900 Section - A Systematic Review and Meta-Analysis of Neutralizing Antibodies After Treatment with AbobotulinumtoxinA, IncobotulinumtoxinA and OnabotulinumtoxinA Across Multiple Indications

Botulinum neurotoxin A (BoNT-A) is recommended for the treatment of several neurologic and muscular conditions, including cervical dystonia (CD), spasticity, and blepharospasm. The biologic nature of BoNT-A means some patients can develop neutralizing antibodies (NAbs) against BoNT-A, which may result in secondary treatment failure. This meta-analysis aimed to investigate the incidence of NAb-positivity after first-line treatment with BoNT-A formulations.

Design:

A systematic review was conducted and meta-analysis was performed of publications reporting data on immunogenicity after treatment with abobotulinumtoxinA, incobotulinumtoxinA or onabotulinumtoxinA (excluding original formulation) in patients with CD, spasticity or blepharospasm. NAb status (positive/negative) after BoNT-A treatment was determined by the DerSimonian–Laird random-effects method, and the Freeman–Tukey double arcsine transformation was performed before each analysis to stabilize the variances. Differences in NAb-positivity between the different BoNT-A formulations were assessed by the significance of the test for heterogeneity between groups.

Results:

A total of 29 unique studies were identified. There were 12 publications that reported on NAb positivity in CD, 15 in spasticity, and 3 in blepharospasm. The proportion of patients with CD developing NAbs was significantly higher after treatment with abobotulinumtoxinA (2.1%; p=0.02) versus incobotulinumtoxinA (0%).There was no difference between the proportion of patients testing positive for NAbs after treatment with onabotulinumtoxinA (1.5%) versus abobotulinumtoxinA (p=0.72) or incobotulinumtoxinA (p=0.07). The proportion of patients with spasticity developing NAbs after treatment with onabotulinumtoxinA (1.2%; p=0.01) was significantly higher than with incobotulinumtoxinA (0%).There was no difference between the proportions of patients developing NAbs after treatment with abobotulinumtoxinA (0.4%) versus onabotulinumtoxinA (p=0.71) or incobotulinumtoxinA (p=0.11). The proportion of patients with blepharospasm developing NAbs was significantly higher after abobotulinumtoxinA (12.5%) than after onabotulinumtoxinA (0%; p=0.04).

Conclusion:

No patients exclusively treated with incobotulinumtoxinA developed persistent NAbs, supporting the low antigenicity of this BoNT-A formulation. IncobotulinumtoxinA is recommended to avoid immunogenicity.