Chronic obstructive pulmonary disease (COPD) is a common, preventable and treatable condition of the lungs. Patients with COPD experience various symptoms including shortness of breath, coughing and wheezing.
There are a wide range of drugs that are available for the treatment of COPD in the UK. The most severe patients who experience “flare-ups” in their symptoms (called exacerbations) are usually given a combination of three different drugs; this is called triple therapy. Often, the three different drug components of triple therapy will be given as either two or three separate inhalers; this is termed multiple inhaler triple therapy (MITT). The different inhalers will often have varying instructions regarding how they should be taken, for instance the number of required inhalations per day. Use of multiple inhalers can therefore be complex for the patient and can influence whether or not patients will take them according to how they should be taken, a concept known as adherence. Low adherence can lead to increased exacerbations and worsening of other COPD symptoms. Single inhaler triple therapies (SITT) have recently been introduced, whereby the three drug components of triple therapy are combined into a single inhaler, reducing some of the complexities and burden of using multiple inhalers.
The objective of this study is to observe to what extent patients adhere to MITT, and to compare this to adherence in patients receiving SITT.
Aim: The overall study aim is to evaluate medication adherence and persistence for patients with chronic obstructive pulmonary disease (COPD) who have newly initiated either multiple inhaler triple therapy (MITT) or single inhaler triple therapy (SITT).
Objectives: The primary objective is to compare medication adherence in COPD patients using MITT versus SITT. Comparisons will be made between patients i) initiating MITT vs SITT; ii) initiating MITT vs each of the two SITTs currently available in the UK a) fluticasone furoate (FF), umeclidinium (UMEC) and vilanterol (VI) and b) beclomethasone (BDP), formoterol (FF) and glycopyrronium bromide (GB); Persistence will be evaluated for each comparison as a secondary objective. A FF/UMEC/VI vs BDP/FF/GB comparison for adherence and persistence will also be conducted as secondary objectives.
Primary exposures: MITT and/or SITT use.
Primary outcomes: Medication adherence to MITT and SITT therapies at 6, 12 and 18 months post-triple therapy initiation.
Methods: A new-user, active comparator, retrospective cohort study using inverse probability of treatment weighting (IPTW) of COPD patients initiating triple therapy between November 2017 and June 2019 in CPRD Aurum. Linked Hospital Episode Statistics-Admitted Patient Care data will also be used. The minimum required follow-up period will be 6 months to assess adherence.
Data analysis: Adherence will be classified using proportion of days covered (PDC); PDC<80% representing non-adherence, PDC≥80% adherent. A propensity score (PS) based methodology will be implemented for all treatment comparisons to minimise potential confounding and evaluate the average treatment effect in the entire population. It is proposed that PSs’ will be generated via logistic regression modelling and applied using IPTW. Persistence will be assessed using Kaplan Meier survival analysis and Cox proportional hazards models to assess time-to-non-persistence.
Adherence to multiple inhaler triple therapy (MITT) and single inhaler triple therapy (SITT) as a categorical variable; Persistence to MITT and SITT; Adherence to MITT and SITT as a continuous variable.
Kieran Rothnie - Chief Investigator - GlaxoSmithKline Services Unlimited (UK)
Victoria Banks - Corresponding Applicant - Adelphi Real World
Afisi Ismaila - Collaborator - GSK
Alexandrosz Czira - Collaborator - GlaxoSmithKline Services Unlimited (UK)
Joseph Thomas - Collaborator - Adelphi Real World
Olivia Massey - Collaborator - Adelphi Real World
Robert Wood - Collaborator - Adelphi Real World
Stuart Blackburn - Collaborator - Adelphi Real World
Theo Tritton - Collaborator - Adelphi Real World
HES Admitted Patient Care;Patient Level Index of Multiple Deprivation