Prof Terry Everitt reports on a lively debate at the 2023 ASCD Symposium, which asked the question: is immunogenic resistance to botulinum toxin treatment real?
The 2023 Australasian Society of Cosmetic Dermatologists (ASCD) Symposium took place in Melbourne on March 24-26. One of the ongoing themes was “challenges”, and the various challenges facing cosmetic practitioners was explored in depth over the three-day educational experience.
The opening plenary session explored various challenges and beliefs with a most exciting debate: is toxin resistance fact or fiction?
The affirmative was presented by Dr Phillip Artemi (Fellow of the Australasian College of Dermatologists), with Dr Stefania Roberts (Fellow of the Australasian College of Phlebology) taking the dissenting side of the topic.
The Debate
Most experienced cosmetic injectors have experienced one (or more) patient(s) who appear to have developed resistance to toxin injections. Many think this is due to the proteins in some products, yet is this the case? Perhaps it could be injector technique, dosage or other possibilities?
Other injectors claim to have had zero non-responders. But what if patients are leaving their clinics due to toxin resistance and not telling them why? Indeed, market research of 1,000 patients, conducted by Metis Healthcare Research, showed that 44% of patients who changed clinics/ injectors did so due to the results not lasting as long or because the injector was using more units to achieve the same result and therefore cost was increasing.
Both speakers had 10 minutes to present their case and a five-minute rebuttal.
The case for toxin resistance
Dr Artemi began the debate basing his affirmative proof of toxin resistance on four points: possible, plausible, provable and preventable.
He presented various definitions (as some terminology appears to be confusing) and several scientific papers exploring differing reasons toxin resistance is real and much more common than realised.
Virtually all therapeutic proteins (biologics) can create ‘anti-drug antibodies’ as an immune response, thus negating the full therapeutic effects of the drug. While most patients respond initially to botulinum toxin, secondary non-responsiveness may be a spectrum of Partial – Moderate – Complete (complete is infrequent).
Ono, Abo and Inco BoNT-A, of course, present a variance of unnecessary complexing proteins and inactive neurotoxin, and the total each patient gets changes – certainly this is a more significant variable over a lifetime, in addition to differences between dosage in aesthetic and medical concerns, with increasing indications of use.
Dr Artemi reports that the studies show no indication of concern with the Inco, only the Ono or Abo BoNT-A use.
The case against toxin resistance
Dr Stefania Roberts presented her case that toxin resistance is fiction based on three factors: incorrect dose, incorrect placement, and not meeting patient expectations.
Dr Roberts contended that neutralising antibodies is a non-event in terms of clinical non-response in day-to-day aesthetic practice; it is an assumption rather than a fact.
She rebutted a paper by Dr Artemi showing the response to antibodies is clinically very low. While accepting neutralising antibodies is found, this does not necessarily correlate to a clinical non-response, she argued. She then shared the findings from a meta-analysis*, which found patients responded to treatment regardless of positive finds for neutralising antibodies.
Dr Roberts conceded that higher non-response is recorded in medical condition indications than aesthetic, yet this is only due to the increased dose of toxin used. While a non-response is possible, it is not the antibodies but rather one’s capacity in some way that is the causation, she said.
Dr Roberts presented ‘real-world experience’ of toxin resistance with short videos of prominent cosmetic injectors. Prof Greg Goodman said he has had some non-responders but this is more likely due to user error;
Dr Ada de Alameda, a dermatologist in Brazil with over 25 years’ experience in toxin injections, said she has had two secondary non-responders – cause not established; Dr Steven Liew, a Sydney plastic surgeon with over 5,000 active injection patients, has had one secondary non-responder eight years post first injection; Dr Patricia Ogilvy, a dermatologist in Munich with 28 years of experience, stated no indication of primary or secondary non-response in all that time.
Dr Michael Kane, a plastic surgeon in New York with over 100,000 patients, said he has had two non-responders (though they were not antibody indicative of non-response). However,
it should be noted that Dr Kane has previously argued that toxin resistance is real. Indeed, in his case for the affirmative, Dr Artemi shared an excerpt from an Inside Aesthetics podcast in which Dr Kane said the following about toxin resistance: “In the past five to 10 years, more and more people are becoming non-responders… It’s not an epidemic and it’s not zero – but the number is getting higher and higher.”
Dr Roberts summarised that non- response is highly unlikely to be caused by BoNT-A and most likely due to practitioner ‘error’. These include toxin dose, placement or not addressing patient expectations, whereby patients report non-response or ‘it did not work’.
The Rebuttals
Dr Artemi came well prepared for a rebuttal with a slide presentation detailing many of the points he thought would be raised (and indeed they were) by Dr Roberts in her presentation.
Although some of the injectors Dr Roberts featured in her presentation admitted to a few non-responders, how many non-responders would this total from all the injectors across the world? Experts they are, but they are giving only their subjective personal opinions, which cannot be objectively verified, Dr Artemi asserted.
As in all cases, one must look at the details of scientific papers, he said, especially methodology and longevity of study follow-up. He emphasised that toxin resistance, rather than practitioner error, is a fact and a growing concern.
Dr Roberts’ rebuttal rebutted Dr Artemi’s rebuttal. She advised that as clinicians we should be cautious in what is provided (doses, placement, expectations), rather than using the possibility of neutralising antibodies as first thought.
The Takeaways
The final result of the debate was left to the individual to decide as no overall audience reaction was undertaken due to time constraints (not surprisingly, the debate went over time).
Both presenters gave insightful information as to their position. While neutralising antibodies exist, they remain relatively low in total number yet are growing. Whatever your opinion, the debate raised significant points on both sides and most certainly renewed interest in those attending the discussion. AMP
*Supplement; not peer-reviewed
