Current Concepts in the Use of Bellafill

7232019 Current Concepts in the Use of Bellafill

httpslidepdfcomreaderfullcurrent-concepts-in-the-use-of-bellafill 19

Copyright copy 2015 American Society of Plastic Surgeons Unauthorized reproduction of this article is prohibited

wwwPRSJournalcom 171S

Moderate-to-severe acne affects around 20of young people and may persist into the20s and 30s in around 64 and 43 of indi-

viduals respectively1 Unfortunately atrophic acnescarring is a common complication of acne vulgaris which may be associated with significant psychologi-cal distress2 The incidence of acne scarring is not well studied but it may occur to some degree in upto 95 of people with acne vulgaris3 Until recentlyno injectable fillers were approved and on the mar-ket by the US Food and Drug Administration (FDA)for treatment of acne scarring however soft-tissuefillers ranging from temporary to permanent (eghyaluronic acid collagen and liquid injectable sili-cone) have been used ldquooff-labelrdquo to treat patients with acne scarring for many years These soft-tissuefillers have proven to be effective in treating patients with shallow rolling acne scars24ndash9 Many dermatolo-gists and plastic surgeons are comfortable using der-mal fillers for other cosmetic purposes thereforethe transition to treatment of acne scars with thesesame agents is natural2

Bellafill (previously named ArteFill) has beenmarketed and sold in the United States since 2007as a permanent dermal filler for the correction of

nasolabial folds (NLFs) After meeting predefinedclinical endpoints in the US Acne Scar pivotalstudy Bellafill received an expanded FDA labelingindication in December 2014 for the correctionof moderate-to-severe atrophic distensible facialacne scars on the cheeks of patients over the ageof 21 years With this new FDA approval Bellafillis now the only ldquoon-labelrdquo dermal filler approved

Disclosure Dr Joseph contributed conceptuallyand intellectually to this work He was a treatinginvestigator in the US Acne Scar Pivotal Trial andPost Market Approval Safety Study He has been a paid investigator and consultant for Suneva Medi- cal and is a minor shareholder of Suneva MedicalMs Eaton contributed conceptually and intellectually to this work She is an aesthetic nurse and an independent clinical research consultant She has been a paid consultant for Suneva Medical Dr Cohen contributed conceptually and intellectually to this work

He was a treating investigator in the US Acne ScarPivotal Trial He has been a paid investigator consultant and minor shareholder of Suneva Medical

Copyright copy 2015 by the American Society of Plastic Surgeons

DOI 101097PRS0000000000001839

John H Joseph MD

Laura L Eaton RN BSNSteven R Cohen MD

Beverly Hills Huntington Beach and

San Diego Calif

Summary As demonstrated by American Society of Plastic Surgeons statistics

(2013) patients seeking nonsurgical facial rejuvenation are increasing A vari-ety of temporary and semipermanent soft-tissue fillers such as hyaluronic acidpoly-L-lactic acid and calcium hydroxylapatite are readily available howeverthey have not been proven effective in treating facial acne scarring Patienttolerance for the inconvenience and repeat cost of short-term temporary fill-ers is waning as newer generation fillers with longer durations are coming onthe market Permanent injectable fillers such a Bellafill (Suneva Medical IncSan Diego Calif) represent a desirable solution for patients who want a long-term result With the recent Food and Drug Administration approval for thetreatment of moderate-to-severe atrophic distensible facial acne scars on thecheek(s) in patients over the age of 21 years Bellafill (polymethylmethacrylatecollagen) represents an effective solution for the treatment of facial acne scar-ring of the face while maintaining an excellent safety profile (Plast ReconstrSurg 136 171S 2015)

From the John H Joseph Medical Corporation UltaMedCorporation and Division of Plastic Surgery University ofCaliforniaReceived for publication March 2 2015 accepted August 52015

Current Concepts in the Use of Bellafill

Supplemental digital content is available forthis article A direct URL citation appears inthe text simply type the URL address into any Web browser to access this content A clickablelink to the material is provided in the HTMLtext of this article on the Journal rsquos website( wwwPRSJournalcom)

FILLERS




172S

Plastic and Reconstructive Surgery bull November Supplement 2015

in the United States for the treatment of acnescarring

BELLAFILL PRODUCT OVERVIEW Bellafill (ArteFill) is a long-lasting polymeth-

ylmethacrylate (PMMA) injectable filler9 It isnonbiodegradable and composed of 30ndash50 983221msmooth and round PMMA microspheres (20 by volume) suspended in a water-based gel contain-ing 35 bovine collagen gel (80 by volume)and 03 lidocaine10 While the collagen carrier isabsorbed 1ndash3 months after injection the PMMAmicrospheres remain as a scaffold for the develop-ment of autologous tissue9 The bovine collagencarrier is replaced by the patientrsquos own connectivetissue over an estimated period of 3 months10

US ACNE SCAR PIVOTAL STUDY The Bellafill (ArteFill) US Acne Scar pivotal

study was a prospective randomized placebo-con-trolled double-blinded multicenter clinical trialof subjects over the age of 18 years who desiredcorrection of moderate-to-severe atrophic disten-sible facial acne scarring on the cheek(s) Prior toscreening and enrollment subjects provided writ-ten informed consent The study was conducted with institutional review board approvals in accor-dance with Good Clinical Practices and registered

with ClinicalTrialsgov (NCT01559922) The studytreated 147 subjects at 10 centers Subjects whomet all inclusion criteria and no exclusion criteria were randomized in a 21 fashion to either Bel-lafill (ArteFill) or sterile normal saline solutionfor injection (control group) Randomization wasstratified by study site for gender and Fitzpatrickskin phototype The study included 57 male subjects (39) and 35 subjects (24) with darker skintypes (Fitzpatrick V and VI) Prior to treatmentsubjects received a skin test to determine possiblesensitivity to bovine collagen At 6 months all con-trol subjects were eligible to receive open-labeltreatment with Bellafill

US Acne Scar Study Clinical Endpoints

The primary effectiveness endpoint was the suc-cess rate at 6 months based on the blinded evaluat-ing investigatorrsquos (EI) assessment using the validated4-point Acne Scar Rating Scale (ASRS) (Table 1) with success defined as at least a 2-point improve-ment on the ASRS for at least 50 of treated scars

The primary safety objective was to identify theincidence of all treatment-related adverse events

(TRAEs) This included subject AE outcomes

recorded during the first 14 days after each treat-ment in a patient diary and the treating investiga-torrsquos safety assessments that were collected duringa telephone call at 72 hours postinjection andfollow-up visits at weeks 2 4 6 and 8 and months3 6 9 and 12 Subjects in the control group whoreceived Bellafill injections in the open-label phaseof the study were followed in a similar manner for12 months

US Acne Scar Study Inclusion Criteria

Key study inclusion criteria included men and women 18 years old or older who presented with atleast 4 moderate-to-severe atrophic acne scars perthe ASRS on the cheek(s) which were sufficientlydistant from one another to allow for individualtreatment and grading Treatment scars had to

be depressed rolling scars with rounded bordersdistensible and not significantly hypopigmentedor hyperpigmented with no underlying papulesor nodules Icepick boxcar or bound-down acnescars could not be included as treatable scars butcould be present in the treatment area

US Acne Scar Study Exclusion Criteria

Subjects were excluded from the pivotal studyif they had previously undergone treatment ofacne scarring with any of the prohibited treat-ments or procedures including the use of soft-

tissue fillers in the face during the study as wellas concurrent administration of other aesthetictreatments in the face during the study (eg lasersimplants peels and microdermabrasion) Femalesubjects who were pregnant (positive urine preg-nancy test) breast-feeding or were of childbear-ing potential and not practicing a reliable methodof birth control were excluded Subjects were alsoexcluded if they presented with any skin pathol-ogy or condition that could interfere with evalu-ation of the treatment areas or worsen due to theproposed treatment Subjects with a recent or cur-

rent history of inflammatory skin disease infec-tion cancerousprecancerous lesions unhealed wounds or clinically significant acne were alsoexcluded Clinically significant acne was definedas greater than 3 active inflammatory lesions ineither the left or right treatment area Additionalstudy exclusion criteria included a history of sys-temic granulomatous diseases connective tissuedisorders hypertrophic acne scarring keloidscarring predominantly icepick scarring or sinustract scars and a known hypersensitivity or previ-ous allergic reaction to any of the components

Bellafill including lidocaine and bovine collagen




Volume 136 Number 5S bull Current Concepts in the Use of Bellafill

173S

US Acne Scar Study Follow-Up Visit Schedule

Subject follow-up included telephone contact

at 72 hours after each treatment and clinic visitsat weeks 2 4 (with touch-up if needed) 6 and 8 weeks after treatment as well as at months 3 6 9and 12 Subjects initially randomized to controlcould elect to receive open-label Bellafill injec-tions at the 6-month visit with subsequent follow-ups that exactly mirrored the treatment group

Endpoints measured after treatment includedthe following (1) the blinded EIrsquos determinationof acne scar appearance via the 4-point-validated ASRS (2) assessment of safety outcomes at each visit (3) the blinded EIrsquos assessment of subject

appearance improvement using the PhysicianGlobal Aesthetic Improvement Scale (PGAIS)(4) the subjectrsquos completion of a 14-day treatmentdiary (5) the subjectrsquos evaluation of appearanceusing the Subject Global Aesthetic ImprovementScale (SGAIS) and (6) the subjectrsquos assessment ofscar correction (SASC)

US Acne Scar Study Population

The Bellafill and control groups were wellbalanced with regard to demographics and base-line characteristics with no significant differencesbetween groups The mean age was 446 years inthe Bellafill group and 453 years in the controlgroup The study enrolled a substantial portion ofmen which included 381 in the Bellafill groupand 400 in the control group and subjects withFitzpatrick skin phototypes V and VI with 257in the Bellafill group and 200 in the controlgroup The number of qualifiedtreated scars was89 in the Bellafill group and 85 scars in the con-trol The mean severity score of scars was 33 inthe Bellafill and 33 in the control group per the ASRS

US Acne Scar Study Injection Volumes

The average initial injection volume of Bel-lafill in randomized subjects was 011 mL per scarand the average initial volume injected per subject was 093 mL The average injection volume attouch-up was 010 mL per scar and 069 mL persubject The majority of subjects received a touch-up injection with 825 in the Bellafill group and820 in the control group

US Acne Scar Study Primary EffectivenessResults

The primary effectiveness endpoint was aresponder rate analysis in which the criterionfor success was defined as gt50 of treated scarsper subject improving by 2 or more points on the4-point ASRS at the 6-month visit as evaluated bya live blinded EI The primary effectiveness end-point was achieved with 644 responders in the

Table 1 Acne Scar Rating Scale

Acne Scar RatingScale Score Description

1 Minimal depth up to 05 mm Visibility = perceptible with tangential

lighting

2 Mild depth gt05 mm to lt15 mm Visibility = moderately detectable with

tangential lighting3 Moderate depth ge15 mm to lt25 mm

Visibility = easily seen with tangentiallighting

4 Severe depth ge25 mm Visibility = substantial shadowing with

tangential lighting

Fig 1 Subject A (left ) baseline (pretreatment with Bellafill for acne scar treatment) (right )

6 months after Bellafill acne scar treatment




174S


Bellafill group and 326 responders in the con-trol group (P = 00005) at 6 months11 Refer to Fig-ures 1 through 5 for comparison of baseline and6-month (primary endpoint) clinical outcomephotographs of subjects who received acne scartreatment with Bellafill

US Acne Scar Study Safety Results

There were no deaths treatment-related seri-ous AEs infections or vascular occlusions reportedin this pivotal study Subjects were asked to keep

a 14-day diary after each treatment to record anysigns and symptoms of injection site responsesuch as erythema swelling bruising pain itch-ing lumpsbumps and skin discoloration Eighty-nine percent (89) of Bellafill subjects reportedat least 1 sign or symptom however the majorityof events was mild to moderate in intensity and

resolved within 1ndash7 days Similar rates of injectionsite response were noted in patient diaries follow-ing touch-up treatments

The investigator-reported TRAEs includedimplant site mass injection site pain injectionsite reaction (eg lumpiness and papule forma-tion) swelling and 1 case of acne These eventsoccurred in 8 of 97 subjects who were randomizedto receive Bellafill Five of these events resolvedand 3 cases of injection site reaction (lumpinessand papule formation directly after injection) per-sisted throughout the study All 3 of these eventsoccurred within the first month after injectionand were thought to be due to superficially placedproduct that became palpable Two of these events were deemed by the investigator to be mild and1 event of papule formation was deemed to be ofmoderate severity

Fig 2 Subject B (left ) baseline (pretreatment with Bellafill for acne scar treatment) (right )


Fig 3 Subject C (left ) baseline (pretreatment with Bellafill for acne scar treatment) (right )






175S

The FDA identified AEs of special interestprior to initiation of the investigation which werefollowed separately AEs of special interest to theagency included hyperpigmentation and hypopig-mentation hypertrophic scarring or keloid for-mation and the appearance of granulomas Noneof these AEs were reported in this 12-month acnescar pivotal study

Global Aesthetic Improvement and SubjectSatisfaction

Subject satisfaction was assessed using the6-point SASC scale Greater than 83 of Bellafillsubjects judged themselves to be at least some- what to very satisfied with the appearance of theirtreated scars at all time points Global aestheticimprovement was evaluated by both the EI and

the subjects Greater than 77 of Bellafill subjectsindicated that their appearance was improved ormuch improved on the SGAIS assessment from3 months onward The proportion of blindedEIs indicating improvement as per the PGAISassessment was greater than 83 from 3 monthsonward

US Acne Scar Study Discussion

The 6-month primary effectiveness endpoint was met and results demonstrated statisticallysignificant effectiveness in the treatment of atro-phic acne scarring of the face while maintainingan excellent safety profile11 Based on the resultsof the PGAIS SGAIS and SASC the majority ofsubjects and physicians saw an improvement inthe appearance of acne scars when treated with

Fig 4 Subject D (left ) baseline (pretreatment with Bellafill for acne scar treatment) Note each

subject needed to have 4 scars in total (with any distribution across both cheeks) to be eligible for

the Acne Scar clinical study (Right ) 6 Months after Bellafill acne scar treatment

Fig 5 Subject E (left ) baseline (pretreatment with Bellafill for acne scar treatment) (right )





176S


Bellafill versus a saline control injection at the6-month primary endpoint Unblinded evalua-tion out to 12 months confirmed a consistent levelof effectiveness Based on these results acne scartreatment with Bellafill was shown to occur rela-tively quickly was sustained and was effective in

all races genders and adults of all ages11

5-YEAR NLF POSTAPPROVAL STUDY

Introduction and Overview

A concern for use of dermal fillers and Bel-lafill in particular is the potential for developmentof granulomas Some practitioners have avoidedthe use of PMMA collagen due to concerns ofpotentially higher granuloma rates over otherdermal fillers The information that practitionershave used to base decisions surrounding PMMA

has primarily come from small single-center stud-ies or case reports in which the precise materialadministered was not clearly identified or evenFDA approved12 Therefore as a condition of FDAapproval for the correction of NLFs the agencyrequired the manufacturer of Bellafill (SunevaMedical Inc San Diego Calif) to conduct alarge-scale 5-year postapproval study on the inci-dence of granuloma formation and satisfaction oflong-term treatment As required a prospectivemulticenter open-label postapproval study wasconducted at 23 centers across the United States

Prior to screening and enrollment subjects provided written informed consent The study wasconducted with institutional review board approv-als using Good Clinical Practices and was regis-tered at ClinicalTrialsgov (NCT 00778531) Onethousand two hundred seventeen subjects werescreened and 1008 were enrolled Compliance with follow-up was outstanding with an 87 com-pletion rate (8711008) at 5 years

For this study subjects received treatment with Bellafill only for the approved indication ofcorrecting NLFs Clinic visits were conducted at

3 months 60 months and as needed for safetyfollow-up Subjects completed mail-in question-naires at 6 12 18 24 36 and 48 months followingtheir final injections A granuloma was defined asa cutaneous lesion typically appearing 3 monthsor more after treatment frequently associated with change and histologic evidence of granulo-matous inflammation as diagnosed by a team ofindependent dermatopathologists

Granuloma surveillance included subjectreporting of enlargement of the implant paintenderness increased sensitivity redness swell-

ing itching burning skin discoloration scabbing

skin ulceration or any other symptom that couldbe the result of an inflammatory or granuloma-tous process Subjects reporting any of thesesymptoms were scheduled for an in-office evalua-tion The protocol for this study required that alllate lesions (those occurring ge90 days post injec-

tion) that could represent a granuloma be biop-sied sent to a central laboratory and analyzed by3 independent dermatopathologists

NLF Post-approval Study Safety Results

A total of 177 treatment-related AEs werereported in 118 of the 1008 Bellafill-treated subjects The majority (74) of TRAEs was mild inseverity and resolved within 180 days The mostcommonly reported TRAEs were lumpiness at theinjection site (29) and redness (10)

Seventeen subjects presented with lesions that

were classified per protocol and confirmed bybiopsy as granulomas for an overall incidencerate of 17 The majority of confirmed granu-lomas were mild to moderate in severity Of the17 subjects with granuloma 8 had complete reso-lution 8 were improving with ongoing treatmentat the end of the study and 1 granuloma initiallyimproved and then remained stable for the last2 visits of the study The average time of onsetfor granuloma was 31 months and of the lesionsthat resolved the average duration was 10 months(range 25ndash21 months)

Investigators were allowed to treat subjects with granulomas based on their medical judg-ment The most commonly used treatment wasintralesional corticosteroid injections with and without 5-fluorouracil No implants were excisedor removed Additionally there were no reports ofmigration no scarring in the subjects who devel-oped granulomas and no symptoms of vascularcompromise (including infarction and blindness)in this 5-year study of over 1000 patients

The 5-year NLF Postapproval Study providesstrong supporting evidence of the long-term safety

and expected long-term effectiveness profile thatmay be experienced by acne scar patients treated with Bellafill The method of use of Bellafill inthis study was very similar to that used for acnescar treatment in that the implantation techniqueis largely the same From an anatomic and histo-logic perspective there are no significant differ-ences between the NLF and the cheek Thereforethe authors believe that the 5-year postapprovalstudy of 1008 subjects provides strong evidenceof the long-term safety of Bellafill and reasonableassurance regarding the long-term effectiveness

for acne scar indication





177S

5-Year NLF Postapproval Study Discussion

This 5-year NLF Postapproval Study repre-sents the largest and longest follow-up study ofa US-approved dermal filler product to date andfound an overall incidence rate of 17 granu-

loma formation over 5 years with Bellafill Thenumber of subjects affected by a granuloma wassmall and the events were typically mild to moder-ate in severity and treatable with medical therapy Although the short-term safety of Bellafill wasalready well known this larger study further con-firms the overall mild and transient nature of AEsthat can occur with PMMA collagen

BEST PRACTICES FOR CORRECTIONOF ATROPHIC ACNE SCARRING

WITH BELLAFILL

Acne scars selected for treatment should beatrophic distensible scars The best results withBellafill are achieved in defects requiring deepdermal implant placement with full correctionbeing achieved gradually over time The rateand degree of correction in the implanted area varies with the patient treatment site and planeof injection The key to success with Bellafill isa conservative approach with avoidance of over-correction13 Final correction should be limitedto no more than 100 of the skin defect dur-ing treatment One or 2 touch-up treatmentsat intervals of at least 2 weeks may be requiredto achieve the desired effect Refer to Figures 1through 5 for baseline and 6-month posttreat-ment photographs of acne scar treatment withBellafill

Acne Scar Treatment Patient Consultation

Using a hand-held mirror during the initialpatient consultation visit you should have thepatient point out the scars that bother him or hermost Review the degree of acne scar correction

that can be achieved with Bellafill and explain thatit may take a series of injections of to obtain opti-mal correction Examine the skin of the cheek(s)to insure that the patient has distensible acnescars (scars that smooth out when stretched) asthese rolling broad-based scars respond best totreatment

Skin Testing

Four weeks prior to treatment with Bellafill askin test should be conducted to screen for preex-isting allergies to bovine collagen and lidocaine

The skin test dose of 01 mL should be injected

in the volar aspect of the forearm and the patientshould be provided with the skin test card to takehome and complete A positive skin test responseincludes symptoms of erythema induration andor swelling appearing within 24 hours and lastinggreater than 24 hours after injection or appear-

ing greater than 24 hours after injection for anyperiod of time An equivocal response includes nolocal signs or symptoms of skin reaction howeversystemic signs and symptoms of arthralgias ormyalgias are present A patient with a positive or2 equivocal responses should not be treated withBellafill1415

Pre- and Postacne Scar Treatment Photography

Pre- and posttreatment photographs arehighly recommended as this is the best tool for

demonstrating results of acne scar treatment With acne scar patients it is recommended totake photographs using optimal angles includ-ing frontal view and photographs from 45 and90 degrees16 Lighting makes all the differencein the effectiveness of your before and afteracne scar photos The appearance of acne scarschanges with the angles of light and is less appar-ent in flat light16 When photographing acnescars use a focused (point) light source thatcasts a narrow beam of light rather than a softdiffuse source and minimize daylight and ambi-ent lighting16 Turn off fluorescent or overheadlighting and insure that the flash on your cam-era is turned off It is also important to positionthe light source tangential to the surface of thearea of skin to be photographed This will createshallow contours and produce long shadows thathighlight scars16

Acne Scar Treatment Injection Procedure

Prior to injection the patient should be fullyinformed of the indications contraindications warnings precautions treatment responses

adverse reactions and method of administrationof Bellafill Confirm the negative skin test Thetreatment area should be thoroughly washed withsoap and water and the area should be cleaned with an antiseptic The Bellafill syringe must bebrought to room temperature before injectionEach Bellafill syringe comes supplied with a26-gauge needle that is 58ʺ long14

Acne Scar Treatment Injection Technique

Before injecting the patient prime the syringeby depressing the plunger until the product is

visible at the tip of the needle Enter the skin at




178S


approximately a 30-degree angle proximal to theedge of the scar Advance the needle under thebase of the scar and explore for any fibrotic tissueIf scar fibrosis exists then pass the needle backand forth a few times to open up a pocket forinjecting the product You can use either a linearthreading or serial puncture technique directlyunderneath the scar in both cases injecting in aretrograde manner You may need to replace theneedle if it becomes occluded or dull during thetreatment session After injection palpate andmassage the injected acne scar with your finger-tips to confirm uniform deposition of BellafillThe area and the borders of Bellafill injectionshould be recorded on an illustration of a face forlater comparison Instruct the patient to promptlyreport any evidence of adverse texture changein the surrounding treatment site and any otherproblems possibly associated with the use of Bel-lafill Refer to Video Supplemental Digital Con-tent 1 which demonstrates an acne scar injectionprocedure by Dr John Joseph available in theldquoRelated Videosrdquo section of the full-text article onPRSJournalcom or for Ovid users at httplinkslwwcomPRSB441) for more detailed informa-tion on treatment of acne scarring with Bellafill

CONCLUSIONSHistorically first- and second-generation

PMMA fillers such as Arteplast and Artecoll hada greater number of smaller microspheres ofPMMA (lt20 983221m in diameter) which are proposedto engender a greater foreign body response andhigher rates of granuloma formation1017 In those

cases host cellular reaction was histologicallyattributed to PMMA impurities and PMMA par-ticles smaller than 20 983221m in diameter which couldbe phagocytized18 Bellafill is a third-generationPMMA with smooth surface morphology PMMAdeveloped to minimize inflammatory response asa result of more uniform PMMA microsphere sizeand shape10

Bellafill has been proven to be safe and welltolerated with excellent posttreatment outcomesdespite the additional step of skin testing There were no events of granuloma present in the US Acne Scar pivotal trial and only a 17 incidenceof granuloma formation (09 unresolved butimproving at study conclusion) seen in a long-term5-year NLF Postapproval study of over 1000 patientstreated with Bellafill for correction of NLFs

John H Joseph MD Clinical Testing Center of Beverly Hills

9400 Brighton Way Suite 203Beverly Hills CA 90210

drjohnjosephsbcglobalnet

PATIENT CONSENT

The patient provided written consent for the use ofhis image

REFERENCES

1 Bhate K Williams HC Epidemiology of acne vulgaris Br J Dermatol 2013168474ndash485

2 Fife D Practical evaluation and management of atrophicacne scars tips for the general dermatologist J Clin Aesthet Dermatol 2011450ndash57

3 Layton AM Henderson CA Cunliffe WJ A clinical evalu-ation of acne scarring and its incidence Clin Exp Dermatol 199419303ndash308

4 Beer K A single-center open-label study on the use of inject-able poly-L-lactic acid for the treatment of moderate to severescarring from acne or varicella Dermatol Surg 200733(Suppl2)S159ndashS167

5 Epstein RE Spencer JM Correction of atrophic scars with artefill an open-label pilot study J Drugs Dermatol 201091062ndash1064

6 Goldberg DJ Amin S Hussain M Acne scar correction usingcalcium hydroxylapatite in a carrier-based gel J Cosmet LaserTher 20068134ndash136

7 Sadove R Injectable poly-L-lactic acid a novel sculptingagent for the treatment of dermal fat atrophy after severeacne Aesthetic Plast Surg 200933113ndash116

8 Sadick NS Palmisano L Case study involving use of inject-able poly-L-lactic acid (PLLA) for acne scars J DermatologTreat 200920302ndash307

9 Rose AE Therapeutic update on acne scarring J Drugs Dermatol 201413651ndash654

10 Lemperle G Knapp TR Sadick NS et al ArteFill perma-nent injectable for soft tissue augmentation I Mechanismof action and injection techniques Aesthetic Plast Surg

201034264ndash272

Video Supplemental Digital Content 1 which demonstrates an

acne scar injection procedure by Dr John Joseph is available in

the ldquoRelated Videosrdquo section of the full-text article on PRSJour-

nalcom or for Ovid users at httplinkslwwcomPRSB441




179S

11 Karnik J Baumann L Bruce S et al A double-blind random-ized multicenter controlled trial of suspended polymethyl-methacrylate microspheres for the correction of atrophicfacial acne scars J Am Acad Dermatol 20147177ndash83

12 Piacquadio D Smith S Anderson R A comparison of com-mercially available polymethylmethacrylate-based soft tissuefillers Dermatol Surg 200834(Suppl 1)S48ndashS52

13 Hilinski JM Cohen SR Soft tissue augmentation with ArteFill Facial Plast Surg 200925114ndash119

14 Suneva Bellafill Instructions for Use San Diego Calif Suneva2014

15 Suneva Bellafill Skin Test Instructions for Use San Diego CalifSuneva 2014

16 Suneva Suneva Before and After Photo Taking Guide San DiegoCalif Suneva 2014

17 Lemperle G Gauthier-Hazan N Wolters M et al Foreignbody granulomas after all injectable dermal fillers part 1Possible causes Plast Reconstr Surg 20091231842ndash1863

18 Lemperle G Morhenn VB Pestonjamasp V et alMigration studies and histology of injectable microspheresof different sizes in mice Plast Reconstr Surg 20041131380ndash1390




172S


in the United States for the treatment of acnescarring

BELLAFILL PRODUCT OVERVIEW Bellafill (ArteFill) is a long-lasting polymeth-

ylmethacrylate (PMMA) injectable filler9 It isnonbiodegradable and composed of 30ndash50 983221msmooth and round PMMA microspheres (20 by volume) suspended in a water-based gel contain-ing 35 bovine collagen gel (80 by volume)and 03 lidocaine10 While the collagen carrier isabsorbed 1ndash3 months after injection the PMMAmicrospheres remain as a scaffold for the develop-ment of autologous tissue9 The bovine collagencarrier is replaced by the patientrsquos own connectivetissue over an estimated period of 3 months10

US ACNE SCAR PIVOTAL STUDY The Bellafill (ArteFill) US Acne Scar pivotal

study was a prospective randomized placebo-con-trolled double-blinded multicenter clinical trialof subjects over the age of 18 years who desiredcorrection of moderate-to-severe atrophic disten-sible facial acne scarring on the cheek(s) Prior toscreening and enrollment subjects provided writ-ten informed consent The study was conducted with institutional review board approvals in accor-dance with Good Clinical Practices and registered

with ClinicalTrialsgov (NCT01559922) The studytreated 147 subjects at 10 centers Subjects whomet all inclusion criteria and no exclusion criteria were randomized in a 21 fashion to either Bel-lafill (ArteFill) or sterile normal saline solutionfor injection (control group) Randomization wasstratified by study site for gender and Fitzpatrickskin phototype The study included 57 male subjects (39) and 35 subjects (24) with darker skintypes (Fitzpatrick V and VI) Prior to treatmentsubjects received a skin test to determine possiblesensitivity to bovine collagen At 6 months all con-trol subjects were eligible to receive open-labeltreatment with Bellafill

US Acne Scar Study Clinical Endpoints

The primary effectiveness endpoint was the suc-cess rate at 6 months based on the blinded evaluat-ing investigatorrsquos (EI) assessment using the validated4-point Acne Scar Rating Scale (ASRS) (Table 1) with success defined as at least a 2-point improve-ment on the ASRS for at least 50 of treated scars

The primary safety objective was to identify theincidence of all treatment-related adverse events

(TRAEs) This included subject AE outcomes

recorded during the first 14 days after each treat-ment in a patient diary and the treating investiga-torrsquos safety assessments that were collected duringa telephone call at 72 hours postinjection andfollow-up visits at weeks 2 4 6 and 8 and months3 6 9 and 12 Subjects in the control group whoreceived Bellafill injections in the open-label phaseof the study were followed in a similar manner for12 months

US Acne Scar Study Inclusion Criteria

Key study inclusion criteria included men and women 18 years old or older who presented with atleast 4 moderate-to-severe atrophic acne scars perthe ASRS on the cheek(s) which were sufficientlydistant from one another to allow for individualtreatment and grading Treatment scars had to

be depressed rolling scars with rounded bordersdistensible and not significantly hypopigmentedor hyperpigmented with no underlying papulesor nodules Icepick boxcar or bound-down acnescars could not be included as treatable scars butcould be present in the treatment area

US Acne Scar Study Exclusion Criteria

Subjects were excluded from the pivotal studyif they had previously undergone treatment ofacne scarring with any of the prohibited treat-ments or procedures including the use of soft-

tissue fillers in the face during the study as wellas concurrent administration of other aesthetictreatments in the face during the study (eg lasersimplants peels and microdermabrasion) Femalesubjects who were pregnant (positive urine preg-nancy test) breast-feeding or were of childbear-ing potential and not practicing a reliable methodof birth control were excluded Subjects were alsoexcluded if they presented with any skin pathol-ogy or condition that could interfere with evalu-ation of the treatment areas or worsen due to theproposed treatment Subjects with a recent or cur-

rent history of inflammatory skin disease infec-tion cancerousprecancerous lesions unhealed wounds or clinically significant acne were alsoexcluded Clinically significant acne was definedas greater than 3 active inflammatory lesions ineither the left or right treatment area Additionalstudy exclusion criteria included a history of sys-temic granulomatous diseases connective tissuedisorders hypertrophic acne scarring keloidscarring predominantly icepick scarring or sinustract scars and a known hypersensitivity or previ-ous allergic reaction to any of the components

Bellafill including lidocaine and bovine collagen





173S















lighting





tangential lighting






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175S















176S



























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WITH BELLAFILL





Skin Testing

















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PATIENT CONSENT


REFERENCES











201034264ndash272








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lighting





tangential lighting






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WITH BELLAFILL





Skin Testing

















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PATIENT CONSENT


REFERENCES











201034264ndash272








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WITH BELLAFILL





Skin Testing

















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PATIENT CONSENT


REFERENCES











201034264ndash272








179S













175S















176S



























177S





WITH BELLAFILL





Skin Testing

















178S










PATIENT CONSENT


REFERENCES











201034264ndash272








179S












176S



























177S





WITH BELLAFILL





Skin Testing

















178S










PATIENT CONSENT


REFERENCES











201034264ndash272








179S













177S





WITH BELLAFILL





Skin Testing

















178S










PATIENT CONSENT


REFERENCES











201034264ndash272








179S












178S










PATIENT CONSENT


REFERENCES











201034264ndash272








179S












179S









Current Concepts in the Use of Bellafill

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Transcript of Current Concepts in the Use of Bellafill