Predictive Modeling of Immunogenicity to Botulinum Toxin A Treatments for Glabellar Lines

BACKGROUND: Botulinum toxin A (BoNT-A), derived from Clostridium botulinum , is widely used in medical and aesthetic treatments. Its clinical application extends from managing chronic conditions like cervical dystonia and migraine to reducing facial wrinkles. Despite its efficacy, a challenge associated with BoNT-A therapy is immunogenicity, where the immune system produces neutralizing antibodies (NAbs) against BoNT-A, reducing its effectiveness over time. This issue is important for patients requiring repeated treatments. The authors compared BoNT-A products, examining the factors influencing NAb development using advanced machine-learning techniques. METHODS: The authors analyzed data from randomized controlled trials involving 5 main BoNT-A products. Trials were selected on the basis of detailed reports of immunogenic responses to these treatments, particularly for glabellar lines. Machine-learning models, including logistic regression, random forest classifiers, and Bayesian logistic regression, were used to assess how treatment specifics and BoNT-A product types affect the development of NAbs. RESULTS: Analysis of 14 studies with 8190 participants revealed that dosage and treatment frequency are key factors influencing the risk of NAb development. Among BoNT-A products, incobotulinumtoxinA shows the lowest, and abobotulinumtoxinA, the highest likelihood of inducing NAbs. The machine-learning and logistic regression findings indicated that treatment planning must consider these variables to minimize immunogenicity. CONCLUSIONS: The study underscores the importance of understanding BoNT-A immunogenicity in clinical practice. By identifying the main predictors of NAb development and differentiating the immunogenic potential of BoNT-A products, the research provides insights for clinicians in optimizing treatment strategies. It highlights the need for careful treatment customization to reduce immunogenic risks, advocating for further research into the mechanisms of BoNT-A immunogenicity.

Rahman E, Carruthers J D A, Rao P, Yu N, Philipp-Dormston W G, and Webb W R. (2025) Predictive Modeling of Immunogenicity to Botulinum Toxin A Treatments for Glabellar Lines. Plast Reconstr Surg 155(4):676e-688e . [article]