Tiotropium bromide step-up therapy for adults with uncontrolled asthma

Stephen P. Peters, Susan J. Kunselman, Nikolina Icitovic, Wendy C. Moore, Rodolfo Pascual, Bill Ameredes, Homer A. Boushey, William Calhoun, Mario Castro, Reuben M. Cherniack, Timothy Craig, Loren Denlinger, Linda L. Engle, Emily A. DiMango, John V. Fahy, Elliot Israel, Nizar Jarjour, Shamsah D. Kazani, Monica Kraft, Stephen C. Lazarus & 13 others Robert F. Lemanske, Njira Lugogo, Richard J. Martin, Deborah A. Meyers, Joe Ramsdell, Christine A. Sorkness, E. Rand Sutherland, Stanley J. Szefler, Stephen I. Wasserman, Michael J. Walter, Michael E. Wechsler, Vernon M. Chinchilli, Eugene R. Bleecker

Research output: Contribution to journalArticle

395 Citations (Scopus)

Abstract

BACKGROUND: Long-acting beta-agonist (LABA) therapy improves symptoms in patients whose asthma is poorly controlled by an inhaled glucocorticoid alone. Alternative treatments for adults with uncontrolled asthma are needed. METHODS: In a three-way, double-blind, triple-dummy crossover trial involving 210 patients with asthma, we evaluated the addition of tiotropium bromide (a long-acting anticholinergic agent approved for the treatment of chronic obstructive pulmonary disease but not asthma) to an inhaled glucocorticoid, as compared with a doubling of the dose of the inhaled glucocorticoid (primary superiority comparison) or the addition of the LABA salmeterol (secondary noninferiority comparison). RESULTS: The use of tiotropium resulted in a superior primary outcome, as compared with a doubling of the dose of an inhaled glucocorticoid, as assessed by measuring the morning peak expiratory flow (PEF), with a mean difference of 25.8 liters per minute (P<0.001) and superiority in most secondary outcomes, including evening PEF, with a difference of 35.3 liters per minute (P<0.001); the proportion of asthmacontrol days, with a difference of 0.079 (P = 0.01); the forced expiratory volume in 1 second (FEV1) before bronchodilation, with a difference of 0.10 liters (P = 0.004); and daily symptom scores, with a difference of -0.11 points (P<0.001). The addition of tiotropium was also noninferior to the addition of salmeterol for all assessed outcomes and increased the prebronchodilator FEV1 more than did salmeterol, with a difference of 0.11 liters (P = 0.003). CONCLUSIONS: When added to an inhaled glucocorticoid, tiotropium improved symptoms and lung function in patients with inadequately controlled asthma. Its effects appeared to be equivalent to those with the addition of salmeterol. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT00565266.).

Original languageEnglish (US)
Pages (from-to)1715-1726
Number of pages12
JournalNew England Journal of Medicine
Volume363
Issue number18
DOIs
StatePublished - Oct 28 2010

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Glucocorticoids
Asthma
Forced Expiratory Volume
National Heart, Lung, and Blood Institute (U.S.)
Therapeutics
Cholinergic Antagonists
Cross-Over Studies
Chronic Obstructive Pulmonary Disease
Tiotropium Bromide
Lung
Salmeterol Xinafoate

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Peters, S. P., Kunselman, S. J., Icitovic, N., Moore, W. C., Pascual, R., Ameredes, B., ... Bleecker, E. R. (2010). Tiotropium bromide step-up therapy for adults with uncontrolled asthma. New England Journal of Medicine, 363(18), 1715-1726. https://doi.org/10.1056/NEJMoa1008770

Tiotropium bromide step-up therapy for adults with uncontrolled asthma. / Peters, Stephen P.; Kunselman, Susan J.; Icitovic, Nikolina; Moore, Wendy C.; Pascual, Rodolfo; Ameredes, Bill; Boushey, Homer A.; Calhoun, William; Castro, Mario; Cherniack, Reuben M.; Craig, Timothy; Denlinger, Loren; Engle, Linda L.; DiMango, Emily A.; Fahy, John V.; Israel, Elliot; Jarjour, Nizar; Kazani, Shamsah D.; Kraft, Monica; Lazarus, Stephen C.; Lemanske, Robert F.; Lugogo, Njira; Martin, Richard J.; Meyers, Deborah A.; Ramsdell, Joe; Sorkness, Christine A.; Sutherland, E. Rand; Szefler, Stanley J.; Wasserman, Stephen I.; Walter, Michael J.; Wechsler, Michael E.; Chinchilli, Vernon M.; Bleecker, Eugene R.

In: New England Journal of Medicine, Vol. 363, No. 18, 28.10.2010, p. 1715-1726.

Research output: Contribution to journalArticle

Peters, SP, Kunselman, SJ, Icitovic, N, Moore, WC, Pascual, R, Ameredes, B, Boushey, HA, Calhoun, W, Castro, M, Cherniack, RM, Craig, T, Denlinger, L, Engle, LL, DiMango, EA, Fahy, JV, Israel, E, Jarjour, N, Kazani, SD, Kraft, M, Lazarus, SC, Lemanske, RF, Lugogo, N, Martin, RJ, Meyers, DA, Ramsdell, J, Sorkness, CA, Sutherland, ER, Szefler, SJ, Wasserman, SI, Walter, MJ, Wechsler, ME, Chinchilli, VM & Bleecker, ER 2010, 'Tiotropium bromide step-up therapy for adults with uncontrolled asthma', New England Journal of Medicine, vol. 363, no. 18, pp. 1715-1726. https://doi.org/10.1056/NEJMoa1008770
Peters, Stephen P. ; Kunselman, Susan J. ; Icitovic, Nikolina ; Moore, Wendy C. ; Pascual, Rodolfo ; Ameredes, Bill ; Boushey, Homer A. ; Calhoun, William ; Castro, Mario ; Cherniack, Reuben M. ; Craig, Timothy ; Denlinger, Loren ; Engle, Linda L. ; DiMango, Emily A. ; Fahy, John V. ; Israel, Elliot ; Jarjour, Nizar ; Kazani, Shamsah D. ; Kraft, Monica ; Lazarus, Stephen C. ; Lemanske, Robert F. ; Lugogo, Njira ; Martin, Richard J. ; Meyers, Deborah A. ; Ramsdell, Joe ; Sorkness, Christine A. ; Sutherland, E. Rand ; Szefler, Stanley J. ; Wasserman, Stephen I. ; Walter, Michael J. ; Wechsler, Michael E. ; Chinchilli, Vernon M. ; Bleecker, Eugene R. / Tiotropium bromide step-up therapy for adults with uncontrolled asthma. In: New England Journal of Medicine. 2010 ; Vol. 363, No. 18. pp. 1715-1726.
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abstract = "BACKGROUND: Long-acting beta-agonist (LABA) therapy improves symptoms in patients whose asthma is poorly controlled by an inhaled glucocorticoid alone. Alternative treatments for adults with uncontrolled asthma are needed. METHODS: In a three-way, double-blind, triple-dummy crossover trial involving 210 patients with asthma, we evaluated the addition of tiotropium bromide (a long-acting anticholinergic agent approved for the treatment of chronic obstructive pulmonary disease but not asthma) to an inhaled glucocorticoid, as compared with a doubling of the dose of the inhaled glucocorticoid (primary superiority comparison) or the addition of the LABA salmeterol (secondary noninferiority comparison). RESULTS: The use of tiotropium resulted in a superior primary outcome, as compared with a doubling of the dose of an inhaled glucocorticoid, as assessed by measuring the morning peak expiratory flow (PEF), with a mean difference of 25.8 liters per minute (P<0.001) and superiority in most secondary outcomes, including evening PEF, with a difference of 35.3 liters per minute (P<0.001); the proportion of asthmacontrol days, with a difference of 0.079 (P = 0.01); the forced expiratory volume in 1 second (FEV1) before bronchodilation, with a difference of 0.10 liters (P = 0.004); and daily symptom scores, with a difference of -0.11 points (P<0.001). The addition of tiotropium was also noninferior to the addition of salmeterol for all assessed outcomes and increased the prebronchodilator FEV1 more than did salmeterol, with a difference of 0.11 liters (P = 0.003). CONCLUSIONS: When added to an inhaled glucocorticoid, tiotropium improved symptoms and lung function in patients with inadequately controlled asthma. Its effects appeared to be equivalent to those with the addition of salmeterol. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT00565266.).",
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T1 - Tiotropium bromide step-up therapy for adults with uncontrolled asthma

AU - Peters, Stephen P.

AU - Kunselman, Susan J.

AU - Icitovic, Nikolina

AU - Moore, Wendy C.

AU - Pascual, Rodolfo

AU - Ameredes, Bill

AU - Boushey, Homer A.

AU - Calhoun, William

AU - Castro, Mario

AU - Cherniack, Reuben M.

AU - Craig, Timothy

AU - Denlinger, Loren

AU - Engle, Linda L.

AU - DiMango, Emily A.

AU - Fahy, John V.

AU - Israel, Elliot

AU - Jarjour, Nizar

AU - Kazani, Shamsah D.

AU - Kraft, Monica

AU - Lazarus, Stephen C.

AU - Lemanske, Robert F.

AU - Lugogo, Njira

AU - Martin, Richard J.

AU - Meyers, Deborah A.

AU - Ramsdell, Joe

AU - Sorkness, Christine A.

AU - Sutherland, E. Rand

AU - Szefler, Stanley J.

AU - Wasserman, Stephen I.

AU - Walter, Michael J.

AU - Wechsler, Michael E.

AU - Chinchilli, Vernon M.

AU - Bleecker, Eugene R.

PY - 2010/10/28

Y1 - 2010/10/28

N2 - BACKGROUND: Long-acting beta-agonist (LABA) therapy improves symptoms in patients whose asthma is poorly controlled by an inhaled glucocorticoid alone. Alternative treatments for adults with uncontrolled asthma are needed. METHODS: In a three-way, double-blind, triple-dummy crossover trial involving 210 patients with asthma, we evaluated the addition of tiotropium bromide (a long-acting anticholinergic agent approved for the treatment of chronic obstructive pulmonary disease but not asthma) to an inhaled glucocorticoid, as compared with a doubling of the dose of the inhaled glucocorticoid (primary superiority comparison) or the addition of the LABA salmeterol (secondary noninferiority comparison). RESULTS: The use of tiotropium resulted in a superior primary outcome, as compared with a doubling of the dose of an inhaled glucocorticoid, as assessed by measuring the morning peak expiratory flow (PEF), with a mean difference of 25.8 liters per minute (P<0.001) and superiority in most secondary outcomes, including evening PEF, with a difference of 35.3 liters per minute (P<0.001); the proportion of asthmacontrol days, with a difference of 0.079 (P = 0.01); the forced expiratory volume in 1 second (FEV1) before bronchodilation, with a difference of 0.10 liters (P = 0.004); and daily symptom scores, with a difference of -0.11 points (P<0.001). The addition of tiotropium was also noninferior to the addition of salmeterol for all assessed outcomes and increased the prebronchodilator FEV1 more than did salmeterol, with a difference of 0.11 liters (P = 0.003). CONCLUSIONS: When added to an inhaled glucocorticoid, tiotropium improved symptoms and lung function in patients with inadequately controlled asthma. Its effects appeared to be equivalent to those with the addition of salmeterol. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT00565266.).

AB - BACKGROUND: Long-acting beta-agonist (LABA) therapy improves symptoms in patients whose asthma is poorly controlled by an inhaled glucocorticoid alone. Alternative treatments for adults with uncontrolled asthma are needed. METHODS: In a three-way, double-blind, triple-dummy crossover trial involving 210 patients with asthma, we evaluated the addition of tiotropium bromide (a long-acting anticholinergic agent approved for the treatment of chronic obstructive pulmonary disease but not asthma) to an inhaled glucocorticoid, as compared with a doubling of the dose of the inhaled glucocorticoid (primary superiority comparison) or the addition of the LABA salmeterol (secondary noninferiority comparison). RESULTS: The use of tiotropium resulted in a superior primary outcome, as compared with a doubling of the dose of an inhaled glucocorticoid, as assessed by measuring the morning peak expiratory flow (PEF), with a mean difference of 25.8 liters per minute (P<0.001) and superiority in most secondary outcomes, including evening PEF, with a difference of 35.3 liters per minute (P<0.001); the proportion of asthmacontrol days, with a difference of 0.079 (P = 0.01); the forced expiratory volume in 1 second (FEV1) before bronchodilation, with a difference of 0.10 liters (P = 0.004); and daily symptom scores, with a difference of -0.11 points (P<0.001). The addition of tiotropium was also noninferior to the addition of salmeterol for all assessed outcomes and increased the prebronchodilator FEV1 more than did salmeterol, with a difference of 0.11 liters (P = 0.003). CONCLUSIONS: When added to an inhaled glucocorticoid, tiotropium improved symptoms and lung function in patients with inadequately controlled asthma. Its effects appeared to be equivalent to those with the addition of salmeterol. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT00565266.).

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