Neutralizing Antibody Formation with OnabotulinumtoxinA (BOTOX®) Treatment from Global Registration Studies across Multiple Indications: A Meta-Analysis

Abstract

Though the formation of neutralizing antibodies (NAbs) during treatment with botulinum neurotoxin is rare, their presence may nonetheless affect the biological activity of botulinum toxin and negatively impact clinical response. The goal of this updated meta-analysis was to evaluate and characterize the rate of NAb formation using an expanded dataset composed of 33 prospective placebo-controlled and open-label clinical trials with nearly 30,000 longitudinal subject records prior to and following onabotulinumtoxinA treatment in 10 therapeutic and aesthetic indications. Total onabotulinumtoxinA doses per treatment ranged from 10 U to 600 U administered in ≤15 treatment cycles. The NAb formation at baseline and post-treatment was tested and examined for impact on clinical safety and efficacy. Overall, 27 of the 5876 evaluable subjects (0.5%) developed NAbs after onabotulinumtoxinA treatment. At study exit, 16 of the 5876 subjects (0.3%) remained NAb positive. Due to the low incidence of NAb formation, no clear relationship was discernable between positive NAb results and gender, indication, dose level, dosing interval, treatment cycles, or the site of injection. Only five subjects who developed NAbs post-treatment were considered secondary nonresponders. Subjects who developed NAbs revealed no other evidence of immunological reactions or clinical disorders. This comprehensive meta-analysis confirms the low NAb formation rate following onabotulinumtoxinA treatment across multiple indications, and its limited clinical impact on treatment safety and efficacy.

Update on Non-Interchangeability of Botulinum Neurotoxin Products

“…This study also showed that neutralizing antibody status can vary over time, as only 4/2240 had a positive test at the final post-treatment study visit. A change in antibody status over time has also been reported by others [213,215,226] and, notably, in a recent meta-analysis of 5876 subjects treated with onabotA across 10 therapeutic and aesthetic indications in which 0.5% developed neutralizing antibodies at some point but only 0.3% remained positive at the end of the study [213].…”

The Patient Journey in Facial Aesthetics: Findings from a European Consensus Meeting on Improving the Quality of Life for Patients Receiving Botulinum Toxin Injections

“… 31 , 33 The panelists agreed that performing a full repeat treatment in less than 3 months should be avoided due to the risk of neutralizing antibodies; 34 however, a recent meta-analysis by Jankovic et al found no clear relationship between neutralizing antibody formation and dosing interval, with the overall incidence of neutralizing antibodies being low (≤1.4%). 35 …”

“…31,33 The panelists agreed that performing a full repeat treatment in less than 3 months should be avoided due to the risk of neutralizing antibodies; 34 however, a recent meta-analysis by Jankovic et al found no clear relationship between neutralizing antibody formation and dosing interval, with the overall incidence of neutralizing antibodies being low (≤1.4%). 35 To ensure optimal results, some panelists have found it useful to request that patients bring videos to their next appointment demonstrating their facial muscle movements 14 days posttreatment. This technique tends to be popular with patients in clinical practice.…”

The Role of Botulinum Toxin Type-A in Spasticity: Research Trends from a Bibliometric Analysis

“…It is important to note that the study by Hefter et al merged data on OnabotulinumtoxinA and AbobotulinumtoxinA into a single group, despite these being distinct formulations with differing potencies. Jankovic et al’s meta-analysis, spanning 33 clinical trials with nearly 30,000 subject records, found an overall low NAb formation rate of 0.5% following OnabotulinumtoxinA treatment [ 155 ]. Importantly, this study showed no clear association between NAb-positive events and higher doses, number of treatment cycles, or other clinical variables.…”