Factors Associated with Seizure Recurrence in Epilepsy Patients Treated with Antiepileptic Monotherapy: A Retrospective Observational Cohort Study using US Administrative Insurance Claims

Abstract

Few studies examine predictors of seizures in medically treated patients with epilepsy receiving antiepileptic monotherapy using a large patient population. Our objective was to identify clinical, medication, and demographic factors associated with seizure recurrence in medically treated patients with epilepsy receiving one of four antiepileptic monotherapy regimens: lamotrigine, levetiracetam, oxcarbazepine, or topiramate. A retrospective cohort study was conducted using Innovus Invision™ Data Mart paid medical and prescription US commercial insurance claims data from January 2007 to September 2010. Patients aged 18-64 years with a primary or secondary diagnosis of epilepsy and one or more prescription claim for an antiepileptic drug (AED) pre-index were included. The primary outcome was incidence of a seizure or seizure-related event, defined as an emergency room visit, ambulance service use, or inpatient hospitalization medical claim with a primary or secondary diagnosis of epilepsy during the 1-year follow-up. The factors included AED adherence, somatic comorbidity (measured via Charlson Comorbidity Index), mental health comorbidity, pre-index seizure, type of epilepsy diagnosis, presence of AED-interacting medications and any bioequivalent AED switch. The covariates included age, gender, and geographic region of residence. A total of 5.3 % (166/3,140) of patients on AED monotherapy had experienced a seizure or a seizure-related event requiring urgent care at 1-year follow-up. The multivariate analysis of the combined cohort showed that pre-index seizures/seizure-related events (odds ratio [OR] 4.23; 95 % confidence interval [CI] 2.77-6.46), any mental health comorbidity (OR 3.50; 95 % CI 2.14-5.70), and Charlson Comorbidity Index ≥1 (OR 2.91; 95 % CI 1.98-4.28) were significantly associated with post-index seizures/seizure-related events. Patients residing in Northeastern USA had a higher likelihood of a post-index seizure (OR 1.90; 95 % CI 1.17-3.08) than patients residing in the Southern region of the USA. Bioequivalent AED switch, type of epilepsy diagnosis, AED adherence, and presence of AED-interacting medications were not associated with seizure recurrence in the combined cohort analysis (p > 0.05). Epilepsy patients with comorbid conditions (both mental and somatic diseases) and prior seizures were more likely to experience seizures at 1-year follow-up. Non-adherent patients and patients with bioequivalent AED switches appeared to show no increased likelihood of seizure at follow-up. Clinicians may consider these findings before starting or transitioning to an AED monotherapy.