Botulinum toxin type A products are not interchangeable: a review of the evidence

Abstract

Botulinum toxin type A (BoNTA) products are injectable biologic medications derived from Clostridium botulinum bacteria. Several different BoNTA products are marketed in various countries, and they are not interchangeable. Differences between products include manufacturing processes, formulations, and the assay methods used to determine units of biological activity. These differences result in a specific set of interactions between each BoNTA product and the tissue injected. Consequently, the products show differences in their in vivo profiles, including preclinical dose response curves and clinical dosing, efficacy, duration, and safety/adverse events. Most, but not all, published studies document these differences, suggesting that individual BoNTA products act differently depending on experimental and clinical conditions, and these differences may not always be predictable. Differentiation through regulatory approvals provides a measure of confidence in safety and efficacy at the specified doses for each approved indication. Moreover, the products differ in the amount of study to which they have been subjected, as evidenced by the number of publications in the peer-reviewed literature and the quantity and quality of clinical studies. Given that BoNTAs are potent biological products that meet important clinical needs, it is critical to recognize that their dosing and product performance are not interchangeable and each product should be used according to manufacturer guidelines.

Pharmacological differences and clinical implications of various botulinum toxin preparations: a critical appraisal

“…Two BoNTs have been authorized for clinical use, serotypes A and B. BoNTA has historically been the most widely studied serotype for therapeutic purposes. OnabtulinumtoxinA and abobotulinumtoxinA contain neurotoxin protein complexes, although of different sizes, whereas incobotulinumtoxinA contains only the ∼150 kDa neurotoxin, which is devoid of any NAPs (Brin et al, 2014). There are five BoNTA NAPs (4 different hemagglutinins and 1 non-hemagglutinin), which are synthesized by Clostridium botulinum and protect the neurotoxin from degradation (Chen et al, 1998).…”

“…However, a direct correlation between neutralizing antibodies and clinical response cannot be established, and the relationship is not fully understood (Brin et al, 2014). Antibodies may also develop against NAPs, but these are 'non-neutralizing', i.e., they do not impair clinical activity (Joshi et al, 2011).…”

“…The three main BoNTA products currently marketed worldwide are onabotulinumtoxinA (Botox ® , Allergan Inc., Irvine, CA, USA), abobotulinumtoxinA (Dysport ® , Ipsen Ltd, Slough, © C I C E d i z i o n i I n t e r n a z i o n a l i Functional Neurology 2018;33(1):7-18 UK), and incobotulinumtoxinA (Xeomin ® , Merz Pharmaceuticals GmbH, Frankfurt am Main, Germany). There exist important pharmacological differences between BoNTA preparations, which affect clinical activity, and the availability of different products has given rise to intense debate on dose equivalence and comparative effectiveness (Brin et al, 2014). This was acknowledged in 2009 by the FDA, which stated that "Potency units are specific to each single BoNT product and doses or biologic activity units cannot be compared or converted from one product to the other."…”

Experience of the Type a Botulinum Toxin Type (Onabotulinumtoxina) Drug in Treatment of Cerebral Palsy Patients

“…Сегодня однозначно установлено, что лекар-ственные препараты БТА не являются идентичными, так же как и не являются взаимозаменяемыми [2,27]. Каждый препарат обладает уникальными индивидуальными осо-бенностями и отличиями, хотя иногда дублируются основ-ные показания к клиническому применению.…”

Efficacy and patient satisfaction with incobotulinumtoxinA for the treatment of glabellar frown lines

“…(2) Variants of BoNT/A that have been produced and marketed commercially include onabotulinumtoxinA (Allergan Inc, Irvine, CA, USA), abobotulinumtoxinA (Ipsen Ltd, Slough, Berkshire, UK) and incobotulinumtoxinA (Merz Pharmaceuticals GmbH, Frankfurt am Main, Hesse, Germany). (1) IncobotulinumtoxinA (marketed under the trademark Xeomin®) has been shown to be effective for the treatment of glabellar frown lines (GFLs). (3)(4)(5)(6) It contains only the active neurotoxin and none of the complexing proteins commonly found in other BoNT/A products.…”