Adding second-line therapy ineffective for seizure cessation in status epilepticus subset

Patients with benzodiazepine-refractory convulsive status epilepticus who received a home medication vs. non-home medication did not differ in cessation of clinical seizures with improved consciousness by 60 minutes after drug initiation.

Researchers published these findings in Neurology.

“Because up to half of patients with status epilepticus do not respond to first-line benzodiazepine therapy, and outcomes decline with prolonged seizure duration, optimizing second-line anticonvulsant therapy is critical to improving patient outcomes,” Rafael Wabl, MD, a fellow in the department of neurology at the University of Washington in Seattle, and colleagues wrote. “In the recent Established Status Epilepticus Treatment Trial (ESETT), 462 patients refractory to benzodiazepine treatment were [randomly assigned] to levetiracetam, fosphenytoin or valproate as second-line treatment. The trial found no difference in the primary outcome of clinical seizure cessation with improved consciousness.”

In this prior trial, the researchers conducted an analysis of prespecified patient characteristics, such as sex, race, ethnicity, time from seizure onset and status epilepticus etiology, but did not pinpoint factors that influenced the likelihood of success for any of the second-line medications. Also, the ESETT trial did not assess a priori whether patients’ home anticonvulsant regiments affected response to second-line treatment.

In the current study, Wabl and colleagues sought to determine whether receipt of a second-line anticonvulsant medication as part of a patient’s home regimen affected outcomes in benzodiazepine-refractory convulsive status epilepticus. They analyzed ESETT data to compare allocation to a study drug included in the patient’s home anticonvulsant medication regimen with receipt of an alternative, second-line study medication. Cessation of clinical seizures with improved consciousness by 60 minutes following initiation of the study drug served as the primary outcome. Seizure cessation adjudicated via medical records and adverse events served as secondary outcomes. Wabl and colleagues conducted inverse probability of treatment-weighted (IPTW) logistic regressions.

Results showed 50% of all study patients (n = 232) took one to two of the three study medications at home. Most patients were taking levetiracetam alone (74%).

The researchers observed the primary outcome among 44% of patients allocated to their home medication compared with 53% allocated to a non-home medication (IPTW OR = 0.66; 95% CI, 0.39-1.14). They observed the adjudicated seizure cessation outcome among 42% of patients treated with a home medication vs. 57% of patients treated with a non-home medication (unadjusted OR = 0.53; 95% CI, 0.31-0.9; IPTW OR = 0.52; 95% CI, 0.3-0.89). They also reported no interaction between study levetiracetam and home levetiracetam, nor any differences in adverse events.

“The significant benefit seen on the secondary adjudicated outcome and the direction of the point estimates on the primary outcome suggests that it may be preferable to treat those who present in status epilepticus with a non-home anticonvulsant,” Wabl and colleagues wrote. “Selecting a non-home anticonvulsant medication could inform a novel and practical approach to a key therapeutic decision, often under the clinician’s immediate control at the bedside, with potential to improve outcomes for patients with status epilepticus.”