BACKGROUND Fibrous septae play a role in contour alterations associated with cellulite. OBJECTIVE To assess collagenase clostridium histolyticum-aaes (CCH) for the treatment of cellulite. MATERIALS AND METHODS Two identically designed phase 3, double-blind, randomized studies (RELEASE-1 and RELEASE-2) were conducted. Adult women with moderate/severe cellulite (rating 3–4 on the Patient Reported Photonumeric Cellulite Severity Scale [PR-PCSS] and Clinician Reported PCSS [CR-PCSS]) on the buttocks received up to 3 treatment sessions of subcutaneous CCH 0.84 mg or placebo per treatment area. Composite response (≥2-level or ≥1-level improvement from baseline in both PR-PCSS and CR-PCSS) was determined at Day 71. RESULTS Eight hundred forty-three women received ≥1 injection (CCH vs placebo: RELEASE-1, n = 210 vs n = 213; RELEASE-2, n = 214 vs n = 206). Greater percentages of CCH-treated women were ≥2-level composite responders versus placebo in RELEASE-1 (7.6% vs 1.9%; p = .006) and RELEASE-2 (5.6% vs 0.5%; p = .002) and ≥1-level composite responders in RELEASE-1 (37.1% vs 17.8%; p < .001) and RELEASE-2 (41.6% vs 11.2%; p < .001). Most adverse events (AEs) in the CCH group were injection site related; few CCH-treated women discontinued because of an AE (≤4.3%). CONCLUSION Collagenase clostridium histolyticum-aaes significantly improved cellulite appearance and was generally well tolerated.

Background: Collagenase clostridium histolyticum-aaes (CCH) enzymatically releases fibrous septa that contribute to the skin dimpling characteristic of cellulite. Long-term safety/duration of efficacy (durability) results from an open-label extension (OLE) of a randomized, double-blind, placebo-controlled trial (RCT) evaluating CCH efficacy/safety for moderate-to-severe cellulite of the buttocks or posterolateral thighs in women was assessed. Efficacy/safety of CCH treatment/retreatment during OLE was also evaluated. Methods: After RCT unblinding, women could enroll in OLE for assessment of long-term CCH durability (observation only, up to day 720) or CCH treatment/retreatment, the latter in women with moderate-to-severe buttock/posterolateral thigh cellulite [Clinician Reported Photonumeric Cellulite Severity Scale (CR-PCSS) and Patient Reported PCSS (PR-PCSS) scores of 3/4; Hexsel Cellulite Severity Scale score ≤13]. A treatment/retreatment course comprised 1 or 2 courses of 3 sessions (0.84-mg CCH injected at days 1, 22, and 43). CCH efficacy/safety was assessed at baseline, days 22, 43, 71, and quarterly at day 360. Results: Of the 259 OLE participants, 53 were observed for long-term CCH durability. For those who were ≥2-level composite responders during RCT (≥2-point CR-PCSS/PR-PCSS score improvements), CCH effect was durable (scores did not reach RCT baseline levels) in all women on days 180 (19/19), 360 (16/16), and 720 (7/7). Of the 200 women receiving CCH treatment/retreatment, more than 75% had ≥1-level improvement in patient and clinical assessments at day 71. The most common adverse events were injection-site bruising and pain. Conclusions: CCH treatment provided durable improvement in moderate-to-severe buttock/thigh cellulite and was generally well tolerated. Repeated CCH exposure did not increase adverse event risk or reduce efficacy.

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Background Given differences in buttock versus thigh cellulite, collagenase clostridium histolyticum‐aaes (CCH‐aaes) injection technique may impact treatment effects at these sites. Aim To evaluate efficacy and safety of 5 CCH‐aaes injection techniques. Methods A phase 2A, open‐label trial enrolled women with mild‐to‐severe cellulite (Clinician Reported Photonumeric Cellulite Severity Scale) on both buttocks or thighs. CCH‐aaes 0.84 mg was administered as 12 injections in each of two buttock or two thigh treatment areas (total dose, 1.68 mg) during three treatment sessions (Days 1, 22, 43). On Day 1, women were sequentially assigned to: Technique A = shallow injection/3 aliquots; Technique B = shallow injection/1 aliquot; Technique C = deep injection/1 aliquot; Technique D = deep and shallow injections/5 aliquots; or Technique E = shallow injection/4 aliquots. Change from baseline in Hexsel Cellulite Severity Scale (CSS) depression depth (range, 0 [no depressions] to 3 [deep depressions]) was assessed at Day 71. Safety was evaluated via adverse events. Results Sixty‐three women with buttock (n = 31) or thigh (n = 32) cellulite received ≥1 CCH‐aaes dose. For buttock cellulite, CCH‐aaes injection Technique A resulted in the greatest baseline‐adjusted improvement in CSS score on Day 71 (least‐squares mean, 1.17‐point improvement). For thigh cellulite, CSS score improvement was greatest with Technique D (least‐squares mean, 1.40‐point improvement). CCH injection Techniques A, D, and E were associated with more favorable safety profiles than Techniques B and C. Conclusion Different CCH‐aaes injection techniques are required with buttock (Technique A) versus thigh (Technique D) cellulite to optimize treatment outcomes.

Cosmetic INTRODUCTIONCellulite is a condition characterized by alterations in skin topography, frequently described as dimpling, in affected areas. 1,2 Cellulite affects between 80% and 98% of postpubertal women, 2,3 and although not completely understood, 4,5 the pathophysiology of cellulite is multifactorial. Both collagen-rich fibrous septae and associated protrusions of subcutaneous adipose tissue play a role. 4,[6][7][8] Collagenase clostridium histolyticum-aaes (CCH-aaes; Qwo, Endo Aesthetics‚ LLC, Malvern, Pa.) was approved by the US Food and Drug Administration in 2020 for the treatment of moderate-to-severe cellulite in the buttocks of adult women. 9 CCH-aaes is composed of two purified bacterial collagenases [AUX-I and AUX-II (clostridial class I and II collagenases)] that hydrolyze Types I and III collagen with high specificity. 9,10 The CCH-aaes mechanism