Because the pharmacokinetics of three popular botulinum toxin products differ, there's no shortcut to determining equivalent therapeutic doses, according to one expert.
National report - Because the pharmacokinetics of three popular botulinum toxin products differ, there's no shortcut to determining equivalent therapeutic doses, according to one expert.
Botox (onabotulinumtoxinA, Allergan) first earned Food and Drug Administration (FDA) approval in 1989. Dysport (abobotulinumtoxinA, Medicis) was approved in 2009. Xeomin (incobotulinumtoxinA, Merz) was FDA-approved in July 2010 for treatment of adults with cervical dystonia or blepharospasm.
Neurotoxins diffuse differently, in part because Botox and Dysport have protective proteins clustered around the active part of the molecule, while Xeomin has no protective proteins.
"Botox has a full complement of protective proteins and weighs about 900 kD. Dysport is a mixture of 500 kD and 300 kD complexes of protective proteins and botulinum toxin A," Dr. Smith says.
Being heavier, these complexes migrate more slowly than Xeomin/NT-201, which is BTX-A without protective proteins. As such, "Xeomin/NT-201 is going to migrate probably faster and further, because there's nothing dragging it down. Conversely, you'll have less precision," he says.
Additionally, "The protective proteins cluster around the C-terminal end of the BTX-A molecule, which is the part that binds to the post-synaptic nerve terminal. That's the way botulinum toxin exists in nature, and in Botox and Dysport," Dr. Smith says. These protective proteins also may shield the active part of the molecule from the immune system. This way, "While it is being protected by protective proteins, the binding site part of the molecule may not stimulate the immune system. And if there are antibodies against that part of the molecule floating around, they would have a harder time getting at it," he says.
From the ground up
Considering those differences, Dr. Smith says based on the experience of European physicians familiar with all three toxins, "The best, safest way is to start with a clear mind and learn each product from the ground up, the same way we learned Botox when we were starting out with that." This method also produces the happiest patients, he says. "If you try to take a shortcut, you're asking for trouble in terms of not getting the result the patient is looking for." This would be due to insufficient, excess or unwanted muscle relaxation, he explains.
Regarding the learning curve for new treatments in general, "Most of your problems and disappointments will occur in your first 100 cases, because you're still learning," Dr. Smith says. To reduce these problems, "Learn about the physiology and biochemistry of the different drugs. Talk to colleagues. And don't rely on what experts on the podium say." He adds that with most new treatments, "My general bias is to let other physicians try it on their patients first and get all the bugs out of it."