Mometasone or Tiotropium in Mild Asthma with a Low Sputum Eosinophil Level.
Lazarus, Stephen C. M.D.; Krishnan, Jerry A. M.D., Ph.D.; King, Tonya S. Ph.D.; Lang, Jason E. M.D.; Blake, Kathryn V. Pharm.D.; Covar, Ronina M.D.; Lugogo, Njira M.D.; Wenzel, Sally M.D.; Chinchilli, Vernon M. Ph.D.; Mauger, David T. Ph.D.; Dyer, Anne-Marie M.S.; Boushey, Homer A. M.D.; Fahy, John V. M.D.; Woodruff, Prescott G. M.D.; Bacharier, Leonard B. M.D.; Cabana, Michael D. M.D.; Cardet, Juan C. M.D.; Castro, Mario M.D.; Chmiel, James M.D.; Denlinger, Loren M.D., Ph.D.; DiMango, Emily M.D.; Fitzpatrick, Anne M. Ph.D.; Gentile, Deborah M.D.; Hastie, Annette Ph.D.; Holguin, Fernando M.D.; Israel, Elliot M.D.; Jackson, Daniel M.D.; Kraft, Monica M.D.; LaForce, Craig M.D.; Lemanske, Robert F. Jr. M.D.; Martinez, Fernando D. M.D.; Moore, Wendy M.D.; Morgan, Wayne J. M.D.; Moy, James N. M.D.; Myers, Ross M.D.; Peters, Stephen P. M.D., Ph.D.; Phipatanakul, Wanda M.D.; Pongracic, Jacqueline A. M.D.; Que, Loretta M.D.; Ross, Kristie M.D.; Smith, Lewis M.D.; Szefler, Stanley J. M.D.; Wechsler, Michael E. M.D.; Sorkness, Christine A. Pharm.D.; the National Heart, Lung, and Blood Institute AsthmaNet
[Article]
New England Journal of Medicine.
380(21):2009-2019, May 23, 2019.
(Format: HTML, PDF)
BACKGROUND: 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. (Funded by the National Heart, Lung, and Blood Institute; SIENA ClinicalTrials.gov number, NCT02066298.)
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