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 Knecht; Juan 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

doi:10.1002/mds.22157

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

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185 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 language	English (US)
Pages (from-to)	1353-1360
Number of pages	8
Journal	Movement Disorders
Volume	23
Issue number	10
DOIs	https://doi.org/10.1002/mds.22157
State	Published - Jul 30 2008

Keywords

Antigenicity
Botulinum toxin
Cervical dystonia
Immunogenicity
Neutralizing antibodies

ASJC Scopus subject areas

Neurology
Clinical Neurology

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10.1002/mds.22157

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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

Brin, MF, Comella, CL, Jankovic, J, Lai, F, Naumann, M, Ahmed, F, Brashear, A, Chehrenama, M, Erjanti, H, Evatt, M, Gordon, MF, Grimes, D, Hauser, R, Hefter, H, Hermanowicz, N, Ilmavirta, M, Jennings, D, Jolma, T, Kaiňovský, P, Knecht, S, Martinez-Castrillo, JC, Massey, JM, Molho, E, Miyasaki, J, Rajput, A, Reiners, K, Ružčka, E, Schramm, A, Seeberger, L, Sherman, S, Subramanian, T, Suchowersky, O, Swope, D, Tsui, J, Velickovic, M & Walker, F 2008, 'Long-term treatment with botulinum toxin type A in cervical dystonia has low immunogenicity by mouse protection assay', Movement Disorders, vol. 23, no. 10, pp. 1353-1360. https://doi.org/10.1002/mds.22157

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

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 na{\"i}ve 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.",

keywords = "Antigenicity, Botulinum toxin, Cervical dystonia, Immunogenicity, Neutralizing antibodies",

author = "Brin, {Mitchell F.} and Comella, {Cynthia L.} and Joseph Jankovic and Francis Lai and Markus Naumann and Fayyaz Ahmed and Allison Brashear and Mahan Chehrenama and Hanna Erjanti and Marian Evatt and Gordon, {Mark Forrest} and David Grimes and Robert Hauser and Harald Hefter and Neil Hermanowicz and Matti Ilmavirta and Danna Jennings and Tapani Jolma and Petr Kai{\v n}ovsk{\'y} and Stefan Knecht and Martinez-Castrillo, {Juan Carlos} and Massey, {Janice M.} and Eric Molho and Janis Miyasaki and Alex Rajput and Karlheinz Reiners and Ev{\v z}en Ru{\v z}{\v c}ka and Axel Schramm and Lauren Seeberger and Scott Sherman and Thyagarajan Subramanian and Oksana Suchowersky and David Swope and Joseph Tsui and Miodrag Velickovic and Francis Walker",

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language = "English (US)",

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T1 - Long-term treatment with botulinum toxin type A in cervical dystonia has low immunogenicity by mouse protection assay

AU - Brin, Mitchell F.

AU - Comella, Cynthia L.

AU - Jankovic, Joseph

AU - Lai, Francis

AU - Naumann, Markus

AU - Ahmed, Fayyaz

AU - Brashear, Allison

AU - Chehrenama, Mahan

AU - Erjanti, Hanna

AU - Evatt, Marian

AU - Gordon, Mark Forrest

AU - Grimes, David

AU - Hauser, Robert

AU - Hefter, Harald

AU - Hermanowicz, Neil

AU - Ilmavirta, Matti

AU - Jennings, Danna

AU - Jolma, Tapani

AU - Kaiňovský, Petr

AU - Knecht, Stefan

AU - Martinez-Castrillo, Juan Carlos

AU - Massey, Janice M.

AU - Molho, Eric

AU - Miyasaki, Janis

AU - Rajput, Alex

AU - Reiners, Karlheinz

AU - Ružčka, Evžen

AU - Schramm, Axel

AU - Seeberger, Lauren

AU - Sherman, Scott

AU - Subramanian, Thyagarajan

AU - Suchowersky, Oksana

AU - Swope, David

AU - Tsui, Joseph

AU - Velickovic, Miodrag

AU - Walker, Francis

PY - 2008/7/30

Y1 - 2008/7/30

N2 - 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.

AB - 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.

KW - Antigenicity

KW - Botulinum toxin

KW - Cervical dystonia

KW - Immunogenicity

KW - Neutralizing antibodies

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JO - Movement Disorders

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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