Mometasone or Tiotropium in Mild Asthma with a Low Sputum Eosinophil Level.
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.).
Lazarus, SC; Krishnan, JA; King, TS; Lang, JE; Blake, KV; Covar, R; Lugogo, N; Wenzel, S; Chinchilli, VM; Mauger, DT; Dyer, A-M; 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; National Heart, Lung, and Blood Institute AsthmaNet,
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