Murad Alam1,2,3, Rosemara Hughart1, Amelia Geisler1, Kapila Paghdal1, Amanda Maisel1, Alexandra Weil1, Dennis P West1, Emir Veledar4,5,6,7, Emily Poon1. 1. Department of Dermatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. 2. Department of Otolaryngology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. 3. Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Illinois. 4. Center for Research and Grants, Baptist Health South Florida, Coral Gables. 5. Rollins School of Public Health, Department of Epidemiology, Emory University, Atlanta, Georgia. 6. School of Medicine, Department of Medicine, Emory University, Atlanta, Georgia. 7. Robert Stempel College of Public Health and Social Work, Department of Biostatistics, Florida International University, Miami.
Abstract
Importance: Although hyaluronidase is known to remove hyaluronic acid fillers, use of low doses has not been well studied. Objective: To assess the effectiveness and dose-related effect of small quantities of hyaluronidase to treat hyaluronic acid filler nodules. Design, Setting, and Participants: 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. Interventions: 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. Main Outcomes and Measures: Both a blinded dermatologist and the participant independently assessed detectability. Results: 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; P < .001; palpability: mean difference = 1.22; 95% CI, 0.61-1.83; P < .001) and 4 months (visual detection: mean difference = 0.77; 95% CI, 0.33-1.26; P = .001; palpability: mean difference = 0.82; 95% CI, 0.38-1.25; P < .001) that was mirrored by participant self-assessment at 4 weeks (visual detection: mean difference = 0.87; 95% CI, 0.26-1.48; P = .006; palpability: mean difference = 1.59; 95% CI, 1.41-1.77; P < .001) and 4 months (visual detection: mean difference = 1.31; 95% CI, 1.09-1.53; P < .001; palpability: mean difference = 1.52; 95% CI, 1.03-2.01; P < .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; P = .045) and 4 months (mean difference = 0.47; 95% CI, 0.14-0.81; P = .007). Dose dependence was more notable for Restylane-L. Conclusions and Relevance: Although very small doses of hyaluronidase can remove hyaluronic acid fillers from patient skin, slightly higher doses often result in more rapid resolution. Trial Registration: clinicaltrials.gov Identifier: NCT01722916.
RCT Entities:
Importance: Although hyaluronidase is known to remove hyaluronic acid fillers, use of low doses has not been well studied. Objective: To assess the effectiveness and dose-related effect of small quantities of hyaluronidase to treat hyaluronic acid filler nodules. Design, Setting, and Participants: 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. Interventions: 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. Main Outcomes and Measures: Both a blinded dermatologist and the participant independently assessed detectability. Results: 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; P < .001; palpability: mean difference = 1.22; 95% CI, 0.61-1.83; P < .001) and 4 months (visual detection: mean difference = 0.77; 95% CI, 0.33-1.26; P = .001; palpability: mean difference = 0.82; 95% CI, 0.38-1.25; P < .001) that was mirrored by participant self-assessment at 4 weeks (visual detection: mean difference = 0.87; 95% CI, 0.26-1.48; P = .006; palpability: mean difference = 1.59; 95% CI, 1.41-1.77; P < .001) and 4 months (visual detection: mean difference = 1.31; 95% CI, 1.09-1.53; P < .001; palpability: mean difference = 1.52; 95% CI, 1.03-2.01; P < .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; P = .045) and 4 months (mean difference = 0.47; 95% CI, 0.14-0.81; P = .007). Dose dependence was more notable for Restylane-L. Conclusions and Relevance: Although very small doses of hyaluronidase can remove hyaluronic acid fillers from patient skin, slightly higher doses often result in more rapid resolution. Trial Registration: clinicaltrials.gov Identifier: NCT01722916.
Authors: Wim H De Jong; Danyel Jennen; Peter H J Keizers; Hennie M Hodemaekers; Jolanda P Vermeulen; Frank Bakker; Paul Schwillens; Marcel van Herwijnen; Marlon Jetten; Jos C S Kleinjans; Robert E Geertsma; Rob J Vandebriel Journal: Int J Mol Sci Date: 2022-06-30 Impact factor: 6.208