JMIR Publications

ABSTRACT

Background:

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

Objective:

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 (NAbs) that hinder the toxin’s pharmacologic effects. Furthermore, we sought to examine the management strategies for SNR.

Methods:

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

Results:

There are limited data on SNR prevalence in aesthetic applications compared to therapeutic uses. Trigger factors of SNR relate to the 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 (i.e., <3 months apart), higher cumulative dosages, elevated treatment dosage, and booster injections (re-treatment within 3 weeks of the initial injection). NAbs developed with first-generation formulations, like onabotulinumtoxinA and abobotulinumtoxinA, that contain clostridial proteins, but not with second-generation BoNT-As like incobotulinumtoxinA and daxibotulinumtoxinA that lack such proteins. For patients who developed SNR after using first-generation BoNT-A for aesthetic purposes, switching to incoBoNT-A therapy did not result in the development of immune responses. Switching to a protein-free BoNT-A formulation, such as incobotulinumtoxinA, once SNR develops has been advocated. To effectively manage SNR, it is crucial to minimize the identified trigger factors.

Conclusions:

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