Effectiveness of Low Doses of Hyaluronidase to Remove Hyaluronic Acid Filler Nodules : A Randomized Clinical Trial

Abstract

<div class="section"> <a class="named-anchor" id="ab-doi180011-1"> <!-- named anchor --> </a> <h5 class="section-title" id="d5523998e387">Question</h5> <p id="d5523998e389">Can low doses of hyaluronidase safely and effectively dissolve hyaluronic acid filler nodules? </p> </div><div class="section"> <a class="named-anchor" id="ab-doi180011-2"> <!-- named anchor --> </a> <h5 class="section-title" id="d5523998e392">Findings</h5> <p id="d5523998e394">In this randomized clinical trial of 9 women and 72 injection sites, small unit doses of hyaluronidase allowed removal of minute quantities of filler without removing the entire implant. </p> </div><div class="section"> <a class="named-anchor" id="ab-doi180011-3"> <!-- named anchor --> </a> <h5 class="section-title" id="d5523998e397">Meaning</h5> <p id="d5523998e399">Minor asymmetries after filler can be corrected by the injector in a manner convenient for patients. </p> </div><p class="first" id="d5523998e402">This parallel-group, randomized clinical trial assesses the effectiveness and dose-related effect of small quantities of hyaluronidase vs saline to treat hyaluronic acid filler nodules in healthy women. </p><div class="section"> <a class="named-anchor" id="ab-doi180011-4"> <!-- named anchor --> </a> <h5 class="section-title" id="d5523998e406">Importance</h5> <p id="d5523998e408">Although hyaluronidase is known to remove hyaluronic acid fillers, use of low doses has not been well studied. </p> </div><div class="section"> <a class="named-anchor" id="ab-doi180011-5"> <!-- named anchor --> </a> <h5 class="section-title" id="d5523998e411">Objective</h5> <p id="d5523998e413">To assess the effectiveness and dose-related effect of small quantities of hyaluronidase to treat hyaluronic acid filler nodules. </p> </div><div class="section"> <a class="named-anchor" id="ab-doi180011-6"> <!-- named anchor --> </a> <h5 class="section-title" id="d5523998e416">Design, Setting, and Participants</h5> <p id="d5523998e418">Split-arm, parallel-group, randomized clinical trial at an urban academic center. Participants were 9 healthy women. Recruitment and follow-up occurred from February 2013 to March 2014; data analysis occurred from February to July 2016. </p> </div><div class="section"> <a class="named-anchor" id="ab-doi180011-7"> <!-- named anchor --> </a> <h5 class="section-title" id="d5523998e421">Interventions</h5> <p id="d5523998e423">Each participant received aliquots (buttons) of either of 2 types of hyaluronic acid fillers into bilateral upper inner arms, respectively. At 1, 2, and 3 weeks each button was treated with a constant volume (0.1 mL) of variable-dose hyaluronidase (1.5, 3.0, or 9.0 U per 0.1 mL) or saline control. </p> </div><div class="section"> <a class="named-anchor" id="ab-doi180011-8"> <!-- named anchor --> </a> <h5 class="section-title" id="d5523998e426">Main Outcomes and Measures</h5> <p id="d5523998e428">Both a blinded dermatologist and the participant independently assessed detectability.</p> </div><div class="section"> <a class="named-anchor" id="ab-doi180011-9"> <!-- named anchor --> </a> <h5 class="section-title" id="d5523998e431">Results</h5> <p id="d5523998e433">Seventy-two treatment sites on 9 women (mean [SD] age, 45.8 [15.7] years) received all interventions and were analyzed. There was a significant difference in physician rater assessment between saline and hyaluronidase at 4 weeks (visual detection: mean difference = 1.15; 95% CI, 0.46-1.80; <i>P</i> &lt; .001; palpability: mean difference = 1.22; 95% CI, 0.61-1.83; <i>P</i> &lt; .001) and 4 months (visual detection: mean difference = 0.77; 95% CI, 0.33-1.26; <i>P</i> = .001; palpability: mean difference = 0.82; 95% CI, 0.38-1.25; <i>P</i> &lt; .001) that was mirrored by participant self-assessment at 4 weeks (visual detection: mean difference = 0.87; 95% CI, 0.26-1.48; <i>P</i> = .006; palpability: mean difference = 1.59; 95% CI, 1.41-1.77; <i>P</i> &lt; .001) and 4 months (visual detection: mean difference = 1.31; 95% CI, 1.09-1.53; <i>P</i> &lt; .001; palpability: mean difference = 1.52; 95% CI, 1.03-2.01; <i>P</i> &lt; .001), and hyaluronidase was associated with greater resolution of buttons compared with normal saline. The 9.0-unit hyaluronidase injection sites were significantly less palpable than the 1.5-unit sites at both 4 weeks (mean difference = 0.50; 95% CI, 0.01-.99; <i>P</i> = .045) and 4 months (mean difference = 0.47; 95% CI, 0.14-0.81; <i>P</i> = .007). Dose dependence was more notable for Restylane-L. </p> </div><div class="section"> <a class="named-anchor" id="ab-doi180011-10"> <!-- named anchor --> </a> <h5 class="section-title" id="d5523998e467">Conclusions and Relevance</h5> <p id="d5523998e469">Although very small doses of hyaluronidase can remove hyaluronic acid fillers from patient skin, slightly higher doses often result in more rapid resolution. </p> </div><div class="section"> <a class="named-anchor" id="ab-doi180011-11"> <!-- named anchor --> </a> <h5 class="section-title" id="d5523998e472">Trial Registration</h5> <p id="d5523998e474">clinicaltrials.gov Identifier: <a data-untrusted="" href="https://www.clinicaltrials.gov/ct2/show/NCT01722916" id="d5523998e476" target="xrefwindow">NCT01722916</a> </p> </div>