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There are a several myths and misconceptions which have risen through the population of unregulated, non peer-reviewed information. Unfortunately, it tends to be this miss information which is readily available in the public domain. There have been several studies carried out in high impact journals which have aimed to lay these myths to rest.
The myth that, ‘Different products yield different results’ has been thoroughly investigated(1). It is important to pay attention to the well designed, randomised studies which have compared Botulinum toxin type A (BTX-A) in ‘routine’ clinical settings.
The conclusion drawn from the evidence shows there is no compelling evidence of a superior efficacy of Botox compared with Azzalure.
However, when the doses are not equivalent, the results are not equivalent for clear and obvious reasons: high quantities of BTX were injected(1).
Current brands:
Botulinum toxin (BTX) has been used since the 1980s. There are eight subtypes available (A,B,C1,C2,D,E,F and G). Botulinum toxin type A (BTX-A) and type B (BTX-B) are the most commercially available (2). BTX-A is the subtype used in clinical practice and within this there are several brands in the market today. Despite all the brands using BTX-A they differ in their individual strains. Currently there are three commonly used formulations of BTX. Namely; onabotulinum toxin A (Botox or Vistabel (Allergen, Irvine, CA, USA), incobotulinum toxin A (Xeomin or Bocouture), and abobotulinum toxin A (Dysport or Azzalure)(3).
In simple terms, the manufactures of BTX produce their products as a 150 to 900 kDa protein. This protein has a primary active component (150 kDa) which, once cleaved into a light and heavy chains gives the toxin the ability to exert its effect. This protein includes complexing proteins and one of the primary differences between BTX formulations is the presence or absence of these complexing proteins.
How can we compare the brands?
Each producer claims there to be factors that distinguish their product from their competitors. Typically the factors they compare include: dose potency and/or equivalency(4), the onset of action(5), duration of action (6), local diffusion of the toxin (7,8), side effect profile(9), and differences in immunogenicity.
In 2017, the Eight Key Clinical Postulates were formulated as a guide for the aesthetic practitioner to help understand the pharmacodynamics of BTX-A and to compare the different toxins. These have now been updated and are as follows(10):
All type A toxins act identically
The mathematical relationship between toxin and receptor is the basis of efficacy, and clinical efficacy is influenced by molecular potency and patient attributes including muscle mass, gender, age and ethnicity.
Efficacy, onset, and duration are functions of ‘molecular potency’ defined as the number of active 150kDa molecules available for binding.
‘molecular potency’ is difficult to objectively quantify for commercially available toxins.
Up to a point, increased molecular potency decreases time to onset and increases duration of effect and the ‘molecular potency quotient’ is a construct for comparing molecular potency commercial cost.
The area of a toxin injection is dependent upon molecular potency, diffusion (passive), and spread (active).
Differing reconstitution volumes
Increased number of injection sites can affect spread, onset, and duration of effect.
The outcome of the controlled trials and evidence in journals state that the different formulations of BTX-A are not interchangeable based on dose units or, potentially, immunogenicity. This is in part because of the inappropriate dose comparisons (as I mentioned above) and due to the marketing campaigns. As a consequence the existing evidence suggests that experienced practitioners should achieve equivalent results regardless of BTX-A formulation(1).
There are several variables that lead to patient satisfaction with BTX treatment. One key area is the duration of effect. This factor influences re-treatment intervals as well as affecting cost and convenience to the patient(11). One review(11) showed on average patients can expect treatments to last ≥3 months with many reaching 4-5 months. Factors affecting this included the area treated, the dose and the formulation. Other areas which could also contribute, but were not mentioned, range from the patient sex, repeated treatments, baseline rhytid severity and age. It is common that those who have had repeated treatments with BTX have longer duration of effect. Azzalure as a brand has also been reported to have a faster onset time.
A large Cochrane systematic review(12), assessed the effects of all the commercially available BTX-A products in the treatment for any type of facial wrinkles. Prior to this there had be no systematic review conducted on the effectiveness and safety of BTX-A in cosmetic procedures. This large systematic review found that the formulations of BTX-A tested appeared to be similarly effective in short-term assessment. The longer-term effects of treatment are still unclear, and this applies to both efficacy and adverse effects.
Product Diffusion by Brand:
Azzalure has a small molecular structure compared with BTX. This means that typically Azzalure is thought to have a greater range of diffusion for a given volume(13). One study of 20 patients showed that when injected for hyperhidrosis of the face with half 0.06cc of BTX and half with 0.06cc of Azzalure, there was a larger area of anhidrosis produced by Azzalure(14). This could infer that a patient may require more injections with BTX to produce the same affect with less Azzalure.
Overall, it comes down to the skill and experience of the injector as Azzalure has a higher risk of spread to nearby muscles outside of the target area(15). The area of effect of a toxin is compared by diffusion, which is the same for all toxins, and spread which we control and, ultimately, with the others being equal, molecular potency. The spread of the toxin itself will influence efficacy, onset, and duration of effect and can be maximized by optimizing reconstitution volume and increasing the number of injection sites.
The negatives impact of Azzalure diffusing in the tissues more is that it is less accurate. When requiring delicate accuracy in treating areas such as eyebrow lifts, there can be a higher risk when using Azzalure of spread to other areas which might cause a negative outcome from the treatment. When treating hyperhidrosis, the increased diffusion associated with Azzalure can be an advantage.
It is easy to get side tracked and taken in by the marketing, hearsay and unfounded claims about each of the different formulations of BTX. Research has attempted to demonstrate the differences in efficacy of the BTX-A products based on inherent differences in the composition and pharmacological behaviours of the toxins themselves. Various clinical studies have been designed to compare the toxins between patients, however ended up producing a heterogeneous pool of results due to the challenge of controlling the many variables. When attempting to compare a toxin’s efficacy or potency, it is the time to onset and longevity of effect which are investigated. Both of which the mechanisms are still being brought to light.
The overriding outcome of the studies is that the differences are minimal and all have the same risks. The core difference in patient outcomes and satisfaction comes from the skill and experience of the practitioner carrying out the treatment. This highlights the importance to get treatment from a fully qualified and experienced medical professional.
There is still much work needed on intra-patient studies to further delineate the three established toxins and compare the new ones on the market.
References:
1- Dover, J., Monheit, G., Greener, M. and Pickett, A., 2018. Botulinum Toxin in Aesthetic Medicine: Myths and Realities. Dermatologic Surgery, 44(2), pp.249-260.
2- Berry, M. and Stanek, J., 2012. Botulinum neurotoxin A: A review. Journal of Plastic, Reconstructive & Aesthetic Surgery, 65(10), pp.1283-1291.
3- Bonaparte, J., Ellis, D., Quinn, J., Ansari, M., Rabski, J. and Kilty, S., 2013. A comparative assessment of three formulations of botulinum toxin A for facial rhytides: a systematic review and meta-analyses. Systematic Reviews, 2(1).
4- DeBoulle, Glogau, Steven Fagien and Sommer, 2010. Treating glabellar lines with botulinum toxin type A-hemagglutinin complex: A review of the science, the clinical data, and patient satisfaction. Clinical Interventions in Aging, p.101.
5- Schlessinger, J., Monheit, G., Kane, M. and Mendelsohn, N., 2011. Time to Onset of Response of AbobotulinumtoxinA in the Treatment of Glabellar Lines: A Subset Analysis of Phase 3 Clinical Trials of a New Botulinum Toxin Type A. Dermatologic Surgery, 37(10), pp.1434-1442.
6- Rzany, B., Ascher, B. and Monheit, G., 2010. Treatment of glabellar lines with botulinum toxin type A (Speywood Unit): a clinical overview. Journal of the European Academy of Dermatology and Venereology, 24, pp.1-14.
7- Cliff, S., Judodihardjo, H. and Eltringham, E., 2008. Different formulations of botulinum toxin type A have different migration characteristics: a double-blind, randomized study. Journal of Cosmetic Dermatology, 7(1), pp.50-54.
8- Almeida, A. and Boulle, K., 2007. Diffusion characteristics of botulinum neurotoxin products and their clinical significance in cosmetic applications. Journal of Cosmetic and Laser Therapy, 9(sup1), pp.17-22.
9- Stephan, S. and Wang, T., 2011. Botulinum Toxin: Clinical Techniques, Applications, and Complications. Facial Plastic Surgery, 27(06), pp.529-539.
10- Nestor, M., Arnold, D. and Fischer, D., 2020. The mechanisms of action and use of botulinum neurotoxin type A in aesthetics: Key Clinical Postulates II. Journal of Cosmetic Dermatology, 19(11), pp.2785-2804
11- Flynn, T., 2010. Botulinum Toxin. American Journal of Clinical Dermatology, 11(3), pp.183-199.
12- Camargo, C., Xia, J., Costa, C., Gemperli, R., Tatini, M., Bulsara, M. and Riera, R., 2021. Botulinum toxin type A for facial wrinkles. Cochrane Database of Systematic Reviews, 2021(7).
13- Janes, L., Connor, L., Moradi, A. and Alghoul, M., 2021. Current Use of Cosmetic Toxins to Improve Facial Aesthetics. Plastic & Reconstructive Surgery, 147(4), pp.644e-657e.
14- Trindade de Almeida, A., Marques, e., de Almeida, J., Cunha, T. and Boraso, r., 2007. Pilot Study Comparing the Diffusion of Two Formulations of Botulinum Toxin Type A in Patients with Forehead Hyperhidrosis. Dermatologic Surgery, 33(s1), pp.S37-S43.
15- Dr Aesthetica. 2021. Azzalure Vs. BOTOX®: Which one Is Best For You. [online] Available at: <https://draesthetica.co.uk/azzalure-vs-botox-which-one-is-best-for-you/#:~:text=Botox%20has%20a%20bigger%20molecular,muscles%20outside%20the%20target%20area.> [Accessed 10 November 2021].
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