ACNE BOOT CAMP TOPICAL THERAPY BASICS Lawrence J Green, MD Associate Clinical Professor of Dermatology George Washington University School of Medicine Washington 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 unit 1,2 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 lesions 1 Reduce P acnes Reduce dilated pores Reduce inflammatory response Prevent sequelae 2 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) Mechanism 1 P acnes (bactericidal) Comedolysis 2 Preparations 1 OTC/Rx (2.5% 10%) Safety 1 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 Mechanisms 1 Normalizes follicular keratinization Inflammation Clinical utility 2 Treatment of comedonal and inflammatory lesions Available in 3 forms: tretinoin, adapalene, tazarotene Safety 1,2 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.
/wepdwu 64912ABF ACZONE (dapsone) 7.5% w/w Topical gel: A Product for the Topical Treatment of Acne Once-daily dosing 1 Proven efficacy and tolerability 1,2 Studied in large pivotal trials used for a topical acne drug 2 4340 acne patients studied 2 100% had moderate acne 1, 3 Features a pump design 1 1. ACZONE Gel 7.5% w/w topical gel Australian Approved Product Information. 2. Thiboutot DM et al. J Clin Aesthet Dermatol 2016; 9(10): 18-27. 3. Eichenfield MD et al. J Drugs in Dermatol 2016; 15(8) 962-69
Inflammatory Lesion Count Reduction At Week 12 1,* Mean Percentage Reduction From Baseline 0% -10% -20% -30% -40% -50% -60% -70% (29.8) ACZONE 7.5% w/w Topical gel (21.1) Vehicle ACZONE (dapsone) 7.5% w/w gel (n = 2162) P<0.01 P<0.001 Vehicle (n = 2178) 0 1 2 3 4 5 6 7 8 9 10 11 12 Week P<0.001 Adapted from Thiboutot 2016-48.1% (-13.9) -54.6% (-15.8) P <.001 Study design: Pooled analysis of 4,340 patients in 2 identical, 12-week, multicenter, randomized, double-blind, vehicle-controlled, parallel-group studies. Aczone Vehicle 1. Thiboutot DM et al. J Clin Aesthet Dermatol 2016; 9(10): 18-27.
Comedonal (Noninflammatory) Lesion Count Reduction at Week 12 1, * Mean Percentage Reduction From Baseline 0% -10% -20% -30% -40% -50% -60% (46.8) ACZONE 7.5% w/w Topical gel (47.6) Vehicle Aczone ACZONE (dapsone) 7.5% w/w gel (n = 2162) Vehicle (n = 2178) P<0.001-39.39.47% (-18) -45.1% (-20.7) P <.001-70% 0 1 2 3 4 5 6 7 8 9 10 11 12 Week 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. 1. Thiboutot DM et al. J Clin Aesthet Dermatol 2016; 9(10): 18-27..
Local Dermal Tolerability Assessments 1 Pooled Tolerability: Erythema Scaling Dryness Stinging/Burning (PATIENT ASESSED) (n=2175) (n=2161) Mean Severity Score 0 = none 1 = mild 2 = moderate 3 = severe 1. Thiboutot DM et al. J Clin Aesthet Dermatol 2016; 9(10): 18-27..
Use of Aczone 5% Gel as Maintenance Treatment of Acne Vulgaris Following Completion of Oral Doxycycline and Aczone 5% Gel Treatment 18
Results Mean % decrease in inflammatory lesion counts Decrease Compared to Baseline 0.0% -20.0% -40.0% -60.0% -39.8% -54.7% -80.0% -79.4% -80.5% -78.0% -77.8% -100.0% Week 4 Week 8 Week 12 Week 16 Week 20 Week 24 All results are statistically significant (p<.0001) 19
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
Adapalene 0.1%/BPO 2.5% Gel: Long Term Study Efficacy: Lesion Count Reduction (Per protocol population [N=327]) Median Change in Lesion Counts (%) 0-10 -20-30 -40-50 -60-70 -80 n=452 2 4 6 8 10 12 n=397 (88%) 3+ mos n=366 (81%) 6+mos n=334 (73.9%) 9+mos 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 70.8% Inflammatory 76% Non-inflammatory n=327 (72.3%) 12 mos 70%
Inflammatory Lesion Reduction With Topical Combination Product 0-10 Mean Change From Baseline (%) -20-30 -40-50 -60-36% -34% -19% Clindamycin 1%-BPO 5% gel BPO 5% gel -70-65% * Clindamycin 1% gel Vehicle * P < 0.05 versus other treatments. Duac Topical Gel [package insert]. Stiefel Laboratories, Inc; 2004.
Reduction of P acnes: Topical Combinations Versus Antibiotics Alone 0 Erythromycin Clindamycin + BPO + BPO BPO Clindamycin Erythromycin Azelaic Acid Reduction in P acnes (Log cm 2 ) 0.5 1 1.5 2 2.5 3 Adapted from Leyden. Semin Cutan Med Surg. 2001;20:139-143.
BPO 3.75 / CP 1.2 Long Term Lesion Count Reductions Kircik LH. J Drugs Dermatol. 2017 Jun 1;16(6):543-546.
Greater Efficacy When Combined With a Retinoid Patients (%) 100 80 60 40 20 80% 90% 56% 73% 24% 29% 0 50% Global Improvement 75% Global Improvement 90% Global Improvement Tazarotene Tazarotene + Clindamycin/benzoyl peroxide 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.
Significant Clearing of Moderate-to-Severe Acne Median Change in Papule and Pustule Count (%) 0-10 -20-30 -40-50 -60-70 -80-17% -30% Week 0 4 8 12-42% -52% Tazarotene 0.1% cream Tazarotene 0.1% cream + Duac Topical Gel (clindamycin 1%, benzoyl peroxide 5%) -52% * -63% * P 0.01 versus tazarotene alone. Significant reduction with combination regimen from baseline inflammatory 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. 27
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 RESULTS 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: Total Atrophic Acne Scar Count at Week 24 Atrophic Acne Scar Count at Week 24 Atrophic Acne Scars (Mean Number) 16 14 12 10 8 6 4 * 13.3 9.5 9.6 * 13.9 9 * 12.1 A/BPO 0.3%/2.5% Epiduo Forte Vehicle * P-value <.0001 * 2 0 Total scar - ITT/LOCF Total scar - PP Scar 2-4mm - ITT/LOCF Scar >4mm - ITT/LOCF 0.6 1.2 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 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: Total Atrophic Acne Scar Count by Visit Atrophic Acne Scars (Mean) 16 14 12.5 12 10 8 6 12.8 13.6 13.8 13.5 13.7 13.4 13.3 11.7 11.9 Total Atrophic Acne Scar Count by Visit (ITT/LOCF) 11.3 * * * Epiduo Forte Vehicle * P-value <.01 10.7 10.7 10.3 * 9.5 * * * 4 Week 0 4 8 12 16 20 24 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% 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 Percent Change From Baseline: Total Atrophic Acne Scar Count by Visit (ITT/LOCF) 30 Percent Change (Mean) 20 10 0 5.8 9.8 12.3 16.2 17.1 * P-value <.001 15.2 14.4-10 -20-2.5-1.0 * * -4.5 * -7.3-7.0 * * -8.7 * -15.5 * Week -30 0 4 8 12 16 20 24 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
THANK YOU! Larry Green drgreen@looking-younger.com