Philipp Albrecht1, Alexander Jansen2, John-Ih Lee2, Marek Moll2, Marius Ringelstein2, Dietmar Rosenthal2, Hans Bigalke2, Orhan Aktas2, Hans-Peter Hartung2, Harald Hefter2. 1. From the Department of Neurology (P.A., A.J., J.-I.L., M.M., M.R., O.A., H.-P.H., H.H.), Medical Faculty, Heinrich Heine University Düsseldorf; and Toxogen GmbH (D.R., H.B.), Hannover, Germany phil.albrecht@gmail.com. 2. From the Department of Neurology (P.A., A.J., J.-I.L., M.M., M.R., O.A., H.-P.H., H.H.), Medical Faculty, Heinrich Heine University Düsseldorf; and Toxogen GmbH (D.R., H.B.), Hannover, Germany.
Abstract
OBJECTIVE: To investigate the prevalence of neutralizing antibodies (NAbs) against botulinum neurotoxin type A (BoNT/A) during long-term BoNT/A treatment in different neurologic indications. METHODS: In this monocentric, observational cross-sectional study, 596 outpatients treated with BoNT/A for different indications were tested for BoNT/A binding antibodies by ELISA. Positive samples were investigated for NAbs with the mouse hemidiaphragm test. The prevalence of NAbs was analyzed for different indications: facial hemispasm, blepharospasm, cervical dystonia, other dystonia, and spasticity. Besides the rate of NAb-positive patients overall and per patient subgroup, a Kaplan-Meier analysis of the probability of remaining NAb negative with duration of treatment is provided, and a stepwise binary logistic regression analysis is performed to identify factors significantly contributing to the induction of NAbs. RESULTS: Overall, 83 of 596 patients (13.9%) had measurable NAbs. The probability of developing NAbs increased with the single and cumulative dose of treatment and was influenced by the BoNT/A formulation, while all other factors analyzed, including disease entity and treatment duration, had no additional influence. CONCLUSIONS: We present the largest study to date of the prevalence of BoNT/A NAbs in a large unbiased cohort of patients including the relevant neurologic indications. Repeated injections of BoNT/A inevitably bear the risk of developing NAbs. However, in addition to avoiding booster injections and providing short intervals between injections, reducing the individual injected doses may diminish the risk of NAb induction independently of the indication for which BoNT/A is used.
OBJECTIVE: To investigate the prevalence of neutralizing antibodies (NAbs) against botulinum neurotoxin type A (BoNT/A) during long-term BoNT/A treatment in different neurologic indications. METHODS: In this monocentric, observational cross-sectional study, 596 outpatients treated with BoNT/A for different indications were tested for BoNT/A binding antibodies by ELISA. Positive samples were investigated for NAbs with the mouse hemidiaphragm test. The prevalence of NAbs was analyzed for different indications: facial hemispasm, blepharospasm, cervical dystonia, other dystonia, and spasticity. Besides the rate of NAb-positive patients overall and per patient subgroup, a Kaplan-Meier analysis of the probability of remaining NAb negative with duration of treatment is provided, and a stepwise binary logistic regression analysis is performed to identify factors significantly contributing to the induction of NAbs. RESULTS: Overall, 83 of 596 patients (13.9%) had measurable NAbs. The probability of developing NAbs increased with the single and cumulative dose of treatment and was influenced by the BoNT/A formulation, while all other factors analyzed, including disease entity and treatment duration, had no additional influence. CONCLUSIONS: We present the largest study to date of the prevalence of BoNT/A NAbs in a large unbiased cohort of patients including the relevant neurologic indications. Repeated injections of BoNT/A inevitably bear the risk of developing NAbs. However, in addition to avoiding booster injections and providing short intervals between injections, reducing the individual injected doses may diminish the risk of NAb induction independently of the indication for which BoNT/A is used.
Authors: Wilson W S Ho; Philipp Albrecht; Pacifico E Calderon; Niamh Corduff; David Loh; Michael U Martin; Je-Young Park; Lis S Suseno; Fang-Wen Tseng; Vasanop Vachiramon; Rungsima Wanitphakdeedecha; Chong-Hyun Won; Jonathan N T Yu; Mary Dingley Journal: Plast Reconstr Surg Glob Open Date: 2022-06-20
Authors: Marenka Smit; Alberto Albanese; Monika Benson; Mark J Edwards; Holm Graessner; Michael Hutchinson; Robert Jech; Joachim K Krauss; Francesca Morgante; Belen Pérez Dueñas; Richard B Reilly; Michele Tinazzi; Maria Fiorella Contarino; Marina A J Tijssen Journal: Front Neurol Date: 2021-06-03 Impact factor: 4.003
Authors: Shannon Y Chiu; Bhavana Patel; Matthew R Burns; Joseph Legacy; Aparna Wagle Shukla; Adolfo Ramirez-Zamora; Wissam Deeb; Irene A Malaty Journal: Tremor Other Hyperkinet Mov (N Y) Date: 2020-02-27