Long-term treatment with botulinum toxin type A in cervical dystonia has low immunogenicity by mouse protection assay

Mitchell F. Brin, Cynthia L. Comella, Joseph Jankovic, Francis Lai, Markus Naumann, Fayyaz Ahmed, Allison Brashear, Mahan Chehrenama, Hanna Erjanti, Marian Evatt, Mark Forrest Gordon, David Grimes, Robert Hauser, Harald Hefter, Neil Hermanowicz, Matti Ilmavirta, Danna Jennings, Tapani Jolma, Petr Kaiňovský, Stefan KnechtJuan Carlos Martinez-Castrillo, Janice M. Massey, Eric Molho, Janis Miyasaki, Alex Rajput, Karlheinz Reiners, Evžen Ružčka, Axel Schramm, Lauren Seeberger, Scott Sherman, Thyagarajan Subramanian, Oksana Suchowersky, David Swope, Joseph Tsui, Miodrag Velickovic, Francis Walker

Research output: Contribution to journalArticle

125 Scopus citations

Abstract

To evaluate the immunogenicity of botulinum toxin type A (BoNTA; BOTOX) in cervical dystonia (CD). Subjects diagnosed with CD for ≥1 year and previously naïve to BoNTs were treated with BoNTA in a prospective, open-label, multi-center 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 ≤4 years.

Original languageEnglish (US)
Pages (from-to)1353-1360
Number of pages8
JournalMovement Disorders
Volume23
Issue number10
DOIs
StatePublished - Jul 30 2008

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

Cite this

Brin, M. F., Comella, C. L., Jankovic, J., Lai, F., Naumann, M., Ahmed, F., Brashear, A., Chehrenama, M., Erjanti, H., Evatt, M., Gordon, M. F., Grimes, D., Hauser, R., Hefter, H., Hermanowicz, N., Ilmavirta, M., Jennings, D., Jolma, T., Kaiňovský, P., ... Walker, F. (2008). Long-term treatment with botulinum toxin type A in cervical dystonia has low immunogenicity by mouse protection assay. Movement Disorders, 23(10), 1353-1360. https://doi.org/10.1002/mds.22157