Fluticasone Furoate for Asthma in Adults and Adolescents
FF 100 μg and 200 μg resulted in improvements from baseline in lung function and symptomatic endpoints in a population of moderate-severe asthma patients uncontrolled on mid-high dose ICS, and displayed an acceptable safety profile. The AEs seen in this study were consistent with those expected in this patient population. There were no treatment-related serious AEs, and no safety signals of clinical concern were seen with either dose. As in previous studies testing clinical dosages of FF, alone or with vilanterol, there was no evidence of cortisol suppression in patients receiving either dose.
A numerically greater effect of FF 200 μg was observed for FEV1 and for attainment of asthma control, with similar effects seen with both doses of FF for rescue-free and symptom-free 24-hour periods. A placebo control was not included in this study, as FF 100 μg has previously been shown to be superior to placebo in a number of studies, and it was not thought to be ethical for patients symptomatic on mid-high dose ICS to receive placebo for 24 weeks. The purpose of this study was to investigate whether incremental benefits of the higher FF dose could be seen in a population with a requirement for high-dose ICS. In this study, it was observed that patients using higher-dose ICS at baseline showed a comparatively greater lung function benefit with FF 200 μg than with FF 100 μg. Improvements from baseline were seen for all secondary endpoints with both FF 100 μg and FF 200 μg, with little difference between treatments for most secondary endpoints. Clinically meaningful improvement in ACT score was seen with both strengths of FF in both strata, and patients treated with FF 200 μg were 42% more likely to be well controlled (ACT score ≥ 20) after 24 weeks than those receiving FF 100 μg. However, it is important to note that none of the CIs for the primary and secondary treatment comparisons excluded the null value, and the study was not designed to statistically test for a differential treatment effect on any efficacy endpoint.
The findings of this study should be interpreted in light of the ongoing debate about the therapeutic options for patients whose asthma is uncontrolled on medium-dose ICS. Current guidelines recommend the addition of a LABA to ongoing ICS therapy in patients uncontrolled on medium-dose ICS. While the addition of a LABA is generally recommended, in a subset of patients an increase in ICS dose may be more appropriate. For instance, patients whose asthma is characterised by elevated sputum eosinophil levels have been found to display substantially greater response to ICS than patients with non-eosinophilic asthma. There is evidence to suggest that increasing ICS dose in such patients may be effective in reducing asthma exacerbations. However, the investigation of such factors was outside the scope of the present study.
Strengths of this study include its 6-month duration and the recruitment of patients uncontrolled on mid-high dose ICS, who represent a patient population for whom the prescription of high-dose ICS maintenance therapy is appropriate. A potential limitation is that the study was not formally designed or powered to detect statistically significant treatment differences between the two treatment groups. As non-inferiority of FF 200 μg once daily to FP 500 μg twice daily has previously been demonstrated in patients uncontrolled on mid-high dose ICS, an active, positive-control arm was not included.
Discussion
FF 100 μg and 200 μg resulted in improvements from baseline in lung function and symptomatic endpoints in a population of moderate-severe asthma patients uncontrolled on mid-high dose ICS, and displayed an acceptable safety profile. The AEs seen in this study were consistent with those expected in this patient population. There were no treatment-related serious AEs, and no safety signals of clinical concern were seen with either dose. As in previous studies testing clinical dosages of FF, alone or with vilanterol, there was no evidence of cortisol suppression in patients receiving either dose.
A numerically greater effect of FF 200 μg was observed for FEV1 and for attainment of asthma control, with similar effects seen with both doses of FF for rescue-free and symptom-free 24-hour periods. A placebo control was not included in this study, as FF 100 μg has previously been shown to be superior to placebo in a number of studies, and it was not thought to be ethical for patients symptomatic on mid-high dose ICS to receive placebo for 24 weeks. The purpose of this study was to investigate whether incremental benefits of the higher FF dose could be seen in a population with a requirement for high-dose ICS. In this study, it was observed that patients using higher-dose ICS at baseline showed a comparatively greater lung function benefit with FF 200 μg than with FF 100 μg. Improvements from baseline were seen for all secondary endpoints with both FF 100 μg and FF 200 μg, with little difference between treatments for most secondary endpoints. Clinically meaningful improvement in ACT score was seen with both strengths of FF in both strata, and patients treated with FF 200 μg were 42% more likely to be well controlled (ACT score ≥ 20) after 24 weeks than those receiving FF 100 μg. However, it is important to note that none of the CIs for the primary and secondary treatment comparisons excluded the null value, and the study was not designed to statistically test for a differential treatment effect on any efficacy endpoint.
The findings of this study should be interpreted in light of the ongoing debate about the therapeutic options for patients whose asthma is uncontrolled on medium-dose ICS. Current guidelines recommend the addition of a LABA to ongoing ICS therapy in patients uncontrolled on medium-dose ICS. While the addition of a LABA is generally recommended, in a subset of patients an increase in ICS dose may be more appropriate. For instance, patients whose asthma is characterised by elevated sputum eosinophil levels have been found to display substantially greater response to ICS than patients with non-eosinophilic asthma. There is evidence to suggest that increasing ICS dose in such patients may be effective in reducing asthma exacerbations. However, the investigation of such factors was outside the scope of the present study.
Strengths of this study include its 6-month duration and the recruitment of patients uncontrolled on mid-high dose ICS, who represent a patient population for whom the prescription of high-dose ICS maintenance therapy is appropriate. A potential limitation is that the study was not formally designed or powered to detect statistically significant treatment differences between the two treatment groups. As non-inferiority of FF 200 μg once daily to FP 500 μg twice daily has previously been demonstrated in patients uncontrolled on mid-high dose ICS, an active, positive-control arm was not included.
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