Transient use of oral corticosteroids and the risk of acute severe adverse events among asthma patients: a population-based real-world study

Study type
Protocol
Date of Approval
Study reference ID
24_004080
Lay Summary

Asthma is a chronic respiratory disease with frequent flare ups that worsen symptoms and reduce breathing capacity. These are usually treated with short courses of oral corticosteroids (OCS), along with asthma inhalers. Studies of other diseases, mainly in older patients, have shown that OCS can lead to heart attacks, high blood sugar or diabetes, stomach complications, and infections. However, such studies in asthma are scarce and many asthma patients are younger. Since OCS are given to most asthma patients for brief periods to treat the flare-ups, we will assess if short-term use of OCS in patients with asthma can trigger these complications.

Our research will use a technique that compares patients to themselves by measuring if the adverse event occurs more frequently when the patient is taking the drug compared to when they are not. We propose a study using electronic health data from the UK’s Clinical Practice Research Datalink (CPRD) to form a cohort of patients with asthma. This cohort will be used to examine if short-term OCS use causes lung or blood infections, gastrointestinal bleeding, heart attacks, heart failure, heart arrythmia, psychosis or delirium, and complications related to blood sugar control in asthma patients. This work will advance our knowledge on the safety of OCS use among asthma patients and promote safer clinical practice.

Technical Summary

Asthma is a global health concern with increasing prevalence. Asthma exacerbations occur on average 2-3 times yearly among patients with mild-to-moderate asthma, often treated with short-term (3-14 days) oral corticosteroids (OCS). Regular OCS use in other diseases has been associated with several adverse events, but only one study has investigated these risks in asthma patients. This study did not focus specifically on short-term OCS use and had important methodologic limitations like immortal time and selection biases. We propose to conduct an epidemiological study to investigate the safety of OCS for asthma using a design that minimizes these biases. This project aims to assess the risk of several acute adverse events after transient OCS use among patients with mild-to-moderate asthma.
The United Kingdom’s Clinical Practice Research Datalink (CPRD) will be our data source. Specifically, the ONS Death Registration Data will be used to identify death records and the HES Admitted Patient Care data will provide information on outcome events of interest, all requiring hospitalization. Health records in CPRD have been shown to be accurate and valid. We will first identify a base cohort with all patients first diagnosed with asthma from 2000-2022, who have at least one year of record prior to first asthma diagnosis. Our primary approach will be a case-crossover design where, for a given outcome under study, those who experienced the outcome will be identified from the base cohort and their OCS exposure at the time of the event (i.e. during risk periods) will be compared to their OCS exposure during prior baseline periods. Conditional logistic regressions will be used to account for the correlation between baseline and risk periods contributed by the same individuals. Our research will inform safer clinical practice when treating acute exacerbations among patients with mild-to-moderate asthma, including those from the United Kingdom.

Health Outcomes to be Measured

Pneumonia; sepsis; gastrointestinal (GI) bleeding; cardiovascular events (myocardial infarction, heart failure, and atrial fibrillation); psychosis/delirium; and acute complications of diabetes (hyperosmolar coma or diabetic ketoacidosis), all requiring hospitalization.

Collaborators

Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Samy Suissa - Corresponding Applicant - Sir Mortimer B Davis Jewish General Hospital
Jiaying Li - Collaborator - McGill University
Pierre Ernst - Collaborator - McGill University

Linkages

HES Admitted Patient Care;ONS Death Registration Data;Practice Level Index of Multiple Deprivation