Repeated Botulinum Neurotoxin Type A Injections Increase Antibody Development

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Investigators observed that neutralizing antibodies exist in patients who have been receiving botulinum toxin therapies long-term and recommended neurologists try to use the smallest doses of botulinum toxin therapies possible to achieve a desired clinical outcome.

Repeated botulinum neurotoxin type A (BoNT/A) injections for various neurological indications can increase the development of neutralizing antibodies (NABs); however, decreasing doses can reduce the risk for NAB induction, according to a cross-sectional study published in Neurology.

Patients treated for facial hemispasm, blepharospasm, cervical dystonia, other dystonia, and spasticity with BoNT/A were tested for BoNT/A binding antibodies via enzyme-linked immunosorbent assay (ELISA) (N=596). The mouse hemidiaphragm test was used to investigate ELISA-positive samples for NABs. Study researchers evaluated samples to also identify factors that potentially contributed to NAB induction. In addition, the researchers calculated the estimated prevalence of NABs after a 10-year treatment duration.

Of the 596 patients included in the study, approximately 14% of patients had NABs considered measurable. Each single and cumulative dose of BoNT/A injections were associated with an increased probability of developing NABs. This increased probability was also driven by the treatment’s formulation (P <.01) and single dose per session (P =.023).

Limitations of the study included its small number of patients who had measurable NABs and the recruitment of patients from 1 center in Europe, which may reduce generalizability of the findings.

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Because of the substantial “differences in treatment duration, this finding needs to be corroborated in larger cohorts with more homogeneous follow-up times,” the researchers concluded.


Albrecht P, Jansen A, Lee JI, et al. High prevalence of neutralizing antibodies after long-term botulinum neurotoxin therapy. Neurology. 2019;92(1):e48-e54.