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Commentary

Triple Therapy for Treatment of COPD: Will One Device Improve Patient Outcomes?


December 05, 2018

COPD patients often present with multiple symptoms including dyspnea, chronic cough, sputum production and chest tightness. Often patients require pharmacotherapy intervention to improve symptoms and quality of life. Traditionally, patients would be initiated on single, dual or triple therapy based upon the severity of illness. Most patient would need to use a single respiratory device for treatment of mild disease but may progress to dual or triple therapy (using two different respiratory devices) for moderate to severe disease. The Global Initiative for Obstructive Lung Disease (GOLD) recommend triple therapy for patients who remain symptomatic and /or continue to experience exacerbations with dual bronchodilator or inhaled corticosteroid/long acting beta agonist combinations. 1 Approximately 8 trials including two pivotal trials (TRILOGY and TRINITY) have evaluated triple therapy for COPD and have shown very positive results. 2

Recently the FDA approved Trelegy Ellipta (fluticasone furoate/umeclidinium/vilanterol) the first triple therapy as a single day treatment for patients with COPD. The results of two randomized trials demonstrated that triple therapy demonstrated statistically significant improvements in spirometry function (FEV1), 0-6 hrs post dose and on day 84 compared to dual therapy.  3 In addition, a more recent trial (KRONOS) including more than 3,000 patients administered budesonide/glycopyrrolate and formoterol demonstrated significant improvement over a 24 week study as measured by FEV1 from 0-4 hours. 4

Based upon the results of all trials to date, triple therapy is indeed effective. There is no doubt there will be more triple drug products making it to the market in the near future. Triple therapy will indeed be welcome to assist patients with compliance since only one device will be needed compared to patients needing to understand how to operate two different respiratory devices. One major question is should these agents be used in more severe disease or less severe disease with lower risk of exacerbations? Until more robust trials are designed to answer this question I believe triple therapy will be reserved based upon the GOLD recommendations. 

References

  1. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease 2018 report. Available https://goldcopd.org/wp-content/uploads/2017/11/GOLD-2018-v6.0-FINAL-revised-20-Nov_WMS.pdf. Accessed September 2018.
  2. Singh D, Corradi M, Spinola M et al. Triple therapy in COPD: new evidence with the extrafine fixed combination of beclomethasone dipropionate. Formoterol fumarate, and glycopyrronium bromide. Int J Chron Obstruct Pulmon Dis 2017; 12: 2917-2928,
  3. Siler TM, Kerwin E, Sousa AR et al. Efficacy and safety of umeclindinium added to fluticasone furoate/vilanterol in chronic obstructive pulmonary disease: results of two randomized studies. Respir Med 2015;109 (9):1155-1163.
  4. Ferguson GT, Rabe KF, Martinez FJ et al. Triple therapy with budesonide/glycopyrrolate/formoterol fumarate with co-suspension delivery technology versus dual therapies in chronic obstructive pulmonary disease (KRONOS): a double blind, parallel-group, multicenter, phase 3 randomised controlled trial. The Lancet Respiratory Medicine. Published online September 16, 2018.  

Michael J. Cawley, PharmD, RRT, CPFT, FCCM, is a professor of clinical pharmacy at the Philadelphia College of Pharmacy, University of the Sciences. He has more than 25 years of experience practicing in the areas of medical, surgical, trauma, and burn intensive care as both a critical care clinical pharmacist and registered respiratory therapist.


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