Exploring Nonresponse to Botulinum Toxin in Aesthetics: Narrative Review of Key Trigger Factors and Effective...

Nonresponse to botulinum toxin type A (BoNT-A) has been reported in both medical and aesthetic applications. Secondary nonresponse (SNR) occurs when BoNT-A is initially effective before failure commences at a later point. Most reported cases involve SNR in aesthetics. Several aspects of this complication remain elusive or controversial.

We aimed to address unanswered questions regarding the prevalence and etiology of SNR. Additionally, we investigated the immunogenicity of BoNT-A formulations, mainly focusing on the development of neutralizing antibodies that hinder the toxin's pharmacologic effects. Furthermore, we sought to examine the management strategies for SNR.

The PubMed and Google Scholar databases were searched from inception for articles on nonresponse to BoNT-A therapy. Articles were evaluated based on their contribution to the field. Expert opinions and panel recommendations regarding management and data gaps were also included in the review.

There are limited data on SNR prevalence in aesthetic applications compared to therapeutic uses. Trigger factors of SNR include improper handling of BoNT-A; incorrect injection practices; and impurities present in the formulation, such as clostridial complexing proteins that may increase immunogenicity. Other contributing factors include infection; patient characteristics; and treatment parameters that encompass an increased frequency of BoNT-A injections (ie, <3 months apart), higher cumulative dosages, elevated treatment dosages, and booster injections (retreatment within 3 weeks of the initial injection). Neutralizing antibodies developed with first-generation formulations, such as onabotulinumtoxinA and abobotulinumtoxinA that contain clostridial proteins, but not with second-generation BoNT-As, such as incobotulinumtoxinA and daxibotulinumtoxinA, which lack these proteins. Among patients who developed SNR after using first-generation BoNT-A for aesthetic purposes, switching to incobotulinumtoxinA therapy did not result in the development of immune responses. Switching to a protein-free BoNT-A formulation such as incobotulinumtoxinA upon development of SNR has been advocated. To effectively manage SNR, it is crucial to minimize the identified trigger factors.

Nonresponse to BoNT-A is gaining importance in aesthetic treatments. Considering the potential for immunogenicity is essential when selecting a BoNT-A formulation. Preventing SNR is crucial, given the lack of solid data on effective treatments.