Background A new asthma therapy containing a combination of the inhaled steroid fluticasone propionate (FLUT) and the long-acting β2 agonist (LABA) formoterol fumarate (FORM) in a metered-dose inhaler has been developed (FLUT/FORM; flutiform®). In a double-blind, double-dummy, randomised, multicentre, four arm parallel group study, the efficacy and safety of FLUT/FORM vs. FLUT and FORM administered concurrently (FLUT+FORM) was assessed. Here, we present efficacy results of a posthoc analysis that compared FLUT/FORM 500/20 µg with FLUT/FORM 100/10 µg (both twicedaily) by baseline asthma severity.
Methods In total, 620 patients were randomised 1:1:1:1 to receive FLUT/FORM 500/20 µg, FLUT/FORM 100/10 µg, FLUT+FORM 500 µg + 24 µg or FLUT 500 µg. Randomisation was stratified by percentage predicted FEV1 at baseline [≥40 – ≤60% (‘severe asthma’; 52% of patients) vs. >60% – ≤80% (‘moderate asthma’; 48% of patients)], allowing a post-hoc dichotomised analysis by baseline FEV1 severity of spirometric and symptom-based endpoints.
Results There was no dose-response relationship between FLUT/FORM 500/20 µg and FLUT/FORM 100/10 µg for the spirometric variables overall or in either subgroup.
Treatment effect differences between FLUT/FORM 500/20 µg and 100/10 µg, in favour of the high dose, were however evident for almost all symptom-based endpoints and were more pronounced in the severe asthma group. These included changes in: mean symptom scores, percentage symptomfree days, mean sleep disturbance scores, awakening free nights, percentage rescue medication-free days, percentage asthma control days, AQLQ score and the incidence of any asthma exacerbations. The differences between FLUT/FORM 500/20 µg and 100/10 µg in the severe asthma group were significant at the 5% level for sleep disturbance scores [treatment difference –0.138 (95% CI: –0.265, –0.012) P=0.032], percentage awakeningfree nights [treatment difference 11.754 (95% CI: 2.234, 21.274) P=0.016] and mean AQLQ score [treatment difference 0.302 (95% CI: 0.013, 0.591) P=0.041].
Conclusion High dose FLUT/FORM (500/20 µg) was consistently associated with greater symptomatic treatment benefit than low dose (100/10 µg) treatment in patients with severe asthma. These data provide a rationale for dose escalation with FLUT/FORM, which appears most likely to confer additional treatment benefit in patients with severe asthma.