title: Meta-analysis of neutralizing antibody conversion with onabotulinumtoxinA (BOTOX®) across multiple indications.
abstract: This meta-analysis evaluated the frequency of neutralizing antibody (nAb) conversion with onabotulinumtoxinA (BOTOX®; Allergan) across five studied indications. The analysis was based on large, controlled or prospective, open-label trials (durations 4 months to ≥2 years). Serum samples were analyzed for nAbs using the Mouse Protection Assay. Subjects who were antibody negative at baseline and had at least one analyzable postbaseline antibody assay result were included. The 16 clinical studies included 3,006 subjects; of these, 2,240 met the inclusion criteria for this analysis. Subjects received 1-15 treatments (mean 3.8 treatments) with onabotulinumtoxinA. Total doses per treatment cycle ranged from 10 or 20 units in glabellar lines to 20-500 units in cervical dystonia. The numbers of subjects who converted from an antibody-negative status at baseline to antibody-positive status at any post-treatment time point were: cervical dystonia 4/312 (1.28%), glabellar lines 2/718 (0.28%), overactive bladder 0/22 (0%), post-stroke spasticity 1/317 (0.32%), and primary axillary hyperhidrosis 4/871 (0.46%). Across all indications, 11/2,240 subjects (0.49%) converted from antibody negative at baseline to positive at one or more post-treatment time points, but only three subjects became clinically unresponsive to onabotulinumtoxinA at some point following a positive assay. Based on these large trials, the frequency of antibody conversion after onabotulinumtoxinA treatment is very low, and infrequently leads to loss of efficacy. © 2010 Movement Disorder Society.
authors.affiliation: Department of Neurology, Klinikum Augsburg Neurologische Klinik, Augsburg, Germany. markus.naumann@klinikum-augsburg.de
authors.forename: Markus
authors.initials: M
authors.lastname: Naumann
authors.forename: Alastair
authors.initials: A
authors.lastname: Carruthers
authors.forename: Jean
authors.initials: J
authors.lastname: Carruthers
authors.forename: Sheena K
authors.initials: SK
authors.lastname: Aurora
authors.forename: Ross
authors.initials: R
authors.lastname: Zafonte
authors.forename: Susan
authors.initials: S
authors.lastname: Abu-Shakra
authors.forename: Terry
authors.initials: T
authors.lastname: Boodhoo
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Miller-Messana
authors.forename: George
authors.initials: G
authors.lastname: Demos
authors.forename: Lynn
authors.initials: L
authors.lastname: James
authors.forename: Frederick
authors.initials: F
authors.lastname: Beddingfield
authors.forename: Amanda
authors.initials: A
authors.lastname: VanDenburgh
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Chapman
authors.forename: Mitchell F
authors.initials: MF
authors.lastname: Brin
mesh_terms: D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood*; D019274:Botulinum Toxins, Type A / Q000276:immunology* / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D009069:Movement Disorders / Q000097:blood / Q000188:drug therapy / Q000276:immunology; D011446:Prospective Studies
chemical_list: D057134:Antibodies, Neutralizing; D019274:Botulinum Toxins, Type A