Botulinum Toxin Type A Immunogenicity across Multiple Indications: An Overview Systematic Review

Plast Reconstr Surg. 2022 Apr 1;149(4):837-848. doi: 10.1097/PRS.0000000000008904.


Background: Botulinum toxin type A has been used to treat a wide array of neurologic, medical, and aesthetic indications. Several factors contribute to the formation of neutralizing antibodies, such as shorter intervals of treatment, higher dosage, amounts of antigenic proteins, serotypes, and storage of formulations.

Method: This overview followed the Cochrane guideline for overview reviews. The AMSTAR-2 (revised version of A Measurement Tool to Assess Systematic Reviews) tool was used for the critical appraisal of the selected systematic reviews.

Results: Five systematic reviews consisting of 203 studies (17,815 patients) were included, and their AMSTAR-2 scores were low to critically poor. There was high heterogeneity between the studies. Across the clinical indications, neutralizing antibody prevalence was significantly higher in dystonia, spasticity, and urologic conditions, and nil to insignificant in hyperhidrosis and aesthetic indications. The overall rate for the neutralizing antibody formation across three different formulations, abobotulinumtoxinA, incobotulinumtoxinA, and onabotulinumtoxinA, was 1 to 2.1 percent, with no significant difference between them.

Results: Although there is debate on the prevalence rate across the different botulinum toxin type A formulations in individual systematic reviews, the overall frequency of the development of neutralizing antibodies and the immunogenicity of abobotulinumtoxinA, incobotulinumtoxinA, and onabotulinumtoxinA remain low to insignificant.

Conclusions: Properly designed comparative trials are required to explore the difference in the prevalence of neutralizing antibodies across the commercially available botulinum toxin type A products. Such studies should also examine the relevance of neutralizing antibody titer to clinical responsiveness and nonresponse.

Publication types

  • Review

MeSH terms

  • Antibodies, Neutralizing / therapeutic use
  • Botulinum Toxins, Type A* / therapeutic use
  • Esthetics
  • Humans
  • Neuromuscular Agents* / therapeutic use
  • Systematic Reviews as Topic


  • Antibodies, Neutralizing
  • Neuromuscular Agents
  • Botulinum Toxins, Type A