As-Needed Jabs With New Drug for Blepharospasm Are Safe

Fran Lowry

October 31, 2011

October 31, 2011 (Orlando, Florida) — A new study shows that shorter injection intervals with incobotulinumtoxinA (Xeomin, Merz Pharmaceuticals), given on an as-needed basis, are safe and effective.

The study provides much-needed proof that it is indeed possible to treat patients with benign essential blepharospasm on an as-needed basis, researchers reported here at the American Academy of Ophthalmology 2011 Annual Meeting.

Blepharospasm affects the eyelid muscles and is the second most common focal dystonia, after cervical dystonia. People who suffer from this condition are unable to open their eyes; if it is severe enough, they can be functionally blind, explained lead author Hubert H. Fernandez, MD, who is head of the dystonia clinic at the Cleveland Clinic Foundation in Ohio.

Dr. Hubert Fernandez

"We don't know the cause. We believe it is a short-circuitry problem that's coming from the brain, particularly the basal ganglia, and is ordering the eyelid muscles to contract. When this happens, the eye is closed," Dr. Fernandez told Medscape Medical News.

"If your blepharospasm is severe enough, you can't read, you can't drive, you can't go to the grocery store, you can't watch a movie or television, because your eyes are shut. These are big life-limiting factors for blepharospasm," he said.

The gold-standard treatment for blepharospasm is botulinum toxinA (Botox) injections given once every 3 months. However, symptoms often return sooner, rendering people with blepharospasm essentially blind for a month or more, until they can get another shot.

"Normally, patients have no choice but to be injected every third month. If your drug only lasts for 6 weeks or 8 weeks or 2 months, you have to suffer because standard practice decrees that you have to wait for 3 months until you get another injection," Dr. Fernandez said.

Like botulinum toxinA, incobotulinumtoxinA cleaves the protein that is responsible for muscle contractions to reduce spasm and permit the opening of the eyes. The 2 drugs have "exactly the same mechanism of action and have more similarities than differences," noted Dr. Fernandez.

However, one important difference with incobotulinumtoxinA is that, unlike botulinum toxinA, it contains no additional protein complexes. Theoretically, these protein complexes could contribute to immune resistance and, because incobotulinumtoxinA lacks such complexes, it might be less immunogenic, Dr. Fernandez explained.

"This is a theoretical possibility; it is not proven in clinical data," he cautioned.

Dr. Fernandez and his colleagues studied the dosing profile of incobotulinumtoxinA for up to 48 weeks in 102 patients. In this study, patients received up to 5 additional treatments, with 6 or more weeks between sessions. They found that 6% to 17% of patients were reinjected in 6 to 8 weeks, a similar percentage of patients were reinjected in 8 to 10 weeks, a larger percentage, 17% to 27%, were reinjected in 10 to 12 weeks, and the majority, 27% to 52%, were reinjected in 12 weeks or more.

"Patients could be injected as early as 6 weeks if they needed it, or as late as 4 months if they did not. All patients tolerated [incobotulinumtoxinA] with this flexible dosing schedule, whether they got it sooner or later," Dr. Fernandez said.

"Our point here is that you don't have to be bound to injections every 3 months. Using [incobotulinumtoxinA], you can inject as soon as 6 weeks or as late as or later than 12 weeks and you will achieve the same tolerability and efficacy as someone who gets it every 3 months," he said.

In another poster presentation, Dr. Fernandez and his team compared the adverse-effect profile of incobotulinumtoxinA with placebo in 441 patients. As expected, active treatment was associated with more adverse effects than placebo, including eyelid ptosis (14 vs 3 patients), dry eye (12 vs 4), blurred vision (4 vs 2), dry mouth (12 vs 1), dysphagia (3 vs 0), and headache (5 vs 1).

"This tolerability profile is comparable to that seen with [botulinum toxinA]," Dr. Fernandez said.

In addition, there was no adverse cumulative effect on tolerability with an increased number of incobotulinumtoxinA doses.

"Our basic take-home message is that the adverse-event profile of [incobotulinumtoxinA], as well as the open-label experience of [incobotulinumtoxinA], shows that it is a good, reasonable alternative to [botulinum toxinA] and other botulinum toxin products in the treatment of blepherospasm," Dr. Fernandez said.

"In addition, this has challenged conventional wisdom that you have to inject the patient only every 12 weeks, but not sooner," he concluded.

Dr. Fernandez reports financial relationships with Merz Pharmaceuticals (the manufacturer of Xeomin), Ipsen Pharmaceuticals, United Biosource Corporation, Abbott, Acadia, Biotie Therapeutics, EMD-Serono, Michael J. Fox Foundation, Movement Disorders Society, National Parkinson Foundation, National Institutes of Health/National Institute of Neurological Disorders and Stroke, Novartis, Parkinson Study Group, and Teva; and that he is the head principal investigator for the Xeomin Registry Study but does not receive any personal compensation for this role.

American Academy of Ophthalmology (AAO) 2011 Annual Meeting: Abstracts 440 and 441. Presented October 24, 2011.

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