Long-term treatment with botulinum toxin type A in cervical dystonia has low immunogenicity by mouse protection assay.
To evaluate the immunogenicity of botulinum toxin type A (BoNTA; BOTOX) in cervical dystonia (CD). Subjects diagnosed with CD for > or =1 year and previously naïve to BoNTs were treated with BoNTA in a prospective, open-label, multicenter study. Serum samples were analyzed for BoNTA neutralizing antibodies using the Mouse Protection Assay (MPA). Clinical resistance was assessed with a test injection of 20 U BoNTA placed unilaterally into the frontalis (Frontalis Antibody Test; FTAT) or corrugator muscle (Unilateral Brow Injection; UBI). Efficacy was assessed and adverse events were recorded. Of 326 subjects enrolled, 251 (77%) completed the study. Subjects received a median of 9 BoNTA treatments (mean dose per session ranged from 148.4 to 213.0 U over a mean of 2.5 years [range: 3.2 months-4.2 years]). Only 4 of 326 subjects (1.2%) tested positive for antibodies in the MPA; three of these subjects stopped responding clinically to BoNTA (of whom one also showed clinical resistance in the FTAT) and one continued to respond. Consistent improvements in the signs/symptoms of CD were noted. The most frequent treatment-related adverse events were mild to moderate weakness, dysphagia, neck pain, and injection-site pain. The current formulation of BoNTA rarely causes neutralizing antibody formation in CD subjects treated < or =4 years.
Allergan, Inc., Global Drug Development, Irvine, California, USA.
Mitchell F
MF
Brin
Cynthia L
CL
Comella
Joseph
J
Jankovic
Francis
F
Lai
Markus
M
Naumann
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis* / Q000276:immunology; D000918:Antibody Specificity; D001681:Biological Assay; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007273:Injections, Intramuscular; D008297:Male; D051379:Mice; D008875:Middle Aged; D009500:Neutralization Tests; D011446:Prospective Studies; D014103:Torticollis / Q000188:drug therapy* / Q000276:immunology
D000907:Antibodies, Bacterial; D019274:Botulinum Toxins, Type A