Mometasone or tiotropium in mild asthma with a low sputum eosinophil level

Stephen C. Lazarus, Jerry A. Krishnan, Tonya S. King, Jason E. Lang, Kathryn V. Blake, Ronina Covar, Njira Lugogo, Sally Wenzel, Vernon M. Chinchilli, David T. Mauger, Anne Marie Dyer, Homer A. Boushey, John V. Fahy, Prescott G. Woodruff, Leonard B. Bacharier, Michael D. Cabana, Juan C. Cardet, Mario Castro, James Chmiel, Loren DenlingerEmily DiMango, Anne M. Fitzpatrick, Deborah Gentile, Annette Hastie, Fernando Holguin, Elliot Israel, Daniel Jackson, Monica Kraft, Craig LaForce, Robert F. Lemanske, Fernando Martinez, Wendy Moore, Wayne J Morgan, James N. Moy, Ross Myers, Stephen P. Peters, Wanda Phipatanakul, Jacqueline A. Pongracic, Loretta Que, Kristie Ross, Lewis Smith, Stanley J. Szefler, Michael E. Wechsler, Christine A. Sorkness

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

In many patients with mild, persistent asthma, the percentage of eosinophils in sputum is less than 2% (low eosinophil level). The appropriate treatment for these patients is unknown. METHODS In this 42-week, double-blind, crossover trial, we assigned 295 patients who were at least 12 years of age and who had mild, persistent asthma to receive mometasone (an inhaled glucocorticoid), tiotropium (a long-acting muscarinic antagonist), or placebo. The patients were categorized according to the sputum eosinophil level (<2% or ≥2%). The primary outcome was the response to mometasone as compared with placebo and to tiotropium as compared with placebo among patients with a low sputum eosinophil level who had a prespecified differential response to one of the trial agents. The response was determined according to a hierarchical composite outcome that incorporated treatment failure, asthma control days, and the forced expiratory volume in 1 second; a two-sided P value of less than 0.025 denoted statistical significance. A secondary outcome was a comparison of results in patients with a high sputum eosinophil level and those with a low level. RESULTS A total of 73% of the patients had a low eosinophil level; of these patients, 59% had a differential response to a trial agent. However, there was no significant difference in the response to mometasone or tiotropium, as compared with placebo. Among the patients with a low eosinophil level who had a differential treatment response, 57% (95% confidence interval [CI], 48 to 66) had a better response to mometasone, and 43% (95% CI, 34 to 52) had a better response to placebo (P=0.14). In contrast 60% (95% CI, 51 to 68) had a better response to tiotropium, whereas 40% (95% CI, 32 to 49) had a better response to placebo (P=0.029). Among patients with a high eosinophil level, the response to mometasone was significantly better than the response to placebo (74% vs. 26%) but the response to tiotropium was not (57% vs. 43%). CONCLUSIONS The majority of patients with mild, persistent asthma had a low sputum eosinophil level and had no significant difference in their response to either mometasone or tiotropium as compared with placebo. These data provide equipoise for a clinically directive trial to compare an inhaled glucocorticoid with other treatments in patients with a low eosinophil level.

Original languageEnglish (US)
Pages (from-to)2009-2019
Number of pages11
JournalNew England Journal of Medicine
Volume380
Issue number21
DOIs
StatePublished - May 23 2019

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Mometasone Furoate
Sputum
Eosinophils
Asthma
Placebos
Confidence Intervals
Glucocorticoids
Tiotropium Bromide

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Lazarus, S. C., Krishnan, J. A., King, T. S., Lang, J. E., Blake, K. V., Covar, R., ... Sorkness, C. A. (2019). Mometasone or tiotropium in mild asthma with a low sputum eosinophil level. New England Journal of Medicine, 380(21), 2009-2019. https://doi.org/10.1056/NEJMoa1814917

Mometasone or tiotropium in mild asthma with a low sputum eosinophil level. / Lazarus, Stephen C.; Krishnan, Jerry A.; King, Tonya S.; Lang, Jason E.; Blake, Kathryn V.; Covar, Ronina; Lugogo, Njira; Wenzel, Sally; Chinchilli, Vernon M.; Mauger, David T.; Dyer, Anne Marie; Boushey, Homer A.; Fahy, John V.; Woodruff, Prescott G.; Bacharier, Leonard B.; Cabana, Michael D.; Cardet, Juan C.; Castro, Mario; Chmiel, James; Denlinger, Loren; DiMango, Emily; Fitzpatrick, Anne M.; Gentile, Deborah; Hastie, Annette; Holguin, Fernando; Israel, Elliot; Jackson, Daniel; Kraft, Monica; LaForce, Craig; Lemanske, Robert F.; Martinez, Fernando; Moore, Wendy; Morgan, Wayne J; Moy, James N.; Myers, Ross; Peters, Stephen P.; Phipatanakul, Wanda; Pongracic, Jacqueline A.; Que, Loretta; Ross, Kristie; Smith, Lewis; Szefler, Stanley J.; Wechsler, Michael E.; Sorkness, Christine A.

In: New England Journal of Medicine, Vol. 380, No. 21, 23.05.2019, p. 2009-2019.

Research output: Contribution to journalArticle

Lazarus, SC, Krishnan, JA, King, TS, Lang, JE, Blake, KV, Covar, R, Lugogo, N, Wenzel, S, Chinchilli, VM, Mauger, DT, Dyer, AM, Boushey, HA, Fahy, JV, Woodruff, PG, Bacharier, LB, Cabana, MD, Cardet, JC, Castro, M, Chmiel, J, Denlinger, L, DiMango, E, Fitzpatrick, AM, Gentile, D, Hastie, A, Holguin, F, Israel, E, Jackson, D, Kraft, M, LaForce, C, Lemanske, RF, Martinez, F, Moore, W, Morgan, WJ, Moy, JN, Myers, R, Peters, SP, Phipatanakul, W, Pongracic, JA, Que, L, Ross, K, Smith, L, Szefler, SJ, Wechsler, ME & Sorkness, CA 2019, 'Mometasone or tiotropium in mild asthma with a low sputum eosinophil level', New England Journal of Medicine, vol. 380, no. 21, pp. 2009-2019. https://doi.org/10.1056/NEJMoa1814917
Lazarus SC, Krishnan JA, King TS, Lang JE, Blake KV, Covar R et al. Mometasone or tiotropium in mild asthma with a low sputum eosinophil level. New England Journal of Medicine. 2019 May 23;380(21):2009-2019. https://doi.org/10.1056/NEJMoa1814917
Lazarus, Stephen C. ; Krishnan, Jerry A. ; King, Tonya S. ; Lang, Jason E. ; Blake, Kathryn V. ; Covar, Ronina ; Lugogo, Njira ; Wenzel, Sally ; Chinchilli, Vernon M. ; Mauger, David T. ; Dyer, Anne Marie ; Boushey, Homer A. ; Fahy, John V. ; Woodruff, Prescott G. ; Bacharier, Leonard B. ; Cabana, Michael D. ; Cardet, Juan C. ; Castro, Mario ; Chmiel, James ; Denlinger, Loren ; DiMango, Emily ; Fitzpatrick, Anne M. ; Gentile, Deborah ; Hastie, Annette ; Holguin, Fernando ; Israel, Elliot ; Jackson, Daniel ; Kraft, Monica ; LaForce, Craig ; Lemanske, Robert F. ; Martinez, Fernando ; Moore, Wendy ; Morgan, Wayne J ; Moy, James N. ; Myers, Ross ; Peters, Stephen P. ; Phipatanakul, Wanda ; Pongracic, Jacqueline A. ; Que, Loretta ; Ross, Kristie ; Smith, Lewis ; Szefler, Stanley J. ; Wechsler, Michael E. ; Sorkness, Christine A. / Mometasone or tiotropium in mild asthma with a low sputum eosinophil level. In: New England Journal of Medicine. 2019 ; Vol. 380, No. 21. pp. 2009-2019.
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title = "Mometasone or tiotropium in mild asthma with a low sputum eosinophil level",
abstract = "In many patients with mild, persistent asthma, the percentage of eosinophils in sputum is less than 2{\%} (low eosinophil level). The appropriate treatment for these patients is unknown. METHODS In this 42-week, double-blind, crossover trial, we assigned 295 patients who were at least 12 years of age and who had mild, persistent asthma to receive mometasone (an inhaled glucocorticoid), tiotropium (a long-acting muscarinic antagonist), or placebo. The patients were categorized according to the sputum eosinophil level (<2{\%} or ≥2{\%}). The primary outcome was the response to mometasone as compared with placebo and to tiotropium as compared with placebo among patients with a low sputum eosinophil level who had a prespecified differential response to one of the trial agents. The response was determined according to a hierarchical composite outcome that incorporated treatment failure, asthma control days, and the forced expiratory volume in 1 second; a two-sided P value of less than 0.025 denoted statistical significance. A secondary outcome was a comparison of results in patients with a high sputum eosinophil level and those with a low level. RESULTS A total of 73{\%} of the patients had a low eosinophil level; of these patients, 59{\%} had a differential response to a trial agent. However, there was no significant difference in the response to mometasone or tiotropium, as compared with placebo. Among the patients with a low eosinophil level who had a differential treatment response, 57{\%} (95{\%} confidence interval [CI], 48 to 66) had a better response to mometasone, and 43{\%} (95{\%} CI, 34 to 52) had a better response to placebo (P=0.14). In contrast 60{\%} (95{\%} CI, 51 to 68) had a better response to tiotropium, whereas 40{\%} (95{\%} CI, 32 to 49) had a better response to placebo (P=0.029). Among patients with a high eosinophil level, the response to mometasone was significantly better than the response to placebo (74{\%} vs. 26{\%}) but the response to tiotropium was not (57{\%} vs. 43{\%}). CONCLUSIONS The majority of patients with mild, persistent asthma had a low sputum eosinophil level and had no significant difference in their response to either mometasone or tiotropium as compared with placebo. These data provide equipoise for a clinically directive trial to compare an inhaled glucocorticoid with other treatments in patients with a low eosinophil level.",
author = "Lazarus, {Stephen C.} and Krishnan, {Jerry A.} and King, {Tonya S.} and Lang, {Jason E.} and Blake, {Kathryn V.} and Ronina Covar and Njira Lugogo and Sally Wenzel and Chinchilli, {Vernon M.} and Mauger, {David T.} and Dyer, {Anne Marie} and Boushey, {Homer A.} and Fahy, {John V.} and Woodruff, {Prescott G.} and Bacharier, {Leonard B.} and Cabana, {Michael D.} and Cardet, {Juan C.} and Mario Castro and James Chmiel and Loren Denlinger and Emily DiMango and Fitzpatrick, {Anne M.} and Deborah Gentile and Annette Hastie and Fernando Holguin and Elliot Israel and Daniel Jackson and Monica Kraft and Craig LaForce and Lemanske, {Robert F.} and Fernando Martinez and Wendy Moore and Morgan, {Wayne J} and Moy, {James N.} and Ross Myers and Peters, {Stephen P.} and Wanda Phipatanakul and Pongracic, {Jacqueline A.} and Loretta Que and Kristie Ross and Lewis Smith and Szefler, {Stanley J.} and Wechsler, {Michael E.} and Sorkness, {Christine A.}",
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TY - JOUR

T1 - Mometasone or tiotropium in mild asthma with a low sputum eosinophil level

AU - Lazarus, Stephen C.

AU - Krishnan, Jerry A.

AU - King, Tonya S.

AU - Lang, Jason E.

AU - Blake, Kathryn V.

AU - Covar, Ronina

AU - Lugogo, Njira

AU - Wenzel, Sally

AU - Chinchilli, Vernon M.

AU - Mauger, David T.

AU - Dyer, Anne Marie

AU - Boushey, Homer A.

AU - Fahy, John V.

AU - Woodruff, Prescott G.

AU - Bacharier, Leonard B.

AU - Cabana, Michael D.

AU - Cardet, Juan C.

AU - Castro, Mario

AU - Chmiel, James

AU - Denlinger, Loren

AU - DiMango, Emily

AU - Fitzpatrick, Anne M.

AU - Gentile, Deborah

AU - Hastie, Annette

AU - Holguin, Fernando

AU - Israel, Elliot

AU - Jackson, Daniel

AU - Kraft, Monica

AU - LaForce, Craig

AU - Lemanske, Robert F.

AU - Martinez, Fernando

AU - Moore, Wendy

AU - Morgan, Wayne J

AU - Moy, James N.

AU - Myers, Ross

AU - Peters, Stephen P.

AU - Phipatanakul, Wanda

AU - Pongracic, Jacqueline A.

AU - Que, Loretta

AU - Ross, Kristie

AU - Smith, Lewis

AU - Szefler, Stanley J.

AU - Wechsler, Michael E.

AU - Sorkness, Christine A.

PY - 2019/5/23

Y1 - 2019/5/23

N2 - In many patients with mild, persistent asthma, the percentage of eosinophils in sputum is less than 2% (low eosinophil level). The appropriate treatment for these patients is unknown. METHODS In this 42-week, double-blind, crossover trial, we assigned 295 patients who were at least 12 years of age and who had mild, persistent asthma to receive mometasone (an inhaled glucocorticoid), tiotropium (a long-acting muscarinic antagonist), or placebo. The patients were categorized according to the sputum eosinophil level (<2% or ≥2%). The primary outcome was the response to mometasone as compared with placebo and to tiotropium as compared with placebo among patients with a low sputum eosinophil level who had a prespecified differential response to one of the trial agents. The response was determined according to a hierarchical composite outcome that incorporated treatment failure, asthma control days, and the forced expiratory volume in 1 second; a two-sided P value of less than 0.025 denoted statistical significance. A secondary outcome was a comparison of results in patients with a high sputum eosinophil level and those with a low level. RESULTS A total of 73% of the patients had a low eosinophil level; of these patients, 59% had a differential response to a trial agent. However, there was no significant difference in the response to mometasone or tiotropium, as compared with placebo. Among the patients with a low eosinophil level who had a differential treatment response, 57% (95% confidence interval [CI], 48 to 66) had a better response to mometasone, and 43% (95% CI, 34 to 52) had a better response to placebo (P=0.14). In contrast 60% (95% CI, 51 to 68) had a better response to tiotropium, whereas 40% (95% CI, 32 to 49) had a better response to placebo (P=0.029). Among patients with a high eosinophil level, the response to mometasone was significantly better than the response to placebo (74% vs. 26%) but the response to tiotropium was not (57% vs. 43%). CONCLUSIONS The majority of patients with mild, persistent asthma had a low sputum eosinophil level and had no significant difference in their response to either mometasone or tiotropium as compared with placebo. These data provide equipoise for a clinically directive trial to compare an inhaled glucocorticoid with other treatments in patients with a low eosinophil level.

AB - In many patients with mild, persistent asthma, the percentage of eosinophils in sputum is less than 2% (low eosinophil level). The appropriate treatment for these patients is unknown. METHODS In this 42-week, double-blind, crossover trial, we assigned 295 patients who were at least 12 years of age and who had mild, persistent asthma to receive mometasone (an inhaled glucocorticoid), tiotropium (a long-acting muscarinic antagonist), or placebo. The patients were categorized according to the sputum eosinophil level (<2% or ≥2%). The primary outcome was the response to mometasone as compared with placebo and to tiotropium as compared with placebo among patients with a low sputum eosinophil level who had a prespecified differential response to one of the trial agents. The response was determined according to a hierarchical composite outcome that incorporated treatment failure, asthma control days, and the forced expiratory volume in 1 second; a two-sided P value of less than 0.025 denoted statistical significance. A secondary outcome was a comparison of results in patients with a high sputum eosinophil level and those with a low level. RESULTS A total of 73% of the patients had a low eosinophil level; of these patients, 59% had a differential response to a trial agent. However, there was no significant difference in the response to mometasone or tiotropium, as compared with placebo. Among the patients with a low eosinophil level who had a differential treatment response, 57% (95% confidence interval [CI], 48 to 66) had a better response to mometasone, and 43% (95% CI, 34 to 52) had a better response to placebo (P=0.14). In contrast 60% (95% CI, 51 to 68) had a better response to tiotropium, whereas 40% (95% CI, 32 to 49) had a better response to placebo (P=0.029). Among patients with a high eosinophil level, the response to mometasone was significantly better than the response to placebo (74% vs. 26%) but the response to tiotropium was not (57% vs. 43%). CONCLUSIONS The majority of patients with mild, persistent asthma had a low sputum eosinophil level and had no significant difference in their response to either mometasone or tiotropium as compared with placebo. These data provide equipoise for a clinically directive trial to compare an inhaled glucocorticoid with other treatments in patients with a low eosinophil level.

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