Six-Month Safety Results of Calcium Hydroxylapatite for Treatment of Nasolabial Folds in Fitzpatrick Skin Types IV to VI

Transcription

1 Six-Month Safety Results of Calcium Hydroxylapatite for Treatment of Nasolabial Folds in Fitzpatrick Skin Types IV to VI ELLEN S. MARMUR, MD, SUSAN C. TAYLOR, MD, y PEARL E. GRIMES, MD, z CHARLES M. BOYD, MD, y JENNIFER P. PORTER, MD, z AND JANE Y. YOO, MPP BACKGROUND Recently, the cosmetic market has seen an increase in the options for treatment for people with dark skin. OBJECTIVES This study evaluates the use of calcium hydroxylapatite (CaHA), a dermal filler indicated for the correction of moderate to severe facial wrinkles and folds, including the nasolabial folds (NLFs) in individuals with dark skin. METHODS This open-label, nonrandomized, prospective, five-center trial enrolled 100 patients aged 18 and older with Fitzpatrick skin types IV to VI. CaHA was injected subdermally with a 25- to 27-gauge needle. Participants received a range of 0.6 to 2.8 ml of CaHA and returned at 3 and 6 months to be assessed for keloid formation, hypertrophic scarring, and hyper- or hypopigmentation. If necessary, each subject was offered a touch-up at the conclusion of the 6-month visit. RESULTS No reports of keloid formation, hypertrophic scarring, hypo- or hyperpigmentation, or other clinically significant adverse events were recorded. CONCLUSIONS People with dark skin injected subdermally with CaHA do not show signs of keloid formation, hypertrophic scarring, or hyper- or hypopigmentation. Because of this safety feature, as well as other characteristics of the product already shown in clinical literature, CaHA is an attractive dermal filler in this population. BioForm Medical, Inc. provided the products and equipment for this study. Drs. Marmur and Boyd are members of the Medical Education Faculty of Bioform. There has been an increase in discussions of cosmetic treatment for people with dark skin in recent years, 1 and differences in skin types 2 have become key features in determining the best cosmetic outcomes for this population. Perhaps because of the differences in skin types, people with dark skin are perceived as being more prone to keloid formation, hypertrophic scarring, and hypo- and hyperpigmentation than other skin types. Indeed, the manufacturers of several notable dermal fillersfthis one includedfhave been required to provide follow-up studies specifically in persons of color. 3 Although published dermal filler studies have included patients of a variety of races and skin tones, the authors found scant mention of studies published on the outcomes in patient populations with only darker skin types. 4,5 This study evaluated the use of calcium hydroxylapatite (CaHA; Radiesse, BioForm Medical, San Mateo, CA), a dermal filler indicated for the correction of moderate to severe facial wrinkles and folds, including the nasolabial folds (NLFs), in people with dark skin. As a condition of approval, the Food and Drug Administration requested a postapproval study to assess the likelihood of hypertrophic scarring, keloid formation, and hyper- or hypopigmentation in patients with dark Division of Dermatologic and Cosmetic Surgery, Department of Dermatology, Mount Sinai Medical Center, New York, New York; y Society Hill Dermatology, Philadelphia, Pennsylvania; z Vitiligo and Pigmentation Institute of Southern California, Los Angeles, California; y Boyd Gillard Institute of Aesthetic and Dermatologic Surgery, Ypsilanti, Michigan; z Chevy Chase Facial Plastic Surgery, Chevy Chase, Maryland & 2009 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc. ISSN: Dermatol Surg 2009;35: DOI: /j x 1641

2 SIX-MONTH SAFETY RESULTS OF CALCIUM HYDROXYLAPATITE skin color, the results of which are presented in this article. TABLE 1. Fitzpatrick Skin Type Fitzpatrick Skin Type Description Patients % Mechanism of Action of CaHA Composed of CaHA microspheres (25 45 mm) in an aqueous carboxymethylcellulose gel carrier, CaHA provides immediate correction after injection that is predictable and controllable. Within several weeks, the body absorbs the gel carrier, leaving the microspheres to serve as a scaffold for the development of new collagen. The duration of effect in the face may depend on the motility of the area injected, but rough estimates suggest facial duration of approximately 1 year The product has been commercially available in the United States as a cosmetic dermal filler since late Study Objective This study was designed to assess the incidence of hypertrophic scarring, keloid formation, and hyperor hypopigmentation after CaHA injection for NLF treatment in patients with Fitzpatrick skin types IV, V, and VI. Materials and Methods Patient Selection This open-label, nonrandomized, prospective, fivecenter trial enrolled 100 patients aged 18 and older (94 women, 6 men) with Fitzpatrick skin types IV to VI (Table 1). Patients ranged in age from 25 to 78; mean patient age was In the study population, 85% of patients were African American, 12% were Hispanic, 2% were Asian, and 1% self-defined as other. Inclusion criteria were aged 18 and older; Fitzpatrick skin type IV, V, or VI; and understanding and acceptance of the obligation not to receive any other procedures or treatments in the NLF for 6 months. I Burns easily, never tans 0 II Burns easily, tans minimally 0 with difficulty III Burns moderately, tans 0 moderately and uniformly IV Burns minimally, tans 24 moderately and easily V Rarely burns, tans profusely 35 VI Never burns, tans profusely 41 Astner and Anderson, 2 p. 2. Exclusion criteria were history of hyper- or hypopigmentation in the NLFs, keloid formation, or hypertrophic scarring; known bleeding disorder or current drug therapy that could increase the risk of bleeding; NLFs that were too severe to be corrected in one treatment session; received any dermal filler or other injections, grafting, or surgery in either NLF; and pregnant, lactating, or not using acceptable contraception. Treatment At the initial visit, CaHA was injected subdermally with a 25- to 27-gauge needle using a linear threading and fanning technique. Injection volumes to bring the patient to full correction were at the discretion of the investigator. Overcorrection was not permitted. Anesthetization of the area was performed at the discretion of the treating physician. Ice or cool compresses could be applied pre- and postinjection. Medications to reduce swelling and bruising could also be prescribed at the discretion of the treating physician. Participants received a range of 0.6 to 2.8 ml of CaHA (mean 1.24 ml). Patients were scheduled to return at 3 and 6 months to be assessed for keloid formation, hypertrophic scarring, and hyper- or hypopigmentation. Incidence, type, severity, duration, and causality of adverse reactions were also recorded at both visits DERMATOLOGIC SURGERY

3 MARMUR ET AL At the conclusion of the 6-month visit, if necessary, each subject was offered a touch-up. Photographs were taken at the discretion of the investigator. 3-Month and 6-Month Follow-Up Visits At days from the injection visit (3-month visit), patients returned for a safety assessment of their NLFs. Assessment included the presence of keloid formation (firm, smooth, hard growth), hypertrophic scarring (red, raised bump), and hypoor hyperpigmentation (lightened or darkened area of the skin) in their NLFs. At days from the initial injection (6-month visit), patients returned for an additional safety assessment of their NLFs. Patients were assessed in the same manner as described for the 3-month visit. Subject participation was considered complete at the end of the 6-month visit. TABLE 2. Adverse Events at 3 and 6 Months Adverse Event Patients, % 3 Months (n = 100) Keloid formation 0 0 Hypertrophic 0 0 scarring Hypopigmentation 0 0 Hyperpigmentation Months (n = 98) received a follow-up assessment (3 of 98 were by phone, also because of scheduling conflicts). Two subjects were lost to follow-up at 6 months. Figures 1 to 3 are representative before-and-after results of patients participating in the study. Note the absence of any keloids, hyper- or hypopigmentation, Statistical Considerations The incidence, type, severity, and duration of all adverse events were reported. Incidence rates of local implant site adverse events were also provided, in addition to any other systemic adverse events reported. The number of patients with events and the total number of adverse events were recorded for each adverse event type and overall at study completion. Overall adverse event rates were presented using exact 95% confidence intervals. Baseline demographic and procedural information was summarized for all patients. This study was not designed for efficacy analyses or statistical power. Results Three-month and 6-month study results are shown in Table 2. No reports of keloid formation, hypertrophic scarring, hypo- or hyperpigmentation, or other clinically significant adverse events were recorded. All 100 subjects received a 3-month followup assessment (4 of 100 were by phone because of scheduling conflicts). At 6 months, 98 subjects Figure 1. (A) This 44-year-old man received a total of 1.4 ml of calcium hydroxylapatite (0.5 ml in his left nasolabial fold, 0.9 ml in his right nasolabial fold). (B) Post-treatment photograph at 6 months. 35:S2:OCTOBER

4 SIX-MONTH SAFETY RESULTS OF CALCIUM HYDROXYLAPATITE Figure 2. (A) This 43-year-old man received a total of 1.2 ml of calcium hydroxylapatite (0.6 ml in his left nasolabial fold, 0.6 ml in his right nasolabial fold). (B) Post-treatment photograph at 3 months. or hypertrophic scarring in the postinjection photographs. Discussion People with dark skin and their providers must understand the differences between skin types that could make a cosmetic procedure unattractive or attractive. It is therefore important to have data on the effect of cosmetic procedures on persons with dark skin before initiation of any procedures that might cause an adverse event, and this study has shed light on some of the questions. CaHA was found to be safe and well tolerated, with no reports of keloid formation, hypertrophic scarring, hypo- or hyperpigmentation, or other clinically significant adverse events for the correction of NLFs in patients with Fitzpatrick skin types Figure 3. (A) This 64-year-old woman received a total of 0.8 ml of calcium hydroxylapatite (0.4 ml in her left nasolabial fold, 0.4 ml in her right nasolabial fold). (B) Posttreatment photograph at 3 months. IV to VI. The lack of hypo- or hyperpigmentation may be because the filler is placed at a deeper level than hyaluronic acids, allowing for shorter-lived erythema. In addition, patients were instructed to stay out of the sun after the injection, lessening the incidence of postinflammatory hyperpigmentation. The scarcity of clinical data in aesthetic dermatology on persons with dark skin color is self-apparent; we believe that any new data, especially in soft tissue augmentation, in this population will be of great benefit to providers and patient. Our data show that people with dark skin, if injected subdermally with CaHA, do not show signs of keloid formation, hypertrophic scarring, or hyper- or hypopigmentation. Because of this safety feature, as well as other characteristics of the product already shown in clinical literature, CaHA is an attractive dermal filler in this population DERMATOLOGIC SURGERY

5 MARMUR ET AL References 1. Grimes PE. Aesthetics and Cosmetic Surgery for Darker Skin Types. Chicago, IL: Lippincott Williams and Wilkins (Wolters Kluer Health); Astner S, Anderson RR. Skin phototypes J Invest Dermatol 2004;122:xxx xxxi. 3. Injectable Cosmetic Wrinkle Fillers [on-line]. Available at and Drug Administration (Accessed September 9, 2008). 4. Guttman C. Skin of color. Safety, efficacy of hyaluronic acids profiled. Dermatol Times 2008;29: Taylor SC. Utilizing combination therapy for ethnic skin. Cutis 2007;80: Busso M, Karlsberg PL. Cheek augmentation and rejuvenation using injectable calcium hydroxylapatite (Radiesse s ). Cosmetic Dermatol 2006;19: Felderman LI. Radiesset for facial rejuvenation. Cosmetic Dermatol 2005;18: Goldberg DJ. Calcium hydroxylapatite. In: Goldberg DJ, editor. Fillers in Cosmetic Dermatology. Abingdon, UK: Informa UK Ltd; p Sadick NS, Katz BE, Roy D. A multicenter, 47-month study of safety and efficacy of calcium hydroxylapatite for soft tissue augmentation of nasolabial folds and other areas of the face. Dermatol Surg 2007;33:S Werschler WP. Treating the aging face: a multidisciplinary approach with calcium hydroxylapatite and other fillers, part 2. Cosmetic Dermatol 2007;20: Address correspondence and reprint requests to: Ellen S. Marmur, MD, Chief, Division of Dermatologic & Cosmetic Surgery, Department of Dermatology, The Mount Sinai Medical Center, 5 East 98th Street, Fifth Floor, Box 1048, New York, NY , or Ellen.Marmur@MountSinai.org 35:S2:OCTOBER