Immunogenicity to Botulinum Toxin Type A: A Systematic Review With Meta-Analysis Across Therapeutic Indications.

BACKGROUND Botulinum toxin A (BTX-A) is a commonly used as neuromodulator in several neurological diseases and aesthetic indications. Formation of neutralizing antibodies (Nabs) after BTX-A injections may be responsible for treatment failure. OBJECTIVES To quantify the prevalence of Nabs following treatment with Abobotulinumtoxin A (ABO), Incobotulinumtoxin A (INCO) and Onabotulinumtoxin A (ONA) for approved therapeutic indications. METHODS An electronic systematic search (2000-2020) using Pubmed, Scopus, Web of science, and Embase was conducted. Original studies reporting prevalence of Nabs were included. Risk of bias was evaluated using cochrane and Newcastle-Ottawa scale tools. Data analysis was carried out through open meta-analyst and comprehensive meta-analysis softwares. RESULTS A total of 43 studies involving 8,833 patients were included in a meta-analysis. The incidence of NAbs was 1.8% (summary estimate= 0.018, 95% CI [0.012, 0.023]); A meta-regression analysis revealed that BTX-A duration was significantly associated with increased incidence of NAbs (p= 0.007). Patients with dystonia had the highest incidence incidence (7.4%) of NAbs against botulinum toxin A (summary estimate= 0.074, 95% CI= [0.045, 0.103], I2=93.%, p< 0.00) followed by patients with spasticity (6.7%) and urological indications (6.2%). ABO was associated with the highest incidence of NAbs (7.4%), (summary estimate= 0.074, 95% CI= [0.053, 0.096], I2=97.24%, p< 0.00) by the INCO AND ONA 0.3% (Summary Estimate < 0.003%, 95% CI= [ -0.001, 0.007], p< 0.003). CONCLUSIONS While the overall incidence of Nabs following BTX-A injections is relatively low, patients with secondary non-response to BTX-A with no apparent causes, should be investigated for Nabs. A consensus needs to be developed for the optimal management of such patients.