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ADV-sculptra-INTERCALLAIRES.indd 1 02/08/13 17:39

Ageing provokes structural changes in multiple tissue layers

• Facial ageing process begins with surface and subsurface structural changes in multiple facial tissue layers, including skin, fat, muscle and bone.1-5

• Facial tissue layers age independently, contributing to the overall facial appearance.2-4

Expert Recommendation6

It is useful to first evaluate the face in terms of the integrity of each structural tissue – skin, fat, muscle, bone. Then, look at what those changes are doing to the face in terms of morphologic changes – the shape, proportions, and topography of the face. Do not focus on just “lines and folds,” but consider all the structural changes in the face and the interdependency between them. Look at the whole face as a 3D interlocking puzzle where losing or correcting one thing may have a negative or positive impact on another.

BONE MUSCLE FAT SKIN

Skeletal dimensions and bony skeletal support change.

Bone resorption leads to biometric volume loss 2,4

Redistribution, accumulation and atrophy of fat lead to facial volume loss 1,2,4,5

Modification of fat pads leads to changes in shape and contour of the face deficiencies 2-5

Relaxation of muscle and loss of muscle tone are attributed to ageing 4

Permanent alterations in physical appearance occur over time.

Thinner skin

Drier skin

Less elastic skin

Skin more likely to wrinkle or sag

Reduction in collagen

FACIAL AGEING PROCESS

Youthful face Ageing face Youthful face Ageing face

ANATOMY OF FACIAL AGEING

FA C I A L A G E I N G P R O C E S S

ANATOMY OF FACIAL AGEING

FA C I A L A G E I N G P R O C E S S

Without the structural support of bone, there are noticeable changes in the other layers of overlying soft tissue and skin.3,4

• Some areas lose fat (forehead, cheeks)• Other areas gain fat (mouth, jaw)• Modification of the fat pads leads to contour deficiencies.2-3

In addition, the areas of fat tend to become farther apart. Instead of a smooth, almost continuous layer, the fat pads appear as separate structures4

Bone resorption

There is a significant loss of facial bone with age4. Ageing of the craniofacial skeleton may be due to changes in the relative dynamics of bone expansion and bone resorption. Bone resorption leads to biometric volume loss. 2-4

Fat loss & redistribution

A youthful look depends on having the right amount of facial fat in the right places. Redistribution, accumulation, and atrophy of fat lead to facial volume loss.1,2,4,5

Age 35-45 Age 45-55 Age 55-65

The subcutaneous and deep adipose tissues do not consitute a uniform and unique structure, but they are separated in different anatomical compartments. These compartments do not behave in the same way during ageing process.Their evolution leads to volumetric changes.

Volume loss in this deep compartment, similar to what may occur in the temporal fat, may lead to the cascade effect observed and described in the ageing face.

Loss of superficial fat may further accentuate a contour deformity (e.g. fold, prominence, concavity).

With age, skin undergoes several changes that include4:

• Thinner skin• Drier skin• Less elastic skin• Skin more likely to wrinkle or sag• Reduction in collagen

Skin changes

Facial ageing is due to changes in several types of tissue, including skin, fat, muscle and bone 1-5 Changes in one tissue layer have an effect on the other layers.

Collagen loss is a key factor in the ageing process

As skin ages, the middle layer of skin (dermis) thins due to collagen loss. This reduces the skin’s ability to retain elasticity (from elastin) and moisture (from hyaluronic acid).

COLLAGEN IN YOUTHFUL SKIN COLLAGEN LOSS IN AGEING SKIN

Age 35 Age 45 Age 55

S C u L P t R A ®

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SCULPTRA® Composition

Sculptra® is composed of poly-L-lactic acid, a component that has been used for more than 30 years in the medical field (sutures, orthopaedic surgery, crano-facial surgery) and whose safety has been established.

PLLA is biodegradable7

The only biodegradable collagen stimulator that undergoes a well understood non-enzymatic degradation that induces only weak tissue reaction 8

PRESENTATION

S C U L P T R A ®

PLLA is completely resorbable9

PLLA is fragmented into lactic acid naturally present in the body and follows a natural elimination cycle.

Lactic acid is metabolised by the lung under the form of CO

2.

Histologic examination (original magnification x400) exhibiting microparticles of PLLA at 12 months after last treatment, with adjacent aggregation of giant cells, histiocytes and collagen fibers.

Histologic examination (original magnification x400) of the injected PLLA at 30 months after last treatment, showing the absence of PLLA microparticles.

A = COLLAGEN TYPE 1 B = SCULPTRA®

S C U L P T R A ®

SCULPTRA® is suitable for increasing the volume of depressed areas, particularly to correct skin depressions, such as in skin creases, wrinkles, folds, scars, and for skin ageing.

SCULPTRA® is also suitable for large volume corrections of the signs of facial fat loss (lipoatrophy).

SCULPTRA® indication for use in aesthetics

A long clinical experience

PRESENTATION

1999 2004 2009

CE Mark obtained in aesthetics

CE Mark and FDA approval obtained in

HIV lipoatrophy

FDA approval obtained in aesthetics

SCULPTRA® mechanism of action

Dual mechanism of action

• Immediate volumisation due to fluid injection• Re-absorption of fluid within 2-3 days resulting in pretreatment appearance• Delayed action by fibroblastic stimulation and neo-collagenesis

A wrinkle before treatment When SCULPTRA® is injected, the injected volume immediately fills out the wrinkles and volume defects

SCULPTRA® stimulates patients own facial collagen production resulting in a natural, soft build-up of the connective tissue, smoothing out wrinkles and contour defects

After approximately 6 weeks clear improvement can be seen. Larger volume defects may involve further treatment

Within a few days, the water in SCULPTRA® is absorbed by the body with a slight increase in wrinkle depth

E F F E C t I v E C O L L A G E N S t I m u L A t O R

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COLLAGEN STIMULATION

E F F E C T I V E C O L L A G E N S T I M U L A T O R

Sculptra® stimulates collagen gradually and naturally 9,10

Histologic examination (original magnification x400) exhibiting microparticles of PLLA at 12 months after last treatment, with adjacent aggregation of giant cells, histiocytes and collagen fibers.

Collagen is the most important component of the extracellular matrix, that forms a super-family of many members which are divided into different subgroups. The type I and type III collagens belong to the fibrillar proteins and confer tensile strength, type I accounting for 80 % and type III for approximately 10% of the total collagen in human adult skin. PLLA was shown to induce at 3 and 6 months and a significant increase in collagen I and a non-significant increase in collagen III.

Histologic examination (original magnification x400) of the injected PLLA at 30 months after last treatment, showing the absence of PLLA microparticles.

Post auricular biopsies demonstrated significant increase of collagen type I at 3 months and 6 months after injection.

A = COLLAGEN TYPE 1 B = SCULPTRA®

10

15

20

25

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Baseline

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Month 3 Month 60

5P = 0.2023P = 0.2396

P = 0.0264Type I Collagen

Type III Collagen

COLLAGEN STIMULATION

E F F E C T I V E C O L L A G E N S T I M U L A T O R

Baseline I :8,9%- III : 0% 3 months I : 36,4 % -III :10% 6 months I : 32% -III : 9,8%

Micrographs of the Picro Sirius Red collagen staining in samples in one subject at baseline and 3 and 6 months after injection show large yellow fibers consistent with collagen type I and smaller green fibers consistent with collagen type III at 3 and 6 months (figure)

Study design: exploratory, phase 2, single-arm, open-label study in 14 healthy subjectsTreatment: administration of PLLA in the postauricular area with 3 treatment sessions spaced 4 weeks apart.Biopsies taken at baseline, 3, 6 and 12 months after the first injection session. Biopsies microscopically evaluated for collagen and inflammation using hematoxylin and eosin-stained sections. Collagen evaluated histochemically by Picro Sirius red stainResults: quantitatively, the mean level of type I collagen intensity increased significantlythe mean levels of type III intensity increased but significance was not reached (Figure showing collagen levels)

S C U L P T R A ® S T I M U L A T E S

N A T U R A L C O L L A G E N T O P R O V I D E F A C I A L V O L U M E

S C U L P T R A ® S T I M U L A T E S

N A T U R A L C O L L A G E N T O P R O V I D E F A C I A L V O L U M E

E F F I C A C y A N d S A F E t y

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CLINICAL DATA

E F F I C A C Y A N D S A F E T Y

In the aesthetic field, more than 20 studies including 4000 patients demonstrated a good safety and efficacy profile for Sculptra®

• Sculptra® allows a visible volumising effect lasting for up to 2 years• The level of patient satisfaction is 80% at 2 years• The patient overall improvement is noted in 81% of the patients at 2 years (investigator 86%)• Good tolerance until 25 months

An effective collagen stimulator that provides natural results that last more than 2 years 11

A good Safety profile 11

Proven efficacy that lasts over 25 months

Study design: Randomised, evaluator-blinded, parallel-group, multicenter study of 233 patients. The treatment phase consisted of 1 to 4 visits at 3-week intervals during which patients received bilateral injections (average of all injections was 2.3 vials) of Sculptra® (n=116) or collagen (n=117) into the left and right nasolabial fold wrinkles. The follow-up phase consisted of visits at week 3 and months 3, 6, 9, and 13 after the last treatment. Of the 116 patients treated with Sculptra®, 106 patients completed the study and continued into the long-term surveillance phase, which extended to 25 monthsObjective: to evaluate efficacy and safety in the treatment of nasolabial wrinkles in healthy immunocompetent subjectsPrimary efficacy endpoint: change in WAS (Wrinkle Assessment Scale) scores from baseline to 13 months and baseline to 19 and 25 months. Secondary endpoints: WAS at all times, Treatment Success Rate, Investigator/Subject Global Assessment, Subject Satisfaction Scores. Each Wrinkle Assessment Score, or WAS, at the time points shown represent the median of 3 investigators’ scores, and each of the investigator’s evaluations represent an average of scores for the left and right nasolabial folds.In the WAS coding system, 0 equals no wrinkles; 1 refers to a just-perceptible wrinkle; 2 indicates a shallow wrinkle; 3 a moderately deep wrinkle; 4 a deep wrinkle with well-defined edges; and 5 a very deep wrinkle or redundant fold.

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At 25 months:

• Frequency of papules (<5mm) and of nodules (>5mm) occurrence related to the product is 1.9% and 0.9% respectively for Poly-L-lactic acid; pain at the injection site is reported in 0.9% of patients

• No case of granuloma was reported during the 25 months of follow-up.

*Randomised, evaluator-blinded, parallel-group, multicenter study of 233 patients.7 †Based upon good, very good, and excellent scores.

*Investigators used a 5-point scale (4=excellent improvement, 3=much improved, 2=improved, 1=no change, 0=worse) for global evaluations.†Randomised, evaluator-blinded, parallel-group, multicenter study of 233 patients.

Rating post-treatment results: Patients are highly satisfied by Sculptra® 12

Investigator Global Efficacy Evaluation 13

80% of patients still rated their results as “good to excellent” at 25 months after first injection 12

86.3% of patients still showed overall improvement at 25 months after treatment, as rated by investigators 13

CLINICAL DATA

E F F I C A C Y A N D S A F E T Y

0 20 40 60 80 100

PERCENTAGE OF SATISFIED PATIENTS

TIM

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FTE

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AS

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month 25

month 13 84.9%

80.0%

0 20 40 60 80 100

month 13 88.7%

month 25 86.3%

INVESTIGATOR GLOBAL EVALUATIONS 1

TIM

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FTE

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13 19

0 20 40 60 80 100

PERCENTAGE OF SATISFIED PATIENTS

TIM

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FTE

R L

AS

T IN

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month 25

month 13 84.9%

80.0%

0 20 40 60 80 100

month 13 88.7%

month 25 86.3%

INVESTIGATOR GLOBAL EVALUATIONS 1

TIM

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FTE

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13 19

d E E P t I S S u E R E G E N E R A t I O N

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NATURAL AESTHETIC OUTCOMES

D E E P T I S S U E R E G E N E R A T I O N

Sculptra® provides a Deep Tissue Regeneration

Sculptra® allows you to gradually create a natural look that lasts up to 2 years.

Total vials and sessions: 5 vials over 3 sessionsIndividual results may vary.

Total vials and sessions: 5 vials over 4 sessionsIndividual results may vary.

Before treatment (All photos unretouched)

After the first session Month 7 after first injection Month 20 after first injection

Before After After After

Before treatment (All photos unretouched)

After the first session Month 7 after first injection Month 20 after first injection

Before After After After

NATURAL AESTHETIC OUTCOMES

D E E P T I S S U E R E G E N E R A T I O N

Individual results may vary (all photos unretouched).

Before After

Terry: 57 Years Old (7 vials). 9 months

Before After

JB: 40 Years Old (4 vials). 5 months

Individual results may vary (all photos unretouched).

Before

Before

After

After

Pam: 63 Years Old (6 vials). 9 months

G u I d E L I N E S

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RECONSTITUTION AND INJECTION TECHNIQUES

G U I D E L I N E S

Remove the flip-off cap and clean the penetrable vial stopper with antiseptic.

Just prior to injection, gently agitate upright vial until suspension becomes uniform and translucent.

Attach 18 G needle to sterile single-use 5 mL syringe, draw 5 mL WFI into syringe. Introduce needle into stopper and slowly add all of the WFI into the vial.

Clean stopper of vial and withdraw suspension using 18 G single-use, 1 or 3 mL sterile syringe.

Do not shake. Leave undisturbed for at least 2 hours (or preferably overnight) up to 72 hours at room temperature to ensure complete hydration.

Switch to 26 G sterile needle before injecting. Do not use needles with internal diameter smaller than 26 G for injection.

Correct Reconstitution 14, 15

Correct reconstitution and product handling/storage are essential steps for effective Sculptra® injections, which may help to minimise device-related adverse events such as the formation of nodules and papules.

Remove cap and clean

Prior to injection, agitate upright vial

Attach 18 G needle to slowly inject Water for Injection (WFI) into vial

Use 18 G needle to withdraw suspension

Do not shakeWait for at least two hours

Do not use needles with internal diametersmaller than 26 G for injection

Product placement16

Product placement precautions


G U I D E L I N E S

Avoid superficial (intradermal) injections or injections in hyperdynamic muscles such as those in the perioral and orbital region.

• Avoid product placement in hyperdynamic muscles, such as present in the periorbital and perioral region• Never inject in or through the orbicularis oculi, the modiolus, or depressor angul oris (DAO)

• For Volumising the perioral or periorbital region the product should be placed submuscular or supraperiostal

• Deeply under temporalis fascia, close to the bone:• Typical depot in clinical practice: 0.2-

0.3 cc/cm² of a 9 ml dilution • + firm massage

• Deep subcutaneous plan under the muscle

• Superficial subcutaneous fat in the lateral face• Cross-hatching/fanning• 0.1-0.3 cc/cm²

• Supraperiorbitally along zygoma, maxilla and mandible• 0.2-0.3 cc/cm² + massage

Intra Muscular placement in these areas may clump the product

Localised overcorrection

Temples

Malar area

Cheeks

Nasolabial folds

Mandibles

Treatment Plan with Sculptra®Treatment Plan with Sculptra®

At least 4 weeks between treatments.

Treat, Wait, Assess. Do not overcorrect.

TREAT WAIT ASSESS

1. Inject at level of temporal fascia2. Inject as small bolus3. Remove needle and massage the area to evenly distribute the product

Illustrations of DepotInjection Techniquefor Sculptra® Only15 17

Basic standardised injection techniques- Depot Injection Technique for Sculptra® Only15,17

• Use for correction in the temples. • Volume of Sculptra® is approximately 0.05 mL per injection. • Always perform reflux maneuver to avoid intravascular injection. • Avoid overcorrection.


G U I D E L I N E S

- Tunneling Cross-Hatch Injection Technique14,15

• Use for correction of the nasolabial folds and other facial wrinkles where the tunneling crosshatch technique is appropriate.

• Use 26 G needle attached to sterile single use 1 or 3 mL syringe. • Volume is 0.1 to 0.2 per individual injection, and should be spaced at a distance of 0.50 cm. • If clogging occurs, remove the needle, expel a small amount of product, attach a new sterile 26 G needle, then

expel a few drops of product to eliminate the air • Always perform reflux manoeuver to avoid intravascular injection. • Avoid overcorrection.

- Illustrations of Tunneling Cross-Hatch Injection Technique14,15

1. Stretch the skin to create a firm surface and lower the needle at a 30° to 40° angle2. Insert needle, bevel up, at 30° to 40° angle, subcutaneously3. When proper depth is reached, lower needle angle and advance needle along same plane4. Achieve crosshatch pattern by injecting with retrograde injection at right angle to first injection, resulting in

crosshatch of 2 tunnels of product5. Remove needle and massage area to evenly distribute the product

Massage and aftercare

Massage14, 15

During the treatment session• It is important to massage the treatment area in a

circular fashion after every 3 to 4 injections to evenly distribute the product

• Massage may help minimise the risk of papule formation at the injection site

Immediately following the treatment session• Perform deep massage in a circular fashion for at

least 2 minutes to fully distribute the product• Apply an ice pack to treated areas to decrease

edema; avoid direct contact of ice with the skin• Instruct patients about important aftercare

procedures

Aftercare14,15

Provide patients with the following instructions• Apply an ice pack to treated areas for at least 24

hours post-treatment, several times per day, to reduce swelling; avoid direct contact of ice with the skin

• Self-massage treated areas in a circular fashion for 5 minutes, 5 times per day, for 5 days

• Avoid sun and/or UV lamp exposure until swelling and redness have resolved

• Make up may be applied several hours post-treatment if no complications are present

REFERENCES

1. Murphy MR, Johnson CM Jr, Azizzadeh B. The ageing face consultation. In: Master Techniques in Facial Rejuvenation. Elsevier; 2006: 1–16.

2. Coleman SR, Grover R. The anatomy of the ageing face: volume loss and changes in 3-dimensional topography. Aesthet Surg J. 2006; 26(suppl 1): S4–S9.

3. Zimbler MS, Kokoska MS, Thomas JR. Anatomy and pathophysiology of facial ageing. Facial Plast Surg Clin North Am. 2001; 9: 179–187.

4. Vleggaar D, Fitzgerald R. Dermatological implications of skeletal ageing: a focus on supraperiosteal volumization for perioral rejuvenation. J Drugs Dermatol. 2008; 7: 209–220.

5. Donofrio LM. Fat distribution: a morphologic study of the ageing face. Dermatol Surg. 2000; 26: 1107–111

6. Fitzgerald R, Vleggar D. Facial volume restoration of the aging face with poly-l-lactic acid Dermatologic Therapy, Vol. 24, 2011, 2–27

7. Masveyraud. Rajeunissement facial par l’acide L-polylactique : à propos de 298 cas consécutifs. Annales de chirurgie plastique esthétique (2011) 56, 120-127.

8. Gogolewski et al. Tissue response and in vivo degradation of selected polyhydroxyacids: polylactides (PLA), poly(3-hydroxybutyrate) (PHB), and poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHB/VA). J Biomed Mater Res 1993; 27(9):1135-1148.

9. Vleggaar D et al. Facial enhancement and the European experience with Sculptra® (poly-l-lactic acid).J Drugs Dermatol. 2004; 3(5):542-547.

10. Goldberg D Single-Arm Study for the Characterization of Human Tissue Response to Injectable Poly-L-Lactic Acid Dermatol Surg 2013 ; 6

11. Narins RS et al A randomized study of the efficacy and safety of injectable Poly-L-lactica cid versus human–based collagen implant in the treatmentt of nasolabial fold wrinkles J Am Acad Dermatol 2010; 62: 448- 462

12. Brown SA et al. Subject global evaluation and subject satisfaction using injectable poly-L-lactic acid versus human collagen for the correction of nasolabial fold wrinkles. Plast Reconstr Surg. 2011 Apr;127(4):1684-92

13. Brandt FS et al, Investigator Global Evaluations of Efficacy of Injectable Poly-L-Lactic Acid Versus Human Collagen in the Correction of Nasolabial Fold Wrinkles Aesthetic Surgery Journal July 2011 31: 521-528

14. Sculptra® Aesthetic [package insert]. Instruction for Use

15. Sculptra® [package insert].

16. Vleggaar D et al. Facial volume restoration of the aging face with poly-l-lactid acid. Dermatologic Therapy 2011, Vol.24: 2-27

17. Vleggaar D. Poly-L-lactic acid: consultation on the injection techniques. J Eur Acad Dermatol Venereol. 2006;20(suppl 1):17-21.

Basic standardized injection techniquesDepot Injection Technique for Sculptra Only15,17

• Use for correction in the temples.• Volume of Sculptra is approximately 0.05 mL per injection.• Always perform reflux maneuver to avoid intravascular injection.• Avoid overcorrection.

Sinclair IS Pharma, Whitfield Court,30-32 Whitfield St, London, W1T 2RQTel: +44 (0) 1244 625 152www.sinclairispharma.com

uK/SipScu/13/0006

the volumiser designed to stimulate collagen with results

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