Emerging Trends in Botulinum Neurotoxin A Resistance: An International Multidisciplinary Review and Consensus

Abstract

Botulinum neurotoxin A (BoNT-A) injection is the most widely performed aesthetic procedure and a first-line therapeutic option for various medical conditions. The potential for BoNT-A immunoresistance and secondary nonresponse related to neutralizing antibody (NAb) formation warrants attention as the range of BoNT-A aesthetic applications continues to expand.

Methods: An international multidisciplinary panel reviewed published evidence on BoNT-A immunoresistance in aesthetic and therapeutic applications and discussed best practices integrating clinical, ethical, and aesthetic considerations. Consensus statements relating to awareness, assessment, and management of the risk of NAb-related secondary nonresponse in aesthetic practice were developed.

Results: There was a consensus that, as doses used in aesthetic practice become like those in therapeutics, rates of NAb formation may be expected to increase. However, the true extent of NAb formation in aesthetics is likely underestimated due to limitations of published evidence and variability in treatment patterns of aesthetic patients. Since BoNT-A therapy is often lifelong, practitioners need to recognize immunogenicity as a potential complication that might affect future therapeutic use and strive to minimize modifiable risk factors. The selection and use of a BoNT-A product with the least immunogenic potential from the beginning may thus be advantageous, especially when treatment with high doses is planned.

Conclusions: In view of current trends in BoNT-A aesthetic use, it is essential for practitioners to conduct thorough clinical assessments, inform patients of treatment risks, and develop BoNT-A treatment plans to minimize immunogenicity. This can help preserve the option of continued or future BoNT-A treatment with satisfactory outcomes.

Fig. 1.

BoNT-A treatment from the immunological perspective. A, Dangerous + foreign? Two key decisions controlling the immune response to biologics. The first decision involves DCs that determine whether or not a particle (eg, a microbe) is likely to be “dangerous.” DCs can recognize microbial surface molecules (eg, flagellin) as “danger signals.” Upon recognition of microbial danger signals, DCs will be activated and phagocytose the particle bearing the danger signal. Subsequently, these activated DCs migrate to lymph nodes and become professional APCs. The second decision involves naive T-helper cells that determine whether a particle is self or foreign. Upon encountering foreign antigen peptides presented by APCs along with co-stimulatory signals, naive T-helper cells become activated and undergo clonal expansion, leading to activation and clonal expansion of antigen-specific B cells. These mature into plasma cells that produce antibodies specific to the antigen that triggered the immune response. B, Development of BoNT-A neutralizing antibodies. C, Composition of FDA-approved BoNT-A formulations. Figure credit: Michael Martin.

Fig. 2.

Patient journey. A, Patient archetypes in aesthetic vs medical practice. B, Hypothetical case example illustrating the potential implications of aesthetic BoNT-A treatment patterns for later therapeutic use in a patient.

Fig. 3.

Key treatment considerations for BoNT-A use in aesthetics.