Frequency and risk factors of antibody-induced secondary failure of botulinum neurotoxin therapy. (19th May 2020)

• Record Type: Journal Article
• Authors: Walter, Uwe; Mühlenhoff, Christopher; Benecke, Reiner; Dressler, Dirk; Mix, Eilhard; Alt, Janes; Wittstock, Matthias; Dudesek, Ales; Storch, Alexander; Kamm, Christoph
• Is Part Of: Neurology. Volume 94:Number 20(2020)
• Publication Date: 2020-05-19
• Subjects: Neurology -- Periodicals; Neurology -- Periodicals; Neurologie -- Périodiques; 616.8
• DOI: 10.1212/WNL.0000000000009444
• Languages: English
• ISSNs: 0028-3878

Abstract

Abstract : Objective: To investigate the risk factors of neutralizing antibody (NAB)–induced complete secondary treatment failure (cSTF) during long-term botulinum neurotoxin (BoNT) treatment in various neurologic indications. Methods: This monocenter retrospective cohort study analyzed the data of 471 patients started on BoNT therapy between 1995 and 2015. Blood samples of 173 patients were investigated for NABs using the mouse hemidiaphragm test (93 with suspected therapy failure, 80 prospective study participants). The frequency of NAB-cSTF was assessed for various indications: hemifacial spasm, blepharospasm, cervical dystonia, other dystonia, and spasticity. A priori defined potential risk factors for NAB-cSTF were evaluated, and a stepwise binary logistic regression analysis was performed to identify independent risk factors. Results: Treatment duration was 9.8 ± 6.2 years (range, 0.5–30 years; adherence, 70.6%) and number of treatment cycles 31.2 ± 22.5 (3–112). Twenty-eight of 471 patients (5.9%) had NAB-cSTF at earliest after 3 and at latest after 103 treatment cycles. None of the 49 patients treated exclusively with incobotulinumtoxinA over 8.4 ± 4.2 (1–14) years developed NAB-cSTF. Independent risk factors for NAB-cSTF were high BoNT dose per treatment, switching between onabotulinumtoxinA and other BoNT formulations (except for switching to incobotulinumtoxinA), and treatment of neck muscles. Conclusions: We present a follow-up study with the longest duration to date on the incidence of NAB-cSTF in patients treated with various BoNT formulations, including incobotulinumtoxinA. Whereas the overall risk of NAB-cSTF is low across indications and BoNT formulations, our findings underpin the recommendations to use the lowest possible dose particularly in cervical dystonia, and to avoid unnecessary switching between different formulations.