3A-05 - Association between leukotriene receptor antagonist use and reduced risk of epileptic seizure in patients with asthma: a self-controlled case series study

Background: Preclinical studies have shown that leukotriene receptor antagonists (LTRAs), a class of medications for asthma and seasonal allergies, reduced seizure attacks and the severity of seizures. However, clinical evidence remains limited. LTRA usage is often intermittent, making traditional cohort study designs challenging for assessing the treatment effects over varying periods.

Objectives: To investigate whether LTRA treatment is associated with a lower risk of epileptic seizures in patients with asthma using a self-controlled case series (SCCS) study design.

Methods: Patients with asthma, who received at least one prescription of LTRA, and had an incident epileptic seizure event during the study period from 2005 to 2020, were identified from the UK Clinical Practice Research Datalink linked to Hospital Episode Statistics and Office for National Statistics. A SCCS study design was used to compare the incidence rates of epileptic seizures during four risk windows to baseline (absence of LTRAs): 90 days before LTRA treatment (pre-LTRA exposure), the first 30 days of LTRA treatment, 31 to 180 days of LTRA treatment, and >180 days of LTRA treatment. Incidence rate ratios (IRRs) were calculated using conditional Poisson regression model, adjusted for age, season, and concomitant medications. Additional analyses examined the association between LTRA use and the risk of recurrent epileptic seizure.

Results: Of 370,222 individuals who had received at least one prescription of LTRA during the study period, 2,656 had an incident epileptic seizure. Compared to baseline, a lower incidence of epileptic seizure was detected during the >180 days of LTRA treatment (IRR=0.83; 95%CI=0.72-0.96), no precise differences in risk was observed during the first 30 days of LTRA treatment (IRR=0.88; 95%CI=0.64-1.22) and 31 to 180 days of LTRA treatment (IRR=0.85; 95%CI=0.69-1.05). A higher risk of epileptic seizure was observed during the pre-LTRA exposure period (IRR=1.37; 95%CI=1.15-1.64). Compared with baseline, the risk of recurrent epileptic seizure was also lower during the >180 days of LTRA treatment (IRR=0.67; 95%CI=0.51-0.87). Results from sensitivity analyses, SCCS extension, and negative control analysis supported the robustness of results.

Conclusions: A decreased risk of epileptic seizure was identified with long-term LTRA treatment. Further studies are needed to validate the findings.