Introduction: Mometasone furoate (MF), an inhaled corticosteroid (ICS), is approved for the treatment
of asthma. Previous studies suggest that MF Twisthaler® doses of 800 and 200 µg and MF Breezhaler® doses of 320 and 80 µg would elicit similar lung function effects, respectively.
These MF doses are also used in an indacaterol/MF combination in development for asthma.
Since sensitivity to ICS is variable, individual patientsʼ ICS sensitivity (as measured
by FEV1 decline on ICS weaning) was used to build a robust analysis model for the
study data.
Methods: This was a randomized, double-blind, double-dummy, parallel-group, non-inferiority
study of 739 adolescents and adults with asthma. MF was delivered with Breezhaler® at daily doses of 80 and 320 µg and corresponding Twisthaler® doses of 200 and 800 µg. The primary endpoint was trough FEV1 on Day 29 (non-inferiority
margin: − 90 mL). Models with and without ICS sensitivity at baseline were used to
analyze the data.
Results: In the model with ICS sensitivity the least squares (LS) mean difference (Δ) in trough
FEV1 between MF 80 µg Breezhaler® and MF 200 µg Twisthaler® was 27 mL (95% CI − 34, 89); for MF 320 µg Breezhaler® and MF 800 µg Twisthaler® Δ was 0 mL (95% CI − 60, 61). In the model without ICS sensitivity Δ between MF 80 µg
Breezhaler® and MF 200 µg Twisthaler® patients was 68 mL (0, 137) and 25 mL (− 43, 92) between MF 320 µg Breezhaler® and MF 800 µg Twisthaler®. Model diagnostics showed that using ICS sensitivity as a covariate improved the
model.
Conclusion: MF 80 and 320 µg, delivered via Breezhaler®, is non-inferior to MF at 200 and 800 µg, delivered via Twisthaler®. Including ICS sensitivity in the model improves model robustness.
