The Cosmetic Treatment of Acne

HILARY E. BALDWIN, M.D.-MEDICAL DIRECTOR

ACNE TREATMENT AND RESEARCH CENTER

MORRISTOWN N.J.

-CLINICAL ASSOCIATE PROFESSOR OF DERMATOLOGY

RUTGERS ROBERT WOOD JOHNSON MEDICAL SCHOOL

Disclosures

Almirall (S)

BioPharmX (I)

Botanix (I)

Dermira (I,A)

Encore (A)

EPIHealth (A)

Foamix (A)

Galderma (A,I,S)

J&J (A)

LaRoche-Posay (A, S)

Novan (I)

Ortho Dermatologics (A,I,S)

Pfizer (S)

Promius (A)

Sol-Gel (A)

Sun (A,S)

S=Speaker’s BureauA=Advisory BoardI=Investigator

The Cosmetic Treatment of Acne

Make the patient better Keep the patient better Get rid of the sequelae Improve the appearance of their skin

Acne is our bread and butter

IT’S NOT ROCKET SCIENCEDoing it well means: *Taking your time

*Educating your patients*Knowledge of what to

use when in whom

Deciding what to use when andin whom

Type of lesions Inflammatory

Non-inflammatory

Number of lesions Size of lesions Distribution

Acne treatment based on pathogenesis

Increased sebum production

Increased P. acnes

Follicular hyperkeratosis

Inflammation

Hormonal TherapyIsotretinoin

AntibioticsIsotretinoin

AntibioticsRetinoids

Clindamycin?

Topical retinoidsBenzoyl peroxide

Isotretinoin

Topical retinoidsBenzoyl peroxide

Isotretinoin

Mild inflammatory acne treatment optionsTopical retinoids aloneBenzoyl peroxide alone

Topical dapsoneCombination product

Oral antibiotic

Topical retinoids alone

BaselineWeek 12

Tazarotene 0.1% Cream

Tazarotene .1% Cream Monotherapy

Baseline Week 12

Tazarotene 1% Cream Monotherapy

Baseline Week 12

Benzoyl Peroxide is the most effective antimicrobial

0

0.5

1

1.5

2

2.5

3

3.5

Clin-BP Ery-Bp Benzoylperoxide

Clindamycin Erythromycin Azelaic acid

Harkaway KA, et al. Brit J Derm. 1992;126:586-590.

Log

cm2

Ability to kill P. acnes

Benzoyl peroxide

BP kills faster and more effectively than topical antibiotics

BP alone significantly reduces both inflammatory and non-inflammatory acne

BP is not associated with antimicrobial resistance

BP can prevent the development of resistance to topical and oral antibiotics

BP can reverse resistance that has already occurred

Gloor M, et al. Z. Hautkr. 1982;57:867-878, Gollnick H, et al. J Am Acad Dermatol. 2003;49;S1-38, Gollnick H, Schramm M. Dermatol. 1998;196:119-125

BPO/Clindamycin vs. Clindamycin Monotherapy

Cunliffe WJ, Holland KT, Bojar R, Levy SF. Clin Ther. 2002;24:1117-1133.

Compliance With Topical Benzoyl Peroxide

Yentzer BA et al. J Am Acad Dermatol. 2009;60(5):879-880.

Individual subjects’ adherence to topical benzoyl peroxide ranged from 14% to 79% for the 6 weeks. No subject was considered “adherent to

treatment” as defined by a mean adherence of ≥80%.

N=11

Baseline: Severe (IGA=4)

Week 12: Mild (IGA=2)

IL: 12 | NIL: 17Subject 8423-007

IL: 80 | NIL: 112Subject 8423-

007

Treatment failure!

BP 2.5%/Adapalene .3% Gel

Dapsone 7.5% Phase III results

Baseline Week 12

Moderate-severe inflammatory acne

Topical therapy alone unlikely to work well enough or fast enough

Oral antibiotics with topicalsHormonal therapy with topicals

Isotretinoin

Acne is a chronic disease

Chronic, relapsing course over many years Severe psychosocial overlay Acute and maintenance therapy necessary Need for maintenance leads to frustration

Delicate balance of: Efficacy Tolerability Acceptability

Need for maintenance adds urgency to bacterial resistance problem

40 mg modified-release doxycycline for acne

662 patients with mod-severe acne Randomized in 1:1:1 ratio to receive QD X 16

weeks: 100 mg doxycyline 40 mg modified-release doxycycline Placebo

At all time points comparable speed of improvement, efficacy and superior safety

Moore et al. JDD 2015;14(6):581-6

Sarecycline (Seysara®)

Sarecycline – a new tetracycline-class antibiotic

Once a day, weight-based dosing

9 and above

Narrow spectrum antibiotic Less effect on GI organisms than mino/doxy

IL reduction of 35%

Well tolerated with low GI complaints

Adult female acne – different?

Spironolactone

• Anti-androgen, androgen-blocker• Reduces masculine characteristics

• Excess hair, hair loss, acne• Not FDA approved for skin issues (hypertension)• Launched in 1950, having a renaissance • Few side effects

Breast tenderness, menstrual irregularities Contraindicated in pregnancy – use in

combination with birth control pills

Severe inflammatory acne

Therapeutic optionsIsotretinoinIsotretinoinIsotretinoin

Baseline 5 MONTHS

Isotretinoin

Unnecessary consequence

Hyperpigmentation

Stop picking!Topical retinoidsHydroquinone

Chemical peelsLasers

Azelaic acid?

Patients like to glow, not shine

Oil control

Sebum: triglycerides, phospholipids, esterified cholesterol

Normal amounts: lubrication for hair and skin In some, excessive

solo or in combination with AV

Commonly used products not intended for oil control Topical retinoids, salicylic and glycolic acid, alcohol-

based washes and foundations to conceal

Thiboutot Cosmetic Dermatology 2001:45-51

Topical sebum inhibitor (Drm01)Olumacostat glasaretil

Inhibits acetyl coenzyme A carboxylase

Reduces saturated and monounsaturated fatty acyl chains in sebaceous lipids

Dose-dependent reduction in sebaceous gland size in animal model

Melnik B. J Invest Dermatol 2017;137(7):1405-1408

Phase IIIFailed both co-primary endpoints:

IGA 2 grade and C/NCPercent reduction of IL/NIL

Did not surpass vehicle

Company has announced intention to discontinue pursuit

Steroidal anti-androgen

Strong topical anti-androgenic activity

Mild anti-inflammatory properties

Easily penetrates human skin

Metabolized in skin into cortexolone (no androgenic effect)

Pilot study vs. placebo and tretinoin microsphere 0.05% (active control)

Cortexolone 17 -propionate 1% cream

Cortexolone 17 -propionate 1% cream Phase IIb study in 363 patients

www.cassiopea.com

Cortexolone 17 -propionate 1% cream Phase IIb study in 363 patients

www.cassiopea.com

Methacrylate copolymer

Microparticles of methacrylate copolymer that imbibes and holds sebum within the molecules

Incorporates into the molecule, swells to many times original size

Once imbibed, cannot leak out

Controls oil/shine for up to 8 hours

Invisible on the skin

Thiboutot Cosmetic Dermatology 2001:45-51

Methacrylate copolymer

Thiboutot Cosmetic Dermatology 2001:45-51

SCARS

Natural History of Atrophic Acne Scar Development: Duration

Scars form continuously

36% of scars are transient (arose and resolved within the 6-month study)

Transient scars had a mean duration of 41 ± 38.4 days

The remaining 64% of scars did not resolve by study end

Scars

Closed Comedones: 1%

Pustules: 1%

Post-inflammatory Lesions: 82%

Papules: 16%

Papule70%

OSCAR Study

A/BPO 0.3%/2.5% vs VehicleScar Formation Risk

Split-face, Investigator-blinded, Vehicle Controlled Whole Face, Open-label

Part I - 24 weeks; 8 visits Part II - 24 weeks, 2 visits

A/BPO 0.3%/2.5% Vehicle

Split Face

Week 1, 4, 8, 12, 16, 20, 24 Week 36, 48

OSCAR Study

A/BPO 0.3%/2.5%67 patients 16-34IGA 3 or 4

Symmetrical distribution of:

≥25 inflammatory lesions≥10 atrophic scars

A/BPO 0.3%/2.5% vs Vehicle Percent Change From Baseline - Total Atrophic Scar Count

-2.5 -1.0 -4.5-7.3 -7.0 -8.7

-15.5

5.89.8 12.3

16.2 17.1 15.2 14.4

-30

-20

-10

0

10

20

30

0 4 8 12 16 20 24

Perc

ent C

hang

e (M

ean)

Week

* * ** * *

*

* P-value < .001

• A/BPO 0.3%/2.5% was significantly superior to vehicle at all study visits and as early as week 1• The mean number of scars decreased over time with A/BPO 0.3%/2.5%• The mean number of scars increased over time with the vehicle• The difference in the mean percent change in scars (A/BPO 0.3%/2.5% vs vehicle) after 24 weeks was 29.9%

Dreno et al. Poster, Winter Clinical, Maui HI, 2018

VehicleA/BPO 0.3/2.5%

Beneficial Effects of Cosmetics

Used to fard1

Camouflage, contour and conceal Response to acne therapy too slow for most Chronic relapsing condition

Enhance oil control Adorn

Improve quality of life Create a sense of well-being

1) OED – to paint the face with cosmetics so as to hide blemishes

Decorative cosmetics improve QOL

23 patients with disfiguring facial conditions including acne (8) and rosacea (9)1

Taught to use cosmetics by professionals

DLQI baseline and 2 weeks

Improvement in all, acne p=0.0078

18 patients with acne treated and taught to use cosmetics2

Improvement of acne and improved QOL at 2/4 weeks

1) Boehncke et al. Eur J Dermatol 2002;12:577-80, 2) Hayashi et al. Eur J Dermatol 15;15:284-7

Cosmetic procedures in acne patients

Laser, peels, MDA, Microneedling

Improved QOL

Chilicka et al. Patient Preference and adherence. 2017, Aug 4

Moisturizers in acne

200 subjects enrolled in Internet-based survey study

15-40 yo - used clindamycin-BP (5%) in past 6 months

Side effects caused sub-optimal use: Spot application

Use only when flaring

Infrequent use

Discontinuation

Feldman and Chen. JDD 2011;10:605-608

Moisturizers in acne

31% Called doctors office to complain

23% physician didn’t understand SE potential

21% loss of confidence in doctor

11% less likely to see doctor again

41% used moisturizer to combat dryness/redness – perhaps the wrong one?

Feldman and Chen. JDD 2011;10:605-608

No acne visit is complete

without discussion of skin

care

Thank You!

HBALDWIN@ACNETRC.COM