Serious Asthma Events with Fluticasone plus Salmeterol versus Fluticasone Alone

David A. Stempel, Ibrahim H. Raphiou, Kenneth M. Kral, Anne M. Yeakey, Amanda H. Emmett, Charlene M. Prazma, Kathleen S. Buaron, Steven J. Pascoe, for the AUSTRI Investigators, Susanna Esposito

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Abstract

BACKGROUND The safe and appropriate use of long-acting beta-agonists (LABAs) for the treatment of asthma has been widely debated. In two large clinical trials, investigators found a potential risk of serious asthma-related events associated with LABAs. This study was designed to evaluate the risk of administering the LABA salmeterol in combination with an inhaled glucocorticoid, fluticasone propionate. METHODS In this multicenter, randomized, double-blind trial, adolescent and adult patients (age, .12 years) with persistent asthma were assigned to receive either fluticasone with salmeterol or fluticasone alone for 26 weeks. All the patients had a history of a severe asthma exacerbation in the year before randomization but not during the previous month. Patients were excluded from the trial if they had a history of lifethreatening or unstable asthma. The primary safety end point was the first serious asthma-related event (death, endotracheal intubation, or hospitalization). Noninferiority of fluticasone.salmeterol to fluticasone alone was defined as an upper boundary of the 95% confidence interval for the risk of the primary safety end point of less than 2.0. The efficacy end point was the first severe asthma exacerbation. RESULTS Of 11,679 patients who were enrolled, 67 had 74 serious asthma-related events, with 36 events in 34 patients in the fluticasone.salmeterol group and 38 events in 33 patients in the fluticasone-only group. The hazard ratio for a serious asthmarelated event in the fluticasone.salmeterol group was 1.03 (95% confidence interval [CI], 0.64 to 1.66), and noninferiority was achieved (P = 0.003). There were no asthma-related deaths; 2 patients in the fluticasone-only group underwent asthmarelated intubation. The risk of a severe asthma exacerbation was 21% lower in the fluticasone.salmeterol group than in the fluticasone-only group (hazard ratio, 0.79; 95% CI, 0.70 to 0.89), with at least one severe asthma exacerbation occurring in 480 of 5834 patients (8%) in the fluticasone.salmeterol group, as compared with 597 of 5845 patients (10%) in the fluticasone-only group (P<0.001). CONCLUSIONS Patients who received salmeterol in a fixed-dose combination with fluticasone did not have a significantly higher risk of serious asthma-related events than did those who received fluticasone alone. Patients receiving fluticasone.salmeterol had fewer severe asthma exacerbations than did those in the fluticasone-only group. (AUSTRI ClinicalTrials.gov number, NCT01475721.)

Original languageEnglish
Pages (from-to)1822-1830
Number of pages9
JournalNew England Journal of Medicine
Volume374
Issue number19
DOIs
Publication statusPublished - May 12 2016

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Asthma
Fluticasone
Salmeterol Xinafoate Drug Combination Fluticasone Propionate
Confidence Intervals
Safety
Intratracheal Intubation
Random Allocation
Salmeterol Xinafoate
Intubation
Glucocorticoids
Hospitalization
Research Personnel
Clinical Trials

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Stempel, D. A., Raphiou, I. H., Kral, K. M., Yeakey, A. M., Emmett, A. H., Prazma, C. M., ... Esposito, S. (2016). Serious Asthma Events with Fluticasone plus Salmeterol versus Fluticasone Alone. New England Journal of Medicine, 374(19), 1822-1830. https://doi.org/10.1056/NEJMoa1511049

Serious Asthma Events with Fluticasone plus Salmeterol versus Fluticasone Alone. / Stempel, David A.; Raphiou, Ibrahim H.; Kral, Kenneth M.; Yeakey, Anne M.; Emmett, Amanda H.; Prazma, Charlene M.; Buaron, Kathleen S.; Pascoe, Steven J.; for the AUSTRI Investigators; Esposito, Susanna.

In: New England Journal of Medicine, Vol. 374, No. 19, 12.05.2016, p. 1822-1830.

Research output: Contribution to journalArticle

Stempel, DA, Raphiou, IH, Kral, KM, Yeakey, AM, Emmett, AH, Prazma, CM, Buaron, KS, Pascoe, SJ, for the AUSTRI Investigators & Esposito, S 2016, 'Serious Asthma Events with Fluticasone plus Salmeterol versus Fluticasone Alone', New England Journal of Medicine, vol. 374, no. 19, pp. 1822-1830. https://doi.org/10.1056/NEJMoa1511049
Stempel DA, Raphiou IH, Kral KM, Yeakey AM, Emmett AH, Prazma CM et al. Serious Asthma Events with Fluticasone plus Salmeterol versus Fluticasone Alone. New England Journal of Medicine. 2016 May 12;374(19):1822-1830. https://doi.org/10.1056/NEJMoa1511049
Stempel, David A. ; Raphiou, Ibrahim H. ; Kral, Kenneth M. ; Yeakey, Anne M. ; Emmett, Amanda H. ; Prazma, Charlene M. ; Buaron, Kathleen S. ; Pascoe, Steven J. ; for the AUSTRI Investigators ; Esposito, Susanna. / Serious Asthma Events with Fluticasone plus Salmeterol versus Fluticasone Alone. In: New England Journal of Medicine. 2016 ; Vol. 374, No. 19. pp. 1822-1830.
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abstract = "BACKGROUND The safe and appropriate use of long-acting beta-agonists (LABAs) for the treatment of asthma has been widely debated. In two large clinical trials, investigators found a potential risk of serious asthma-related events associated with LABAs. This study was designed to evaluate the risk of administering the LABA salmeterol in combination with an inhaled glucocorticoid, fluticasone propionate. METHODS In this multicenter, randomized, double-blind trial, adolescent and adult patients (age, .12 years) with persistent asthma were assigned to receive either fluticasone with salmeterol or fluticasone alone for 26 weeks. All the patients had a history of a severe asthma exacerbation in the year before randomization but not during the previous month. Patients were excluded from the trial if they had a history of lifethreatening or unstable asthma. The primary safety end point was the first serious asthma-related event (death, endotracheal intubation, or hospitalization). Noninferiority of fluticasone.salmeterol to fluticasone alone was defined as an upper boundary of the 95{\%} confidence interval for the risk of the primary safety end point of less than 2.0. The efficacy end point was the first severe asthma exacerbation. RESULTS Of 11,679 patients who were enrolled, 67 had 74 serious asthma-related events, with 36 events in 34 patients in the fluticasone.salmeterol group and 38 events in 33 patients in the fluticasone-only group. The hazard ratio for a serious asthmarelated event in the fluticasone.salmeterol group was 1.03 (95{\%} confidence interval [CI], 0.64 to 1.66), and noninferiority was achieved (P = 0.003). There were no asthma-related deaths; 2 patients in the fluticasone-only group underwent asthmarelated intubation. The risk of a severe asthma exacerbation was 21{\%} lower in the fluticasone.salmeterol group than in the fluticasone-only group (hazard ratio, 0.79; 95{\%} CI, 0.70 to 0.89), with at least one severe asthma exacerbation occurring in 480 of 5834 patients (8{\%}) in the fluticasone.salmeterol group, as compared with 597 of 5845 patients (10{\%}) in the fluticasone-only group (P<0.001). CONCLUSIONS Patients who received salmeterol in a fixed-dose combination with fluticasone did not have a significantly higher risk of serious asthma-related events than did those who received fluticasone alone. Patients receiving fluticasone.salmeterol had fewer severe asthma exacerbations than did those in the fluticasone-only group. (AUSTRI ClinicalTrials.gov number, NCT01475721.)",
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AU - Stempel, David A.

AU - Raphiou, Ibrahim H.

AU - Kral, Kenneth M.

AU - Yeakey, Anne M.

AU - Emmett, Amanda H.

AU - Prazma, Charlene M.

AU - Buaron, Kathleen S.

AU - Pascoe, Steven J.

AU - for the AUSTRI Investigators

AU - Esposito, Susanna

PY - 2016/5/12

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N2 - BACKGROUND The safe and appropriate use of long-acting beta-agonists (LABAs) for the treatment of asthma has been widely debated. In two large clinical trials, investigators found a potential risk of serious asthma-related events associated with LABAs. This study was designed to evaluate the risk of administering the LABA salmeterol in combination with an inhaled glucocorticoid, fluticasone propionate. METHODS In this multicenter, randomized, double-blind trial, adolescent and adult patients (age, .12 years) with persistent asthma were assigned to receive either fluticasone with salmeterol or fluticasone alone for 26 weeks. All the patients had a history of a severe asthma exacerbation in the year before randomization but not during the previous month. Patients were excluded from the trial if they had a history of lifethreatening or unstable asthma. The primary safety end point was the first serious asthma-related event (death, endotracheal intubation, or hospitalization). Noninferiority of fluticasone.salmeterol to fluticasone alone was defined as an upper boundary of the 95% confidence interval for the risk of the primary safety end point of less than 2.0. The efficacy end point was the first severe asthma exacerbation. RESULTS Of 11,679 patients who were enrolled, 67 had 74 serious asthma-related events, with 36 events in 34 patients in the fluticasone.salmeterol group and 38 events in 33 patients in the fluticasone-only group. The hazard ratio for a serious asthmarelated event in the fluticasone.salmeterol group was 1.03 (95% confidence interval [CI], 0.64 to 1.66), and noninferiority was achieved (P = 0.003). There were no asthma-related deaths; 2 patients in the fluticasone-only group underwent asthmarelated intubation. The risk of a severe asthma exacerbation was 21% lower in the fluticasone.salmeterol group than in the fluticasone-only group (hazard ratio, 0.79; 95% CI, 0.70 to 0.89), with at least one severe asthma exacerbation occurring in 480 of 5834 patients (8%) in the fluticasone.salmeterol group, as compared with 597 of 5845 patients (10%) in the fluticasone-only group (P<0.001). CONCLUSIONS Patients who received salmeterol in a fixed-dose combination with fluticasone did not have a significantly higher risk of serious asthma-related events than did those who received fluticasone alone. Patients receiving fluticasone.salmeterol had fewer severe asthma exacerbations than did those in the fluticasone-only group. (AUSTRI ClinicalTrials.gov number, NCT01475721.)

AB - BACKGROUND The safe and appropriate use of long-acting beta-agonists (LABAs) for the treatment of asthma has been widely debated. In two large clinical trials, investigators found a potential risk of serious asthma-related events associated with LABAs. This study was designed to evaluate the risk of administering the LABA salmeterol in combination with an inhaled glucocorticoid, fluticasone propionate. METHODS In this multicenter, randomized, double-blind trial, adolescent and adult patients (age, .12 years) with persistent asthma were assigned to receive either fluticasone with salmeterol or fluticasone alone for 26 weeks. All the patients had a history of a severe asthma exacerbation in the year before randomization but not during the previous month. Patients were excluded from the trial if they had a history of lifethreatening or unstable asthma. The primary safety end point was the first serious asthma-related event (death, endotracheal intubation, or hospitalization). Noninferiority of fluticasone.salmeterol to fluticasone alone was defined as an upper boundary of the 95% confidence interval for the risk of the primary safety end point of less than 2.0. The efficacy end point was the first severe asthma exacerbation. RESULTS Of 11,679 patients who were enrolled, 67 had 74 serious asthma-related events, with 36 events in 34 patients in the fluticasone.salmeterol group and 38 events in 33 patients in the fluticasone-only group. The hazard ratio for a serious asthmarelated event in the fluticasone.salmeterol group was 1.03 (95% confidence interval [CI], 0.64 to 1.66), and noninferiority was achieved (P = 0.003). There were no asthma-related deaths; 2 patients in the fluticasone-only group underwent asthmarelated intubation. The risk of a severe asthma exacerbation was 21% lower in the fluticasone.salmeterol group than in the fluticasone-only group (hazard ratio, 0.79; 95% CI, 0.70 to 0.89), with at least one severe asthma exacerbation occurring in 480 of 5834 patients (8%) in the fluticasone.salmeterol group, as compared with 597 of 5845 patients (10%) in the fluticasone-only group (P<0.001). CONCLUSIONS Patients who received salmeterol in a fixed-dose combination with fluticasone did not have a significantly higher risk of serious asthma-related events than did those who received fluticasone alone. Patients receiving fluticasone.salmeterol had fewer severe asthma exacerbations than did those in the fluticasone-only group. (AUSTRI ClinicalTrials.gov number, NCT01475721.)

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