Utilize the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database to explore decreased therapeutic effect over time amongst botulinum toxin type A (BoNT-A) agents.

Sufficient long term data comparing BoNT-A agents for antibody formation, resistance, and loss of effect is lacking. IncobotulinumtoxinA is the only BoNT-A agent that has removed unnecessary proteins, leaving just the 150 kDa active component.

The FAERS database was utilized. The analysis was conducted on data between March 2014 and June 2019. BoNT-A cases were included when it was considered the “Primary Suspect” drug. The primary outcome was relative rate of decreased therapeutic effect over time by drug, defined as presence of ‘therapeutic response decreased’ and/or ‘drug effect decreased’ being reported as an adverse event. This relative rate methodology has been well described previously in the pharmacovigilance literature.

A total of 23,789 unique BoNT-A cases included for analysis across a wide array of cosmetic and therapeutic indications. Relative incidence of decreased therapeutic effect for patients on ≥ 1 year of treatment versus < 1 year was significantly higher for onabotulinumtoxinA [14.4% (609/4219) vs 7.6% (753/9909); p>0.001] and abobotulinumtoxinA [9.9% (59/597) vs 3.3% (38/1144); p<0.001]. This phenomenon was not observed with incobotulinumtoxinA [0.0% (0/34) vs 3.7% (18/485); p=0.62]. Rates remained steady for treatments beyond 1 year and did not continue to increase (i.e. - 2+ years, etc), potentially negating effect of time on market for present analysis.

Causal relationships cannot be established from pharmacovigilance analyses. However, a safety signal was detected in this analysis of one of the largest BoNT-A safety data sets ever researched. Long term differences in decreased BoNT-A therapeutic effect by agent warrants further study, including whether even lower dose indications are not immune from this phenomenon over time.