ARTICLE IN BRIEF
An analysis of data on epilepsy outcomes found that while a significant percentage of patients will respond to initial treatments and remain seizure free, there has been little improvement in treatment outcome for those who do not respond to initial medication trials despite the introduction of several new medications in recent years.
The percentage of newly diagnosed epilepsy patients who remain free from seizure declines with successive drug regimens, especially from the first medication regimen to the third among patients with localization-related epilepsies, according to a May 9 online report in Neurology.
And while a significant percentage of patients will respond to initial treatments and remain seizure free, there has been little improvement in treatment outcome for patients who do not respond to initial medication trials despite the introduction of several new medications in recent years. Moreover, even among those patients who respond to initial treatment trials, relapse is not unheard of.
Study authors and several neurologists who reviewed the report say the results largely confirm clinical impressions of a mixed prognostic picture for patients with epilepsy: a substantial percentage of patients will become seizure free on the first or second medication trial, but a roughly equal percentage will show a fluctuating pattern of remission and relapse or will never achieve freedom from seizures.
“The overall effectiveness is good in 40 percent who would become seizure free early on and remain so,” study author Patrick Kwan, MD, PhD, professor of neurology at the Royal Melbourne Hospital of the University of Melbourne in Australia, told Neurology Today. “It is not so good in around 20 percent who would take longer to become seizure free, and poor in 25 percent who are never controlled. One in six patients has a remitting-relapsing course.”
In the study, patients in whom epilepsy was diagnosed and the first antiepileptic drug prescribed between July 1, 1982 and April 1, 2006, were followed up until March 31, 2008. Probability of seizure freedom — defined as the absence of seizures for one year or more — with successive drug regimens was compared. Outcomes were categorized into four patterns: A) early and sustained seizure freedom; B) delayed but sustained seizure freedom; C) fluctuation between periods of seizure freedom and relapse; D) seizure freedom never attained.
A total of 1,098 patients were included. At the last clinic visit, 68 percent of patients were seizure-free, of whom 62 percent were on monotherapy.
During the follow-up period, the investigators reported that 37 percent of patients had sustained freedom from seizures after initial treatment, while 22 percent of patients achieved freedom from seizures but only after two or more medication trials. Sixteen percent of patients showed a pattern of remission and relapse, while 25 percent of patients never achieved seizure freedom despite successive treatments.
There was a higher probability of seizure freedom in patients receiving one compared with two drug regimens, and two compared with three regimens. Less than two percent of patients became seizure-free on subsequent regimens though a few did so on their sixth or seventh regimen, according to the study.
Dr. Kwan said the study results underscore the importance of response to initial treatment in long-term prognosis. “Clinicians should choose the first two regimens very carefully to maximize the chance of seizure freedom, particularly for patients with poor prognostic factors, such as high pre-treatment seizure frequency and a symptomatic cause,” he said, adding that clinicians should refer patients to a center specializing in epilepsy for assessment after failure of two antiepileptic medications.
Epilepsy experts said the study offers mixed news. Selim Benbadis, MD, professor and director of the comprehensive epilepsy program at the University of South Florida and Tampa General Hospital, said: “The main finding is that intractability declares itself early. If patients do not respond to the first two or three regimens, they are not likely to ever achieve seizure control. This is not new, but what is new is that since the last publication of this center's cohort we see only a few more percentage points in improvement. So, despite the availability of several new drugs, the general response profile has not really changed.”
“Patients should not go years and years trying 20 medication regimens,” he said. “Instead, they should be evaluated early, after two-to-three drug failures, with EEG-video monitoring to assess their surgery candidacy. This is unfortunately not being done, even in Western countries where EEG-video is readily available.”
Cynthia Harden, MD, chief of the Division of Epilepsy and Electroencephalography at Hofstra North Shore-LIJ School of Medicine, drew attention to the fact that even among patients who immediately responded to an initial medication with freedom from seizure, approximately a quarter experienced a relapse.
“Even when patients are seizure free there is still the chance of relapse and we probably need to be more nuanced in our satisfaction with treatment even among those patients who respond favorably,” she told Neurology Today. “Epilepsy remains a mysterious disease and we are using drugs that only suppress the seizures while patients are taking them. They are still susceptible to ongoing seizure activity.
“It's a disease that has a vitality of its own, and for many patients we haven't found the medical treatment that will stop the illness,” she said. “Surgical resection of an epileptic focus in appropriate patients may be a more definitive treatment that could actual change the course of the disease.”
CLASSIFYING DRUG RESISTANT EPILEPSY
Patrick Kwan, MD, PhD, professor of neurology at the Royal Melbourne Hospital of the University of Melbourne in Australia, recommended an online “Classifier of Drug Resistant Epilepsy” that he and colleagues at the Chinese University of Hong Kong developed to help clinicians classify drug response based on the recent International League Against Epilepsy (ILAE) definition of drug resistance: www.drugresistantepilepsy.com.
• Brodie MJ, Barry SJE, Kwan P, et al. Patterns of treatment response in newly diagnosed epilepsy. Neurology 2012; E-pub 2012 May 9.