Neurotoxin Impurities: A Review of Threats to Efficacy.

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.

Comparison of botulinum neurotoxin type A formulations in Asia.

RESULTS: All protein-based therapeutics, such as botulinum neurotoxin type A (BoNT/A), are potentially immunogenic and can lead to anaphylaxis, autoimmunity, or diminished or complete absence of therapeutic efficacy, especially if administered repeatedly. Therefore, the protein quantity in BoNT/A products is an important consideration when selecting products for treatment. However, essential formulation data are not always publicly accessible. MATERIALS AND METHODS: The neurotoxin protein content of products newly introduced in Asia, such as (listed alphabetically) Botulax®, Meditoxin®, Nabota®, and Relatox®, was measured by sandwich enzyme-linked immunosorbent assay with antisera directed against BoNT/A compared to Xeomin®. RESULTS: Compared to Xeomin with no inactive neurotoxin, although Botulax and Nabota contained 844 and 754 pg of neurotoxin protein, respectively, the percentage of inactive neurotoxin was calculated to be 103 and 81, respectively, while the potency per pg of neurotoxin was 0.118 and 0.133 U, respectively. Meditoxin and Relatox had 575 and 578 pg of neurotoxins, respectively, marginally higher than that of Xeomin, while the percentage of inactive neurotoxins was 38 and 33, respectively, and the potency per pg of neurotoxin was 0.174 and 0.173 U, respectively. However, Xeomin, which has 416 pg/vial of purified neurotoxin and 0.240 U of efficacy per pg of neurotoxin, has the lowest neurotoxin protein content and consequently the highest specific potency compared to the four Asian BoNT/A preparations in this study. CONCLUSION: Although Botulax and Nabota had more neurotoxin than Xeomin in an equivalent volume, they contained greater amounts of inactive neurotoxin. In addition, although Meditoxin and Relatox had slightly more neurotoxin than Xeomin, both contained greater amounts of inactive neurotoxin.

Efficacy and patient satisfaction with incobotulinumtoxinA for the treatment of glabellar frown lines.

INTRODUCTION: This study describes the physician experience relating to the effectiveness of incobotulinumtoxinA and patient satisfaction with its use for the treatment of glabellar frown lines (GFLs). METHODS: A total of 17 patients from six dermatological clinics, aged > 18 years and with mild to very severe GFLs at maximum frown, were included. Patients were excluded if they had treatment with resorbable fillers and botulinum toxins in the preceding six months, or non-resorbable fillers or surgery in the treatment area. Injection sites (range 3-5) were chosen depending on their severity (dose range 12-20 U), covering corrugators and procerus muscles. Physicians assessed improvements to GFLs using the Merz scale on Days 4 and 14 after treatment. Patients completed a self-reported questionnaire on their facial wrinkles on Days 2 and 4 after treatment. RESULTS: Most (76.5%) patients were women. The mean age of the patients was 46.9 ± 10.0 years. Mean severities (on the Merz scale) for at-rest and dynamic (with expression) GFLs at baseline were 1.3 ± 1.10 and 3.4 ± 0.38, respectively, and decreased on Day 14 (p < 0.05). Treatment response rates (> 1-point improvement) for at-rest and dynamic (with expression) GFLs on Day 4 were 40% and 100%, respectively. All patients reported being satisfied or very satisfied, and 64.3%-71.4% indicated that their facial wrinkles had improved on Day 2. CONCLUSION: IncobotulinumtoxinA was fast acting with visible improvements by Day 4 and all patients expressed satisfaction with their treatment after two days. GFLs saw the most improvement among the facial characteristics measured.