Neurotoxin Impurities: A Review of Threats to Efficacy

Abstract

Recently launched esthetic botulinum toxin serotype A (BoNT/A) products include Nabota/Jeuveau, Meditoxin/Neuronox, and Botulax, which contain nontoxic accessory proteins and excipients. Clinical evidence supporting these formulations, including their purity and potential immunogenicity or their link to treatment failures, is limited. Any nonhuman protein, including nontoxin accessory proteins, can initiate immune reactions, especially if administered repeatedly, yet the issue of BoNT/A-induced immunogenicity is widely contested. However, there have been multiple reports of treatment failures and observations of BoNT/A-induced neutralizing antibodies. Compared with the purified formulation in Xeomin, these recently launched toxins contain higher total neurotoxin quantities, much of which is inactive and exposes patients to potentially immunogenic nontoxin proteins or inactive neurotoxins that increase their risk of developing treatment failure. Well-established products [especially abobotulinumtoxinA (Dysport), onabotulinumtoxinA (Botox) and Xeomin] are accompanied by comprehensive and long-ranging clinical evidence on safety and efficacy in esthetic facial indications, which still remains undisclosed for many of the recently introduced toxins. Clinicians need this information as patients will require repeated BoNT treatments and may be unnecessarily but cumulatively exposed to potential immunogens. To underscore the need for caution and further evidence, we review some of the issues surrounding BoNT/A-induced immunogenicity and antibody-induced treatment failures and argue that using highly purified toxins that do not negatively impact patient outcomes is a prudent clinical decision.