Comparative in vivo degradation of hyaluronic acid‐based fillers following injection of hyaluronidase

Hyaluronic acid (HA) fillers are one of the most popular minimally invasive cosmetic procedures for facial rejuvenation owing to their fast results, minimal downtime, and low rate of adverse events. Despite an overall favorable safety profile, one of the key attributes of HA fillers is their reversibility by hyaluronidase to address treatment-related complications.1 Knowledge of how hyaluronidase affects specific HA fillers is paramount for aesthetic practitioners to ensure patient safety and optimal satisfaction with treatment results. Several HA filler products are currently available, each with distinct rheological characteristics influenced by their physicochemical properties.2 In vitro studies suggest that these physicochemical properties may impact hyaluronidase-mediated HA filler degradation, whereby more concentrated or crosslinked fillers may be more resistant to hyaluronidase.3 However, previous results from in vivo models and clinical studies showed no significant difference in susceptibility to higher doses of hyaluronidase among different HA fillers.4, 5 VYC-25L is a high-concentration and tightly crosslinked HA filler whose high cohesivity and elasticity make it suitable for facial volumizing (Table 1). These characteristics are expected to render VYC-25L more resistant to hyaluronidase-mediated degradation; however, this has not been empirically tested. Therefore, this study aimed to evaluate the degradation of VYC-25L alongside several other volumizing HA fillers after a single administration of hyaluronidase in vivo. A previously described rat model designed to control for biological factors that may impact sensitivity to hyaluronidase was used.4 Detailed methods are described in Supporting information (Data S1). Briefly, fixed-volume boluses of a panel of fillers with similar indications to VYC-25L, but varied viscoelastic properties were injected subcutaneously (Table 1). After 4 days, 15U of recombinant human hyaluronidase was injected into the center of each projecting bolus. After hyaluronidase administration, 3D images of each bolus were captured at baseline and over time, and the mean change in filler projection was tracked to measure degradation. After 1 h, RHA4 demonstrated significantly faster degradation as compared to VYC-25L (p < 0.05, Figure 1). Any differences among these fillers were no longer observed starting at the 2-h time point. At 48 h, HA filler projections ranged from 6% (VYC-25L) to 25% (TEO-UD) of baseline height. In summary, this data showed that all HA fillers tested in this panel were susceptible to degradation by hyaluronidase at the dose used here. The results suggest that in vivo, differences in properties among HA fillers do not significantly impact the sensitivity to enzymatic degradation beyond early time points. These findings extend on previous studies by using an animal model that mimics the local tissue environment, thus enabling a direct comparison of many HA fillers in a more biologically relevant manner. Similar to the previous report from Shumate et al., any differences in the degradation rate may be clinically insignificant when sufficiently high doses of hyaluronidase are used.4 The 15U injections of hyaluronidase used here are consistent with consensus recommendations for mild–moderate adverse effects.6 However, in practice, the appropriate amount of hyaluronidase varies based on different factors, such as whether the patient needs micro-adjustments or complete erasure of filler. Nonetheless, the large reduction in the volume of the filler bolus observed for all products studied here adds confidence to the aesthetic practitioners' ability to address over-correction or other complications with appropriate doses of hyaluronidase. While this study provides a head-to-head comparison of fillers under controlled conditions in vivo, a limitation of this study is that it does not consider the variables introduced from routine clinical use, such as the injection depth, shape, and volume. Further investigation is needed to determine the specific factors that impact the sensitivity of HA fillers to hyaluronidase in a clinical setting. Alex Pierce and Lauren Nakab were involved in the conception and design of the study. Alex Pierce contributed to the collection of the data. Alex Pierce, Lauren Nakab, and Maurizio Cavallini were involved in the analysis and interpretation of the data. All authors were involved in reviewing and revising the manuscript and have read and approved the final manuscript. Writing assistance was provided to the authors by Elizabeth Selwan-Lewis, PhD, of AbbVie Inc, and funded by AbbVie Inc. Editorial assistance was provided by Angela T. Hadsell of AbbVie Inc, and funded by AbbVie Inc. This study was sponsored by Allergan Aesthetics, an AbbVie company. All authors met the ICMJE criteria for authorship, and neither honoraria nor other forms of payment were made for authorship. Financial arrangements of the authors with companies whose products may be related to the present report are as follows, as declared by the authors. M Cavallini is an investigator for Allergan Aesthetics, an AbbVie Company. A Pierce and L Nakab are employees of AbbVie Inc and may own stock/stock options in the company. The authors confirm that the ethical policies of the journal, as noted on the journal's author guidelines page, have been adhered to, and the appropriate ethical review committee approval has been received. The guidelines set by the AbbVie Animal Care and Use Committee were followed. Data S1: Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.