Relative Potency of IncobotulinumtoxinA vs OnabotulinumtoxinA A Meta-Analysis of Key Evidence

June 2012 | Volume 11 | Issue 6 | Original Article | 731 | Copyright © June 2012

Botulinum neurotoxin-A (BoNT-A) has become widely used in aesthetic applications over the past 20 years with several formulations now available. Although widely assumed to be equipotent, recent claims that the original commercial formulation, onabotulinumtoxinA (Botox®/Vistabel®, Allergan UK, Marlow, UK) is more potent than incobotulinumtoxinA (Bocouture®/Xeomin®, Merz Pharma, UK) have raised concerns that clinicians may be persuaded to increase doses to the potential detriment of their patients. To investigate this further, a review of the clinical evidence for the commercially available cosmetic formulations of BoNT-A was undertaken alongside a meta-analysis, carried out using mixed treatment analysis (MTA) methodology, of the available clinical data in the aesthetic setting. This demonstrated that at a dose of 24 units, there was a 94% likelihood that incobotulinumtoxinA was more effective than onabotulinumtoxinA in achieving a response as defined in the included studies; however, the scale of this advantage was not clinically meaningful. Of 11 clinical and preclinical studies identified comparing incobotulinumtoxinA and onabotulinumtoxinA directly, the weight of evidence suggested that there was no difference in the relative potency of the two products. As such, clinicians should continue to consider the formulations to be equipotent until such time that compelling clinical evidence to the contrary becomes available.

J Drugs Dermatol. 2012;11(6):731-736.


Following its first use in aesthetic procedures over 20 years ago, the popularity of botulinum toxin type A (BoNT-A) has grown rapidly, and usage continues to increase. Several formulations are now available and three are licensed in the UK for the treatment of glabellar lines: Clostridium botulinum toxin (type) onabotulinumtoxinA (Botox®/Vistabel®, Allergan UK, Marlow, UK), incobotulinumtoxinA (Bocouture®/Xeomin®, Merz Pharma, UK), and abobotulinumtoxinA (Azzalure®, Galderma, Watford, UK/Dysport ®, Ipsen, Slough, UK). In the absence of unequivocal clinical data in favor of one toxin, these formulations have typically been assumed to be equipotent. Indeed, in a study by Sattler et al.,1 that compared 24 units of incobotulinumtoxinA with 24 units of onabotulinumtoxinA, both toxins were found to be equally effective at treating glabellar lines. However, over the past 24 months, it has been claimed, on the basis of a single clinical study of different doses of the two formulations,2 not yet fully published, and two preclinical studies,3,4 that onabotulinumtoxinA is potentially more potent than incobotulinumtoxinA. The clinical study reported that 20 units of onabotulinumtoxinA is as effective as 30 units of incobotulinumtoxinA in reducing the severity of glabellar lines 28 days post injection, and demonstrated a non-significant trend in favor of onabotulinumtoxinA at days 84, 98, and 112.2 It is conceivable that aesthetic clinicians may alter their established dosing of incobotulinumtoxinA on the basis of these studies, with potentially harmful results due to overdose. This highlights the importance of carrying out a definitive review of the data surrounding relative potency of these two products in order to put the issue to rest.


Due to the acknowledged paucity of head-to-head data, to inform the review, a meta-analysis was carried out using a mixed treatment analysis (MTA) methodology to provide insight into the comparative efficacy of incobotulinumtoxinA and onabotulinumtoxinA. The MTA approach is able to combine data from direct comparisons (ie, treatment a versus treatment b) with information from indirect comparisons (ie, use of the results of treatment a versus treatment b and treatment b versus treatment c to provide an estimate of the comparative efficacy of treatment a versus treatment c) to provide a measure of their comparative efficacy. As such, it is ideally suited to situations where head-to-head trials are lacking. The results of this MTA were combined with a review of the relevant literature, including information sourced from Merz Pharma and Allergan UK.

Identification of Studies for Inclusion in the MTA

To identify relevant studies, a literature review was conducted using PubMed (NCBI, US National Library of Medicine). The following search terms/criteria were used: "botulinum toxin*" and "cosmetic" or "aesthetic" or "glabellar" or "wrinkle," or "crow's feet" or "rhytid," for citations from 1980 to 2011. Manual searching of bibliographies of key studies and reviews was also undertaken to identify additional references. To supplement the results of the literature review, Merz Pharma and Allergan UK were asked to provide any information they felt would be pertinent to the review of the relative potency of incobotulinumtoxinA versus onabotulinumtoxinA in the aesthetic setting. Studies that compared botulinum toxin A formulations (incobotulinumtoxinA, onabotulinumtoxinA,