An observational retrospective cohort study to evaluate chronic disease onset associated with long-term oral corticosteroid use and the related cost impact on patients in the OPCRD / CPRD databases

Date of ISAC Approval: 
03/04/2017
Lay Summary: 
Oral corticosteroids (OCS) are often prescribed for patients with lung conditions such as asthma and chronic obstructive pulmonary disease (COPD). Prolonged use of OCS has been linked to increased risk of conditions such as diabetes, and high blood pressure. Research by the Observational and Pragmatic Research Institute (OPRI) in patients with lung disease and diabetes showed that inhaled corticosteroid (ICS) therapy may have a negative impact on diabetes control, and that patients given increasing doses of ICS could face a higher risk of diabetes progression. However, previous studies on OCS use did not explore the effects of prolonged exposure in large patient populations, and did not provide specific OCS doses at which the risk of additional disease occurrence significantly increased. The aim of this study is to investigate the impact of long-term OCS exposure, average total daily dose, total duration of exposure and current OCS exposures on disease onset, burden and healthcare resource utilisation, over a minimum two-year timescale, in a broad patient population and in a subgroup of patients with asthma. Studying the effects of long-term exposure to oral corticosteroids in a broader patient population will help to show whether OCS has any side effects on populations presenting various conditions.
Technical Summary: 
Long term use of oral corticosteroids (OCS) has been associated with increased risk of chronic conditions such as diabetes, osteoporosis, hypertension and cataracts. Previous research found an association between OCS use and morbidity among patients with severe asthma. Research by the Observational and Pragmatic Research Institute (OPRI) in patients with COPD and comorbid type 2 diabetes mellitus suggested that inhaled corticosteroid (ICS) therapy may have a negative impact on diabetes control and that patients prescribed higher cumulative doses of ICS may be at greater risk of diabetes progression. However, previous studies examining OCS use did not explore the effects of long term total exposure in a broader patient population, and did not provide specific OCS doses where the risk of comorbid disease onset significantly increased. The aim of this study is to investigate the impact of long-term OCS exposure defined as: the total dose (g); categorised into courses per year, average total daily dose (mg/day) and total duration of exposure and current OCS exposures on disease onset, burden and healthcare resource utilisation (HRU) over a minimum two-year timescale in a broad patient population and also in a subgroup of patients with asthma. Disease conditions of interest are type 2 diabetes mellitus, osteoporosis/ osteoporotic fractures, hypertension, glaucoma, sleep apnoea, weight gain, depression/anxiety as primary and pneumonia, cataracts, sleep disorders, cardiovascular disease, chronic kidney disease, dyslipidaemia and peptic ulcer disease as secondary outcomes. Different time-dependent OCS exposure measures will be explored. For each corticosteroid-related condition, multivariable Cox proportional hazard models will be fitted separately for each of the time-dependent OCS exposure measures. We will explore the independent predictive ability of each exposure measure in the models. To determine critical OCS dose thresholds, total dose and daily dose will be categorised into relevant levels, and the risk of developing the outcome of interest will be compared between corticosteroid arm and control arm. The HRU outcomes and associated costs will be calculated as annualised HRU and annualised costs for each of the outcomes of interest.
Health Outcomes to be Measured: 
- Type 2 diabetes mellitus - Glaucoma - Depression/anxiety - Osteoporosis/osteoporotic fractures - Sleep apnoea - Pneumonia - Hypertension - Sleep disorders - Dyslipidaemia - Weight gain - Cardiovascular disease - Peptic ulcer disease - Cataracts - Chronic kidney disease
Collaborators: 

Professor David Price - Chief Investigator - OPRI - Observational and Pragmatic Research Institute Pte Ltd
Elizabeth Gardener - Collaborator - Cambridge Research Support Ltd.
Erica Velthuis - Collaborator - PPD - UK
Frank J Trudo - Collaborator - Astra Zeneca Inc - USA
Shreyasee Karnik - Corresponding Applicant - OPRI - Observational and Pragmatic Research Institute Pte Ltd
Professor Trung Tran (Tan) (Tang) - Collaborator - MedImmune
Xiao Xu - Collaborator - Astra Zeneca Inc - USA

Linkages: 
HES A&E;HES Admitted;HES Outpatient;ONS