Are you a ‘botox’ regular or just about to explore this wonder treatment? Here’s what recent findings on botulinum toxin immunoresistance mean for your aesthetic journey.
In the fast-paced world of aesthetic medicine, botulinum toxin treatments, often touted as the gold standard for smoothing wrinkles and refreshing appearances, have become as ubiquitous as skincare routines. More people are getting the neurotoxin, with many more younger patients getting the anti-wrinkle, skin smoothening injections compared to decades ago. With over nine million botulinum toxin aesthetic procedures performed globally in 2022, it’s clear that the allure of quick, non-invasive enhancements is here to stay. But beneath the surface of this cosmetic phenomenon lies a complex issue that’s gaining attention: botulinum toxin immunoresistance.
Botulinum Toxin 101: The Science of Smooth
Botulinum toxin, derived from the bacterium Clostridium botulinum, works by temporarily paralyzing muscles through the inhibition of nerve signals. Its applications range from cosmetic wrinkle reduction to therapeutic uses such as treating chronic migraines and hyperhidrosis. However, the effectiveness of this wonder treatment hinges on the body’s acceptance of the toxin—and this is where immunoresistance comes into play.
All commercially available botulinum toxin formulations are derived from the same bacterial source, but differences in manufacturing processes can lead to variations in purity. Impurities, such as inactive neurotoxin proteins and bacterial remnants, can apparently heighten the risk of an immune response. This is where the concept of pure+ formulations—products designed to isolate only the active neurotoxin—comes into the conversation. Such formulations aim to reduce the likelihood of neutralizing antibody formation, ensuring treatments remain effective over time.
This was the topic of the DASIL/Merz ASCEND Council Meeting convened at the 12th Dermatology, Aesthetics, and Surgery International League (DASIL) World Congress in Hanoi, Vietnam, attended by hundreds of doctors from around the world. The panel was moderated by brilliant doctor Dr. Niamh Corduff, a plastic surgeon and Clinical Director of the Cosmetic Refinement Clinic in Australia, and was composed of Dr. Pacifico Calderon, Dr. Michael Martin, Dr. Je-young Park, Dr. Siew Tuck Wah, Dr. Tseng Fang-Wen and Dr. Vasanop Vachiramon.
“If you develop resistance due to aesthetic treatments, it might render the toxin ineffective when you need it most,” said Dr. Corduff. This can result in patients losing access to one of the most effective treatments available, potentially leading to invasive surgeries or less effective alternatives.
The ASCEND panel’s efforts are grounded in rigorous research and collaboration, as evidenced by their latest study, which they also presented: “Real-world Implications of Botulinum Neurotoxin A Immunoresistance for Consumers and Aesthetic Practitioners.” At the event, Merz Aesthetics, the world’s largest dedicated medical aesthetics business, also announced the findings of two Asia Pacific-wide surveys into botulinum toxin immunoresistance. The international multidisciplinary panel introduced the survey findings during its discussion of best practices and ethical considerations surrounding botulinum neurotoxin-A (BoNT-A) use for aesthetic and therapeutic applications.
The Immunoresistance Issue: Why Your Botulinum Toxin Might Stop Working
Immunoresistance occurs when the body’s immune system recognizes botulinum toxin as a foreign entity and produces neutralizing antibodies to counteract it. Symptoms include “dose creep” (needing higher doses for the same result) and “interval creep” (requiring more frequent treatments). Factors like impurities in formulations, high dosages, or frequent injections can contribute to this response. This resistance, often triggered by impurities in the toxin formulation or treatment-related factors like high doses or frequent injections, can render subsequent treatments less effective or entirely ineffective.
Dr. Niamh Corduff has been a leading voice in addressing the challenges of botulinum toxin treatments. With decades of experience in both surgical and non-surgical rejuvenation, she brings a multidisciplinary perspective to understanding immunoresistance. As Chair of the ASCEND panel, she has been pivotal in advocating for patient education and safer practices in aesthetic medicine.
“The bottom line is, we’re trying to do the right thing for our patients,” said Dr. Corduff. “If it stops working, what happens when you need it for a medical condition? It’s well known that people can become immune to it, and in high-dose treatments, the incidence can be as high as 27%.”
Merz Aesthetics gave us a helpful analogy, which is caffeine tolerance: regular coffee drinkers may find that the effects of caffeine diminish over time, requiring them to consume more for the same boost. Similarly, repeated or high-dose botulinum toxin treatments can lead to diminished efficacy.
The Real-Life Impact
The risks of becoming immunoresistant to botulinum toxin extend far beyond aesthetic concerns. For individuals who rely on botulinum toxin to manage medical conditions, resistance can have profound consequences. Botulinum toxin is widely used for therapeutic purposes, including chronic migraines, offering relief to patients who suffer from debilitating headaches; spasticity management, helping children and adults with conditions like cerebral palsy or post-stroke spasticity regain mobility and comfort; bladder dysfunction, providing relief for conditions like overactive bladder; dystonia and tremors, alleviating symptoms in patients with neurological disorders that cause involuntary muscle contractions; and more.
“If you develop resistance due to aesthetic treatments, it might render the toxin ineffective when you need it most,” said Dr. Corduff. This can result in patients losing access to one of the most effective treatments available, potentially leading to invasive surgeries or less effective alternatives.
“[Complexing proteins in impure formulations] have no role. No pharmacological role, whatsoever. The only reason they are there is [because] that bacteria produces these proteins when creating the toxin. Some companies simply don’t remove the complexing proteins, which bacteria produce to protect the toxin. But in practice, these proteins are irrelevant. Once you inject the toxin, you don’t need them. They are unnecessary, full stop.” —Prof. Michael Martin, retired Professor of Immunology, Justus Liebig University, Germany
“We are already seeing patients where it slowly stops working,” Dr. Corduff noted. “Clinically, they need it more often and in higher doses just to get the same effect. This is linked to expanding off-label treatments, where doses are creeping close to those used in medical indications.”
For many consumers, the idea that their botulinum toxin treatments could lose efficacy is both surprising and frustrating. The study, which was conducted across Asia-Pacific, revealed that 81% of respondents reported declining results from their treatments. This number has risen steadily from 69% in 2018. Feelings of anxiety, sadness, and frustration are common among those affected.
While 52% of surveyed consumers attribute declining efficacy to immunoresistance, many take counterproductive measures such as increasing dosages or shortening treatment intervals. Unfortunately, these actions often exacerbate the issue, creating a vicious cycle.
The consequences extend beyond aesthetics. Botulinum toxin is also used to manage medical conditions such as migraines and spasticity. If a patient develops resistance due to aesthetic treatments, they could lose access to a crucial therapeutic tool.
The Science Behind Purity
During the panel discussion, The Beauty Edit posed a critical question that delved into the heart of formulation science: “You have discussed the value of pure formulations extensively. What purpose do impurities or complexing proteins serve anyway in non-pure formulations?” Dr. Niamh Corduff was thrilled, “What an excellent question!”
Prof. Michael Martin, a retired Professor of Immunology from Justus Liebig University in Germany, offered a direct and unequivocal response: “They have no role. No pharmacological role, whatsoever. The only reason they are there is [because] that bacteria produces these proteins when creating the toxin. All the brands on the market rely on bacteria to produce their toxins—these are bi products purified from this culture. Some companies simply don’t remove the complexing proteins, which bacteria produce to protect the toxin. But in practice, these proteins are irrelevant. Once you inject the toxin, you don’t need them. They are unnecessary, full stop. And if anyone claims otherwise, it’s just not true.”
Dr. Corduff expanded on the point, dismissing outdated assumptions: “There’s a historical context to this. About 10 or 15 years ago, we believed those proteins were essential to stabilize the neurotoxin. But now we know that’s [not true]. To be effective, you only need the tiny active component in the middle. The rest? Forget it.”
Their insights underscored the evolving understanding of botulinum toxin formulations, highlighting the importance of scientific rigor and transparency in product development.
Merz Aesthetics’ Anti-Wrinkle Injectable Treatment makes this pure formulation, which has been available in the Philippines for over a decade.
How to Avoid Immunoresistance
Preventing immunoresistance begins with informed choices. “Medical practitioners need to counsel patients carefully,” said Dr. Corduff. “We need to rethink what we’re doing to create a better-informed patient base and more coordinated care.”
Starting with a pure+ formulation or switching to one at the first sign of resistance can reduce the risk of neutralizing antibody formation. Best practices include using the lowest effective dose, spacing out treatments as much as possible, and avoiding unnecessary top-ups.
Consumers should also engage in open conversations with their providers about the formulations being used and their long-term treatment plans. Asking questions like, “What brand are you using?” and “How pure is the formulation?” can help ensure better outcomes.
Why Doctors Play a Critical Role
Doctors and aesthetic practitioners have a responsibility to educate patients about the risks of immunoresistance. Survey findings indicate that while 84% of doctors recognize brand differences in formulation and purity, many fail to communicate these nuances effectively to patients.
The adoption of standardized screening protocols and management frameworks is essential. Initial consultations should set realistic expectations, and informed consent processes should include discussions about the potential for immunoresistance. Transparency builds trust and helps patients make better decisions.
The Future of Neurotoxins
Ongoing research and education initiatives, such as those led by the ASCEND panel (Aesthetic Council for Ethical use of Neurotoxin Delivery), are bringing much-needed attention to the issue of immunoresistance. Their latest study, for instance, calls for heightened awareness, improved guidelines, and regulatory oversight to ensure the safe use of botulinum toxin.
Case studies, like that of Dr. Siew Tuck Wah’s Singapore-based patient who regained responsiveness to botulinum toxin after years of resistance, offer hope. However, prevention remains the best strategy. Starting with a pure+ formulation from the outset is often the most prudent approach.
The Beauty Edit Takeaway
In a landscape where the quest for beauty often overshadows the science, understanding the complexities of botulinum toxin immunoresistance empowers consumers to make smarter, safer choices. When choosing a provider or a product, knowledge is your best defense against diminishing results. True beauty isn’t just about looking good—it’s about being informed.
+Pure refers to the absence of complexing proteins, inactive neurotoxin, flagellin and bacterial DNA contaminants.