Botox resistance

Botox resistance is when the immune system of a patient who has undergone botulinum treatment develops antibodies that neutralise the botulinum toxin. These antibodies attach to the botulinum toxin molecule before the molecule has a chance to affect the target muscle. The rapid action of the immune system prevents the botulinum toxin from working as intended. When botulinum toxin is blocked, the treatment outcome is also modest, if not non-existent.

Have I become resistant to botox?
Why does botox not work?
Botox stopped working after just one and a half months. In the past, the result has remained good for at least three months. What is the problem?

These are questions that surgeon Ville Männistö, a specialist in aesthetic medicine, gets to answer a few times a year, both on Instagram and in his consulting room. In addition to his work with patients, Ville is working on his doctoral thesis, which deals, among other things, with the treatment of bite physiological disorders with botulinum.

This blog article was written based on questions from patients and comments from Ville.

What is botox resistance?

Botox resistance is a very rare condition. Almost always, so-called resistance is revealed by further investigation to be something other than genuine Botox resistance. However, resistance is an interesting phenomenon and therefore deserves some attention. (Ville Männistö, surgeon)

Botox resistance is a rare condition. It is possible, for example, in patients who have been treated with botulinum toxin for years at too short intervals. Metabolism also plays a role: some people's bodies metabolise neurotoxins at an abnormally fast and high rate. Some studies suggest that vaccines may also affect the effectiveness of botulinum toxins.

botox resistance ville männistö nefertiti lift

Why does botox not work?

True botulinum toxin resistance is rarely encountered by the professional. However, as the social media debate on the subject has become more lively, the issue of resistance has been on the lips of many, including here in Finland.

US doctors estimate that more patients are coming to their surgeries with suspected botulinum toxin resistance. In reality, only 0.01% of patients have botox immunity. Usually, there is something else at the root of a decrease in treatment efficacy. (Ville Männistö)

Behind the perceptions of resistance, the doctors who participated in the debate have found variables such as:

  • Incorrect dosage. Too low doses of Botox produce poor - or at least short-lived - results.
  • Wrong injection site. Every person's face is different. Finding the right injection sites requires a very strong knowledge of facial anatomy. Even the right dose size will not save the day if the dose is injected in the wrong place. A few millimetres off the mark can make all the difference.
  • Ineffectiveness of botulinum toxin. This is usually due to improper storage of the substance. There are also some counterfeits or other illegal products on the market, the composition of which is uncertain.
  • Skin ageing. The amount of collagen, elastin and hyaluronic acid decreases with age. Botox prevents and fades age-related changes in muscle activity. It does not affect the production of collagen, elastin and hyaluronic acid. The older you get, the more holistic your skin's condition and appearance becomes.

It is common, for example, for frown lines to be completely hidden by botox up to the age of 45. Then the day comes when botox alone no longer evens out the onion line. This is a normal phenomenon of ageing. There are two options: you can be satisfied with the situation or you can supplement the botox treatment result with a small amount of filler.

Avoid pitfalls

Don't save in the wrong place

In Finland, botulinum treatments are almost always priced by region. It is possible that the practitioner treats one, two or even three areas with too low a dose of botulinum, either for reasons of economy or precaution. Consumers should be vigilant when they come across offers of botox. Sometimes - but not always - the price of the offer is hidden behind a very low dosage. Unless for some reason the provider enters the trade name and unit quantities of the botulinum toxin in the Kanta service, the details of the treatment remain obscure.

Value experience and qualifications

Accuracy and diligence are a matter of honour for an ethical healthcare professional. However, one should not be too careful when administering botox. The longer the experience of the practitioner, the more solid his or her knowledge of anatomy and dosage. It pays to stick with a good botox practitioner.

Trust your pharmacy goods and their proper storage

Botulinum preparations are prescription-only medicines and can only be obtained from a pharmacy. Botulinum toxin purchased from a Finnish pharmacy is correctly manufactured and stored at every stage of the production and transport chain. When the medicine is stored according to the instructions, including in the aesthetic clinic, the medicine works properly. Botulinum toxin purchased from a non-Finnish pharmacy may be genuine (but not always), but if it has been stored incorrectly, there is no guarantee of efficacy.

Don't build your skincare regime on botox alone

Botox treatment is not a substitute for skin care. If you want to enjoy good Botox results for years and decades to come, your skin should be treated. If your skin care routine at home is not in order, you should get it right by the age of 35 at the latest. It's worth starting to stimulate collagen, elastin and hyaluronic acid regeneration from your thirties onwards. A once-yearly series of microneedling treatments is an excellent support to botulinum treatments. The microneedling treatment extends to all areas of the face, including the forehead, where it provides excellent support for regular botulinum treatments.

The most enlightened consumers are already waiting for the latest botulinum innovation (daxibotulinumtoxinA-lanm) to arrive in Europe from the US. This new type of botulinum toxin may also solve many of the problems associated with botulinum immunity.

Genuine and real botox resistance

Botox resistance is a rare, yet real phenomenon. As it has only been discovered on a larger scale in recent years, there is still no comprehensive scientific research data. However, the scarce scientific research and professional reports suggest some risk factors:

Too frequent botulinum treatments

You should always leave at least three months between Botox treatments. The risk of Botox immunity is likely to increase if the treatment is given at too short an interval over a period of years.

Too much botox

Too cautious a dose of botulinum toxin will give a poor result. On the other hand, the substance should not be overused. The high total amount of botulinum toxin injected over the years may be associated with botulinum immunity. Although Botox treatment is quick and easy, the individual dosage of the drug requires a lot of skill and constant brain work, even passion, on the part of the practitioner.

The professional's task is to find the lowest possible dose of Botox to achieve the maximum effect, says Ville Männistö.

Non-toxic proteins in the preparation

Botulinum toxin is a protein wrapped in a shell of non-toxic proteins. The non-toxic proteins in the drug increase the stability of the product, but in some patients these very important additional proteins may stimulate the formation of antibodies.

Research

Neutralizing antibodies to botulinum neurotoxin type A in aesthetic medicine: five case reports (Torres, Hamilton et al. 2013)

Finnish summary

The study deals with the formation of antibodies that neutralise botulinum toxin A in aesthetic medicine and the failure of treatment caused by antibodies. Here is a summary of five patient cases in which secondary treatment failed due to neutralising antibodies.

Case 1: Dr Torres

  • Patient: 55-year-old woman
  • First treatment: September 2011, 33 U of onabotulin toxin A (Vistabel®) in the upper third of the face.
  • Results: no response to the first treatment. In October 2011, switch to 80 Speywood U abobotulinitoxin A (Dysport®). This produced a mild response that lasted three months. Neutralising antibodies were positive.

Case 2: Dr Hamilton

  • Patient: 54-year-old woman
  • First treatment: April 2009, 50 Speywood U abobotulinitoxin A (Dysport®) on glabella, 20 U frontalis muscle, 50 U orbicularis oculi muscle, 50 U jawline.
  • Results: in May 2010, treatment was not working as well as before. In December 2010, a switch to onabotulinitoxin A (BOTOX®) was made, but the effect was limited. Follow-up treatments with abobotulinitoxin A (Dysport®) and incobotulinitoxin A (Xeomin®) had no effect. The patient was positive for antibodies.

Case 3: Dr Sanches

  • Patient: 41-year-old woman
  • First treatment: 2006, 100 U onabotulin toxin A (BOTOX®) for hyperhidrosis, duration 5 months.
  • Results: 2009 and 2010 treatments lasted 2-3 months. 2011-2012 500 U abobotulinitoxin A (Dysport®) produced an effect that lasted only 1.5 months. The patient was antibody positive.

Case 4: Dr Gubanova

  • Patient: 43-year-old woman
  • First treatment: 2004, a total of 1,000 U of abobotulinitoxin A (Dysport®) over eight injections.
  • RESULTS: For the first 3 years, the effect lasted 6-8 months. After 2007, the treatment effect lasted only 3 months. The patient had high levels of neutralising antibodies.

Case 5: Dr Reshetnikova

  • Patient: 38-year-old man
  • First treatment: 2010, 120 U abobotulinitoxin A (Dysport®) in frontalis, corrugator and procerus muscles, effect lasted 6 months.
  • Results: 2011 treatment with 200 U lasted 2 months. 2012 treatment with 250 U had no effect. The patient had high antibody levels.

Summary

Research shows that the formation of neutralising antibodies can occur even at low doses of botulinum toxin A in aesthetic use, which can lead to treatment failure. To minimise the risk of developing neutralising antibodies, it is recommended to use the lowest possible effective doses, avoid additional injections and wait at least 3 months between treatments.

 

Immunogenicity Associated with Botulinum Toxin Treatment (Bellows, Jankovic 2019)

Finnish summary

The study addresses the immunogenicity associated with botulinum toxin treatment and its impact on treatment efficacy. Botulinum toxin (BoNT) is used to treat a wide range of neurological, medical and cosmetic conditions. Two serotypes, type A (BoNT-A) and type B (BoNT-B), are in clinical use. Although they are considered safe and effective, their use is rarely associated with antibody formation, which may reduce or prevent their therapeutic effect.

Key observations:

1. Immunogenicity

- Short dosing intervals and high doses increase the risk of antibody formation.

- Characteristics of some BoNT serotypes, such as composition, preparation and storage, may affect immunogenicity.

- In new formulations with purified core neurotoxin without additional proteins, immunogenicity may be lower.

2. Detection of antibodies

- Several tests for antibody detection (ELISA and mouse-based biological tests) are available for research use.

- Structural tests are sensitive in detecting antibodies, but they cannot distinguish between neutralising and non-neutralising antibodies.

3. Primary and secondary treatment resistance:

- Primary treatment resistance (PNR) refers to a situation where patients do not benefit from BoNT from the first injection.

- Secondary treatment resistance (SNR) occurs when patients initially benefit from an injection but lose this benefit in subsequent rounds of treatment.

4. Patient cases and risk factors:

- Studies have shown that in some patients it can take a long time for antibodies to build up.

- Certain groups of patients, such as those with a history of botulism or vaccination, may be more susceptible to antibody formation.

- Tetanus vaccines have been suggested to affect BoNT antibody formation, but this has not been supported in animal studies.

5. The structure and functioning of the BoNT:

- BoNT consists of nuclear neurotoxins and non-toxic accessory proteins (NAPs).

- BoNT-A and BoNT-B affect different SNARE proteins, which interferes with the release of acetylcholine into the synaptic cleft.

6. Clinical tests and practical recommendations:

- Clinical tests, such as the unilateral eyebrow injection test (UBI), can be used to detect SNR.

- Patients should wait at least 3 months between injections to reduce the risk of antibody formation.

Conclusions:

Botulinum toxin is a safe and effective treatment option for many neurological and non-neurological conditions. Although the formation of neutralising antibodies is a concern, several strategies can reduce the development of immunoresistance, such as using products with a low protein load, avoiding adjuvants, maintaining safe injection intervals and using the lowest possible dose that produces an optimal clinical response.

 

Am I immune to botox?

Botox resistance is relatively new, so there are no tests on the commercial market yet. An American study on the subject is currently underway. These have already used scientific methods and tests to investigate the subject. More information is therefore on the way.

We still lack easy testing methods, but a diagnosis can still be made. It is always done by a professional. Diagnosis is not a cakewalk, but requires medical expertise, long experience and, above all, time. Almost always, the apparent botox immunity is due to something other than real antibodies.

botox resistance

If you are wondering, you should

  • examine their own patient records - mainly the botulinum preparations used and the quantities injected
  • examine their own before-and-after pictures from over the years
  • try alternative botulinum preparations, known as "botox".
  • go to an experienced service provider to find solutions

Can botox resistance be treated?

TIME HEALS ALL WOUNDS...

If a healthcare professional qualified in botulinum treatments diagnoses botox resistance, the game is not yet lost. The formation of antibodies that neutralise botulinum toxin will diminish over time. A four to five year break from botulinum treatment is likely to restore the body to its "factory settings", after which treatment can be resumed if necessary.

... BUT WHEN I CAN'T AND DON'T WANT TO WAIT

If waiting doesn't work, other solutions have been developed.

A WASHOUT treatment protocol for a botulinum-resistant patient, based on current research and the everyday observations of professionals, might look like the following:

  • 6-12 months break from botulinum treatments. During this break, the focus is on collagen stimulation treatments (microneedling, skin boosters, mesotherapy, Profhilo).
  • Changing the botulinum toxin ("brand") to one that does not stimulate antibody formation.
  • The new botulinum preparation will be used for a two-year WASHOUT or "cleansing" period, during which treatment intervals will be kept longer than normal.

Zinc may improve the efficacy of botulinum toxin or at least prolong the duration of the treatment. There is still a lack of research data on this, but zinc supplementation is still worth considering; there is no real harm from temporary zinc supplementation. Start taking zinc (50 mg/day) five days before your botox treatment and continue to take zinc on the day of treatment.

Summary

  • Botulinum treatment is the most effective, safest and most affordable way to prevent and correct wrinkles and other age-related changes.
  • Botulinum toxin immunity (resistance) is a very rare phenomenon. Usually it is not resistance but incorrect dosing, wrong injection site or accelerated skin ageing.
  • To prevent Botox resistance, it’s important to maintain adequate intervals between treatments. Choose an experienced professional who has a deep understanding of facial anatomy and botulinum toxin administration. If possible, try different brands of botulinum toxin to find the best fit for you.
  • When you find a trusted professional, stick with them. A strong client-provider relationship ensures timely responses to any concerns, including potential resistance issues.
  • Genuine botox resistance is helped by time and/or the BOTOX WASHOUT treatment protocol.

Botox in brief

Botulinum treatment effectively prevents and corrects wrinkles and other age-related changes, especially on the upper face. The treatment is carried out with a prescription medicine sold in pharmacies under a variety of brand names:

  • Botox
  • Vistabel
  • Dysport
  • Azzalure
  • Bocouture
  • Xeomin

The best known of the above trade names is Botox, and the trade name Botox has become a generic term for all types of botulinum treatments. We are therefore talking about Botox treatments even if the procedure is carried out with, for example, Xeomin or Dysport.

Botulinum treatment is a classic. Medical botulinum treatments have been performed since the 1970s and aesthetic ones for more than three decades.

The safety profile of botulinum toxin treatment is robust, and with a history of almost 50 years of use, there is a wealth of long-term research on the procedure.

Botulinum treatment always gives temporary results. If you want to maintain the results, you should repeat the treatment every 3-6 months.

Customer feedback

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*Respondents to customer satisfaction surveys in 2024 (n = 694).

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