Highlights from

ATS 2019

American Thoracic Society international conference

Dallas, USA 17-22 May 2019

No Benefit Mometasone or Tiotropium in Mild Asthma with a Low Sputum Eosinophil Level

A recent trial, led by Prof. Stephen C. Lazarus (University of California, USA), may lead to changes in the way mild asthma is managed. Mometasone or tiotropium show no significant difference in efficacy as compared with placebo for the treatment of mild persistent asthma with a low sputum eosinophil level the SIENA trial. The findings were presented at the ATS 2019 Conference and simultaneously published in the New England Journal of Medicine [1].

Patients with persistent asthma are usually treated with a rescue inhaler, a fast-acting bronchodilator that opens the airways, plus inhaled steroids to prevent or reduce further attacks. Current guidelines recommend the use of inhaled glucocorticoids in all patients with persistent asthma, regardless if patients have low or high sputum eosinophil levels. However, the anti-inflammatory drug may target a specific type of inflammation that is found in fewer patients than previously thought, and, thus, it is questionable if all asthma patients benefit from inhaled glucocorticoids. Investigators considered alternative treatment for asthma patients reporting insufficient benefit for inhaled glucocorticoids and suggested tiotropium, a long-acting muscarinic antagonist (LAMA), as a safe alternative.

Prof. Lazarus et al. conducted a 42-week, double-blind, crossover study including 295 patients (≥12 years) with mild, ongoing asthma. Patients were categorised by baseline sputum eosinophil level: either <2% (n=221) or ≥2% (n=74). Interestingly, investigators observed that 74% of the patient population had low eosinophil levels, much greater than has been reported in previous clinical trials. After a 6-week, single-blind, placebo run-in period, patients in both groups were randomised to active mometasone plus placebo tiotropium; placebo mometasone plus active tiotropium; or placebo mometasone plus placebo tiotropium. In the 12-week treatment period, patient visits were scheduled for every 6 weeks. 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. The response was determined according to outcomes such as treatment failure, asthma control days, and the forced expiratory volume in 1 second. A secondary outcome was a comparison of results in patients with a high sputum eosinophil level and those with a low level.

A total of 73% of the patients had a low eosinophil level. Of these patients, 59% reported a differential response to a trial agent. Among those, 57% (95% CI, 48-66) had a better response to mometasone, and 43% (95% CI, 34-52) had a better response to placebo (P= 0.14). On the other hand, 60% (95% CI, 51-68) reported a better response to tiotropium, versus 40% (95% CI, 32-49) who had a better response to placebo (P=0.029). Neither differential response was considered statistically significant. 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%).

Prof. Lazarus and his team concluded that most patients with mild, persistent asthma had a low sputum eosinophil level and showed no significant difference in their response to either mometasone or tiotropium as compared with placebo. Future clinical trials are needed to compare an inhaled glucocorticoid with other treatments in patients with a low eosinophil level.

  1. Lazarus SC, et al. Mometasone or Tiotropium in Mild Asthma with a Low Sputum Eosinophil Level. N Engl J Med; May 19,2019. DOI: 10.1056/NEJMoa1814917.

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