Comparative Effectiveness of Umeclidinium + Vilanterol versus Inhaled corticosteroids + long- acting beta-agonists as inhaled maintenance therapy among patients with Chronic Obstructive Pulmonary Disease in a UK real-world primary care setting

Date of Approval
Application Number
Technical Summary

Aim: To conduct a head-to-head comparative effectiveness study of single inhaler Umeclidinium/Vilanterol (UMEC/VI) (a once-daily long-acting muscarinic antagonist [LAMA]/long-acting β2-agonist [LABA]) versus single inhaler twice-daily inhaled corticosteroid (ICS)/LABAs in a COPD General Practice cohort in England. Greater understanding of the effectiveness of these initial maintenance therapy options will better-inform early treatment choices for patients with COPD in the UK.

Objectives: To compare i) medication adherence; ii) time-to-triple therapy; iii) time-to-first acute exacerbation of COPD; iv) all-cause and COPD-related healthcare resource utilisation (HCRU) and direct medical costs among COPD patients newly initiating UMEC/VI versus ICS/LABAs (also beclomethasone/formoterol fumarate [BDP/FF] - one of the currently available twice-daily ICS/LABAs). The mean number of rescue medications prescribed per patient will also be reported.

Primary exposures: Single inhaler UMEC/VI or ICS/LABAs (also BDP/FF) initiation.

Primary outcome: Medication adherence 12 months post therapy initiation.

Methods: A new-user, active comparator, retrospective cohort study using inverse probability of treatment weighting (IPTW) to assess UMEC/VI versus ICS/LABAs (also BDP/FF) efficacy using linked CPRD Aurum and Hospital Episode Statistics (HES) data. The earliestearliest date of therapy initiation between July 2014 and September 2019 will determine the index date. No minimum follow-up is required for study inclusion; a 24 months maximum follow-up will be used to assess study outcomes.

Data analysis: A propensity score (PS) method will be implemented to minimise potential confounding and evaluate average effects in the population. Logistic regression will generate the PS, which will be applied via IPTW. Adherence will be classified using proportion of days covered (PDC): PDC<80% considered non-adherent, PDC≥80% adherent. Time-to-triple therapy and COPD exacerbations will be assessed using Kaplan-Meier survival analysis and Cox proportional hazards models. HCRU and costs (derived via application of unit costs/tariffs) will be compared using IPTW-weighted RRs from negative binomial regression and relative rates from generalised linear models respectively.

Health Outcomes to be Measured

Medication adherence (PDC ≥80%); time to triple therapy use (single or multiple inhaler triple therapy); time to first on-treatment AECOPD (moderate-to-severe, moderate, severe); HCRU (all-cause and COPD-related); Direct medical costs (all-cause and COPD-related); Mean number of rescue medication prescriptions per patient (inhaled or nebulised short-acting muscarinic agonists [SAMA] or short-acting β2-agonists [SABA] containing medications)


Alexandrosz Czira - Chief Investigator - GSK
Victoria Banks - Corresponding Applicant - Adelphi Real World
Afisi Ismaila - Collaborator - GSK
Catherine Castillo - Collaborator - Adelphi Real World
Eunmi Ha - Collaborator - Adelphi Real World
Gema Requena - Collaborator - GlaxoSmithKline - UK
Jie Yeap - Collaborator - Adelphi Real World
Robert Wood - Collaborator - Adelphi Real World
Rosie Wild - Collaborator - Adelphi Real World
Theo Tritton - Collaborator - Adelphi Real World


HES Accident and Emergency;HES Admitted Patient Care;Patient Level Index of Multiple Deprivation