Despite the perceptions of many physicians and patients, an expert says, in practical use, the three neuromodulators approved for use in the United States are more similar than dissimilar.
Boston - Despite the perceptions of many physicians and patients, an expert says, in practical use, the three neuromodulators approved for use in the United States are more similar than dissimilar.
"People are looking at Botox (onabotulinumtoxinA, Allergan) and Dysport (abobotulinumtoxinA, Medicis) and trying to come up with differences between them," says Thomas E. Rohrer, M.D., clinical associate professor of dermatology, Boston University School of Medicine. However, "Recent studies show that they are more similar than different."
All botulinum toxin products have the same 150 kDa molecule at their core, he says. AbobotulinumtoxinA surrounds this molecule with a 350 kDa to 750 kDa shell of complexing proteins, while onabotulinumtoxinA uses a 750 kDa protein complex for this purpose. Conversely, Xeomin (incobotulinumtoxinA, Merz) has no complexing proteins.
"When we dilute these products, they're already mostly broken down into the 150 kDa free form," Dr. Rohrer says. "The proteins around the botulinum toxin molecule, which are what differentiate Dysport for Botox, are nearly all gone. The complexing proteins have a half-life of approximately one minute in a solution with a pH greater than seven. Therefore, all this talk about the differences between Botox, Dysport and Xeomin becomes less relevant because the very thing that differentiates the products appears to dissociate before or immediately after we inject them into the patient. If you look at the onset of action, efficacy and duration of action, they all wind up being equivalent."
Some experts believe that abobotulinumtoxin provides a quicker onset of action than onabotulinumtoxin, Dr. Rohrer says. Although the large phase 3 abobotulinumtoxin trials showed an onset of action as quick as one day, the median was three to four days.
"When we try to compare that to Botox, the original phase 3 Botox studies didn't look very closely at that parameter. We didn't have a good comparison," so people perhaps assumed that abobotulinumtoxin works faster, he says.
According to a study published in January 2011 examining onabotulinumtoxin's onset of action, however, showed that 48 percent of patients reported action by day one and 87 percent by day two.2
"That closely matches Dysport's numbers in this area. Both products also have a very similar duration of action," Dr. Rohrer says.
Regarding diffusion of onabotulinumtoxin versus abobotulinumtoxin, although study results sometimes conflict, "No one has been able to show conclusively that one spreads more than the other," Dr. Rohrer says.
For example, research in a mouse model has shown no differences in terms of spread to adjacent muscles over time.3 In a clinical trial, injections of abobotulinumtoxin and onabotulinumtoxin, using a 2.5 to one conversion rate, respectively, performed with the same technique and at the same volume and depth, resulted in similar action halos with regard to muscular and sweat gland activity.4
"The spread of the toxin depends more on how the toxin is mixed and injected than the toxin itself," Dr. Rohrer says.
Spread occurs quickly and depends on the amount of saline used to dilute the toxin and how quickly the mixture is injected.
Conversely, "Diffusion is a slower, passive process in which the unbound toxin moves down the concentration gradient to attain equilibrium. This relates to particle size, so one might expect there would be a difference between onabotulinumtoxin and abobotulinumtoxin," he says. "But since the toxin dissociates from complexing proteins when we mix it or within a minute of injecting it, there should be no significant difference in diffusion between Dysport and Botox."