Efficacy and safety of novel topical pigment‐correcting regimen with biweekly diamond tip microdermabrasion procedures on facial hyperpigmentation

Facial hyperpigmentation can negatively affect an individual's emotional and psychosocial well‐being.


| INTRODUC TI ON
Hyperpigmentation of the skin results from increased melanin production that may occur as a result of skin trauma, genetic predisposition, and ultraviolet (UV) light-induced photodamage. 1,2mmon types of facial hyperpigmentation include melasma, postinflammatory hyperpigmentation (PIH), and solar lentigines. 1,3lasma manifests as irregular brown patches, and is acquired primarily on sun-exposed areas, often in association with pregnancy, hormonal changes, photosensitizing medications, or as a result of a genetic predisposition. 2,4PIH occurs after a cutaneous inflammatory process, such as scarring caused by acne or secondary to irritants, trauma, or cosmetic procedures. 5,6Solar lentigines, commonly referred to as age spots, are well-circumscribed, brown to dark brown spots appearing on areas most often exposed to the sun. 1 Melasma and solar lentigines are often some of the first signs of aging and represent a major concern of individuals 20-40 years of age with melasma and > 60 years of age with solar lentigines, irrespective of skin type. 1,4PIH resulting from acne is more common among teens and young adults, and in those with darker skin tone; however, PIH can affect anyone, regardless of age, skin color, and gender. 5,68][9] Patients with hyperpigmentation disorders, including melasma and PIH, report embarrassment, self-consciousness, and effects on social and leisure activities because of their condition. 7,9Similarly, individuals with melasma report feeling inferior to others, not wanting to leave their house, and constantly thinking about their condition. 8[12] Hyperpigmentation is a difficult-to-treat chronic condition requiring continuous, long-term treatment, and frequent relapses often compromise adherence. 2,4,13,146][17] In addition, combination treatments that involve an in-office procedure, along with an at-home topical regimen, have demonstrated greater efficacy than single treatments alone, and help to reduce risk of recurrence of hyperpigmentation. 18[21] DiamondGlow® (DG; Allergan Aesthetics, an AbbVie Company, Irvine, CA, USA) is a noninvasive, in-office procedure using a pro- The objective of this study was to assess cosmetic changes in subjects with mild to severe overall facial hyperpigmentation who received a combination of a series of 6 DG procedures using EC-DG, along with an at-home skincare regimen comprising ABT and spot cream.on a modified Griffiths 10-point scale).The study design required enrollment of at least 15 subjects with moderate or severe overall hyperpigmentation (including but not limited to melasma, PIH, and dark spots), and 3-5 subjects with mild overall hyperpigmentation, with the majority of subjects having moderate to severe photodamage.Subjects also had to be willing to use only the provided study products, to withhold all facial treatments, to avoid direct and prolonged sun exposure for the duration of the study, and to report any adverse effects immediately in order to be eligible to participate in the study.Subjects were excluded from the study if they were nursing, pregnant, or planning to become pregnant during the study; had a preexisting or dormant dermatologic condition (e.g., psoriasis, atopic dermatitis); were currently or routinely using prescription medications for acne; had received chemical peel or microdermabrasion procedures during or within 4 weeks of entering the study; or had filler and/or neurotoxin injections, non-ablative laser, or fractional laser resurfacing procedures during or within 6 months of study entry.

| Study design
Subjects underwent a series of 6 in-office DG procedures using EC-DG, with one procedure administered every 2 weeks.Subjects used the targeted at-home products incorporated into a daily skincare regimen, comprising a facial cleanser (am/pm), a thin layer of ABT applied to the entire face (am/pm), Spot Cream applied to affected designated pigmented areas (pm), Replenish Hydrating Cream (am/ pm), and Essential Defense Mineral Shield SPF 35 (am and as needed; SkinMedica, Allergan Aesthetics, an AbbVie Company).Study visits occurred at baseline, immediately after the first DG plus EC-DG procedure, day 3, and weeks 2, 4, 6, 8, 10, and 12.
The study protocol was approved by the WCG Institutional Review Board, and the study was conducted in compliance with the Declaration of Helsinki and in accordance with all applicable guidelines for the protection of human subjects for research, as outlined in the accepted standards for Good Clinical Practice.

| Melasma area and severity index
Melasma severity was assessed using the Melasma Area and Severity Index (MASI) at each study visit. 24

| Moisturization/hydration measurement
Changes in moisturization/hydration were assessed at all visits using five adjacent Corneometer (Courage + Khazaka electronic GmbH, Köln, Germany) measurements and one MoistureMeterD (Delfin Technologies, Kuopio, Finland) measurement with the XS probe (superficial depth) and S probe (deeper depth) of the subject's middle of left cheek.Increases in moisturization and hydration scores from baseline indicated improvement in hydration.

| Antera 3D Imaging
Triplicate Antera 3D images were taken at all visits of the subject's self-identified most bothersome pigmented spot/area to assess improvement in brightness (increase in L* values), pigmentation (decrease in pigmentation score and pigmentation average, and increase in pigmentation uniformity), and texture (decrease in Ra roughness score, i.e., smoother skin).

| Self-assessment questionnaires
Subjects completed sponsor-provided self-assessment questionnaires immediately after the first DG plus EC-DG procedure and at day 3 and weeks 2, 4, 6, 8, 10, and 12 on self-perceived efficacy (e.g., faded the dark spots on my skin, made my skin feel smooth and soft) and psychosocial and emotional changes (e.g., makes me feel more confident, makes me feel happier about how I look), and overall satisfaction with responses ranging from "strongly agree" to "disagree strongly".

| Standardized digital photography
Photographs (Canfield Imaging Systems, Fairfield, NJ, USA) were taken at baseline, immediately after the first DG plus EC-DG procedure, and at follow-up visits using a Canon Mark II digital SLR camera (Canon Incorporated, Tokyo, Japan).Subjects were instructed to cleanse their face and remove any makeup at least 15 min prior to photography.

| Tolerability parameters
Tolerability evaluations were performed at all visits and included investigator-assessed erythema and dryness/scaling, and subjectreported burning/stinging and itching rated on a 4-point scale, where 0 = none, 1 = mild, 2 = moderate, and 3 = severe.Adverse events (AEs) were captured during the study.

| Statistical methods
The intent-to-treat (ITT) population was defined as all subjects who were enrolled and applied the test product.Descriptive statistics (e.g., mean, standard deviation [SD]) were conducted for all subjects who completed the baseline and any follow-up visits.Changes from baseline were assessed for significance with Student's paired t-test.

| Subjects
Eighteen female and male subjects 26-63 years of age (mean, 48 years) with FST I-IV were enrolled in the 12-week clinical study.
Overall, 56% were White, 39% were Asian, and 6% were Hispanic, and the majority of subjects had FST type III (67%).Seventeen subjects completed the study; one subject discontinued the study early due to an AE.Subject demographics and baseline characteristics of the ITT population are summarized in Data S1, Table 1.

| Investigator-assessed clinical efficacy end points
Significant reductions from baseline in facial pigmentation were observed with the combination treatment of DG plus EC-DG procedure and the targeted topical at-home skincare regimen for all study visits through week 12, starting as early as day 3 as measured by MASI (p < 0.03) and at week 4 for overall hyperpigmentation (p < 0.011) (Table 1).
Immediately after the first DG plus EC-DG procedure, significant improvements versus baseline were observed in radiance and tactile roughness, with continued improvements in these attributes observed as early as day 3 (roughness; p < 0.02) and week 2 (radiance; p < 0.04) through week 12 (Table 1).Significant improvements from baseline in skin tone evenness were reported at weeks 4 and 6 (mean change of 9.5% and 15.2%, respectively; p < 0.04).

| Subject self-assessment questionnaire
Favorable subject perceptions of treatment effects were reported immediately after the first DG plus EC-DG procedure and at week 12 (Figure 1).High rates of subject agreement were noted on items evaluating effectiveness of treatment and positive effect of treatment on psychosocial and emotional domains at week 12.
All subjects (100%) agreed or strongly agreed that the treatment faded their age spots, made them feel more confident and happier about how they looked, and helped them feel more confident about how their skin looked.In addition, subjects agreed that treatment helped their skin looked at least 5 years younger (77%), reduced at least 5 years' worth of sun damage off their skin (85%), and faded their dark spots (92%).Overall, 94.1% of subjects reported overall satisfaction with the treatment at week 12.

| Photographic evidence
Representative images of two subjects at baseline and after treatment are shown in Figures 2 and 3.

| DISCUSS ION
8][9] Successful treatment of hyperpigmentation has been associated with subjectreported positive effects on QoL and increased satisfaction with appearance. 25The current study demonstrated that a combination treatment of a series of 6 DG procedures using EC-DG along with a targeted at-home skincare regimen comprising ABT and Spot Cream over 12 weeks was well tolerated and effective, producing significant, rapid, and sustained improvements in skin quality attributes and pigmentation levels, including subjects' Multiple mechanisms contribute to the increased melanin levels characteristic of hyperpigmentation, which complicates its treatment. 11,14,15PIH involves inflammation and increased melanin synthesis, and varies with the source of the inflammation. 6Pathogenesis of melasma is multifactorial and includes melanocyte proliferation, increased mast cells and production of reactive oxygen species, and decreased barrier function. 4,14Development of dark spots is thought to involve DNA damage in keratinocytes, which activates multiple melanogenic paracrine networks, such that treatment with tyrosinase inhibitors alone may not be sufficient. 15ven the complexity of the condition, successful treatment of hyperpigmentation often requires a multimodal treatment approach utilizing a combination of topical treatments and/or combining topical products with in-office procedures. 11,14,15,17DG is a versatile in-office microdermabrasion procedure for treating skin quality concerns and may be combined with any one of several pro-infusion serums, depending on patient needs.In the current study, DG was combined with EC-DG, a novel pro-infusion serum developed to improve hyperpigmentation.This procedure was used in conjunction tranexamic acid, which targets melanocyte activation 16 ; and niacinamide, which has anti-inflammatory properties in addition to effects on melanocyte activation and melanin distribution. 16ABT was recently compared with 4% HQ as a stand-alone treatment in individuals with moderate to severe facial hyperpigmentation, including melasma, across multiple races and ethnicities, including darker skin types, and was shown to be effective, well tolerated, and preferred over 4% HQ.Data requests can be submitted at any time after approval in the US and Europe and after acceptance of this manuscript for publication.The data will be accessible for 12 months, with possible extensions considered.For more information on the process or to submit a request, visit the following link: https:// vivli.org/ ourme mber/ abbvie/ then select "Home".
F I G U R E 3 Representative images of a 50-year-old Asian female with FST IV at baseline and week 12. FST, Fitzpatrick skin type.

E TH I C S S TATEM ENT
The authors confirm that the ethical policies of the journal, as noted on the journal's author guidelines page, have been adhered to and the appropriate ethical review committee approval has been received.
This study was approved by the WCG Institutional Review Board (IRB) on September 29, 2021 for study number 1317721 (IRB tracking number 20214762).All participants followed an appropriately administrated informed consent process using the IRB-approved ICF prior to any study procedures, and the study was conducted in compliance with the Declaration of Helsinki and in accordance with all applicable guidelines for the protection of human subjects for research, as outlined in the accepted standards for Good Clinical Practice.

CO N S E NT
Patients provided written consent for their photos to be published.

R E FE R E N C E S
prietary diamond tip microdermabrasion skin-resurfacing technology that simultaneously exfoliates, extracts, and infuses targeted pro-infusion serums into the skin to address specific skin quality concerns.DG can be used in conjunction with Even & Correct Advanced Brightening Pro-Infusion Serum (EC-DG; SkinMedica, Allergan Aesthetics, an AbbVie Company), a novel, brightening pro-infusion serum to improve the appearance of uneven or excess pigmentation.Even & Correct Advanced Brightening Treatment (ABT; SkinMedica, Allergan Aesthetics, an AbbVie Company) and Even & Correct Dark Spot Cream (Spot Cream; SkinMedica, Allergan Aesthetics, an AbbVie Company) are novel, hydroquinone(HQ)-free, pigment-correcting topical skincare products that target multiple cellular pathways in melanogenesis to treat broadly dispersed hyperpigmentation and dark spots (such as PIH and solar lentigines), respectively.22,23

This 12 -
week, open-label, single-center, clinical usage study conducted from October 18, 2021 to May 19, 2022 aimed to enroll healthy adults 18-65 years of age with Fitzpatrick skin type (FST) I-VI with mild to severe overall facial hyperpigmentation (score of 3-9 Significant improvements versus baseline in skin moisturization/hydration were observed immediately after the first DG plus EC-DG procedure, as measured via Corneometer (mean change, 13.0), MoistureMeter D with the XS probe (mean change, 3.0), and MoistureMeter D with the S probe (mean change, 3.2; all p ≤ 0.012 vs. baseline; Data S2, Figure 1).Antera 3D imaging analysis revealed significant improvements in mean percent change from baseline in brightness of the most-bothersome spot among all subjects at weeks 2, 4, and 6 (all p < 0.0095 vs. baseline).A significant improvement in pigmentation uniformity (mean change, 4.9%), but not pigmentation score or average score, was observed from baseline to week 12. Skin roughness score (Ra) decreased significantly from baseline to weeks 4 and 6 (−10.2% and −8.5%, respectively; both p < 0.02), indicating an increase in skin smoothness.
Mean tolerability scores remained ≤1.4 for erythema and <1.0 for dryness, burning/stinging, and itching at all time points.Treatmentrelated AEs that occurred on the face were reported by eight subjects (dryness [n = 2], facial burning [n = 3], breakouts [n = 2], facial redness [n = 2]; one subject experienced more than one AE).
Abbreviations: MASI, Melasma Area and Severity Index; NA, not applicable.

1
Subject perceptions of treatment effects and satisfaction (A) immediately after the initial DG procedure using EC-DG (N = 18) and (B) at week 12 (n = 17).*At week 10.feel hydrated Made my skin feel smooth and soft Made my skin look radiant Made my skin look refreshed Felt my skin received a deep clean/felt my skin was thoroughly cleansed Reduced the appearance of pores, blackheads, post-acne scars/marks % of Participants Agreed or Strongly Agreed Immediately after DG plus ED-DG procedure… more confident Makes me feel happier about how I look Faded the dark spots on my skin Improved the evenness of my skin tone Reduced the look of sun damage on my skin Faded even the most stubborn spots on my skin* Faded the age spots on my skin Improved current and helps prevent future uneven pigment in my skin Would recommend to a friend Took 5+ years of sun damage off my skin Made my skin look 5+ years younger Made my complexion look more radiant Helped me feel more confident about how my skin looks Gave my skin a healthy glow Improved overall appearance of my skin Made my skin and pores look clearer % of Participants Agreed or Strongly Agreed With continued use of combination treatment with DG plus ED-DG procedure and at-home skincare regimen… with an at-home daily skincare regimen consisting of a brightening serum and spot cream to provide additional treatment for facial hyperpigmentation.EC-DG, ABT, and Spot Cream all contain a proprietary complex that includes lotus sprout extract, which interferes with melanosome function and promotes melanosome degradation;

AF I G U R E 2
AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor.This includes access to anonymized, individual, and trial-level data (analysis data sets), as well as other information (eg, protocols, clinical study reports, or analysis plans), as long as the trials are not part of an ongoing or planned regulatory submission.This includes requests for clinical trial data for unlicensed products and indications.These clinical trial data can be requested by any qualified researchers who engage in rigorous, independent, scientific research, and will be provided following review and approval of a research proposal, Statistical Analysis Plan (SAP), and execution of a Data Sharing Agreement (DSA).
23Spot Cream has previously been shown to provide significant improvement in dark spots from PIH/acne marks and age spots/solar lentigines by week 2 and through week 12 in a broad range of subject races, ethnicities, and skin types with high tolerability and patient satisfaction.23