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ACNE BOOT CAMPTOPICAL THERAPY BASICS
Lawrence J Green, MDAssociate Clinical Professor of Dermatology
George Washington University School of MedicineWashington DC
Relevant Disclosures
• Investigator-Allergan, Dermira, Foamix, Valeant• Speaker-Valeant• Consultant-Allergan, Dermira, Valeant
Overview
• Acne is a common condition, but can be confused with other facial skin conditions
• Proper diagnosis is key to successful acne treatment
• Recognizing unique acne signs can prevent misdiagnosis
Gollnick. Drugs. 2003:63;1579-1596.
Acne Pathophysiology
• Acne is caused by 4 interrelated processes affecting the pilosebaceous unit1,2
• Altered follicular hyperkeratinization• Sebaceous gland hyperactivity• Propionibacterium acnes (P acnes) proliferation• Inflammation/immune hypersensitivity
to P acnes
References: 1. Thiboutot. J Am Acad Dermatol. 2002;47:109-117. 2. Berson and Shalita. J Am Acad Dermatol. 1995;32:S31-S41.
Comedonal Acne
Mild Inflammatory Acne
Acne Treatment Goals
• Reduce/eliminate comedones/inflammatory lesions1
• Reduce P acnes • Reduce dilated pores• Reduce inflammatory response
• Prevent sequelae2
• Minimize psychological effects• Minimize scarring
References: 1. Leyden. J Eur Acad Dermatol Venereol. 2001;15(suppl 3):51-55. 2. Layton. Am J Clin Dermatol. 2001;2;135-141.
Mechanisms of Topical Acne Therapy
Therapy Comedogenesis ↓ P acnes ↓ Inflammation
BPO √ √
Retinoids √ √
Antibiotics √ √
References: 1. Leyden. N Engl J Med. 1997;336:1156-1162. 2. Bershad. Mt Sinai J Med.2001;68:279-286.
Benzoyl Peroxide (BPO)
• Mechanism1
• ↓ P acnes (bactericidal)• Comedolysis2
• Preparations1
• OTC/Rx (2.5%–10%)
• Safety1
• Irritation, dry skin• Bleaching of fabric• Rare allergic contact dermatitis
References: 1. Bershad. Mt Sinai J Med. 2001;68:279-286. 2. Oh and Myung. J Dermatol. 1996;23:169-180.
Topical Retinoids
• Mechanisms1
• Normalizes follicular keratinization• ↓ Inflammation
• Clinical utility2
• Treatment of comedonal and inflammatory lesions• Available in 3 forms: tretinoin, adapalene, tazarotene
• Safety1,2
• Skin irritation• Photosensitivity• Acne flare prior to perceived improvement
References: 1. Bershad. Mt Sinai J Med. 2001;68:279-286. 2. Layton. Am J Clin Dermatol.2001;2:135-141.
Topical Antibiotics/Anti-Inflammatory(besides BPO)
• Clindamycin• Erythromycin• Dapsone 5% and 7.5%• Azaleic acid• Minocycline (coming soon)• Sebum inhibitors (coming soon)
Mechanisms• Antibacterial
• Anti-inflammatory
• Risk of resistant strains of P acnes with antibiotics alone
References: 1. Bershad. Mt Sinai J Med. 2001;68:279-286. 2. Layton. Am J Clin Dermatol.2001;2:135-141. 3. Toyoda et al. Dermatology. 1998;196:130-134.
ACZONE® (dapsone) 7.5% w/w Topical gel: A Product for the Topical Treatment of Acne
• Once-daily dosing1
• Proven efficacy and tolerability1,2
• Studied in large pivotal trials used for a topical acne drug2
• 4340 acne patients studied2
• 100% had moderate acne1,3
• Features a pump design1
1. ACZONE® Gel 7.5% w/w topical gel Australian Approved Product Information. 2. Thiboutot DM et al. J Clin Aesthet Dermatol2016; 9(10): 18-27. 3. Eichenfield MD et al. J Drugs in Dermatol 2016; 15(8) 962-69
/wEPDwU64912ABF
-70%
-60%
-50%
-40%
-30%
-20%
-10%
0%
0 1 2 3 4 5 6 7 8 9 10 11 12
Mea
n Pe
rcen
tage
Red
uctio
nFr
om B
asel
ine
Week
Aczone Vehicle
(29.8) ACZONE® 7.5% w/w Topical gel(21.1) Vehicle
-48.1%(-13.9)-54.6%(-15.8)P < .001
ACZONE® (dapsone) 7.5% w/w gel (n = 2162)
Vehicle (n = 2178)
Study design: Pooled analysis of 4,340 patients in 2 identical, 12-week, multicenter, randomized, double-blind, vehicle-controlled,parallel-group studies.
P<0.01
P<0.001
P<0.001
Adapted from Thiboutot 2016
Inflammatory Lesion Count Reduction At Week 121,*
1. Thiboutot DM et al. J Clin Aesthet Dermatol 2016; 9(10): 18-27.
-70%
-60%
-50%
-40%
-30%
-20%
-10%
0%
0 1 2 3 4 5 6 7 8 9 10 11 12
Mea
n Pe
rcen
tage
Red
uctio
nFr
om B
asel
ine
Week
Aczone
Vehicle
(46.8) ACZONE® 7.5% w/w Topical gel(47.6) Vehicle
-39.39.47%(-18)-45.1%(-20.7)P < .001
ACZONE® (dapsone) 7.5% w/w gel (n = 2162)
Vehicle (n = 2178)
Comedonal (Noninflammatory) Lesion Count Reduction at Week 121,*
1. Thiboutot DM et al. J Clin Aesthet Dermatol 2016; 9(10): 18-27.
.
P<0.001
Adapted from Thiboutot 2016
Study design: Pooled analysis of 4,340 patients in 2 identical, 12-week, multicenter, randomized, double-blind, vehicle-controlled,parallel-group studies.
Local Dermal Tolerability Assessments1
Pooled Tolerability:
• Erythema
• Scaling
• Dryness
• Stinging/Burning
1. Thiboutot DM et al. J Clin Aesthet Dermatol 2016; 9(10): 18-27.
.
Mean Severity Score 0 = none1 = mild2 = moderate3 = severe
(n=2175)
(n=2161)
(PATIENT ASESSED)
Use of Aczone® 5% Gel as Maintenance Treatment of Acne Vulgaris Following Completion of Oral Doxycycline and
Aczone® 5% Gel Treatment
18
ResultsMean % decrease in inflammatory lesion counts
All results are statistically significant (p<.0001)19
-39.8%
-54.7%
-79.4% -80.5% -78.0% -77.8%
-100.0%
-80.0%
-60.0%
-40.0%
-20.0%
0.0%
Week 4 Week 8 Week 12 Week 16 Week 20 Week 24
Decrease Compared to Baseline
Combination Topical Antibiotic/BPO Products• Topical antibiotic/BPO combinations
• Reduce P acnes proliferation and associated inflammation
• Have mild direct and indirect comedolytic activity
• Provide improved efficacy and reduced risk for resistance
• Appear to be most beneficial in patients with mild-to-moderate inflammatory acne
Combination Therapy Is Standard of Care
D. Pariser, P. Westmoreland, A. Morris, et al. Long-Term Safety and Efficacy of a Unique Fixed-Dose Combination Gel of Adapalene 0.1% and Benzoyl Peroxide 2.5% for the Treatment of Acne Vulgaris. J Drugs Dermatol. 2007;6(9):899-905.
Total
Inflammatory
Non-inflammatory
Med
ian
Cha
nge
in L
esio
n C
ount
s (%
)
2 124 6 8 10
-80
-70
-60
-50
-40
-30
-20
-10
0
Efficacy: Lesion Count Reduction(Per protocol population [N=327])
70.8%
76%
70%n=397(88%)
3+ mosn=366(81%)6+mos
n=452
n=334(73.9%)9+mos
n=327(72.3%)12 mos
Adapalene 0.1%/BPO 2.5% Gel: Long Term Study
Inflammatory Lesion Reduction With Topical Combination Product
-70
-60
-50
-40
-30
-10
0
Mea
n Ch
ange
Fr
om B
asel
ine
(%)
Clindamycin 1%-BPO 5% gel
BPO 5% gel
-34%
-65%
-36%
Duac Topical Gel [package insert]. Stiefel Laboratories, Inc; 2004.
-20-19%
Clindamycin 1% gel
Vehicle*
* P < 0.05 versus other treatments.
Clindamycin+ BPO
Erythromycin+ BPO BPO Clindamycin Erythromycin
Azelaic Acid
Reduction of P acnes: Topical Combinations Versus Antibiotics Alone
0
0.5
1
1.5
2
2.5
3
Redu
ctio
n in
P a
cnes
(L
og c
m2 )
Adapted from Leyden. Semin Cutan Med Surg. 2001;20:139-143.
BPO 3.75 / CP 1.2 Long TermLesion Count Reductions
Kircik LH. J Drugs Dermatol. 2017 Jun 1;16(6):543-546.
Greater Efficacy When Combined With a Retinoid
• 90% of patients achieved ≥50% global improvement with Duac® Topical Gel (clindamycin 1%, benzoyl peroxide 5%) + retinoid (tazarotene), more than with tazarotene alone in 12-week study
Reference: Tanghetti et al. Poster presented at: 63rd Annual Meeting of the American Academy of Dermatology; February 18-22, 2005; New Orleans, La.
Patie
nts
(%)
0
20
40
60
80
100
≥ 50% Global Improvement
≥ 75% Global Improvement
≥ 90% Global Improvement
Tazarotene Tazarotene + Clindamycin/benzoyl peroxide
80%90%
56%
73%
24% 29%
Tazarotene 0.1% cream + Duac® Topical Gel (clindamycin 1%, benzoyl peroxide 5%)
Med
ian
Chan
ge in
Pap
ule
and
Pust
ule
Coun
t (%
)
Week
-17%
-42%
-52%-30%
-52%
-63%
* P ≤ 0.01 versus tazarotene alone.
*
• Significant reduction with combination regimen from baselineinflammatory lesion count ≥25
Reference: Tanghetti et al. Poster presented at: 63rd Annual Meeting of the American Academy of Dermatology; February 18-22, 2005; New Orleans, La.
-80
-70
-60
-50
-40
-30
-20
-10
00 4 8 12
Tazarotene 0.1% cream
Significant Clearing of Moderate-to-Severe Acne
27
RESULTS
Clinical Study RD.03.SPR.105061, Galderma R&D.
The Effect of 24 Weeks of Adapalene 0.3% and Benzoyl Peroxide 2.5% Gel Versus Vehicle Gel on the Risk of Formation of Atrophic Acne Scars in Moderate to Severe Acne Subjects
A/BPO 0.3%/2.5% vs Vehicle and Scar Formation Risk in Moderate to Severe Acne: Total Atrophic Acne Scar Count at Week 24
• After 24 weeks:– There was a mean of about 4 fewer acne scars (total scars) on the A/BPO 0.3%/2.5% Gel treated half-face– Fewer scars of both scar sizes assessed were observed in the A/BPO 0.3%/2.5% Gel treated half-face
9.5 9.69
0.6
13.313.9
12.1
1.2
0
2
4
6
8
10
12
14
16
Total scar - ITT/LOCF Total scar - PP Scar 2-4mm - ITT/LOCF Scar >4mm - ITT/LOCF
Atro
phic
Acn
e Sc
ars
(Mea
n N
umbe
r)
Atrophic Acne Scar Count at Week 24
Epiduo Forte Vehicle***
*
* P-value < .0001
Clinical Study RD.03.SPR.105061, Galderma R&D.
A/BPO 0.3%/2.5%
11.7 11.9 11.310.7 10.7
10.39.5
12.5
12.8 13.6 13.5 13.8 13.7 13.4 13.3
4
6
8
10
12
14
16
0 4 8 12 16 20 24
Atro
phic
Acn
e Sc
ars
(Mea
n)
Week
Total Atrophic Acne Scar Count by Visit (ITT/LOCF) Epiduo Forte
Vehicle
A/BPO 0.3%/2.5% vs Vehicle and Scar Formation Risk in Moderate to Severe Acne: Total Atrophic Acne Scar Count by Visit
* * **
** *
• A/BPO 0.3%/2.5% was significantly superior to its vehicle at all study visits and as early as week 1• Mean scar counts decreased over time with A/BPO 0.3%/2.5%
* P-value < .01
Clinical Study RD.03.SPR.105061, Galderma R&D.
A/BPO 0.3%/2.5% vs Vehicle and Scar Formation Risk in Moderate to Severe Acne: 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
12.316.2 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
Percent Change From Baseline: Total Atrophic Acne Scar Count by Visit (ITT/LOCF)
* * ** *
*
*
* 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%
Clinical Study RD.03.SPR.105061, Galderma R&D.
Take away for your practice…
• New topical drugs are coming over the next few years
• For now, combination therapy is standard of care
• continued improvements over time in the real world
• Non-BPO combos exist • Combine with BPO cleansers to prevent
antibiotic resistance
![Acne and Diaper Rash 2016 [Read-Only] - AAP.org the end of this session, participants will be able to • Describe the role of diet in acne • Identify one herbfor topical use in](https://img.dokumen.tips/doc/110x75/5b0d71c67f8b9a952f8d8669/acne-and-diaper-rash-2016-read-only-aaporg-the-end-of-this-session-participants.jpg)
