Efficacy and safety of the single-capsule combination of fluticasone/formoterol in patients with persistent asthma: a non-inferiority trial

Abstract

OBJECTIVE: Fluticasone and formoterol are effective in the treatment of asthma. When a corticosteroid alone fails to control asthma, combination therapy is the treatment of choice. The objective of this study was to compare the efficacy and safety of formulations containing budesonide/formoterol (BUD/FOR), fluticasone alone (FLU), and the single-capsule combination of fluticasone/formoterol (FLU/FOR) on lung function in patients with mild-to-moderate persistent asthma. METHODS: This was a randomized, multicenter, open phase III trial conducted in Brazil. The primary efficacy analysis was the assessment of non-inferiority between FLU/FOR and BUD/FOR combinations regarding FEV1 (in L) at the final visit. The secondary analyses were PEF, level of asthma control, serum cortisol levels, frequency of adverse events, adherence to treatment, and appropriate inhaler use. RESULTS: We randomized 243 patients to three groups: FLU/FOR (n = 79), BUD/FOR (n = 83), and FLU (n = 81). In terms of the mean FEV1 after 12 weeks of treatment, the difference between the FLU/FOR and BUD/FOR groups was 0.22 L (95% CI: −0.06 to 0.49), whereas the difference between the FLU/FOR and FLU groups was 0.26 L (95% CI: −0.002 to 0.52). Non-inferiority was demonstrated by the difference between the lower limits of the two 95% CIs (−0.06 vs. −0.002). The level of asthma control and PEF were significantly greater in the FLU/FOR and BUD/FOR groups than in the FLU group. There were no significant differences among the groups regarding patient adherence, patient inhaler use, or safety profile of the formulations. CONCLUSIONS: The single-capsule combination of FLU/FOR showed non-inferiority to the BUD/FOR and FLU formulations regarding efficacy and safety, making it a new treatment option for persistent asthma.

Therapeutic preferences and factors determining the use of inhaled corticosteroids with long-acting β2-agonists in patients with asthma and chronic obstructive pulmonary disease

“…In addition, the efficacy and safety of combined therapy with formoterol and fluticasone was comparable to those found in clinical trials and also a non-interventional post-authorization observational study conducted in a group of over 2,500 patients with asthma [ 7 ]. In another non-interventional, post-marketing observational study, similarly to the presented survey, greater efficacy of polytherapy with formoterol and fluticasone was found compared to the therapy with formoterol and budesonide despite the lack of differences in the patients’ compliance with the recommendations [ 8 ]. It should also be emphasized that in the cost-effect assessment study, the change or initiation of a combination therapy with formoterol and fluticasone was associated with a better cost-effect ratio than treatment with a combination of formoterol and salbutamol [ 9 ].…”

A Pilot Study on Effect of Beta2-Adrenergic Receptor Gene Polymorphism on Response to Fluticasone/Formoterol Inhaler in Patients with Persistent Asthma

“…Possible explanation for the difference between these ICSs/LABAs involves the choice of LABA; formoterol versus salmeterol, because investigations about the effects of ADRB2 gene polymorphism on ex vivo and in vivo function of ß2-adrenoceptors in asthmatic patients suggested that ADRB2 gene polymorphism had no significant effect on response to formoterol [27]. Concerning about the differences related to using different ICSs, fluticasone versus budesonide in fluticasone/formoterol and budesonide/formoterol inhalers may mean little clinically [28,29]. In fact, one randomized, double-blind, double-dummy, multicenter 12week phase III study demonstrated comparable efficacy of fluticasone/ formoterol to budesonide/formoterol [28], and the other 12-week, open-label multicenter phase III trial reported fluticasone/formoterol inhaler showed non-inferiority to budesonide/formoterol formulation [29].…”

“…Concerning about the differences related to using different ICSs, fluticasone versus budesonide in fluticasone/formoterol and budesonide/formoterol inhalers may mean little clinically [28,29]. In fact, one randomized, double-blind, double-dummy, multicenter 12week phase III study demonstrated comparable efficacy of fluticasone/ formoterol to budesonide/formoterol [28], and the other 12-week, open-label multicenter phase III trial reported fluticasone/formoterol inhaler showed non-inferiority to budesonide/formoterol formulation [29].…”

Estudo farmacoterapêutico, epidemiológico e impacto econômico da asma em unidades de saúde brasileiras: uma revisão narrativa

“…Segundo dados divulgados, a asma causa cerca de 250 mil mortes por ano em todo o mundo. No Brasil, no período de 1979-2006, a asma foi responsável por uma média de 2.155 mortes anuais, o que representa cerca de 6 mortes por dia (8,10).…”

“…O principal objetivo no manejo da asma é atingir e manter o controle. A manutenção do tratamento deve variar de acordo com o estado de controle do paciente, adicionando ou subtraindo medicamentos/doses (8). Um dos problemas mais frequentes em pacientes portadores de doenças crônicas refere-se à aderência ao tratamento, que pode prejudicar adversamente os resultados.…”