Introduction
Composition of natural BoNTs and BoNT products
Antibodies against botulinum neurotoxins
Immunogenicity versus non-response
Factors affecting the immunogenicity of botulinum neurotoxins products
Product-related factors
Manufacturing processes
Toxin source
Inactive toxin
Antigenic protein load
Botulinum neurotoxin products | Total protein (ng/vial) | Antigenic protein load (ng/vial) |
---|---|---|
AbobotulinumtoxinA (500 U vial) | ~5 | Unknown |
IncobotulinumtoxinA (100 U vial) | ~0.6 | ~0.6 |
OnabotulinumtoxinA (100 U vial) | ~5 | ~0.8 |
RimabotulinumtoxinB (5,000 U vial) | ~50 | ~10.7 |
Accessory proteins and excipients
Treatment-related factors
Dose
Treatment intervals
Previous exposure or vaccinations
Laboratory and clinical tests for detection of anti-BoNT antibodies
In vitro assays
Bioassays
Clinical assays
Clinical immunogenicity of BoNT products
Non-proprietary name | Trade name (Reference) | Indication | Dose | Frequency |
---|---|---|---|---|
OnabotulinumtoxinA | BOTOX® (BOTOX® [package insert] 2011) | Cervical dystonia | 236 U (1.95 ng 150 kD neurotoxin) | Every 3–4 months (BOTOX® [package insert] 2011) |
BOTOX® Cosmetic (BOTOX® Cosmetic [package insert] 2011) | Glabellar lines | 20 U (0.17 ng 150 kD neurotoxin) | Every 4 months | |
Adalimumab | Humira® (HUMIRA® [package insert] 2011) | Rheumatoid arthritis, plaque psoriasis, ankylosing spondylitis, Crohn’s disease | 40 mg (maintenance dose) | Every other week (HUMIRA® [package insert] 2011) |
Interferon β-1a | Avonex® (AVONEX® [package insert] 2006) | Multiple sclerosis | 30 μg (AVONEX® [package insert] 2006) | Weekly |
Rebif® (Rebif® [package insert] 2005) | Multiple sclerosis | 22 or 44 μg | Three times per week (Rebif® [package insert] 2005) | |
Extavia® (Extavia® [package insert] 2009) | Multiple sclerosis | 0.25 mg (Extavia® [package insert] 2009) | Every other day |
Indication | AbobotulinumtoxinA | IncobotulinumtoxinA | OnabotulinumtoxinAa
| RimabotulinumtoxinB |
---|---|---|---|---|
Cervical dystonia | 0–1 %b (2010; Benecke 2009) | |||
Blepharospasm/facial movement disorder | NA | NA | NA | NA |
Spasticity (upper limb) | 0c (Bakheit et al. 2004) | 0d (Kanovsky et al. 2009) | 0e (Brashear et al. 2004) | |
Hyperhidrosis | NA | NA | 0.2 % (BOTOX® [package insert] 2011) | NA |
Chronic migraine | NA | NA | 0 (BOTOX® [package insert] 2011) | NA |
Urinary incontinence due to neurogenic detrusor overactivity | NA | NA | 0 (Cruz et al. 2011) | NA |
Cosmetic | 0 (Imhof and Kühne 2011) | NA |