Understanding Botulinum Toxin Resistance: Causes and Prevention

• Adducts containing botulinum toxin produce antibodies, inducing resistance to antibody production.

• Use the minimum dose for which the drug is effective, and follow the procedure at intervals of 5 to 6 months

Recently, botulinum toxin treatment in the aesthetic field is growing worldwide due to the increase in demand for botulinum toxin and the expansion of indications. In particular, in the Asia-Pacific region, the growth of the related market is expected to accelerate as the income level and the demand for young people are rising.

Accordingly, voices for raising awareness of the problem of botulinum toxin resistance are growing, and experts in related fields have raised an alarm about the safety of botulinum toxin treatment in the aesthetic field. The Aesthetic Committee for the Ethical Use of Neurotoxins, composed of an international multidisciplinary panel of experts, held the International Master Course on Aging Science (IMCAS Asia 2022) in Bangkok, Thailand on the 29th. The committee presented a paper on ‘International Multidisciplinary Review and Consensus on the Latest Trends in Botulinum Toxin Type A Resistance’ at this conference.

Park JeYoung Park, director of Apgujeong Oracle Dermatology, attended this conference as a representative panel of Korea. The next day, Director JeYoung Park conducted a presentation on botulinum toxin resistance and a demonstration to enhance the effect of cosmetic procedures for members of the International Society of Aesthetic Plastic Surgery. I interviewed Director JeYoung Park at the site in Thailand.

- You were invited to participate on Korea's representative panel at the presentation of the research results of 'Botulinum Toxin Resistance of Consumers in the Asia Pacific at the 'IMCAS Asia 2022 MEDIA VISIT'. What are your opinions on the results of this study?

World-class botulinum toxin experts gathered to examine published papers on botulinum toxin resistance in the cosmetic and therapeutic fields and to discuss the best treatment for clinical, ethical, and cosmetic purposes. In addition, we included a consensus on patient treatment, as well as suspicious situations and evaluation of antibody-related botulinum toxin resistance in the cosmetic field. This paper raises the alarm about the significance and gravity of resistance to botulinum toxin.

- What is the underlying cause of botulinum toxin resistance?

The main reason is that antibodies to the neurotoxin component, the main action of botulinum toxin, generate.

- Excessive injection is one of the causes of growing botulinum toxin resistance, but impurities in the botulinum toxin are also known to be the cause. If true, what mechanism raises the resistance?

The higher the cumulative dose of botulinum toxin, the higher probability of developing resistance. A bigger and more influential cause, however, is an unnecessary adduct other than the neurotoxin that causes the main action. A formulation made solely of neurotoxin without additives does not pose a risk of resistance, no matter how high the dose is injected. The adduct induces an immune response in the body like a vaccine, generating the production of antibodies.

- The resistance response to botulinum toxin includes several types of resistant reactions such as second-order non-response, partial second-order reaction, and complete second-order non-response.

Non-response showing no response is divided into primary and secondary. Primary non-response is the absence of response regardless of the antibody due to insufficient dose or the patient's immune status. Secondary non-response is a case in which botulinum toxin is not effective due to antibodies. A partial second reaction indicates the case in which only a minimal reaction appears, while a complete second-order non-response exhibits no reactions.

- Is there a case where the above-listed reactions occur differently for each person? If yes, please explain which people are most likely to have which reaction.

Botulinum toxin may not respond well for a patient with an autoimmune disease, such as myasthenia gravis. The same is true if a patient is taking cholinergic drugs. However, in most cases except for special cases, it is not affected by lifestyle.

- It is also crucial for the patient to be aware of his or her resistance reaction. Is there a way to check the tolerance on their own?

Botulinum toxin resistance may be suspected if the period during which the effect of botulinum toxin lasts is getting shorter than before or if the infusion dose needs to be gradually increased to achieve the same effect.

- What patients should pay special attention to prevent botulinum toxin resistance?

A formulation made exclusively of neurotoxins with no additives is essentail. In addition, patients should receive the appropriate dose at the proper time interbal and from an proficient botulinum toxin specialist.

- What measures should operators make to prevent or reduce resistance to botulinum toxin?

The operator should use the minimum dose at which the drug is effective, keep the procedure period of 5 to 6 months, make a schedule, and use a neurotoxin product without additives. In particular, they should be more careful with patients receiving botulinum toxin for the first time or young patients.