Enzymatic Subcision and Remodeling after Collagenase Clostridium histolyticum-Aaes Subcutaneous Injection: Updated Evidence from Porcine and Human Studies

Abstract

BACKGROUND: CCH injection is approved for the treatment of moderate-to-severe cellulite in the buttocks of adult women. Porcine/human studies were conducted to further determine the subdermal impact of CCH, including that on dermal thickness. METHODS:Porcine study: CCH (0.07 mg) or placebo injections in 10 ventral sites. Human Study 1: Women undergoing abdominoplasty received 1 or 2 CCH doses [Areas 1 (2 doses/site) and 2 (1 dose/site) using a three-aliquot or 7 injection/14-aliquot injection technique] of 0.07 mg. Human (REAL) Study: Women with mild/moderate cellulite on buttocks or posterolateral thighs received up to 0.84 mg of CCH per treatment area per session (up to 12 dimples) for up to three sessions (Days 1, 22, and 43). At a single study site, ultrasound assessed dermal thickness on Days 1, 22, 43, 90, and 180. RESULTS: Porcine Study (n = 3): Histology showed lysis/disintegration of interlobular subdermal septae in CCH-treated tissue. As collagen support was lost, blood leakage from the thinner endothelial venules was observed in Day-4, Day-2, and in Day-23, Day-2 injection sites. This correlated with site bruising/edema. Collagen neogenesis and subdermal structural reorganization were evident as early as 4 days after CCH dosing in Day-4 and clearly defined in Day-8 and in Day-29, Day-8 injection sites. Marked subdermal fat and collagen structural reorganization was evident at Day-21 and at Day-42, Day-21 injection sites. No changes were seen with placebo. Human Study 1 (n=10): In patients who received the three-aliquot injection technique, in 1 patient (pt), new, immature collagen fibers and fragmented mature collagen fibers were present within 1 day of CCH dose, and mainly immature collagen fibers and a homogenous distribution of smaller fat lobules were evident 1 day after the second CCH dose. Three days after CCH injection, in the second pt, there were new, immature collagen fibers, fragmented mature collagen fibers, and hemorrhage. In that pt, less hemorrhaging and a homogenous distribution of smaller fat lobules were evident after second CCH dose versus single-dose findings (Day-3). In the third pt, septae expansion, increase in immature versus mature collagen fibers were evident 14 days after the first CCH dose; immature collagen fibers, fragmented mature collagen fibers, and homogenous distribution of smaller fat lobules were visible 43 days after the first and 22 days after the second CCH dose. In pts who received the seven injection/14-aliquot injection technique, less hemorrhage and less impressive collagen changes were observed compared with three-aliquot pts at the same timepoints, but over a wider area of tissue. In 2 pts, there was further septae expansion and increase in mature versus immature fibers at >90 days after the second injection. Human (REAL) Study: Ultrasound data are pending. CONCLUSIONS: CCH injection was associated with Enzymatic Subcision and Remodeling, which involves lysis of mature, collagen-rich septae, stimulation of neocollagenesis, and reorganization of adipose lobules. A focus injection and grid-like injection techniques both showed histological changes, with the focus injection injection showing more robust changes but over a small area of tissue.