defined as blood eosinophils <0.15 × 109/L, fractional exhaled nitric oxide (FeNO) <25 ppb, and non-allergic phenotype. Patients' adherent to medium- or high-dose ICS were randomized 1:1 to either ICS tapering (50% reduction at randomization and withdrawal after 8 weeks) or continued SoC. The primary endpoint was change in Asthma Control Questionnaire (ACQ) score at 16 weeks. Secondary endpoints included changes in blood and sputum eosinophils, FeNO, periostin, and lung function.

RESULTS

Recruitment proved challenging as only 20 of 2766 screened patients met eligibility criteria, leading to early study termination. Median ACQ remained stable in the tapering group (0 [-0.14; 0.5]) and improved modestly in the SoC group (-0.44 [-0.9; -0.11]; p = 0.211). FeNO (p = 0.038) and periostin (p = 0.031) increased with tapering but remained within the T2 low range. Minimal changes were observed in blood eosinophils (p = 0.3) and FEV1 (p = 0.7).

CONCLUSIONS

Premature trial termination due to recruitment challenges reflects the rarity of stable T2-low asthma. ICS tapering was not associated with greater symptom deterioration compared to SoC, although non-inferiority was not demonstrated.