Early data show no severe visual side effects from anti-epileptic drug

A patient registry was formed to monitor drug safety amid reports of permanent vision loss occurring 2 years or longer after initiation of treatment.

Preliminary data from a patient registry show no visual problems resulting from use of an epilepsy medication at 2 years, according to a poster presentation on early safety surveillance.

The U.S. Food and Drug Administration approved Sabril (vigabatrin, Lundbeck) in August 2009. So far, the drug has proven safe for children and adults using it to control epileptic seizures, Robert C. Sergott, MD, said in an interview with Ocular Surgery News.

Dr. Sergott is chairman of the Risk-Evaluation and Mitigation Strategy (REMS) for vigabatrin. The FDA required the formation of a REMS and patient registry because of permanent vision loss associated with long-term vigabatrin use.

“Most of the cases of visual problems that have been reported in the literature occur after a year or two of exposure, sometimes longer,” Dr. Sergott said. “We’re getting up to that point now but thus far, the registry data seem to be working in the sense that we don’t have anybody who has had a severe visual problem in this country yet with this. The data are early. We’re being very cautious with this.”

Dr. Sergott noted that vigabatrin can adversely affect the retina and visual fields, but at a slow rate.

“Field change does not become symptomatic until we have profound loss of fields. That’s why we have the Sabril patients being monitored every 3 months,” he said.

Dr. Sergott and colleagues presented the poster at the American Epilepsy Society’s annual meeting in Baltimore.

Patients, protocols and data

As of Aug. 22, 2011, a total of 3,093 patients had enrolled in the patient registry; enrollment began on Aug. 21, 2009. Data showed that 1,880 patients had infantile spasms, 1,046 patients had refractory complex partial seizures and 161 patients had other diagnoses. Because the registry data submissions are voluntary and the sites are not asked about potential omissions, the registry does not contain one diagnosis for every patient.

The median duration of treatment after enrollment in the patient registry was 8.2 months. Patients were monitored every 3 months.

Overall, 1,405 patients (45.4%) stopped treatment. Of those 1,405 patients, 12 patients (0.9%) discontinued therapy because of self-reported visual field defects, 499 patients (35.5%) stopped because they had completed the course of treatment, 344 patients (24.5%) discontinued because of prescriber choice, and 112 patients (8%) discontinued because they chose to do so.

Treatment is halted immediately in cases in which vigabatrin is deemed ineffective, Dr. Sergott and colleagues said.

Evaluation, disease severity

Assessing vision, especially visual fields, in children and in some adults with severe epilepsy is difficult, Dr. Sergott said. Electroretinograms are often effective but are not required for the evaluation of patients using vigabatrin.

“Evaluating vision in these infants is difficult. Pediatric ophthalmologists can usually get a very good feel for it. In some cases, we do need to use other tests such as electroretinograms,” Dr. Sergott said.

Infants with severe epilepsy may develop cognitive disabilities and require supportive care their entire lives. Adults with refractory complex seizures are often unable to work, drive or participate in other activities, Dr. Sergott said.

“So, 40% of epilepsy patients now are not fully controlled, so the epilepsy community as well as the FDA are always looking for additional medications to help patients have better control,” he said.

About one in five patients with severe epilepsy who have never used vigabatrin may have some visual problems, according to one study from Scotland and one from the U.S., Dr. Sergott said.

Indications and alternatives

Vigabatrin is indicated as an adjunctive therapy for adults with refractory complex partial seizures who have responded poorly to other therapies and for whom the potential benefits outweigh the risk of vision loss, according to a news release from Lundbeck.

It is indicated as monotherapy for infants 1 to 2 months old with infantile spasms and for whom the potential benefits outstrip the risk of vision loss, the release said.

Investigators conduct annual reviews of data from the patient registry. In addition, patients undergo clinical evaluation and participate in a discussion of risks and benefits every 3 months.

“What we’re really trying to do is make sure that patients, caregivers and parents understand the benefit-risk proposition for Sabril,” Dr. Sergott said. “This is an ongoing benefit-risk discussion.”

Alternatives to vigabatrin include ACTH, an adrenocorticotropic steroid, for infantile spasms and an array of medications for refractory complex seizures in adults, Dr. Sergott said.

“There are a lot of alternatives,” he said. “The epilepsy specialists do a wonderful job trying to find the right combination for the particular patient. And just having one other medication available will always give some patients better control over their seizures than they had before. That’s why the FDA keeps approving additional epilepsy medications.” – by Matt Hasson

• Robert C. Sergott, MD, can be reached at Wills Eye Institute, 840 Walnut St., 10th floor, Philadelphia, PA 19107; 215-928-3130; fax: 215- 592-1923; email: rcs220@comcast.net.
• Disclosure: Dr. Sergott is a consultant for Lundbeck and chairman of the Risk Evaluation and Mitigation Strategy for vigabatrin.