Collagenase Clostridium Histolyticum-aaes for the Treatment of Cellulite in Women: Results From Two Phase 3 Randomized, Placebo-Controlled Trials.


Journal

Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.]
ISSN: 1524-4725
Titre abrégé: Dermatol Surg
Pays: United States
ID NLM: 9504371

Informations de publication

Date de publication:
01 05 2021
Historique:
pubmed: 13 4 2021
medline: 14 9 2021
entrez: 12 4 2021
Statut: ppublish

Résumé

Fibrous septae play a role in contour alterations associated with cellulite. To assess collagenase clostridium histolyticum-aaes (CCH) for the treatment of cellulite. 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. 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%). Collagenase clostridium histolyticum-aaes significantly improved cellulite appearance and was generally well tolerated.

Sections du résumé

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.

Identifiants

pubmed: 33840781
doi: 10.1097/DSS.0000000000002952
pii: 00042728-202105000-00018
pmc: PMC8078112
doi:

Substances chimiques

Antibodies, Neutralizing 0
Microbial Collagenase EC 3.4.24.3

Banques de données

ClinicalTrials.gov
['NCT03428750', 'NCT03446781']

Types de publication

Clinical Trial, Phase III Journal Article Multicenter Study Randomized Controlled Trial

Langues

eng

Sous-ensembles de citation

IM

Pagination

649-656

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society for Dermatologic Surgery.

Références

Friedmann DP, Vick GL, Mishra V. Cellulite: a review with a focus on subcision. Clin Cosmet Investig Dermatol 2017;10:17–23.
Rossi AB, Vergnanini AL. Cellulite: a review. J Eur Acad Dermatol Venereol 2000;14:251–62.
Avram MM. Cellulite: a review of its physiology and treatment. J Cosmet Laser Ther 2005;6:181–5.
Nürnberger F, Müller G. So-called cellulite: an invented disease. J Dermatol Surg Oncol 1978;4:221–9.
Rudolph C, Hladik C, Hamade H, Frank K, et al. Structural gender-dimorphism and the biomechanics of the gluteal subcutaneous tissue—implications for the pathophysiology of cellulite. Plast Reconstr Surg 2019;143:1077–86.
Mirrashed F, Sharp JC, Krause V, Morgan J, et al. Pilot study of dermal and subcutaneous fat structures by MRI in individuals who differ in gender, BMI, and cellulite grading. Skin Res Technol 2004;10:161–8.
Querleux B, Cornillon C, Jolivet O, Bittoun J. Anatomy and physiology of subcutaneous adipose tissue by in vivo magnetic resonance imaging and spectroscopy: relationships with sex and presence of cellulite. Skin Res Technol 2002;8:118–24.
Hexsel D, Siega C, Schilling-Souza J, Stapenhorst A, et al. Assessment of psychological, psychiatric, and behavioral aspects of patients with cellulite: a pilot study. Surg Cosmet Dermatol 2012;4:131–6.
Hexsel DM, Abreu M, Rodrigues TC, Soirefmann M, et al. Side-by-side comparison of areas with and without cellulite depressions using magnetic resonance imaging. Dermatol Surg 2009;35:1471–7.
Hexsel D, Dal Forno T, Hexsel C, Schilling-Souza J, et al. Magnetic resonance imaging of cellulite depressed lesions successfully treated by subcision. Dermatol Surg 2016;42:693–6.
Hexsel DM, Mazzuco R. Subcision: a treatment for cellulite. Int J Dermatol 2000;39:539–44.
Amore R, Amuso D, Leonardi V, Sbarbati A, et al. Treatment of dimpling from cellulite. Plast Reconstr Surg Glob Open 2018;6:e1771.
Kaminer MS, Coleman WP III, Weiss RA, Robinson DM, et al. Multicenter pivotal study of vacuum-assisted precise tissue release for the treatment of cellulite. Dermatol Surg 2015;41:336–47.
Brauer JA, Christman MP, Bae YSC, Bernstein LJ, et al. Three-dimensional analysis of minimally invasive vacuum-assisted subcision treatment of cellulite. J Drugs Dermatol 2018;17:960–5.
Kaminer MS, Coleman WP III, Weiss RA, Robinson DM, et al. A multicenter pivotal study to evaluate tissue stabilized-guided subcision using the Cellfina device for the treatment of cellulite with 3-year follow-up. Dermatol Surg 2017;43:1240–8.
Kaminer M. Multi-center Pivotal Study of the Safety & Effectiveness of a Tissue Stabilized-Guided Subcision Procedure for the Treatment of Cellulite―5-Year Update. Presented at American Society for Dermatologic Surgery Annual Meeting; October 11–14, 2018; Phoenix, AZ.
Xiaflex (collagenase clostridium histolyticum) for Injection, for Intralesional Use [package Insert]. Malvern, PA: Endo Pharmaceuticals Inc; 2019.
Sadick NS, Goldman MP, Liu G, Shusterman NH, et al. Collagenase clostridium histolyticum for the treatment of edematous fibrosclerotic panniculopathy (cellulite): a randomized trial. Dermatol Surg 2019;45:1047–56.
Narins RS, Brandt F, Leyden J, Lorenc ZP, et al. A randomized, double-blind, multicenter comparison of the efficacy and tolerability of Restylane versus Zyplast for the correction of nasolabial folds. Dermatol Surg 2003;29:588–95.
US Department of Health and Human Services. Guidance for Industry: Patient-Reported Outcome Measures: Use in Medical Product Development to Support Labeling Claims. 2009. Available from: https://www.fda.gov/downloads/drugs/guidances/ucm193282.pdf . Accessed April 23, 2019.
Hexsel DM, Siega C, Schilling-Souza J, Porto MD, et al. A bipolar radiofrequency, infrared, vacuum and mechanical massage device for treatment of cellulite: a pilot study. J Cosmet Laser Ther 2011;13:297–302.
Hexsel DM, Dal'Forno T, Hexsel CL. A validated photonumeric cellulite severity scale. J Eur Acad Dermatol Venereol 2009;23:523–8.
De La Casa Almeida M, Suarez Serrano C, Jiménez Rejano JJ, Chillón Martinez R, et al. Intra- and inter-observer reliability of the application of the cellulite severity scale to a Spanish female population. J Eur Acad Dermatol Venereol 2013;27:694–8.
Davis DS, Boen M, Fabi SG. Cellulite: patient selection and combination treatments for optimal results—a review and our experience. Dermatol Surg 2019;45:1171–84.
Peimer CA, Blazar P, Coleman S, Kaplan FT, et al. Dupuytren contracture recurrence following treatment with collagenase clostridium histolyticum (CORDLESS [Collagenase Option for Reduction of Dupuytren Long-term Evaluation of Safety Study]): 5-year data. J Hand Surg Am 2015;40:1597–605.
Carson CC III, Sadeghi-Nejad H, Tursi JP, Smith TM, et al. Analysis of the clinical safety of intralesional injection of collagenase Clostridium histolyticum (CCH) for adults with Peyronie's disease (PD). BJU Int 2015;116:815–22.
Peimer CA, Wilbrand S, Gerber RA, Chapman D, et al. Safety and tolerability of collagenase Clostridium histolyticum and fasciectomy for Dupuytren's contracture. J Hand Surg Eur 2015;40:141–9.

Auteurs

Joely Kaufman-Janette (J)

Skin Associates of South Florida, Coral Gables, Florida.

John H Joseph (JH)

John H. Joseph Facial Plastic and Reconstructive Surgery, Beverly Hills, California.

Michael S Kaminer (MS)

Dermatology, SkinCare Physicians, Chestnut Hill, Massachusetts.

James Clark (J)

Charlottesville Medical Research, Charlottesville, Virginia.

Sabrina G Fabi (SG)

Cosmetic Laser Dermatology and University of California-San Diego, San Diego, California.

Michael H Gold (MH)

Department of Medicine, Division of Dermatology, Tennessee Clinical Research Center, Nashville, Tennessee.

Mitchel P Goldman (MP)

Cosmetic Laser Dermatology and University of California-San Diego, San Diego, California.

Bruce E Katz (BE)

Juva Skin & Laser Center, New York, New York.

Kappa Peddy (K)

The Education & Research Foundation, Lynchburg, Virginia.

Joel Schlessinger (J)

Cosmetic Surgery, Skin Specialists P.C., Omaha, Nebraska.

V Leroy Young (VL)

Research, Mercy Health Research, Washington, Missouri.

Matthew Davis (M)

Research and Development, Endo Pharmaceuticals Inc, Malvern, Pennsylvania.

David Hurley (D)

Medical Affairs, Endo Pharmaceuticals Inc, Malvern, Pennsylvania.

Genzhou Liu (G)

Biostatistics, Endo Pharmaceuticals Inc, Malvern, Pennsylvania; and.

Michael P McLane (MP)

Medical Affairs, Endo Pharmaceuticals Inc, Malvern, Pennsylvania.

Saji Vijayan (S)

Research and Development, Endo Pharmaceuticals Inc, Malvern, Pennsylvania.

Lawrence S Bass (LS)

Bass Plastic Surgery PLLC, New York, New York.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH