Epilepsy is one of the most common brain conditions that causes frequent seizures, which are sudden bursts of electrical activity in the brain. Seizures can cause temporary abnormalities in behaviours, movements, sensations or states of awareness. The available medications relieve symptoms and reduce seizure attacks. However, there are significant challenges with the available medications, such as adverse reactions and a lack of agents that can prevent the development of epilepsy. Hence, alternative treatment methods that can help prevent and control the disease are needed.
Leukotriene receptor antagonists (LTRAs) are currently being used for the treatment of asthma and seasonal allergies. Animal studies have shown that LTRAs reduce seizure attacks and the severity of seizures. This study aims to assess the effect of LTRAs in reducing the risk of seizures at the population level. If we find that the LTRA use could reduce the incidence of seizures, our study will provide useful evidence of the potential of LTRAs to be developed into a class of drugs for epilepsy, which will further inform treatment guidelines and practices, and finally improve patients’ health outcomes.
Epilepsy is a chronic neurological disorder, characterized by the recurrence of unprovoked seizures. Anti-epileptic drugs are the commonly used treatment for epilepsy with the aim of controlling seizures. However, there are significant unmet medical needs and treatment challenges including drug-resistant epilepsy, adverse reactions, and lack of agents capable of averting the onset of epilepsy. Leukotriene receptor antagonists (LTRAs) are currently being used for asthma. Evidence from preclinical animal studies suggests that LTRAs reduce the incidence and severity of seizures.
This study aims to evaluate the association between LTRA use and epileptic seizures in the clinical setting, using data from CPRD. The Hospital Episode Statistics (HES) data will be used for capturing hospital diagnosis of seizures. The Office of National Statistics (ONS) data will be used to determine death. Linkage to Index of Multiple Deprivation will be used to describe the socioeconomic characteristics of the study cohort.
We will conduct a self-controlled case series study including individuals who had received at least one prescription of LTRA, and with at least one outcome event (epileptic seizure) between 1 January 2005 to 31 December 2022. Individuals will serve as their own control, and thus time-invariant confounders will be controlled. The observation period will be divided into the following categories: absence of LTRA period (baseline period), 90 days before LTRA treatment, the first 30 days of LTRA treatment, 31 to 180 days of LTRA treatment, and >180 days of LTRA treatment period. The association between LTRAs and epileptic seizures will be evaluated by comparing the incidence of seizures during exposure periods with that during non-exposure periods. The incidence rate ratio (IRRs) will be calculated using conditional Poisson regression.
The study will allow us to better understand the potential of LTRAs to be developed into anti-epileptic drugs, and further help to guide prescribing in patients.
The main effect estimates will be the incidence rate ratios (IRRs), which will be estimated by comparing the incidence rates of events (i.e., the first epileptic seizures) between LTRA exposure periods and non-exposure periods.
Wallis Lau - Chief Investigator - University College London ( UCL )
Boqing Chen - Corresponding Applicant - University College London ( UCL )
Kenneth Man - Collaborator - University College London ( UCL )
Yogini Jani - Collaborator - University College London ( UCL )
HES Accident and Emergency;HES Admitted Patient Care;HES Outpatient;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation