Systematic analysis of botulinum neurotoxin type A immunogenicity in clinical studies

Controversy exists around the immunogenicity of the various formulations of botulinum neurotoxin type A (BoNT-A). A systematic review of the literature (1968–2013) was performed, including review of materials from the FDA. Neutralizing antibody rates were calculated for overall BoNT-A and for each commercially available BoNT-A (abobotulinumtoxinA, incobotulinumtoxinA, onabotulinumtoxinA), and were compared by using the Chi-squared test. Two different onabotulinumtoxinA products were identified during the specified time-frame and classed as ‘old’ and ‘new’ versions. A total of 31 studies involving 5811 subjects met inclusion criteria and were analyzed. Therapeutic indications included: cervical dystonia, blepharospasm, spasticity, glabellar lines, hyperactive detrusor/sphincter dysfunction. The overall rate of development for neutralizing antibodies to BoNT-A was 2.1%. Individual rates were 1.4% for abobotulinumtoxinA, 0.8 to 1.1% for incobotulinumtoxinA, 7.2% for old onabotulinumtoxinA and 3.6% for new onabotulinumtoxinA. No significant differences were found between abobotulinumtoxinA and incobotulinumtoxinA rates (OR 1.82 [95%CI] [0.96–3.43], p = 0.066; OR 1.30 [0.69–2.46], p = 0.415). Rates of neutralizing antibodies were significantly lower with abobotulinumtoxinA and incobotulinumtoxinA versus either onabotulinumtoxinA formulations. The overall neutralizing antibody rate for BoNT-A was low (≤2.1%). The rate of developing neutralizing antibodies was similar between abobotulinumtoxinA and incobotulinumtoxinA, both significantly lower when compared with onabotulinumtoxinA.