Rufinamide May Be Safe Add-On for Refractory Seizures

Allison Gandey

December 09, 2010

December 9, 2010 — New study results show that 46% of patients with refractory seizures improved with adjunctive rufinamide, with most of these showing a more than 50% decline in seizure frequency.

"Our data show promise that rufinamide therapy may be a relatively safe adjunct in the treatment of refractory epilepsy," reported investigators led by Jacob Joseph, MD, from the Baylor College of Medicine in Houston, Texas. They presented preliminary results at the American Epilepsy Society 64th Annual Meeting.

Rufinamide was recently approved by the US Food and Drug Administration as an adjunctive treatment of seizures associated with Lennox syndrome. The drug is a triazole derivative that maker Esai Corporation says is structurally unrelated to currently available antiepileptic drugs.

A total of 46% of patients responded to therapy and 54% did not.

The product marketed as Banzel is believed to act by regulating the activity of sodium channels in the brain. Some suggest rufinamide is an attractive option because it may have few drug interactions and reportedly provides quick titration.

The numbers do not afford entirely good news, however, the investigators pointed out to delegates attending the meeting in San Antonio, Texas. More than half of patients in the study did not respond to therapy. The mean dose of rufinamide was 827.3 mg/day or 30.1 mg/kg/day. The mean duration of therapy was 21 weeks.

Of these nonresponders, 68% stopped taking the drug because of lack of efficacy and 9% terminated treatment after an adverse event. In all, 23% of patients experienced an increase in seizure frequency.

The goal of the present study was to extend the clinical knowledge with this new drug. "We wanted to examine the safety and efficacy of rufinamide adjunctive therapy in pediatric and young adult patients with a variety of seizure types," the researchers report.

The chart review of 45 patients took place at a comprehensive epilepsy center — the Blue Bird Circle Clinic for Pediatric Neurology at Texas Children’s Hospital. The mean patient age was 9.5 years.

Study participants were having a broad spectrum of partial and generalized seizure types. The vast majority of patients had received previous therapy with one or more antiepileptic drug before starting rufinamide treatment. The mean number of concomitant therapies was 2.14.

"Allowing for the limitation of small sample size and the retrospective nature of the study," Dr. Joseph's team concludes, "our data show promise that rufinamide therapy may be a relatively safe adjunct in the treatment of refractory epilepsy."

Asked by Medscape Medical News to comment, Jacqueline French, MD, from New York University's Comprehensive Epilepsy Center in New York City, said that many questions remain. "This is an open-label chart review, after all."

She pointed out the proposed efficacy rate is about average for patients with refractory seizures. Dr. French said she is also not concerned about the increases in seizure frequency considering the patients were refractory. "This is not surprising and could be evidence of regression to the mean."

Similar Discontinuation Rates

In a separate presentation by a different group, investigators identified similar rufinamide discontinuation rates. In their retrospective study, the team led by Albert Molins, MD, from the Vall d'Hebron Hospital in Barcelona, Spain, looked at 39 patients with Lennox syndrome, generalized epilepsy with impaired mental development, and focal epilepsies.

Patients received adjunctive rufinamide. Almost half, 44%, discontinued therapy. The main reason for stopping use of the drug was lack of efficacy. Other patients, 38%, ended treatment due to adverse events.

"Nausea, vomiting, and weight loss were the most frequent," Dr. Molins reported. These patients were older than those in the previous study. The mean age was 28 years.

Despite the high discontinuation rate, the investigators conclude rufinamide showed efficacy and was generally well tolerated.

Dr. French pointed out that additional study is necessary. However, the discontinuation rates in the current analyses are comparable to other available medications. "About half of patients do generally need to try alternatives," she said.

These studies were funded by Esai Corporation. The investigators received compensation for their work.

American Epilepsy Society (AES) 64th Annual Meeting: Posters 1.266 and 1.309. Presented December 4, 2010.

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