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Dear editor  One of the most surprising and, at the same time, most frustrating aspects of the continual rise in the use of botulinum toxin type A (BoNT-A), particularly in aesthetic applications, is the sheer number of reviews currently being published. So far in 2013, there have been seven single or joint reviews of BoNT products focusing on facial aesthetics.  The frustrating aspects of these reviews cover two areas: Firstly, they inevitably speculate about why there are “apparent differences” between the products. They attempt to use the science of BoNT-A to explain these differences. This speculation is both inappropriate and weak. In fact, the majority of differences between the products seen clinically are, by far, due to simple dose differences used in studies, especially when two or more products are being compared.  Secondly, these reviews usually have tables of data about the products which contain, according to the authors, “clinically relevant” information. They are claimed as “pharmacologic differences”. Again inevitably, they are not. The data are mostly irrelevant to clinical practice and, by far the worst situation, they are actually incorrect. Readers are presented with data that are sometimes not even referenced and clearly have not been cross-checked with the appropriate sources – such as the manufacturers’ own product literature.  The latest review by Prager1 is yet another publication that shows both these traits. Speculation is yet again used, for example, to propose that other components of the BoNT-A protein complex (in certain products) may lead to an increase in neutralizing antibody formation. This speculation is not based on even initial facts or data. Citations of work purporting to support this “hypothesis” are fundamentally flawed, as recently reported.2 Given that Merz Pharmaceuticals GmbH themselves, the sponsors of the Prager review, have already proven that any BoNT-A complex (BoNT-A neurotoxin and other associated proteins produced by the bacteria) is fully dissociated in the product vials before injection,3 then the concept of differential neutralizing antibody formation seems a quite inappropriate attempt at product differentiation for marketing.  The table of product data presented by Prager (Table 2)1 which gives the characteristics of the different products, is a fundamentally flawed part of this review.  To start with (and also applicable even to the title of the paper), the United States approved names for the products (incobotulinumtoxinA, onabotulinumtoxinA, abobotulinumtoxinA) have been used. Why? These names are only applicable to the United States and have no relevance in Europe. They are not generic drug names since there is no such thing as a “generic biologic” product of BoNT-A. The BoNT-A products are each considered very individual and the units of potency are not interchangeable, as required by the regulatory authorities worldwide. Dr Prager is a German clinician, working in Germany, the writers of the article are based in the UK, the sponsor of the article is a German company. Europe has managed perfectly well with the original product trade names for 25 years, so why are these names used by Prager?  There are six full lines of Table 21 with either incorrect or clinically irrelevant data. Even potentially useful clinical information is based upon either incorrect sources or single sources which do not take into account, for example, the differences in dose units of the products.  In particular, the continuing and highly confusing information being supplied in reviews about the so-called “toxin complex size” is given by Prager, yet again.1 But, once more, the data already produced by Merz Pharmaceuticals GmbH show this is totally irrelevant when considering the BoNT-A products in clinical use, due to dissociation within the vial prior to injection.3  Prager has additionally failed to recognize that Galderma is the company marketing Azzalure® within Europe, not Ipsen or Medicis, which is very strange given that Galderma and Azzalure® are strongly represented in Germany. Previous comments in an earlier review by Prager et al,4 that “the number of abobotulinumtoxinA injections was so low (1.6%, which might reflect daily practice in Germany)” are quite ludicrous. The number of Azzalure® units per vial (125 Speywood units) is not even cited. Such errors, omissions and comments are highly misleading and ingenuous for readers.  Finally, if the storage temperature of Xeomin®/Bocouture® (Merz Pharma GmbH & Co. KGaA, Frankfurt, Germany) does rise above 25°C, then refrigeration of those products will be required. A statement “no refrigeration required” cannot be made, as in Table 2 of Prager.1 Merz ship their BoNT-A products to warmer countries in specialized, temperature-controlled packaging in order to keep the product within the approved storage conditions, as per the manufacturers instructions. The reader should refer to the relevant storage data for their own country of use.  All of these errors in the Prager review1 could and should be both avoided and prevented. Tables of such data are regrettably taken by many readers and users of BoNT-A products as definitive sources of information and so must be correct. These issues of error have been raised by myself and others before, yet their continual publication still continues.2,5,6  However what is the final and perhaps most strange aspect of this review is that, given the Merz sponsorship, there should be no errors and no speculation about the BoNT-A products. There is no place for such failures in the world of evidence-based product assessments today.

Reviews of botulinum toxin products in aesthetic use must be accurate, clear and avoid speculation