Effectiveness of triple therapy versus dual therapy in patients with chronic obstructive pulmonary disease who have had one severe or two or more moderate exacerbations within one year

Date of Approval
Application Number
21_000386
Technical Summary

The NICE guidelines state that triple therapy should be considered in patients on dual long-acting beta-agonist (LABA) + long-acting muscarinic antagonist (LAMA) therapy who experience 1 severe exacerbation or 2 or more moderate to severe exacerbations per year. This is based on randomised controlled trial (RCT) evidence that found reductions in severe AECOPD, however these studies also found increases in pneumonia and no affect on mortality. We will therefore assess this recommendation in a population using routinely collected data comparing those eligible for triple therapy who remain on dual therapy to those who step up to triple therapy. We will use a retrospective cohort study design to assess the effect of triple therapy on the primary outcomes of severe AECOPD rate, moderate-severe AECOPD rate, and mortality, and the secondary outcomes of pneumonia rate, A&E attendances, Forced Expiratory Volume in 1 second (FEV1), breathlessness measured using the modified medical research council (mMRC) dyspnoea scale, and drug prescription, using Cox regression, multi-level linear regression and Poisson regression. Demographic variables, comorbidities, COPD baseline variables, and healthcare usage at baseline will be included as covariates in the model to reduce confounding. The study will incorporate trial evidence on the effectiveness on triple therapy using a Bayesian framework to help mitigate the impact of ‘confounding by indication’.

Health Outcomes to be Measured

In order to holistically assess the impact of triple therapy vs dual therapy, we will look at a number of outcomes:

Mortality rate (all cause, COPD related, and cardiovascular disease (CVD) related); severe AECOPD rate (= number of hospitalisations for AECOPD); moderate and severe AECOPD rate; rate of pneumonia diagnosis ; change in lung function (FEV1); change in breathlessness (mMRC) (if allowed by the data); number of A&E visits for AECOPD; Prescription of additional chronic therapy (theophylline or other methylxanthines); maintenance OCS; macrolides (e.g. azithromycin, erythromycin); carbocysteine

Collaborators

Jennifer Quint - Chief Investigator - Imperial College London
Alexander Adamson - Corresponding Applicant - Imperial College London
Cosetta Minelli - Collaborator - Imperial College London

Linkages

HES Accident and Emergency;HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation