Benefit of Prompt versus Delayed Use of Single-Inhaler Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI) Following a COPD Exacerbation

Abstract

Purpose

Triple therapy (TT; inhaled corticosteroid, long-acting muscarinic antagonist, and long-acting β₂-agonist) is recommended for patients with chronic obstructive pulmonary disease (COPD) at risk of exacerbation, although the optimum timing of TT initiation remains unclear. This study evaluated the impact of prompt versus delayed initiation of single-inhaler TT (fluticasone furoate, umeclidinium, and vilanterol [FF/UMEC/VI]) following a COPD exacerbation.

Patients and Methods

This retrospective cohort study used data from the IQVIA PharMetrics^® Plus database. Patients initiating FF/UMEC/VI following a COPD exacerbation between September 18, 2017 and September 30, 2019 (exacerbation = index date) were categorized as prompt (within 30 days of index) or delayed (31–180 days after index) FF/UMEC/VI initiators. Patients were aged ≥40 years at index, had ≥12 months’ continuous health insurance coverage before index (baseline), and ≥6 months’ coverage after index (follow-up). Patients with a COPD exacerbation or claim for FF/UMEC/VI during baseline were excluded. Inverse probability weighting was used to adjust for differences in baseline characteristics between cohorts. Exacerbations (overall, moderate, and severe), healthcare costs, and readmissions were evaluated during follow-up.

Results

A total of 1904 patients (prompt: 529; delayed: 1375) were included. After weighting, baseline characteristics were well balanced between cohorts. Patients in the prompt cohort had significantly lower rates per person-year (PPY) of overall (0.98 vs 1.23; rate ratio [RR] [95% CI] = 0.79 [0.65–0.94], p = 0.004), moderate (0.86 vs 1.03; RR [95% CI] = 0.84 [0.69–0.99], p = 0.038), and severe (0.11 vs 0.20; RR [95% CI] = 0.57 [0.37–0.79], p = 0.002) exacerbations, compared with delayed initiators. Mean all-cause and COPD-related healthcare costs were significantly lower among prompt initiators (all-cause: $26,107 vs $32,400 PPY, p = 0.014; COPD-related: $12,694 vs $17,640 PPY, p = 0.002).

Conclusion

Prompt initiation of FF/UMEC/VI following a moderate or severe COPD exacerbation was associated with significant reductions in exacerbations and healthcare costs relative to delayed initiation.

Keywords:

• chronic obstructive pulmonary disease
• exacerbation
• healthcare cost
• single-inhaler triple therapy

Abbreviations

BUD, budesonide; CI, confidence interval; COPD, chronic obstructive pulmonary disease; ER, emergency room; FDA, Food and Drug Administration; FF, fluticasone furoate; FOR, formoterol fumarate; GLY, glycopyrrolate; GOLD, Global Initiative for Chronic Obstructive Lung Disease; HMO, health maintenance organization; HR, hazard ratio; HRU, healthcare resource utilization; ICS, inhaled corticosteroid; IPTW, inverse probability of treatment weighting; IQR, interquartile range; LABA, long-acting β₂-agonist; LAMA, long-acting muscarinic antagonist; MITT, multiple-inhaler triple therapy; PDE-4, phosphodiesterase-4; POS, point-of-service; PPO, preferred provider organization; PPY, per person-year; Quan-CCI, Quan-Charlson comorbidity index; RR, rate ratio; SABA, short-acting β₂-agonist; SAMA, short-acting muscarinic antagonist; SD, standard deviation; SITT, single-inhaler triple therapy; Std. diff., standardized difference; TT, triple therapy; UMEC, umeclidinium; VI, vilanterol.

Data Sharing Statement

The data reported in this publication are contained in a database owned by IQVIA and contain proprietary elements. Therefore, it cannot be broadly disclosed or made publicly available at this time. The disclosure of this data to third-party clients assumes certain data security and privacy protocols are in place and that the third-party client has executed IQVIA’s standard license agreement, which includes restrictive covenants governing the use of the data.

Ethics Approval and Informed Consent

As this was an analysis of claims data, institutional review board (IRB) approval was not required. Per Title 45 of CFR, Part 46 (www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.html#46.101), the administrative claims data analysis of our study was exempt from the IRB review as it was a retrospective analysis of existing data (hence no patient intervention or interaction), and no patient-identifiable information was included in the claims dataset.

Acknowledgments

Editorial support (in the form of writing assistance, including preparation of the draft manuscript under the direction and guidance of the authors, collating and incorporating authors’ comments for each draft, assembling tables and figures, grammatical editing, and referencing) was provided by Fiona Goodwin and Rebecca Cunningham of Aura, a division of Spirit Medical Communications Group Limited and was funded by GlaxoSmithKline. These data were previously presented in abstract/poster form at the American Thoracic Society 117th International Conference, 2021 (Michael Bogart, Guillaume Germain, Shirley Huang, Afisi Ismaila, Young Jung, François Laliberté, Sean MacKnight, Mei Sheng Duh. Benefit of prompt versus delayed initiation of single inhaler triple therapy on exacerbations and readmissions among patients with chronic obstructive pulmonary disease in the US. American Thoracic Society - 117th International Conference. 2021;203:A2252).

Author Contributions

All authors made a significant contribution to the work reported, whether that was in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising, or critically reviewing the manuscript; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

DM is a previous employee of GlaxoSmithKline and holds stocks/shares in GlaxoSmithKline, and reports personal fees from UptoDate, Inc., outside the submitted work. MB, SPH, ASI, and MAS are GlaxoSmithKline employees and hold stocks/shares in GlaxoSmithKline. ASI is also an unpaid part-time member of the McMaster University faculty. GG, FL, SDM, and MSD are employees of Analysis Group, a consulting company that has received research funds from GlaxoSmithKline. YJ was an employee of Analysis Group, a consulting company that has received research funds from GlaxoSmithKline, at the time of the study. The authors report no other conflicts of interest in this work.

Additional information

Funding

This study was funded by GlaxoSmithKline (study number 209575 [HO-19-19552]). The sponsor was involved in study conception and design, data interpretation, and the decision to submit the article for publication. The sponsor was also given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations.