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 Denlinger; Emily DiMango; Anne M. Fitzpatrick; Deborah Gentile; Annette Hastie; Fernando Holguin; Elliot Israel; Daniel Jackson; Monica Kraft; Craig LaForce; Robert F. Lemanske; Fernando D. 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

doi:10.1056/NEJMoa1814917

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 D. 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 journal › Article › peer-review

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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 language	English
Pages (from-to)	2009-2019
Number of pages	11
Journal	New England Journal of Medicine
Volume	380
Issue number	21
DOIs	https://doi.org/10.1056/NEJMoa1814917
State	Published - May 23 2019

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10.1056/NEJMoa1814917

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Lazarus, S. C., Krishnan, J. A., King, T. S., Lang, J. E., Blake, K. V., Covar, R., Lugogo, N., Wenzel, S., Chinchilli, V. M., Mauger, D. T., Dyer, A. M., Boushey, H. A., Fahy, J. V., Woodruff, P. G., Bacharier, L. B., Cabana, M. D., Cardet, J. C., Castro, M., Chmiel, J., ... 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

@article{7eb46db2ecd94239a945197937fcf76a,

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 Martinez, {Fernando D.} 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.}",

note = "Publisher Copyright: Copyright {\textcopyright} 2019 Massachusetts Medical Society.",

year = "2019",

month = may,

day = "23",

doi = "10.1056/NEJMoa1814917",

language = "English",

volume = "380",

pages = "2009--2019",

journal = "New England Journal of Medicine",

issn = "0028-4793",

number = "21",

}

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, FD, 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

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 D.

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.

UR - http://www.scopus.com/inward/record.url?scp=85066101666&partnerID=8YFLogxK

U2 - 10.1056/NEJMoa1814917

DO - 10.1056/NEJMoa1814917

M3 - Article

C2 - 31112384

AN - SCOPUS:85066101666

SN - 0028-4793

VL - 380

SP - 2009

EP - 2019

JO - New England Journal of Medicine

JF - New England Journal of Medicine

IS - 21

ER -

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

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