By William Elliott, MD, FACP, and James Chan, PharmD, PhD

Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco. Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.

Drs. Elliott and Chan report no financial relationships relevant to this field of study.

Fluticasone furoate, umeclidinium, and vilanterol oral inhalation powder (FF/UMEC/VI) is the first once-daily single inhaler triple therapy for patients with COPD. This fixed-combination includes an inhaled corticosteroid (fluticasone), a long-acting anticholinergic/antimuscarinic (umeclidinium), and a long-acting beta-2-adrenergic agonist (vilanterol). It is marketed as Trelegy Ellipta.

INDICATIONS

FF/UMEC/VI is indicated for the long-term maintenance treatment of patients with COPD, including chronic bronchitis and/or emphysema. It is targeted to patients who are taking fixed-dose combinations of fluticasone and vilanterol to reduce airflow obstruction and reduce exacerbations in those who need additional treatment of airflow obstruction or for patients who are already receiving umeclidinium and fixed-dose combination of fluticasone and vilanterol.1

DOSAGE

The recommended dose is one inhalation orally once daily.1 The product is available as two foil blister strips of powder for oral inhalation. One strip contains 100 mcg of fluticasone furoate. The other contains 62.5 mcg of umeclidinium and 25 mcg of vilanterol.

POTENTIAL ADVANTAGES

FF/UMEC/VI offers the convenience of the first once-daily triple therapy for appropriate patients with COPD.

POTENTIAL DISADVANTAGES

FF/UMEC/VI is contraindicated in patients with severe hypersensitivity to milk proteins as the powder contains lactose, which contains milk protein.1 FF and VI are substrates of CYP3A4; therefore, strong inhibitors of this isoenzyme increase systemic exposure to FF and VI.1 Vilanterol shares the same box warning for asthma-related death as other long-acting beta-2-adrenergic agonists. The individual components also share the same class warnings and precautions.

COMMENTS

The efficacy of FF/UMEC/VI was based primarily on the coadministration of UMEC and FF/VI in two randomized, double-blind, parallel-group, 12-week studies.1 At screening, subjects with COPD exhibited mean postbronchodilator percentage predicted forced expiratory volume (FEV1) of 46% (range, 14-76%), FEV1/ forced vital capacity (FVC) ratio of 0.48 (range, 0.21 to -0.70), and percentage reversibility of 13% (range, -24% to 86%). Each study contained 206 subjects. All subjects were randomized to UMEC or placebo plus FF/VI. The primary endpoint was mean change from baseline in trough (predose) FEV1 at day 85. This was defined as the mean value obtained 23 and 24 hours after the previous dose on day 84. The mean change difference in FEV1 from placebo for the two studies was 124 mL and 122 mL, respectively. Subjects on FF/UMEC/VI used less rescue medication and were more likely to show a decrease in score from baseline of 4 or more on the St. George’s Respiratory Questionnaire.2 This questionnaire is designed to assess health status (quality of life) based on three domains: symptoms, activity, and psychosocial impact.2 A minimum change of four units is considered to be clinically relevant. Responses were 40% vs. 35% in study 1 and 35% vs. 21% for study 2. In a 24-week comparative trial, FF/UMEC/VI once daily (n = 911) was compared to budesonide/formoterol twice daily (n = 899).3 Mean change in FEV1 was 142 mL for FF/UMEC/VI vs. -29 mL for budesonide/formoterol. Additionally, there was a 35% reduction in the moderate/severe exacerbation rate. An economic analysis of the same study suggests that the additional cost of triple therapy is partly offset by lower non-drug costs.4

CLINICAL IMPLICATIONS

FF/UMEC/VI is the first once-daily, fixed-dose, triple regimen to be approved. When patients step up to three drugs, additional benefit may be achieved. This includes improved lung function, health status, and reduced exacerbations.5 The Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) recommends triple therapy (inhaled steroid, long-acting antimuscarinic agent, and long-acting beta-2-adrenergic agonist) in patients with persistent symptoms and further exacerbation (GOLD group D). A large (n = 10,359), 52-week, three-arm study was completed recently. Researchers compared efficacy and safety of FF/UMEC/VI vs. FF/VI or UMEC/VI in this population, with the primary outcome the rate of moderate and severe exacerbations.6,7 The results have not been reported. The cost for FF/UMEC/VI is $247 for a 28-day supply.

REFERENCES

  1. Trelegy Ellipta Prescribing Information. September 2017. GlaxoSmithKline.
  2. St. George’s University of London. St. George’s Respiratory Questionnaire for COPD Patients (SGRQ-C). Available at: http://bit.ly/2zp0OI3. Accessed Nov. 7, 2017.
  3. Lipson DA, Barnacle H, Birk R, et al. FULFIL trial: Once-daily triple therapy for patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2017;196:438-446.
  4. Ismaila AS, Birk R, Shah D, et al. Once-daily triple therapy in patients with advanced COPD: Healthcare resource utilization data and associated costs from the FULFIL trial. Adv Ther 2017 Sep 5. doi: 10.1007/s12325-017-0604-x. [Epub ahead of print].
  5. Global Initiative for Chronic Obstructive Lung Disease. Pocket guide to COPD diagnosis, management, and prevention. Available at: http://bit.ly/2lWQd1F. Accessed Nov. 7, 2017.
  6. Pascoe SJ, Lipson DA, Locantore N, et al. A phase III randomised controlled trial of single-dose triple therapy in COPD: The IMPACT protocol. Eur Respir J 2016;48:320-330.
  7. ClinicalTrials.gov. A study comparing the efficacy, safety and tolerability of fixed dose combination (FDC) of FF/UMEC/VI with the FDC of FF/VI and UMEC/VI; administered once-daily via a dry powder inhaler (DPI) in subjects with chronic obstructive pulmonary disease (COPD). Available at: http://bit.ly/2zp9VZw. Accessed Nov. 7, 2017.