Since it was first used for cosmetic purposes almost 30 year ago, BOTOX has become synonymous with erasing wrinkles (and also become the butt of “frozen face” jokes). Botuinum Toxin (BoNT) type A is, in fact, a deadly toxin produced by the anaerobic bacteria Clostridium botulinum.
BOTOX was the first brand of Botulinum toxin available, but BOTOX is a brand of Botulinum Toxin (just like how Colgate is a brand of toothpate). Today, besides BOTOX (onabotulinumtoxinA), the other brands of BoNT commonly available in USA, Europe and many other parts of the world (including Singapore) are DYSPORT (anobotulinumtoxinA), and XEOMIN (incobotulinumtoxinA).
Botulinum Toxin: Mechanism of Action
Botulinum toxin works by inhibiting the release of a neurotransmitter, acetylcholine, by the nerve cells. This prevents the nerve signals from being released by the cells, and hence, neuromuscular blockage. Cilnically, what we see is reduced muscle movements- and reduction of dynamic wrinkles. The wrinkles are “erased”.
BOTOX: The First Approved Botulinum Toxin
In 2002, the USA FDA approved the use of BOTOX® Cosmetic to temporarily improve the appearance of moderate-to-severe frown lines between the eyebrows (glabellar lines). It ushered in a new era for medical aesthetics.
The second BoNT to be approved for the same purpose was Dysport, in 2009, followed by the 3rd, Xeomin, in 2011. Equivalence studies have shown that all 3 brands of BoNT work on reducing wrinkles. However, there are some significant differences between the 3.
BOTOX, DYSPORT, XEOMIN: Differences
BOTOX, Dysport and Xeomin all contain the same active ingredient: botulinum toxin type A. Numerous studies have been conducted to assess the properties of the 3 leading brands of BoNT, unfortunately, often with conflicting results. Here are some of them:
Onset: Dysport works the fastest1. Patients can feel its effects sometimes within 1 -2 days, and it also peaks faster. BOTOX starts working in 2-3 days, while Xeomin has a more gradual onset. Although it starts working in 1-3 days, patients feel the effects come on more gently. I experience the same in my clinical practice. However, all 3 BoNT brands reach their maximal effects in 2-3 weeks. BoNT also generally works faster in women than in men. Most of my patients prefer Xeomin as the onset is more gradual.
Strength: BoNT is measured in units. Numerous studies find that BOTOX and Xeomin are comparable in strength, with a conversion ratio of 1:1. Dysport, however, is measured differently. 1 unit of BOTOX/Xeomin is equivalent to 2.5-3 units of Dysport2.
Diffusion: The diffusion of BoNT is an important property as it determines how many injection points are needed. Spread of BoNT can also potentially lead to side effects such as ptosis of the eyelids. The scientific concensus is that there is no significant differences in spread between BOTOX, Dysport and Xeomin3.
Duration: There is, unfortunately, no clear proof of which brand of toxin lasts the longest. Most doctors will agree that BOTOX, DYSPORT and XEOMIN last 3- 6 months. One small study4 found that BOTOX may last longer than DYSPORT, but others disagree. A large study with 180 patients found that all 3 brands have a similar duration of action5.
Cost: In general, doctors charge less for Dysport and slightly higher for BOTOX and Xeomin.
Complexing Proteins: the BoNT in BOTOX and Dysport aare bound to complexing proteins. Xeomin, on the other hand, is unique in that during the manufacturing process, the complexing protains are removed to produce a “purer” form of BoNT. Complexing proteins may have a role in BoNT resistance, discussed in more detail below.
|Median Time for Duration of Treatment Effect (Days)|
|Sex||IncobotulinumtoxinA (Xeomin)||OnabotulinumtoxinA (Botox)||AbobotulinumtoxinA (Dysport)|
A Study with 180 patients found that the duration of action of all 3 brands were very similar. (Onset and duration of effect of incobotulinumtoxinA, onabotulinumtoxinA, and abobotulinumtoxinA in the treatment of glabellar frown lines: a randomized, double-blind study. Thomas Rappl)
Botulinum Toxin Resistance and Complexing Proteins
Cases of resistance to BoNT treatments have been reported, both for medical6 and cosmetic indications. The resistance may be partial or full7. When someone becomes resistant to BoNT, they stop responding to the treatment. It is widely agreed that BoNT resistance is a result of the production of antibodies against the Botulinum toxin molecule.
It is also found that the risk of developing antibodies to BoNT increases with the amount of complexing proteins – these are found in BOTOX and Dysport but not Xeomin.
The risk factors for developing BoNT resistance include:
- High dose of BoNT administered (hence it is more commonly seen in medical treatments such as for the treatment of cervical dystonia)
- Frequent treatments
- Treatments with less than 3 weeks in between – i.e touch up treatments.
In medical literature, 11 cases of treatment failure to Botulinum Toxin have been reported, however, I suspect that the numbers are much higher, but not reported. In my practice, I have already encountered 2 such patients – they stopped responding to BOTOX after a few years of treating the masseters for facial contouring.
Botulinum resistance have been reported with BOTOX and Dysport, but not with Xeomin – hence, the claim that Xeomin is “purer” with less tendency to cause BoNT resistance may hold some truth.
Botulinum Toxin Resistance – Prevention is Better Than Cure
Unfortunately, once resistance has developed, there is no known way to cure it. Once someone develops BoNT resistance to one brand, they will likely be resistant to the others too, including Xeomin7. Although rare, It is always a possibility, and prevention is the only way.
Steps to prevention of Botulinum resistance include:
- Treating with smaller dosages
- Less frequent treatments (more than 12 weeks between treatments)
- Touch up treatments at larger intervals (more than 21 days)
- Choosing a brand of BoNT with no complexing proteins
BOTOX vs DYSPORT vs XEOMIN: Conclusions
There is no clear superior Botulinum Toxin amongst the 3 major brands: BOTOX, Dysport and Xeomin. Much of what your doctor chooses will depend on how comfortable he/she is with the product. I avoid using any BoNT which are not these 3 brands (such as the China and Korean made ones) as I am not familiar with them, and am not convinced of their safety profile. Speak to your doctors about which BoNT they are using, and why.
Clinically, I believe all 3 brands produce fantastic and comparable results. Xeomin may have an additional benefit of less chance of treatment failure in the long term, however, treatment failure from Botulinum Toxin antibody production is not a common occurrence, and happens more with frequent treatments with large dosages – such as when using BoNT for facial sculpting of the masseters, and for treatment of bruxing. Personally, I have encountered 2 cases of treatment failure with BOTOX in my career.
A Quantitative Analysis of OnabotulinumtoxinA, AbobotulinumtoxinA, and IncobotulinumtoxinA: A Randomized, Double-Blind, Prospective Clinical Trial of Comparative Dynamic Strain Reduction. Wilson AJ et al
Conversion Ratio between Botox®, Dysport®, and Xeomin®in Clinical Practice. Francesco Scaglione et al
Assay of diffusion of different botulinum neurotoxin type A formulations injected in the mouse leg. Carli L et al
Botulinum toxin: examining duration of effect in facial aesthetic applications. Flynn TC.
Onset and duration of effect of incobotulinumtoxinA, onabotulinumtoxinA, and abobotulinumtoxinA in the treatment of glabellar frown lines: a randomized, double-blind study.Thomas Rappl
New formulation of Botox: complete antibody‐induced treatment failure in cervical dystonia. D Dressler
Antibody-Induced Failure of Botulinum Toxin A Therapy in Cosmetic Indications. DIRK DRESSLER