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

Background: Botulinum toxin A (BTX-A) is commonly employed as a neuromodulator in several neurological diseases and aesthetic indications. Formation of neutralizing antibodies (NAbs) after BTX-A injections may be responsible for treatment failure. Objectives: The authors sought to quantify the prevalence of NAbs following treatment with Abobotulinumtoxin A, Incobotulinumtoxin A, and Onabotulinumtoxin A for therapeutic indications. Methods: An electronic systematic search (2000-2020) of PubMed, Scopus, Web of Science, and Embase was conducted. Original studies reporting prevalence of NAbs were included. Data analysis was carried out through open meta-analysis softwares. Results: Forty-three studies involving 8833 patients were included in this 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 (7.4%) of NAbs against BTX-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%). Abobotulinumtoxin A 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 Incobotulinumtoxin A and Onabotulinumtoxin A 0.3% (summary estimate <0.003%, 95% CI=[-0.001, 0.007], P<0.003). Conclusions: Although the overall incidence of NAbs following BTX-A injections is relatively low, patients with secondary nonresponse 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.