Risk of Exacerbation and Pneumonia with Single-Inhaler Triple versus Dual Therapy in IMPACT.

Abstract

Rationale: In the IMPACT (Informing the Pathway of COPD Treatment) trial, single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy reduced exacerbation risk versus FF/VI and UMEC/VI and mortality risk versus UMEC/VI. However, pneumonia incidence was higher in the inhaled corticosteroid (FF)-containing arms, raising questions about the relative benefit of exacerbation reduction compared with the increased risk of pneumonia.Objectives: Determine benefit-risk of the three treatments by evaluating time-to-first and rates of composite exacerbation or pneumonia outcomes.Methods: We evaluated time-to-first (prespecified) and rates (post hoc) of investigator-reported pneumonia, serious pneumonia leading to hospitalization or death, and the composite endpoints of 1) moderate (required antibiotics/corticosteroids)/severe (hospitalized) exacerbation or pneumonia and 2) severe exacerbation or serious (hospitalized) pneumonia. Analyses were repeated for radiographically confirmed pneumonia (post hoc).Results: Moderate/severe exacerbations occurred in 47%, 49%, and 50% of patients randomized to FF/UMEC/VI, FF/VI and UMEC/VI, and pneumonias in 8%, 7%, and 5%, respectively. FF/UMEC/VI reduced the risk of combined moderate/severe exacerbation or pneumonia (time-to-first) versus FF/VI (hazard ratio, 0.87 [95% confidence interval (CI), 0.82-0.92]) and UMEC/VI (0.87 [0.81-0.94]), as well as the risk of combined severe exacerbation or serious pneumonia versus UMEC/VI (0.83 [0.72-0.96]). FF/UMEC/VI reduced the rate of combined moderate/severe exacerbation or pneumonia (rate ratio, 0.78 [0.72-0.84]) and combined severe exacerbation or serious pneumonia (rate ratio, 0.76 [0.65-0.89]) versus UMEC/VI. Results were similar for radiographically confirmed pneumonia endpoints.Conclusions: Despite higher incidence of pneumonia in FF-containing arms, these composite exacerbation/pneumonia outcomes support a favorable benefit-risk profile of FF/UMEC/VI versus FF/VI and UMEC/VI in patients with symptomatic chronic obstructive pulmonary disease and a history of exacerbations.

• Authors: Mark T Dransfield, Courtney Crim, Gerard J Criner, Nicola C Day, David M G Halpin, MeiLan K Han, C Elaine Jones, Sally Kilbride, David LaFon, David A Lipson, David A Lomas, Neil Martin, Fernando J Martinez, Dave Singh, Robert A Wise, Peter Lange
• Journal: Annals of the American Thoracic Society (Ann Am Thorac Soc) Vol. 18 Issue 5 Pg. 788-798 (05 2021) ISSN: 2325-6621 [Electronic] United States
• PMID: 33108212 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Androstadienes
• Benzyl Alcohols
• Bronchodilator Agents
• Chlorobenzenes

Topics

• Administration, Inhalation
• Androstadienes (therapeutic use)
• Benzyl Alcohols (therapeutic use)
• Bronchodilator Agents (therapeutic use)
• Chlorobenzenes (therapeutic use)
• Double-Blind Method
• Humans
• Nebulizers and Vaporizers
• Pneumonia (drug therapy, epidemiology)
• Pulmonary Disease, Chronic Obstructive (drug therapy)
• Treatment Outcome