No Secondary Treatment Failure during Incobotulinumtoxin-A Long-Term Treatment Demonstrated by the Drawing of Disease Severity

Harald Hefter; Raphaela Brauns; Beyza Ürer; Dietmar Rosenthal; Philipp Albrecht; Sara Samadzadeh

doi:10.3390/toxins15070454

No Secondary Treatment Failure during Incobotulinumtoxin-A Long-Term Treatment Demonstrated by the Drawing of Disease Severity

Toxins (Basel). 2023 Jul 12;15(7):454. doi: 10.3390/toxins15070454.

Authors

Harald Hefter¹, Raphaela Brauns¹, Beyza Ürer¹, Dietmar Rosenthal¹, Philipp Albrecht^{1

2}, Sara Samadzadeh^{1

3

4

5}

Affiliations

¹ Department of Neurology, Moorenstrasse 5, 40225 Düsseldorf, Germany.
² Department of Neurology, Maria Hilf Clinics, 41063, Moenchengladbach, Germany.
³ Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Experimental and Clinical Research Center, 13125 Berlin, Germany.
⁴ Department of Regional Health Research and Molecular Medicine, University of Southern Denmark, 5230 Odense, Denmark.
⁵ Department of Neurology, Slagelse Hospital, 4200 Slagelse, Denmark.

Abstract

The aim of this study was to detect clinical hints regarding the development of secondary treatment failure (STF) in patients with focal dystonia who were exclusively treated with incobotulinumtoxin/A (incoBoNT/A). In total, 33 outpatients (26 with idiopathic cervical dystonia, 4 with Meige syndrome and 3 with other cranial dystonia) who were treated with repeated injections of incoBoNT/A for a mean period of 6.4 years without interruptions were recruited to draw the course of their disease severity (CoD) from the onset of symptoms to the onset of BoNT therapy (CoDB graph) and from the onset of BoNT therapy to recruitment (CoDA graph). At the time of recruitment, the patients assessed the change in severity as a percentage of the severity at the onset of BoNT therapy. Blood samples were taken to test the presence of neutralizing antibodies (NABs) using the mouse hemidiaphragm assay (MHDA). Patients reported an improvement of about 70% with respect to the mean. None of the patients tested positive for MHDA. Three different types of CoDB and three different types of CoDA graphs could be distinguished. The patients with different CoDB graphs reported different long-term outcomes, but there was no significant difference in long-term outcomes between patients with different CoDA graphs. None of the patients produced a CoDA graph with an initial improvement and a secondary worsening as a hint for the development of STF. A primary non-response was not observed in any of the patients. During long-term treatment with BoNT/A, NABs and/or STF may develop. However, in the present study on patients with incoBoNT/A long-term monotherapy, no hints for the development of NABs or STF could be detected, underlining the low antigenicity of incoBoNT/A.

Keywords: CoD graphs; botulinum neurotoxin therapy; course of disease (CoD); focal dystonia; incoBoNT long-term treatment; primary treatment failure; secondary treatment failure.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Neutralizing / therapeutic use
Botulinum Toxins, Type A*
Dystonic Disorders* / drug therapy
Humans
Mice
Neuromuscular Agents* / therapeutic use
Patient Acuity
Torticollis* / drug therapy
Treatment Failure

Substances

Antibodies, Neutralizing
Botulinum Toxins, Type A
Neuromuscular Agents

Grants and funding

This work was supported by a restricted grant of the private institution Inge Diesbach-Stiftung to HH. This funding did not influence the design and performance of the present study.