The Use of High Initial Doses of Botulinum Toxin Therapy for Cervical Dystonia Is a Risk Factor for Neutralizing Antibody Formation—A Monocentric Cross-Sectional Pilot Study

Abstract

Background and Objectives: The present study aims to analyze the complex patient/treating physician interaction at onset of botulinum toxin (BoNT) therapy in patients with idiopathic cervical dystonia (CD) and the influence of high initial doses on long-term outcomes. Materials and Methods: A total of 74 CD patients with well-documented courses of BoNT treatment were consecutively recruited after written informed consent. Patients had to rate the amount of improvement of CD in percent of severity of CD at onset of BoNT therapy. They had to draw the course of disease severity (CoD) of CD from the onset of symptoms until the onset of BoNT therapy and from the onset of BoNT therapy until recruitment. The remaining severity of CD was estimated by the treating physician using the TSUI score. Demographic- and treatment-related data were extracted from the charts of the patients. Seventeen patients with suspected secondary treatment failure (STF) were tested for the presence of antibodies. Results: Depending on the CoD before BoNT therapy, three patient subgroups could be distinguished: rapid onset, continuous onset and delayed onset groups. Time to BoNT therapy, increase in dose and improvement were significantly different between these three groups. In the rapid onset group, with the highest initial doses, the best improvement was reported, but the highest number of patients with an STF and with neutralizing antibodies was also observed. Conclusion: The use of high initial doses in the BoNT therapy of CD is associated with a rapid response and quick success; however, it leads to an elevated risk for the development of a secondary treatment failure and induction of neutralizing antibodies.

Assessment of Patients Receiving Short-Interval Botulinum Toxin Chemodenervation Treatment for Laryngeal Dystonia and Essential Tremor of the Vocal Tract

“…One concern regarding a shorter-interval dosing regimen is the potential to develop neutralizing antibodies against BoNT due to the more frequent antigen exposure. The factors affecting immunogenicity are high-dose treatments, high lifetime cumulative dose, injection frequency, and the overall duration of treatment . In this study, we saw no evidence of neutralizing antibody development with short- or long-interval treatment despite a median lifetime treatment duration of 5 to 8 years in this cohort.…”

Isolated head tremor

“…Более того, начало терапии с высоких доз является одним из факторов формирования вышеупомянутых НАТ. В то же время уменьшение дозового режима может способствовать укорочению периода эффективности действия препарата [31]. Отсутствие данных о вторичной неэффективности инкоботулотоксина типа А даже в условиях частого введения свидетельствует в пользу длительной эффективности и безопасности применения препарата [29].…”