Date Published: December 21, 2017
Publisher: Public Library of Science
Author(s): Laura J. Bonnett, Graham A. Powell, Catrin Tudur Smith, Anthony G. Marson, Hyunmi Choi.
To develop prognostic models for risk of a breakthrough seizure, risk of seizure recurrence after a breakthrough seizure, and likelihood of achieving 12-month remission following a breakthrough seizure. A breakthrough seizure is one that occurs following at least 12 months remission whilst on treatment.
We analysed data from the SANAD study. This long-term randomised trial compared treatments for participants with newly diagnosed epilepsy. Multivariable Cox models investigated how clinical factors affect the probability of each outcome. Best fitting multivariable models were produced with variable reduction by Akaike’s Information Criterion. Risks associated with combinations of risk factors were calculated from each multivariable model.
Significant factors in the multivariable model for risk of a breakthrough seizure following 12-month remission were number of tonic-clonic seizures by achievement of 12-month remission, time taken to achieve 12-month remission, and neurological insult. Significant factors in the model for risk of seizure recurrence following a breakthrough seizure were total number of drugs attempted to achieve 12-month remission, time to achieve 12-month remission prior to breakthrough seizure, and breakthrough seizure treatment decision. Significant factors in the model for likelihood of achieving 12-month remission after a breakthrough seizure were gender, age at breakthrough seizure, time to achieve 12-month remission prior to breakthrough, and breakthrough seizure treatment decision.
This is the first analysis to consider risk of a breakthrough seizure and subsequent outcomes. The described models can be used to identify people most likely to have a breakthrough seizure, a seizure recurrence following a breakthrough seizure, and to achieve 12-month remission following a breakthrough seizure. The results suggest that focussing on achieving 12-month remission swiftly represents the best therapeutic aim to reduce the risk of a breakthrough seizure and subsequent negative outcomes. This will aid individual patient risk stratification and the design of future epilepsy trials.
Epilepsy is one of the most common serious neurological disorders worldwide, affecting approximately 50 million people. Estimates suggest that 60 to 70% of people with epilepsy will achieve a remission from seizures. However, up to 37% of these people may proceed to have a breakthrough seizure. A breakthrough seizure is defined as an epileptic seizure which occurs despite the use of antiepileptic drugs that have otherwise successfully prevented seizures in the patient.
Fig 1 illustrates the disposition of the 2627 participants recruited into both Arm A and Arm B of SANAD. It also identifies participants relevant to each of the outcomes in this analysis.
We have shown that several clinical factors influence the risk of a first breakthrough seizure following an initial period of 12-month remission whilst on treatment, and outcomes following such a seizure. Of the participants recruited into SANAD, 34% went on to have a first breakthrough seizure. According to the multivariable model for this outcome, participants with neurological insult, or with any number of tonic-clonic seizures, or taking over a year to achieve initial period of 12-month remission were at increased risk of a first breakthrough seizure.