Comparison of different preparations of botulinumtoxin A in the treatment of cervical dystonia

Background and Objectives: Botulinum neurotoxin A (BoNT-A) is the fi rst line treatment for cervical dystonia (CD). Three different preparations are available: abobotulinumtoxinA, onabotulinumtoxinA, and incobotulinumtoxinA. However, potencies between these preparations vary and the products are therefore not easily interchangeable. Methods: We retrospectively compared the treatment plans and outcome of 51 patients with CD who were treated either with abobotulinumtoxinA (n = 19), onabotulinumtoxinA (n = 20), or incobotulinumtoxinA (n = 12). Results: There were no differences between the three treatment groups in respect to time of fi rst improvement of symptoms (TIS), duration of symptom relieve (DSR), or maximum benefi t (MaxB). However, the total units used for treatment in the abobotulinumtoxineA group was signifi cantly higher than in both other groups, thus resulting in a conversion ratio of 4:1for abobotulinumtoxinA to onabotulinumtoxinA and a conversion ratio of 4.3:1 for abobotulinumtoxinA to incobotulinumtoxinA. Conclusion: In clinical practice, the conversion ratio between abototulinumtoxinA and onabotulinumtoxineA might be higher than previously indicated by prospective studies or in mouse assays. Consequently, lager studies are needed to determine the conversion ratio of the different preparations available as well as the optimization of doses and selection of preparation, therefore resulting in improved cost-effectiveness of different treatment options in clinical practice. Neurology Asia 2012; 17(2) : 115 – 119 Address correspondence to: Tobias Wächter, German Centre for Neurodegenerative Diseases (DZNE) and Department for Neurodegenerative Diseases of the Hertie Institute for Clinical Brain Research, and, University of Tübingen, Hoppe-Seyler-Str. 3, D-72076 Tübingen, Germany. Email: tobias.waechter@ uni-tuebingen.de. Tel.: 0049-7071-29-80438. Fax: 0049-7071-29-8349 INTRODUCTION Botulinum neurotoxin A (BoNT-A) is the first line treatment for cervical dystonia (CD). BoNT-A is a natural protein derived from clostridium botulinum, of which different preparations, abobotulinumtoxinA (Dysport®), onabotulinumtoxinA (Botox®), and incobotulinumtoxinA (Xeomin®), are commercially available. These various preparations of BoNT-A are produced using different methods and processes ultimately resulting in different potencies of each product, meaning dosing recommendations for each product are not easily interchangeable. 3 Even though potencies are usually determined in mouse LD50 units (U), defi ned as the median lethal dose in a specifi ed mouse population, the potencies are not always comparable, as the essay methodology varies, e.g. with the assay diluents used. Nevertheless, LD50-tests with comparable methodology demonstrated a 1:1 potency ratio of incobotulinumtoxinA and onabotulinumtoxinA and a 2.3:1 potency ratio of abobotulinumtoxinA and onabotulinumtoxinA in saline. In clinical practice, the effi cacy of the different toxins also depends on the solution used as diluent (e.g. saline or gelatin-containing phosphate buffer), as well as the volume of the diluent. In a clinical study on patients with cervical dystonia a dosing ratio of 1:1 between incobotulinumtoxinA and onabotulinumtoxinA has been found to result in comparable effi cacy. In contrast, between abobotulinumtoxinA and onabotulinumtoxinA, the conversion ratio has been disputed. 3 While one double blinded study on patients with CD used a conversion ratio of 3:1 with equivalent treatment effects, another study compared two different conversion ratios of 4:1 and 3:1 in a cross over design and subsequently found no superiority of a treatment ratio higher than 3:1 between abobotulinumtoxinA and onabotulinumtoxinA. These studies led to the conclusion that 3:1 was the most likely conversion rate between abobotulinumtoxinA and onabotulinumtoxinA. In order to further investigate the conversion Neurology Asia June 2012 116 ratio for all three preparations, the doses used for treatment in CD in clinical praxis were analyzed retrospectively.