Systematic Review and Meta-Analysis of Secondary Treatment Failure and Immunogenicity With Botulinum Neurotoxin A in Multiple Indications.

[BACKGROUND] Botulinum neurotoxin A (BoNT-A) is recommended for the treatment of cervical dystonia (CD), spasticity, and blepharospasm. Some patients treated with BoNT-A have been reported to develop neutralizing antibodies (NAbs) against BoNT-A, which may result in reduced efficacy and, in some cases, secondary treatment failure (STF). Our aim was to investigate the incidence of STF and NAb positivity after treatment with one of three commercially-available BoNT-A formulations.

[METHODS] A systematic review and meta-analysis of STF and/or NAb positivity after treatment with abobotulinumtoxinA, incobotulinumtoxinA, or onabotulinumtoxinA in patients with CD, spasticity, or blepharospasm was conducted using PubMed, Embase, and Google Scholar.

[RESULTS] Twenty-nine unique studies reported in 29 publications assessed NAb positivity and were included. The meta-analysis showed that the proportions of patients developing STF were significantly higher after treatment with abobotulinumtoxinA or onabotulinumtoxinA than with incobotulinumtoxinA for CD or spasticity. Depending on the antibody test used, the proportions of patients developing NAbs were also significantly higher after treatment with abobotulinumtoxinA or onabotulinumtoxinA than with incobotulinumtoxinA for CD or spasticity. When data for all indications were pooled, proportions of NAb-positive patients were numerically higher with increasing mean doses of abobotulinumtoxinA or onabotulinumtoxinA. No patients treated exclusively with incobotulinumtoxinA were found to have developed immunogenic STF or persistent NAbs.

[CONCLUSIONS] The risk of developing STF and NAbs appears to vary with indication and BoNT-A formulation. When the efficacy and safety of formulations are comparable, incobotulinumtoxinA may be recommended to avoid developing STF and immunogenicity, particularly for patients requiring higher doses and repeated treatments.