Oral corticosteroids (OCS) are frequently prescribed for patients with respiratory conditions such as asthma. Despite evidence on the adverse outcomes of OCS, their use remains part of the clinical guidelines for asthma. There is evidence showing that relatively low cumulative doses of OCS can increase the risk of adverse outcomes and there is a wide consensus among physicians and researchers that the use of OCS should be limited to a minimum and should only be used when no other treatment option is available. Despite this OCS are still widely prescribed for patients with mild asthma.
Whilst there is evidence showing increased risk of adverse events related to cumulative OCS dose there is little showing how patterns of intermittent OCS use are related to adverse events and related healthcare costs.
Overall Aim: This study aims to investigate the relationship between patterns of intermittent OCS use and adverse events and healthcare resource utilisation (HRU).
Design: This is an historical cohort study combining data from CPRD and Optimum Patient Care UK. The cohort will be patients prescribed with intermittent OCS prescription with a concurrent asthma event, at least 12 months of baseline data, and aged 4 or over at the time of their first OCS prescription.
Exposure and outcomes: The primary exposure will be an acute prescription of OCS with a concurrent asthma event (either prescription or diagnosis). Outcomes will include adverse events (AE) including type 2 diabetes mellitus, osteoporosis/osteoporotic fractures, hypertension, glaucoma, sleep apnoea, weight gain and depression/anxiety, pneumonia, cataracts, sleep disorders, cardiovascular disease, chronic kidney disease, dyslipidaemia and peptic ulcer disease, and in the adolescent population we will look for growth suppression and behavioural disorders.
Analysis: OCS prescriptions will be classed as either intermittent or maintenance based upon their dosing instructions, prescription strength and duration. Patterns of OCS prescription will be categorised according to their prescribing frequency (one off, sporadic, frequent etc). Baseline characteristics will be described for patients according to their patterns of intermittent OCS use by GINA step of treatment, and ICS and SABA use.
A matched historical cohort study will be performed according to their patterns of OCS prescribing. To address potential differences between OCS groups, patients will be matched initially on gender, age, and the index date
HRU events, up for both asthma-related and all-cause events, will be described over the follow up period using the CPRD dataset. CPRD HES linked data will be used to describe hospital admissions, A&E attendances, and Outpatient visits
An analysis of AE will be undertaken according to average annual OCS dose of 250-499mg, 500-999mg, or =>1g during the follow up
Outcomes for Objective 1: Baseline patient characteristics will be collected according to patients OCS patterns of use
• patient characteristics (age, gender, BMI, asthma control RCP3, blood eosinophil count, lung function) described prior to index date
• length of patient record prior and after index date
• age of onset of asthma (age at first asthma diagnosis ever)
• time from first asthma diagnosis date to index date
• ICS and SABA use prior to index date
• patient’s treatment by GINA (2019) treatment step prior to index date
Outcomes for Objectives 2 & 4: Adverse events associated with intermittent OCS use
An adverse event for the following conditions:
Diabetes - A diagnosis, prescription or test result indicating diabetes
Osteoporosis diagnosis
Hypertension diagnosis
Glaucoma diagnosis or treatment
Sleep apnoea diagnosis, referral to sleep clinic or continual use of a CPAP device
Weight gain - Increase in Body Mass Index (BMI) by at least 1 kg/m2 compared to index date
Depression/anxiety – diagnostic code, or diagnostic code AND treatment
Pneumonia – diagnostic code
Cataract – diagnostic code and/or cataract surgery
Sleep disorders – diagnostic code and/or hypnotic medications
Renal impairment - Chronic kidney diagnosis (CKD stages 3a, 3b, 4,5)
Dsyipidaemia onset - Diagnostic code for dyslipidaemia OR hyperlipidaemia OR hypercholesterolaemia OR hypertriglyceridaemia
Peptic ulcer disease - diagnostic code
Adolescent population – Behavioural disorders – Diagnostic codes
Adolescent population - Growth suppression – Diagnostic codes
Outcomes for Objective 3: Annualised healthcare resource utilisation and related costs
HRU categories for all events and asthma specific events for
Physician visits
Outpatient visits
Accident & Emergency
Hospital attendances spells (including and excluding day cases)
Hospital attendances length of stay (overall and >0 night)
Day cases spells
Ekaterina Maslova - Chief Investigator - AstraZeneca Ltd - UK Headquarters
Heath Heatley - Corresponding Applicant - OPRI - Observational and Pragmatic Research Institute Pte Ltd
David Price - Collaborator - OPRI - Observational and Pragmatic Research Institute Pte Ltd
Derek Skinner - Collaborator - Optimum Patient Care Ltd
Marjan Kerkhof - Collaborator - OPRI - Observational and Pragmatic Research Institute Pte Ltd
Trung Tran - Collaborator - Astra Zeneca Inc - USA
HES Accident and Emergency;HES Admitted Patient Care;HES Outpatient