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.
N1 - Publisher Copyright:
Copyright © 2019 Massachusetts Medical Society.
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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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 -