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Antikörpervermitteltes Versagen der Botulinum-Toxin-Therapie

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Zusammenfassung

Botulinum-Toxin (BT) hat in den letzten Jahren einen breiten Einsatz in der Neurologie und in anderen medizinischen Fächern gefunden. Bei einigen Patienten kommt es jedoch zum Auftreten von Antikörpern gegen BT (BTAK) mit vollständigem Wirkungsverlust der BT-Therapie (AKTV). Risikofaktoren für ein AKTV sind die Höhe der BT-Einzeldosis und die Länge des Interinjektionsintervals. Die Behandlungsdauer, die BT-Kumulativdosis und das Alter und das Geschlecht des Patienten stellen keine Risikofaktoren dar. Das Abwarten eines spontanen BTAK-Abfalls ist für eine fortgesetzte BT-Therapie nicht praktikabel, da die hierfür notwendigen Zeiträume zu lang sind. Es bietet jedoch die Möglichkeit, eine BT-Therapie mit modifizierten Parametern und mit neuen BT-Präparationen mit niedrigerer Antigenität erneut zu initiieren. Eine Erhöhung der BT-Dosis kann bei niedrigen BTAK-Titern und bei einem mäßig reduzierten BT-Ansprechen der Zielmuskeln hilfreich sein. Die Verwendung alternativer BT-Typ-A-Präparate führt nicht zu einer Überwindung des AKTV. Alternative BT-Typen, wie BT Typ B und BT Typ F, sind zunächst bei AKTV wirksam, lösen jedoch bei den meisten Patienten bereits nach wenigen Gaben Antikörperbildungen gegen die alternativen BT-Typen aus. Dabei ist die Gabe von BT Typ B mit zum Teil heftigen systemischen anticholinergen Nebenwirkungen verbunden.

Summary

Botulinum toxin (BT) has been used with great success in a large number of medical specialities. In some patients, however, formation of antibodies against BT (BTAB), with therapy failure (ABTF) occurs. Risk factors for ABTF are the amount of BT given at each injection series and the duration of the intervals between injection series. Treatment time and cumulative BT dose as well as patient age and gender are not independent risk factors. BTAB titres drop spontaneously after cessation of BT therapy, but latencies are too long to be compatible with a clinically effective therapy. Once these titres have dropped, BT therapy can be restarted using improved parameters and improved BT preparations with lower antigenicity. Increasing the BT dosage can be successful for overcoming ABTF when BTAB titres are low and target muscle responses are only moderately reduced. The use of alternative BT type A preparations fails to overcome ABTF. Alternative BT types such as types B and F are initially successful in ABTF but stimulate the formation of antibodies against the alternative BT types after few applications. When type B is used, substantial systemic anticholinergic side effects can occur. Prevention of BTAB formation is of paramount importance. Risk factors for BTAB formation have to be taken into account when planning BT therapy. The most interesting perspective, however, seems to be the development of new BT preparations with improved specific potency and reduced antigenicity.

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Dressler, D. Antikörpervermitteltes Versagen der Botulinum-Toxin-Therapie. Nervenarzt 74, 1098–1104 (2003). https://doi.org/10.1007/s00115-003-1611-5

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