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



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.



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.



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.
1 Research Centre on Asthma and COPD, University of Ferrara , Ferrara, Italy .
Alberto
A
Papi
2 Chest Research Institute, Birmingham Heartlands Hospital , Birmingham, United Kingdom .
Adel H
AH
Mansur
3 Dnipropetrovsk State Medical Academy , Dnipropetrovsk, Ukraine .
Tetyana
T
Pertseva
4 Medicinal and Regulatory Development , Skyepharma AG, Muttenz, Switzerland .
Kirsten
K
Kaiser
5 Clinical Data Management and Statistics, Mundipharma Research Limited , Cambridge, United Kingdom .
Tammy
T
McIver
6 Medical Science-Respiratory, Mundipharma Research Limited , Cambridge, United Kingdom .
Birgit
B
Grothe
6 Medical Science-Respiratory, Mundipharma Research Limited , Cambridge, United Kingdom .
Sanjeeva
S
Dissanayake
D000280:Administration, Inhalation; D058666:Adrenergic beta-2 Receptor Agonists / Q000008:administration & dosage* / Q000009:adverse effects; D000328:Adult; D000730:Androstadienes / Q000008:administration & dosage* / Q000009:adverse effects; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001249:Asthma / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002986:Clinical Trials as Topic; D018450:Disease Progression; D004338:Drug Combinations; D004983:Ethanolamines / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D000068298:Fluticasone; D000068759:Formoterol Fumarate; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D015994:Incidence; D008168:Lung / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D055118:Medication Adherence; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
D058666:Adrenergic beta-2 Receptor Agonists; D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D001993:Bronchodilator Agents; D004338:Drug Combinations; D004983:Ethanolamines; D005938:Glucocorticoids; C586520:fluticasone-formoterol; D000068298:Fluticasone; D000068759:Formoterol Fumarate
asthma; fluticasone propionate; fluticasone/formoterol; flutiform®; formoterol; severe exacerbations