Evaluation of rescue medication use and medication adherence receiving umeclidinium/vilanterol versus tiotropium bromide/olodaterol

Abstract

Background

This was the first real-world head-to-head study comparing inhaled long-acting muscarinic antagonist/long-acting β₂-agonist fixed-dose combination treatments as maintenance therapy.

Methods

Retrospective observational study including commercial, Medicare Advantage with Part D or Part D-only enrollees aged ≥40 years from the Optum Research Database. Patients initiated umeclidinium/vilanterol (UMEC/VI) or tiotropium bromide/olodaterol (TIO/OLO) between June 1, 2015 and November 30, 2016 (index date) with 12 months of pre- and post-index continuous enrollment. Outcomes were modeled following the inverse probability of treatment weighting. The primary endpoint, rescue medication use, was modeled using weighted ordinary least squares regression with bootstrapped variance estimation. Intent-to-treat analysis evaluated non-inferiority and superiority of UMEC/VI to TIO/OLO with thresholds of 0.30 and 0 units, respectively. On-treatment sensitivity analysis evaluated the superiority of UMEC/VI to TIO/OLO for rescue medication use. The secondary endpoint, medication adherence (proportion of days covered [PDC]≥80%), was evaluated using weighted logistic regression. Post hoc weighted Cox proportional hazards regression analysis evaluated escalation to multiple inhaler triple therapy (MITT).

Results

The study population included 14,324 patients; 9549 initiated UMEC/VI and 4775 initiated TIO/OLO. During the 12-month post-index period, UMEC/VI initiators used 0.16 fewer adjusted mean units of rescue medication than TIO/OLO initiators (95% CI: −0.28, −0.04), meeting pre-specified non-inferiority (P<0.001) and superiority (P=0.005) criteria; the on-treatment sensitivity analysis for superiority was not statistically significant. Significantly more UMEC/VI than TIO/OLO initiators (28.6% vs 22.7%; P<0.001) achieved a clinically meaningful level (PDC≥80%) of medication adherence. The adjusted risk of escalation to MITT was similar between treatment groups (HR=0.93; 95% CI: 0.81, 1.06; P=0.268).

Conclusion

UMEC/VI was superior to TIO/OLO for rescue medication use and UMEC/VI initiators had better medication adherence than TIO/OLO initiators. This study supports findings from a head-to-head trial that demonstrated significant, clinically meaningful improvements in lung function with UMEC/VI versus TIO/OLO.

Keywords:

• COPD
• long-acting β₂-agonists
• long-acting muscarinic antagonists
• adherence
• rescue medication
• real world

Acknowledgment

This study (207968/HO-17-18427) was funded by GSK. The funders of the study had a role in the study design, data analysis, data interpretation, and writing of the report. Employees of Optum were not paid for manuscript development. The authors would like to acknowledge Michael J Asmus (an employee of GSK at the time of the study) for his role in the design and interpretation of the study. The authors would like to acknowledge the following individuals for their contributions to this study: Lee Brekke of Optum for statistical consultation; Randall Gerdes, Priyanka Koka, and Feng Cao of Optum for programming support; Ashley Sluis of Optum for analytic support; and Megan Sipper and Caroline Jennermann of Optum for project management. Medical writing support was provided by Katie White, PhD, and Mark Condon, DPhil, of Fishawack Indicia Ltd, UK, funded by GSK.

Ethics approval and informed consent

This study utilized de-identified retrospective claims data, and as such, this study does not require institutional review board review and approval or informed consent procedures.

Data sharing statement

Information on GlaxoSmithKline’s (GSK) data sharing commitments and requesting access to anonymized individual participant data and associated documents from GSK-sponsored studies can be found at www.clinicalstudydatarequest.com. The data reported in this publication are contained in a database owned by Optum and contains 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 Optum’s standard license agreement which includes restrictive covenants governing the use of the data.

Author contributions

CM, BH, RHS, and RR were involved in the conception/design of the study and analysis/interpretation of data. LGSB and LS were involved in the conception/design of the study, acquisition of data and analysis/interpretation of data. EK, LL, and JT were involved in the acquisition of data and analysis/interpretation of data. The authors take complete responsibility for the integrity of the data and accuracy of the data analysis, contributed to the writing and reviewing of the manuscript, gave final approval for the version to be published, and agree to be accountable for all aspects of the work.

Disclosure

CM, BH, RR, and RHS are employees of GSK and hold stocks/shares in GSK. LGSB, EK, LL, and JT are employees of Optum. EK reports grant from GlaxoSmithKline, during the conduct of the study. LS was an employee of Optum at the time of the study, which was contracted by GSK to conduct the study. The authors report no other conflicts of interest in this work.