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肉毒杆菌毒素治疗后中和抗体阳性患者使用因卡波糖毒素A治疗中风后上肢痉挛:两例报告

IncobotulinumtoxinA for Post-stroke Upper Limb Spasticity in Neutralizing Antibody-positive Patients after Botulinum Toxin Therapy: A Report of Two Cases.

作者信息

Masakado Yoshihisa, Dekundy Andrzej, Tateishi Shohei, Kaji Ryuji

机构信息

Department of Rehabilitation Medicine, Tokai University School of Medicine, Kanagawa, Japan.

Global Clinical Development Therapeutics, Merz Pharmaceuticals GmbH, Frankfurt am Main, Germany.

出版信息

Prog Rehabil Med. 2022 Mar 8;7:20220012. doi: 10.2490/prm.20220012. eCollection 2022.

DOI:10.2490/prm.20220012
PMID:35342835
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8898682/
Abstract

BACKGROUND

Botulinum toxin type A is an effective treatment widely used to address post-stroke spasticity. Long-term repeated treatment with botulinum toxin type A may result in reduced efficacy due to the induction of neutralizing antibodies. Based on data from a phase 3 study of incobotulinumtoxinA for post-stroke upper limb spasticity, we describe the therapeutic response to botulinum toxin type A treatment in two neutralizing antibody-positive patients previously treated with other preparations of botulinum toxin type A.

CASE

Two patients (a 65-year-old woman and a 36-year-old woman) with post-stroke upper limb spasticity were previously treated with onabotulinumtoxinA, and neutralizing antibodies were detected in their sera at baseline using the mouse hemidiaphragm assay. After onabotulinumtoxinA had been discontinued for at least 16 weeks, incobotulinumtoxinA (400 U) was administered in three or four injection cycles. Good therapeutic responses, manifested by a reduction of 1-2 points on the modified Ashworth scale, were noted after each injection. The patients' sera remained positive for neutralizing antibodies throughout the incobotulinumtoxinA treatment period.

DISCUSSION

These patients, who were previously treated with onabotulinumtoxinA and were neutralizing antibody positive throughout the clinical study period, showed stable therapeutic responses following incobotulinumtoxinA treatment. IncobotulinumtoxinA could be initiated for patients with neutralizing antibodies induced by onabotulinumtoxinA.

摘要

背景

A型肉毒毒素是一种广泛用于治疗中风后痉挛的有效疗法。长期重复使用A型肉毒毒素治疗可能会因诱导中和抗体而导致疗效降低。基于一项关于因可瑞林治疗中风后上肢痉挛的3期研究数据,我们描述了两名先前接受过其他A型肉毒毒素制剂治疗的中和抗体阳性患者对A型肉毒毒素治疗的反应。

病例

两名中风后上肢痉挛患者(一名65岁女性和一名36岁女性)先前接受过阿毒素治疗,在基线时使用小鼠半膈肌试验在其血清中检测到中和抗体。在停用阿毒素至少16周后,分三或四个注射周期给予因可瑞林(400单位)。每次注射后均观察到良好的治疗反应,表现为改良Ashworth量表评分降低1-2分。在整个因可瑞林治疗期间,患者血清中的中和抗体一直呈阳性。

讨论

这些先前接受过阿毒素治疗且在整个临床研究期间中和抗体呈阳性的患者,在接受因可瑞林治疗后显示出稳定的治疗反应。对于由阿毒素诱导产生中和抗体的患者,可以开始使用因可瑞林。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/917c/8898682/a73796842d31/prm-7-20220012-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/917c/8898682/a73796842d31/prm-7-20220012-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/917c/8898682/a73796842d31/prm-7-20220012-g001.jpg

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本文引用的文献

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Immunogenicity of Botulinum Toxin Formulations: Potential Therapeutic Implications.肉毒毒素制剂的免疫原性:潜在的治疗意义。
Adv Ther. 2021 Oct;38(10):5046-5064. doi: 10.1007/s12325-021-01882-9. Epub 2021 Sep 13.
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Efficacy and safety of incobotulinumtoxinA in post-stroke upper-limb spasticity in Japanese subjects: results from a randomized, double-blind, placebo-controlled study (J-PURE).一项随机、双盲、安慰剂对照研究(J-PURE):在日本受试者中,应用依库珠单抗毒素 A 治疗脑卒中后上肢痉挛的疗效和安全性。
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IncobotulinumtoxinA for upper- and lower-limb spasticity in Japanese patients.
重组成人型肉毒毒素 A 治疗日本患者的上下肢痉挛。
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Effective long-term treatment with incobotulinumtoxin (Xeomin®) without neutralizing antibody induction: a monocentric, cross-sectional study.采用 Xeomin®(冻干粉型注射用A型肉毒毒素)进行有效且长期的治疗而不引起中和抗体产生:一项单中心、横断面研究。
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Immunogenicity induced by botulinum toxin injections for limb spasticity: A systematic review.肉毒毒素注射治疗肢体痉挛的免疫原性:系统评价。
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Neurology. 2019 Jan 1;92(1):e48-e54. doi: 10.1212/WNL.0000000000006688. Epub 2018 Nov 21.
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J Neural Transm (Vienna). 2018 Oct;125(10):1481-1486. doi: 10.1007/s00702-018-1911-3. Epub 2018 Jul 31.
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