Chronic obstructive pulmonary disease (COPD) is a lung condition affecting 329 million adults worldwide. The main complaints of patients with COPD are breathlessness and a productive cough. Individuals who suffer from COPD often have periods where their symptoms worsen. These periods of worsening (called exacerbations) can sometimes be linked to high levels of eosinophils (a type of white blood cell) in the body. Some adults with severe COPD continue to experience exacerbations even while treated with the maximum therapy - a combination of three, long-acting inhaled medications known as 'triple therapy'. Mepolizumab is a new treatment currently being evaluated in clinical trials which may help to reduce exacerbations in individuals with high levels of eosinophils. This study will use anonymised electronic medical records to identify a group of COPD patients who may be considered eligible for mepolizumab treatment and then measure how frequently they experience exacerbations, how often they visit their GP or are admitted to hospital, and how many of them die. The results from this study will be used to assess the potential benefit of mepolizumab treatment in patients with very severe COPD by placing the results of the ongoing clinical trials into context of the real world.
This retrospective cohort study aims to generate evidence needed to better understand severe COPD patients who could benefit from therapies which reduce eosinophils such as mepolizumab. Treatment eligibility will be considered in COPD-diagnosed patients who meet all the following criteria: history of moderate or severe exacerbations of COPD; treatment with inhaled triple maintenance therapy for COPD; and, raised peripheral blood eosinophil levels (>150cells/µL). Ascertainment of eligibility will take place on the date of first valid eosinophil test recorded between 2010-2014 (the index date). Using CPRD-GOLD data linked with HES-APC data, we will describe demographic and clinical characteristics of eligible and non-eligible patients [Objective 1]. We will then estimate rates for eligible and non-eligible patients of clinical burden of illness and healthcare resource utilisation outcomes in the period after the index date [Objective 2]. Outcomes include: moderate/severe exacerbations, all-cause mortality, primary-care consultations and unplanned, non-COPD-related hospitalisations. Finally, we will compare rates of outcomes in eligible and non-eligible patients using multivariable regression modelling (Poisson, Cox or negative binomial, as appropriate) [Objective 3]. In further stratified analyses we will limit our study population to three subsets of patients meeting the exacerbation, inhaled triple therapy, and raised eosinophil level criteria.
The following clinical burden of illness outcomes will be assessed using all available patient follow-up after the index date. - Rate of AECOPD expressed as the number of AECOPD per 1,000 person-years of follow-up. All exacerbations occurring during following will be included in the numerator, while the denominator will include all follow-up time after the index date. Exacerbations will be defined using validated algorithms described earlier (Rothnie, 2015; Rothnie, 2016). We will report AECOPD in the following groups: moderate, severe, and 'moderate or severe'. - Rate of all-cause mortality, where deaths are defined using the date of death as recorded in CPRD-GOLD. The rate will be expressed as the number of deaths per 1,000 person-years at risk, where follow-up time for the denominator will end on the date of death. The following healthcare resource utilization outcomes will be assessed for the sub-population of patients with at least 12 months of follow-up after their index date. Rates of outcomes are calculated using a numerator that includes all consultations/hospitalisations occurring within the 12 month period after the index date. The denominator for all rates will be the number of patients. - Annual rate of primary-care consultations, expressed per 1,000 patients. All the non-administrative, primary-care consultations, occurring on separate days will be captured in the numerator for this outcome. An algorithm will classify primary-care consultations as GP consultations or nurse consultations using the 'staffrole' and 'constype' variables in CPRD-GOLD. -Annual rate of non-COPD-related, unplanned and unscheduled hospitalisations, expressed per 1,000 patients. Hospitalisations will be identified using HES-APC data. The numerator will include all unplanned admissions in the 12 months after the index date where the primary reason for admission is not for COPD and is not related to an AECOPD by other definitions of severe exacerbations. Each new spell will be considered as a new admission. Episodes within a spell will not be considered as new hospitalisations. The admimeth flag will be used to identify unplanned/unscheduled admissions (values 21, 22, 23, 24, and 28).
Hana Mullerova - Chief Investigator - AstraZeneca Ltd - UK Headquarters
Wilhelmine Meeraus - Corresponding Applicant - GlaxoSmithKline - UK
Joe Maskell - Collaborator - Amgen Ltd
HES Admitted Patient Care;Patient Level Index of Multiple Deprivation