Resistance Reducing Results: Understanding Resistance to Anti-Wrinkle Injections

Resistance to the effects of botulinum toxin, the active ingredient in anti-wrinkle injections, means that the injections are not as effective as they used to be. 1 This results in needing higher doses or more frequent treatments to achieve the same desired effect. 1 Over time and with repeated treatment, some people can develop complete resistance which means the injections completely stop working. 1

New Zealand consumers can access XEOMIN®, an anti-wrinkle treatment containing purified botulinum toxin which may reduce the risk of developing resistance. 1,2

What is botulinum toxin resistance and why does it matter?

• Resistance to anti-wrinkle toxin therapy is thought to impact 1 in 250 people receiving treatment for aesthetic reasons, however this number is likely underestimated. 1
• Some people may develop resistance to botulinum toxin over time, meaning that consumers may require higher doses or more frequent treatments to achieve the same effect. 1
• Over time and with repeated treatment, some people can develop complete resistance which means the injections stop working. 1
• Resistance stems from the development of antibodies by the body, which attach to and deactivate botulinum toxin, preventing the botulinum toxin from working as intended. 3
• The presence of unnecessary “complexing” proteins and bacterial components in some botulinum toxin products may increase the potential for an immune response in the body. 3
• Specifically, complexing proteins and other bacterial components may encourage the attention of the body’s immune system, falsely recognising the complexing proteins and other bacterial components as harmful together with the active botulinum toxin. This causes the body to produce antibodies to clear the body of all foreign proteins, including the active botulinum toxin. 1
• Naturally, the immune system has a mechanism to “remember” active botulinum toxin and complexing proteins and other bacterial components, and will continue to produce antibodies, resulting in a continued block of the active botulinum toxin. 1
• Resistance can affect the efficacy of botulinum toxin treatments, resulting in reduced or no response to treatment. 1 This may lead to dissatisfaction and frustration among consumers who seek a consistent and optimal outcome.
• Botulinum toxin is not only used for aesthetic purposes and may be prescribed for chronic medical conditions. 4 The development of resistance may lead to suboptimal outcomes for patients who later develop a chronic medical condition that requires BoNT-A treatment. 1

What are the signs of resistance to botulinum toxin?

There are four main signs of resistance to botulinum toxin that patients and their healthcare professionals can look out for. These include:

• Increased dosage requirement: As the body develops antibodies against botulinum toxin, it may take higher doses of the product to achieve the same level of effect. 1 This can increase the cost associated with botulinum toxin treatments.
• Reduced duration of effect: The effects of botulinum toxin usually last for 3 to 6 months, depending on the product and the individual. However, if resistance develops, the effects may wear off sooner and require more frequent injections. 1
• Reduced intensity of effect or partial response: The effects of botulinum toxin may also become less noticeable or pronounced over time, as the body becomes less responsive to the toxin. 1
• No response: In some cases, over time, there may not be any response to treatment at all.

How can healthcare professionals help consumers avoid or overcome resistance?

• Patients should be encouraged to ask their treating healthcare professionals about the risks of treatment, including the potential for developing resistance.
• It is good practice for healthcare professionals to take a comprehensive treatment history, including past botulinum toxin treatment, to evaluate and discuss the risks and benefits of therapy. It is recommended that a thorough discussion of benefits and risks, including the potential for resistance, is undertaken with patients prior to treatment. 1
• It is essential for healthcare professionals to recognise clinical signs of botulinum toxin resistance and make informed decisions on options for management.
• When treating patients using anti-wrinkle injections, the risk of developing resistance is thought to be lower while using the lowest possible dose and avoiding frequent “top-ups”. 1
• One of the options that healthcare professionals can recommend is XEOMIN, a type of botulinum toxin that is free of complexing proteins and has a lower risk of triggering an immune response. 1,4

What makes XEOMIN different to other botulinum toxins when it comes to botulinum toxin resistance?

• There are different types and brands of botulinum toxin products, which all act in the same way, however, may vary in their potency and their level of non-essential proteins such as complexing proteins and other bacterial components. 4
• The ‘father’ of XEOMIN Dr Jürgen Frevert, a biochemist with over 30 years of toxin research, had a desire to create a pure neurotoxin so that patients need only receive the pure active ingredient to achieve desired results. 5
• Over a decade of research produced the first purified botulinum toxin free from complexing proteins. XEOMIN is the first anti- wrinkle toxin injectable that undergoes an additional purification step in the manufacturing process, eliminating complexing proteins leaving only pure active botulinum toxin. 5
• Being free of complexing proteins and other bacterial components is the reason why XEOMIN has a low risk of an immune response leading to botulinum toxin neutralising antibodies, with no known case reports of resistance attributed to XEOMIN when used for aesthetic purposes. 1

What is the difference between botulinum toxin and dermal fillers?

• Botulinum toxin and dermal fillers are both cosmetic injectables that can improve the appearance of the face, but they work in different ways. 2,6
• Botulinum toxin works by relaxing the muscles that cause dynamic wrinkles which occur from muscle movement, such as frown lines, forehead lines, and crow’s feet. 4,7
• Dermal fillers add volume and plumpness to the skin, filling in static wrinkles which occur for many reasons such as thinning skin or loss of elasticity. These wrinkles include nasolabial folds, marionette lines, and lip lines. 7
• Both botulinum toxin and dermal fillers can be used together or separately, depending on the individual needs of a person. 6

How can consumers learn more about XEOMIN?

• Consumers who are interested in XEOMIN or botulinum toxin treatments should consult with a qualified and experienced healthcare professional, who can assess their suitability and expectations, as well as provide personalised advice and care.
• Consumers can refer to the Consumer Medicine Information available on the Medsafe website at https://www.medsafe.govt.nz/Consumers/CMI/x/Xeomin.pdf
• Consumers are encouraged to learn more about XEOMIN at XEOMIN.CO.NZ

References

1. Ho WWS, Albrecht P, Calderon PE, et al. Emerging Trends in Botulinum Neurotoxin A Resistance: An International Multidisciplinary Review and Consensus. Plast Reconstr Surg Glob Open. 2022 Jun 20;10(6):e4407.
2. XEOMIN. Consumer Medicine Information. 11 July 2023
3. Ho WWS, Chan L, Corduff N, et al. Addressing the Real-World Challenges of Immunoresistance to Botulinum Neurotoxin A in Aesthetic Practice: Insights and Recommendations from a Panel Discussion in Hong Kong. Toxins (Basel). 2023 Jul 12;15(7):456.
4. XEOMIN. Healthcare Logistics. Data Sheet. 21 May 2021
5. Kerscher M, Wanitphakdeedecha R, Trindade de Almeida A, Maas C, Frevert J. IncobotulinumtoxinA: A Highly Purified and Precisely Manufactured Botulinum Neurotoxin Type A. J Drugs Dermatol. 2019 Jan 1;18(1):52-57.
6. Sundaram H, Liew S, Signorini M, et al. Global Aesthetics Consensus: Hyaluronic Acid Fillers and Botulinum Toxin Type A-Recommendations for Combined Treatment and Optimizing Outcomes in Diverse Patient Populations. Plast Reconstr Surg. 2016 May;137(5):1410-1423.
7. Peng JH, Peng HP. Cheek wrinkles revisited: Etiological classifications and nonsurgical treatment options. J Cosmet Dermatol. 2023 Jun;22(6):1733-1738.