A Randomized, Noninferiority Trial Comparing ICS + LABA with ICS + LABA + LAMA in Asthma-COPD Overlap (ACO) Treatment: The ACO Treatment with Optimal Medications (ATOMIC) Study

J Allergy Clin Immunol Pract. 2021 Mar;9(3):1304-1311.e2. doi: 10.1016/j.jaip.2020.09.066. Epub 2020 Nov 9.

Abstract

Background: Current guidelines for the treatment of asthma and chronic obstructive pulmonary disease overlap (ACO) recommend initial treatment using inhaled corticosteroids (ICSs) plus 1 or more bronchodilators.

Objective: To clarify which therapeutic effect is better between the ICS + long-acting β2 agonist (LABA) and ICS + LABA + long-acting muscarinic antagonist (LAMA) treatment in patients with ACO.

Methods: We conducted a multicenter, 48-week, randomized, noninferiority trial. Patients with ACO were enrolled if they were treated with a moderate to high dose of ICS + LABA. In total, 303 patients were involved in the present trial, with 149 receiving ICS + LABA + LAMA. The primary end point was the time to first exacerbation. Secondary outcomes included changes in FEV1, forced vital capacity, FEV1/forced vital capacity ratio, asthma control, blood eosinophil count, and fractional exhaled nitric oxide.

Results: In the ICS + LABA treatment group, 29 of 154 patients (18.83%) experienced exacerbation, whereas 28 of 149 patients (18.79%) experienced exacerbation in the ICS + LABA + LAMA treatment group. The results of this noninferiority study were ultimately inconclusive (hazard ratio, 1.1; 95% CI, 0.66-1.84). However, the patients treated with the addition of LAMA showed significant improvements in FEV1 and forced vital capacity (P < .001). Asthma control did not improve in either group.

Conclusions: Although this study was unable to conclude that ICS + LABA treatment is not inferior to ICS + LABA + LAMA in terms of exacerbation, it is obvious that the ICS + LABA + LAMA treatment group had improved lung function in ACO.

Keywords: Asthma-COPD overlap; ICS; LABA; LAMA; Triple therapy.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adrenal Cortex Hormones / therapeutic use
  • Adrenergic beta-2 Receptor Agonists / therapeutic use
  • Asthma* / drug therapy
  • Bronchodilator Agents / therapeutic use
  • Drug Therapy, Combination
  • Humans
  • Muscarinic Antagonists / therapeutic use
  • Pulmonary Disease, Chronic Obstructive* / drug therapy

Substances

  • Adrenal Cortex Hormones
  • Adrenergic beta-2 Receptor Agonists
  • Bronchodilator Agents
  • Muscarinic Antagonists

Associated data

  • CRiS/KCT0002050