Immunogenicity and Long-Term Efficacy of Botulinum Toxin Type B in the Treatment of Cervical Dystonia: Report of 4 Prospective, Multicenter Trials

Objective: Therapeutic botulinum toxins are antigenic proteins with the potential to produce antibodies (Abs). It is, however, unclear whether Abs to Myobloc (R) (rimabotulinumtoxinB, botulinum toxin type B, BoNT-B) impact the efficacy and safety of BoNT-Btreatment of cervical dystonia (CD). The objective was to determine if Abs to BoNT-B impact the efficacy or safety of long-term BoNT-B treatment of CD. Methods: Four separate prospective clinical trials, with a combined total of 1134 subjects evaluable for immunogenicity over total treatment durations of up to 6+ years, were conducted studying the efficacy, safety, and immunogenicity of BoNT-B treatment of CD. Botulinum toxin type B injections were administered approximately every 3 months. Efficacy was assessed using the Toronto Western Spasmodic Torticollis Rating Scale-Total Score, the Subject Global Assessment, or the Treatment Assessment Scale. The presence of Abs to BoNT-B was assessed using the mouse neutralizing antibody (MNA) assay. Cross-sectional and longitudinal statistical analyses were performed to compare efficacy by MNA status at each time point and over time in Ab-positive individuals before and after seroconversion. Safety was assessed by summarizing adverse events by Ab status. Results: Long-term efficacy was observed with multiple treatments of BoNT-B. Across all 4 studies, there was no correlation between MNA status and rates of clinical response, study withdrawal, or safety profile. Conclusions: Botulinumtoxin type B is effective and safe in the repeat, long-term treatment of CD. The presence of Abs to BoNT-B as detected by the MNA assay does not have any meaningful clinical impact or correlation.