Long-Term Fluticasone Propionate/Formoterol Fumarate Combination Therapy Is Associated with a Low Incidence of Severe Asthma Exacerbations

Abstract

Background: A primary goal of asthma management is the reduction of exacerbation risk. We assessed the occurrence of oral corticosteroid-requiring exacerbations (OCS exacerbations) with long-term fluticasone/formoterol therapy, and compared it with the occurrence of similar events reported with other inhaled corticosteroid/long acting β2-agonist (ICS/LABA) combinations.Methods: The occurrence of OCS exacerbations was assessed in two open-label trials of fixed-dose fluticasone/formoterol administered for between 26 to 60 weeks in adults and adolescents with asthma. The incidence of OCS exacerbations with fluticasone/formoterol was compared with those reported in three recent Cochrane meta-analyses of other ICS/LABAs.Results: The pooled incidence of OCS exacerbations with long-term fluticasone/formoterol was 2.1% (95% CI: 1.1, 3.2%, n/N = 16/752). In only two of the nineteen treatment arms summarized by Cochrane did OCS exacerbation incidence approximate that seen in the two fluticasone/formoterol trials (single-inhaler fluticasone/salmeterol [2.9%]; separate inhaler budesonide, beclometasone, or flunisolide plus formoterol [3.4%]). In Lasserson's review the pooled incidence of OCS exacerbations for single-inhaler combinations was 9.5% (95% CI: 8.4, 10.6%; n/N = 239/2516) for fluticasone/salmeterol, and 10.6% (95% CI: 9.3, 11.8%; n/N = 257/2433) for budesonide/formoterol. In Ducharme's and Chauhan's meta-analyses (primarily incorporating separate inhaler combinations [fluticasone, budesonide, beclometasone, or flunisolide plus salmeterol or formoterol]), the pooled incidences of OCS exacerbations were 16.0% (95% CI: 14.2, 17.8%, n/N = 258/1615) and 16.7% (95% CI: 14.9, 18.5, n/N = 275/1643), respectively.Conclusions: The incidence of exacerbations in two fixed-dose fluticasone/formoterol studies was low and less than in the majority of comparable published studies involving other ICS/LABA combinations. This difference could not be readily explained by differences in features of the respective studies and may be related to the favorable pharmacological/mechanistic characteristics of the constituent components fluticasone and formoterol compared to other drugs in their respective classes.

A 12-week open-label, randomized, controlled trial and 24-week extension to assess the efficacy and safety of fluticasone propionate/formoterol in children with asthma

“…It is also notable that there were no severe exacerbations (requiring oral or parenteral steroid use, emergency treatment or hospitalization) in either treatment arm in the core phase or with FP/FORM throughout the extension phase in the current study. This is in line with findings from a previous analysis that assessed the occurrence of severe exacerbations (requiring oral corticosteroids) during two long-term studies with FP/FORM compared with data for other ICS/LABA combinations from published Cochrane analyses [Papi et al 2013;Lasserson et al 2008;Ducharme et al 2010]. A low incidence of corticosteroid-requiring exacerbations was observed during 6-12 months of treatment with FP/FORM in this pooled analysis among a total of 752 patients aged 12 years and above which compared favourably with the incidence observed in long-term studies with single-inhaler FP/SAL and budesonide/formoterol, and with free combinations of individual ICS and LABA formulations [Papi et al 2013].…”

“…As expected based on previous data from adolescents and adults [Papi et al 2013[Papi et al , 2015, a low number of patients experienced asthma exacerbations during either FP/FORM or FP/SAL treatment in the core trial [4 (3.8%) FP/FORM patients and 3 (2.9%) FP/SAL patients]. This finding supports data from the previous pooled analysis of studies with FP/FORM in patients aged 12 years and over that showed a lower incidence of any exacerbation type compared with FP monotherapy [Papi et al 2015].…”

“…FP/FORM had a favourable safety and tolerability profile during the 12 weeks of randomized therapy and throughout the 24-week extension phase in this pediatric population which was consistent with previous published medium-to-long term data from patients aged 12 years and older Papi et al 2013]. Analyses of AEs, laboratory values, and vital signs did not reveal any safety signals relating to the use of FP/FORM in children.…”

Efficacy of fluticasone propionate/formoterol fumarate in the treatment of asthma: A pooled analysis

“…Thus we consider the reduction in short-term exacerbation risk (all severities) to be [33]. Longer term non-comparative studies with fluticasone/formoterol also suggest that it is likely to be an effective long-term treatment to reduce exacerbation risk; in two separate studies in which patients were treated for 6e12 months and 14 months, respectively, the incidence of oral corticosteroid-requiring exacerbations was only 2.3% and 1.8%, respectively [34]. A direct comparison of the treatment effects seen in this pooled analysis versus those from previous landmark ICS/ LABA studies of budesonide/formoterol and fluticasone/ salmeterol such as FACET [35] and GOAL [36] is difficult.…”

Pulmonary deposition of fluticasone propionate/formoterol in healthy volunteers, asthmatics and COPD patients with a novel breath-triggered inhaler

“…Flutiform ® (FP/FORM) is an inhaler product containing a combination of fluticasone propionate (FP) and formoterol fumarate (FORM), approved for maintenance use in asthma following a comprehensive series of studies [1][2][3][4][5][6][7][8][9][10]. It is currently available within a conventional hydrofluoroalkane-propelled pressurised metered-dose inhaler (pMDI).…”