300 Section - Secondary Treatment Failure with AbobotulinumtoxinA, IncobotulinumtoxinA and OnabotulinumtoxinA: A Systematic Review and Meta-Analysis

Botulinum neurotoxin type A (BoNT-A) is recommended for the treatment of several neurologic and muscular conditions, including cervical dystonia (CD) and spasticity, but since these products are biologics, some patients can develop neutralizing antibodies against BoNT-A during treatment. This immunogenicity may result in secondary treatment failure (STF). The aim of this meta-analysis was to investigate the incidence of STF in patients with CD or spasticity after treatment with three BoNT-A formulations.

Design:

A systematic review was conducted. Identified studies reporting neutralizing antibody-induced STF after first-line treatment with abobotulinumtoxinA, incobotulinumtoxinA or onabotulinumtoxinA (excluding original formulation) in patients with CD or spasticity underwent meta-analysis. The occurrence of STF was determined using the DerSimonian-Laird random-effects method, with the Freeman-Tukey double arcsine transformation performed before each analysis to stabilize the variances. The difference in occurrence of STF between the three formulations was assessed by the significance of the test for heterogeneity between groups.

Results:

A total of 19 studies were identified that assessed STF in CD (n=9) or spasticity (n=10 ). Meta-analysis showed that the proportions of patients with CD developing STF were significantly higher after treatment with abobotulinumtoxinA (9%; p< 0.001) or onabotulinumtoxinA (3%; p=0.03) than with incobotulinumtoxinA (0%).There was no significant difference between the proportions of patients                                                                                                            developing STF after treatment with abobotulinumtoxinA versus onabotulinumtoxinA (p=0.08). The proportion of patients with spasticity developing STF was also significantly higher after treatment with abobotulinumtoxinA (5%; p=0.01) than with incobotulinumtoxinA (0%). No patients treated exclusively with first-line incobotulinumtoxinA developed neutralizing antibody-induced STF, irrespective of the treatment indication.

Conclusion:

Our meta-analysis found that incobotulinumtoxinA was associated with a significantly lower risk of developing STF compared with abobotulinumtoxinA (CD and spasticity) and onabotulinumtoxinA (CD). IncobotulinumtoxinA is recommended to avoid developing neutralizing antibody-induced STF in patients with CD or spasticity.