Abstracts of Poster Presentations: MauiDerm 2014 January 26–30, 2014 Wailea, Hawaii J Clin Aesthet Dermatol. 2014;7(11 Suppl):S1–S24
George Martin, MD Program Director, MauiDerm; Dermatology Laser Center Maui Kihei, Hawaii
The 2014 edition of the annual MauiDerm meeting had a wide variety of clinical and scientific data presented not only at the podium, but in its poster sessions as well. A wide range of clinically relevant material was presented in poster format. For those of you who were not on hand to review the posters and discuss them with their authors, we have compiled and indexed selected posters from the 2014 meeting. It is my hope that you will find the posters informative and thought provoking. For an alphabetical index organized by poster title or author, please see page 22 of this supplement.
ACNE AND ROSACEA A Topical Non-Drying Acne Treatment provides Rapid Control of Inflammatory Lesions and Reduces Post-Inflammatory Hyperpigmentation and Erythema Presenters: Makino ET, Mehta R Affiliations: Both authors are from SkinMedica, Inc., an Allergan Company, Carlsbad, California. Objectives: To assess the efficacy and tolerability of a novel acne treatment containing strong antioxidant and anti-inflammatory ingredients as well as salicylic acid (2%) and 4-ethoxybenzaldehyde in
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adult female subjects with mild-tomoderate facial acne. Methods: A 12-week, open-label, single-center study was conducted including female subjects aged 25 years and older with mild-tomoderate facial acne and Fitzpatrick Skin Types I to V. Clinical assessments on a target inflammatory lesion (TIL), a target postinflammatory lesion (TPIL), investigator’s global assessment of acne severity (IGA), acne lesion counts, and tolerability (erythema, burning/stinging, dryness/scaling and itching) were conducted at baseline, 24 and 48 hours, and at Weeks 4, 8, and 12. Standardized digital
photography and self-assessment questionnaires were also performed. Results: Twenty-three female subjects completed the 12-week study. Significant reductions in mean scores for IGA and inflammatory lesion counts were observed at 48 hours and Weeks 4, 8, and 12 (p25cm2 and included portions of the face, the entire scalp, or the entire forearm. In most patients, LSRs developed on Day 2 of treatment and were generally resolved at one week after peak inflammation. Most patients experienced mild-to-moderate LSRs that consisted of erythema, flaking/scaling, and crusting. Patients were assured that the reactions were to be anticipated and they received guidance on the use of emollients or
steroid-sparing lipid-containing barrier creams as treatment. The severity of the LSRs did not correlate with the degree of AK clearance as the proportion of patients with complete clearance of the face or scalp was not higher in patients with moderate LSRs than among patients with mild LSRs. No scarring or dyspigmentation occurred. Patients were treated throughout the spring and summer months in the sunny Nevada climate with no adverse consequences. Photographs of several patients before, during, and after treatment will be presented. Conclusions: Ingenol mebutate treatment was well-tolerated by community dermatology patients who treated AKs on the head and/or body. The severity of the local reaction did not strongly correlate with the degree of AK clearance.
ATOPIC DERMATITIS Safety and Efficacy of AN2728 Topical Ointment, 2% and 0.5%, in a Phase 2 Dose-Ranging Study of Adolescents with Mild-toModerate Atopic Dermatitis Presenters: Stein-Gold L, Spelman L, Spellman MC, Hughes M, Zane LT Affiliation: Stein-Gold L is from Henry Ford Hospital, Detroit, Michigan; Spelman L is from Queensland Institute of Dermatology, Queensland, Australia; Spellman MC is from San Francisco, California; Hughes M and Zane LT are from Anacor Pharmaceuticals, Inc., Palo Alto, California. Purpose: AN2728 is a novel oxaborole compound and phosphodiesterase-4 inhibitor with anti-inflammatory activity. A clinical dose-ranging study was conducted to determine the safety and efficacy of AN2728 Topical Ointment, 2% and 0.5%, administered once daily (QD) or twice daily (BID), in the treatment of mild-to-moderate atopic dermatitis (AD) in adolescents. Methods: This multi-center, randomized, double-blind, bilateral, dose-ranging, Phase 2 study enrolled 86 patients (40% male) aged 12 to
[NOVEMBER 2014 • VOLUME 7 • NUMBER 1 1] SUPPLE MENT T O T H E J O U R N A L O F C L I N I C A L A N D A E S T H E T I C D E R M AT O L O G Y
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17 years with AD involving up to 35 percent of body surface area. Enrolled patients had two target lesions of similar severity based on AD severity index (ADSI) score of 6 to 12, a maximum 1-point difference in ADSI score between the two lesions, and an erythema subscore of at least 2 (moderate). The index comprises the sum of scores ranging from 0 (none) to 3 (severe) for erythema, pruritus, exudation, excoriation, and lichenification. Patients were randomly assigned to a QD or BID treatment frequency. In addition, patients treated one target lesion with AN2728 Topical Ointment, 2%, and the other with AN2728 Topical Ointment, 0.5%. Patients were evaluated on Days 1, 8, 15, 22, and 29. Disease severity was determined based on the ADSI score on Days 8, 15, 22, and 29. The primary endpoint was the change from baseline in ADSI score. Results: AN2728 Topical Ointment, 2% and 0.5%, were found to be generally safe and welltolerated. No serious adverse events (AEs) were reported and no treatment discontinuation occurred due to AEs. Application-site symptoms were uncommon. Based on improved ADSI scores relative to baseline, a clear dose-response was seen across the four dosing regimens. The greatest improvement in ADSI score was noted with treatment with AN2728 Topical Ointment, 2% BID, which yielded a 71-percent improvement in ADSI score from baseline after 28 days, with 62 percent of lesions in this treatment group achieving total or partial clearance. This treatment group also demonstrated the greatest improvement across all five signs and symptoms of AD after 28 days, including a notable 79-percent reduction in pruritus severity. Conclusion: Of the four dosing regimens examined in this Phase 2 study of adolescents with AD, AN2728 Topical Ointment, 2% BID produced the greatest improvements in disease severity and was generally safe and well-tolerated.
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Maximal Use Systemic Exposure (MUSE) Study Evaluating AN2728, A Novel Boron-Based Small Molecule, for the Treatment of Pediatric and Adolescent Subjects with Mildto-Moderate Atopic Dermatitis Presenters: Kircik L, Call R, Tschen E, Draelos ZD, Van Syoc M, Zane L, Hebert AA Affiliations: Kircik L is from DermResearch, PLLC, Louisville, Kentucky; Call R is from Clinical Research Partners, LLC, Henrico, Virginia; Tschen E is from Academic Dermatology Associates, Albuquerque, New Mexico; Draelos ZD is from Dermatology Consulting Services, High Point, North Carolina; Van Syoc M and Zane L are from Anacor Pharmaceuticals, Inc., Palo Alto, California; Hebert AA is from Dermatology Clinical Research Unit, University of Texas Health Science Center, Houston, Texas. AN2728 is a novel boron-based compound that inhibits phosphodiesterase-4 activity and reduces the production of proinflammatory cytokines that may be associated with atopic dermatitis (AD). The objective of this openlabel, maximal use study was to evaluate the systemic exposure, pharmacokinetics, and safety of AN2728 Ointment, 2%, applied twice daily for 28 days for the treatment of AD in children and adolescents. The study enrolled 34 subjects with mildto-moderate AD, defined as a score of 2 (mild) or 3 (moderate) on the 5point Investigator’s Static Global Assessment (ISGA) scale in three patient cohorts based on age and minimum percent of treatable body surface area (%BSA) affected: 2 to 5 years old (≥35%), 6 to 11 years old (≥35%), and 12 to 17 years old (≥25%). During the first eight days when pharmacokinetic assessments were performed, subjects were dosed in the clinic; dosing was performed at home thereafter. Disease severity was measured using ISGA (0, clear to 4, severe), signs/symptoms score (0, none to 3, severe), and %BSA affected. At Day 29, 65 percent of
subjects achieved ISGA scores of clear or almost clear and 47 percent of subjects achieved scores of clear or almost clear with a >2-grade improvement from baseline. Marked reductions from baseline were observed across all the individual signs and symptoms of AD (pruritus, erythema, lichenification, excoriation, and exudation) throughout the treatment period. Notably, mean pruritus scores improved by approximately 60 percent from baseline as early as five days into treatment. The mean %BSA affected decreased by an average of 78 percent across all subjects after four weeks of treatment. The most common treatment-related adverse events were application-site reactions (occurring in 12 subjects), which generally were mild or moderate in severity and resolved spontaneously. One patient withdrew from the study due to application-site pain. Pharmacokinetic results demonstrated low blood levels of AN2728 similar to those previously observed in adults after adjusting for %BSA treated. These results generated under maximal use conditions suggest that AN2728 Ointment, 2%, may be safe and effective in subjects two years of age and older with mild-to-moderate AD.
MELANOMA Assessing the Predictive Probability of Melanoma and Other High-Risk Pigmented Lesions Using Data Provided by a Multispectral Digital Skin Lesion Analysis Device Presenters: Yoo J, Tucker N, Rigel DS Affiliation: Yoo J is from the Department of Dermatology, Albert Einstein School of Medicine, Bronx, New York; Tucker N is from MelaSciences, Irvington, New York; Rigel DS is Clinical Professor of Dermatology, NYU School of Medicine, New York, New York. Background: Risk prediction models are often used as research
SUPPLEMENT TO THE JOURNAL OF CLINICAL AND AESTHETIC DERMATOLOGY [NOVEMBER 2014 • VOLUME 7 • NUMBER 11]
tools to help identify individuals at high risk of specific cancers in the general population. Developing statistical models that evaluate the probability of developing cancer over a defined period of time allows for earlier or more frequent screening and counseling as well as earlier intervention and treatment. While many different diagnostic tools for melanoma have emerged in the past decade, very few have quantified their predictive capacity for melanoma or other high-risk pigmented lesions. Methods: Data from 1,632 pigmented lesions analyzed by a Multispectral Digital Skin Lesion Analysis device (MSDSLA) (MelaFind®, MelaSciences, Inc., Irvington, New York) were used to perform a logistical regression analysis. The MDSLA device assigns classifier scores to pigmented lesions. Final pathological diagnoses were assigned to four distinct categories: high grade dysplastic nevus, atypical melanocytic hyperplasia, malignant melanoma, or other and used as the dependent variable. Using the MSDSLA-derived classifier score (a numerical value based on analytical values from lesion’s level of structural disorder), we derived logistical regression models to determine the probability distribution for malignant melanoma and for lesions that might be considered suitable for biopsy (melanoma or atypical melanocytic hyperplasia or high grade dysplastic nevus). The logistic regression model used was: logit(p) =a + b1 x1+ b2 x2 + ….+ bixi
where p is the calculated probability of melanoma and x1x 2 xi are explanatory variables. The model logit(p)=a+bx is equivalent to p=probability of melanoma (or of lesion considered for biopsy) = e^(a+bx) / 1+e^(a+bx) Results: For the melanoma model: p=probability of melanoma = e (-3.1+0.49x) / 1+e (-3.1+0.49x)
or p / 1-p=odds of melanoma
For every one increase in unit in the MSDLA classifier score, the odds of favoring the presence of melanoma increased by 1.3. For the melanoma/AMH/HGDN model: p=probability of MM/AMH/HGDN = e / 1+e (-3.8+0.53x)
(-3.8+0.53x)
or p/1-p=odds of MM/AMH/HGDN
For every one unit increase the MSDLA classifier score, the odds of favoring the presence of MM/AMH/HGDN increased by 1.7. Conclusion: By performing a multifactorial logistical regression analysis, we were able to calculate the predictive probability of a pigmented lesion for melanoma or for consideration for biopsy based on data obtained from a multispectral digital skin lesion analysis device. This is the first study, to our knowledge, that has evaluated a dermatological technological instrument for its potential quantitative predictive capacity for presence of melanoma and other high-risk pigmented lesions.
MELASMA Efficacy and Safety of Azelaic Acid 15% Gel versus Hydroquinone 4% Cream in the Treatment of Melasma Presenters: Callender V, Young C Affiliations: The authors are from Callender Center for Clinical Research, LLC, Glenn Dale, Maryland. Background: Melasma is a chronic hyperpigmentation of the face for which there are few effective treatments. Hydroquinone (HQ) 4% is often employed as monotherapy or in combination with other agents such as corticosteroids and/or retinoids. Azelaic acid (AA) is a naturally occurring dicarboxylic acid for which several mechanisms of action have been demonstrated, including inhibition of tyrosinase and decreased abnormal melanocyte
synthesis. A previous study of AA 20% cream showed promise versus HQ in melasma treatment. This study is the first to compare the efficacy and safety of AA 15% gel with HQ 4% cream in the treatment of moderatesevere melasma. Methods: Adults of any skin type with stable moderate-severe melasma were enrolled. Exclusion criteria included solely dermal melasma; use of HQ, corticosteroids, or other depigmenting agents within three months; use of a tetracycline or other photosensitizing agent or hormonal medication within three months; or facial procedures within six months. Subjects were randomized 1:1 in double-blind fashion to either treatment. Study medication was applied twice daily for six months. Monthly evaluations included Mexameter M & E readings, Melasma Area & Severity Index (MASI), Physician Global Assessment (PGA), Patient Global Assessment Score (PtGAS), and adverse event reports and laboratory measures. Results: Thirty subjects were enrolled, 15 randomized to each treatment with comparable baseline demographics. Twelve AA-treated subjects (80%) completed the study, while 10 (67%) of HQ subjects completed. Reasons for not completing the study included adverse events (2), lost to follow-up (3), and withdrawal of consent (3). PGA improved significantly for HQ subjects at Months 3, 4, and Final Visit. However, scores were significantly higher for AA versus HQ subjects at Months 1, 2, and 4. PtGAS improved significantly for AA subjects at Months 1, 4, 5, and 6 while HQ treated subjects were significantly better than Baseline at Months 3, 4,and 5. MASI scores improved significantly for AA-treated subjects at Months 1, 2, 3, 4, and Final Visit. HQ subjects showed significant improvement at the Final Visit. Mexameter M mean scores improved significantly from Baseline for AA at Months 5 and 6, and a significant improvement over HQ at Month 5. Significant mean
[NOVEMBER 2014 • VOLUME 7 • NUMBER 1 1] SUPPLE MENT T O T H E J O U R N A L O F C L I N I C A L A N D A E S T H E T I C D E R M AT O L O G Y
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Mexameter E score improvement from Baseline for AA at Month 1, and versus HQ at Month 6. Safety/ tolerability was comparable between treatments. Conclusion: This randomized, double-blind study is the first study to evaluate AA 15% gel versus HQ 4% cream in melasma treatment. While neither product produced substantial improvement, each treatment showed significant improvements from baseline at several time points for the different efficacy parameters. Mean MASI scores were significantly improved at five visits for AA and one visit for HQ. Azelaic acid 15% gel is shown to be a reasonable therapeutic option for the treatment of melasma. Financial disclosures/funding: This study was supported by a grant from Bayer HealthCare.
ONYCHOMYCOSIS Effectiveness and Safety of Tavaborole, A Novel Boron-Based Molecule for the Topical Treatment of Toenail Onychomycosis: Results From Two Phase 3 Studies Presenters: Elewski BE, Rich P, Wiltz H, Aly R, Baldwin SL, Zane LT, González Soto R Affiliation: Elewski BE is from the Department of Dermatology, University of Alabama, Birmingham, Alabama; Rich P is from Oregon Dermatology and Research Center, Portland, Oregon; Wiltz H is from FXM Research Miramar, Miramar, Florida; Aly R is from the Department of Dermatology, University of California, San Francisco, California; Baldwin SL and Zane LT are from Anacor Pharmaceuticals, Inc., Palo Alto, California; González Soto R is from Centro de Dermatologia de Monterrey, Monterrey, Nuevo Leon, Mexico. Onychomycosis is caused primarily by dermatophytes that invade the nail plate and nail bed causing nails to deform, discolor, thicken, split, and separate from the nail bed. Limitations with oral
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treatment options include potential drug interactions and systemic adverse events. Currently approved topical agents are limited by their relatively lower efficacy and the need for adjunctive debridement. Two double-blind, randomized, vehicle-controlled, Phase 3 trials assessed the effectiveness and safety of Tavaborole Topical Solution, 5%, for the treatment of toenail onychomycosis. Both studies enrolled adults with distal subungual onychomycosis affecting 20 to 60 percent of the target great toenail. Study 301 enrolled patients in the United States and Mexico (N=594) and Study 302 enrolled patients in the United States and Canada (N=604). Patients were randomized 2:1 to apply Tavaborole Topical Solution, 5%, or vehicle solution to the affected toenails once daily for 48 weeks. Nail debridement was not permitted. The primary efficacy endpoint was complete cure defined as completely clear nail (no clinical evidence of onychomycosis) and negative mycology (negative KOH and fungal culture). Secondary endpoints included completely clear or almost clear nail, defined as ≤10 percent clinical involvement, negative mycology, and completely clear or almost clear nail with negative mycology. Primary and secondary endpoints were assessed at Week 52. Safety assessments included recording adverse events (AEs), local tolerability, clinical laboratory testing, physical examinations, vital signs, and electrocardiograms. The complete cure rates for tavaborole and vehicle in Study 301 were 6.5 percent and 0.5 percent, respectively (p=0.001), and 9.1 percent and 1.5 percent in Study 302, respectively (p
George Martin, MD Program Director, MauiDerm; Dermatology Laser Center Maui Kihei, Hawaii
The 2014 edition of the annual MauiDerm meeting had a wide variety of clinical and scientific data presented not only at the podium, but in its poster sessions as well. A wide range of clinically relevant material was presented in poster format. For those of you who were not on hand to review the posters and discuss them with their authors, we have compiled and indexed selected posters from the 2014 meeting. It is my hope that you will find the posters informative and thought provoking. For an alphabetical index organized by poster title or author, please see page 22 of this supplement.
ACNE AND ROSACEA A Topical Non-Drying Acne Treatment provides Rapid Control of Inflammatory Lesions and Reduces Post-Inflammatory Hyperpigmentation and Erythema Presenters: Makino ET, Mehta R Affiliations: Both authors are from SkinMedica, Inc., an Allergan Company, Carlsbad, California. Objectives: To assess the efficacy and tolerability of a novel acne treatment containing strong antioxidant and anti-inflammatory ingredients as well as salicylic acid (2%) and 4-ethoxybenzaldehyde in
S6
adult female subjects with mild-tomoderate facial acne. Methods: A 12-week, open-label, single-center study was conducted including female subjects aged 25 years and older with mild-tomoderate facial acne and Fitzpatrick Skin Types I to V. Clinical assessments on a target inflammatory lesion (TIL), a target postinflammatory lesion (TPIL), investigator’s global assessment of acne severity (IGA), acne lesion counts, and tolerability (erythema, burning/stinging, dryness/scaling and itching) were conducted at baseline, 24 and 48 hours, and at Weeks 4, 8, and 12. Standardized digital
photography and self-assessment questionnaires were also performed. Results: Twenty-three female subjects completed the 12-week study. Significant reductions in mean scores for IGA and inflammatory lesion counts were observed at 48 hours and Weeks 4, 8, and 12 (p25cm2 and included portions of the face, the entire scalp, or the entire forearm. In most patients, LSRs developed on Day 2 of treatment and were generally resolved at one week after peak inflammation. Most patients experienced mild-to-moderate LSRs that consisted of erythema, flaking/scaling, and crusting. Patients were assured that the reactions were to be anticipated and they received guidance on the use of emollients or
steroid-sparing lipid-containing barrier creams as treatment. The severity of the LSRs did not correlate with the degree of AK clearance as the proportion of patients with complete clearance of the face or scalp was not higher in patients with moderate LSRs than among patients with mild LSRs. No scarring or dyspigmentation occurred. Patients were treated throughout the spring and summer months in the sunny Nevada climate with no adverse consequences. Photographs of several patients before, during, and after treatment will be presented. Conclusions: Ingenol mebutate treatment was well-tolerated by community dermatology patients who treated AKs on the head and/or body. The severity of the local reaction did not strongly correlate with the degree of AK clearance.
ATOPIC DERMATITIS Safety and Efficacy of AN2728 Topical Ointment, 2% and 0.5%, in a Phase 2 Dose-Ranging Study of Adolescents with Mild-toModerate Atopic Dermatitis Presenters: Stein-Gold L, Spelman L, Spellman MC, Hughes M, Zane LT Affiliation: Stein-Gold L is from Henry Ford Hospital, Detroit, Michigan; Spelman L is from Queensland Institute of Dermatology, Queensland, Australia; Spellman MC is from San Francisco, California; Hughes M and Zane LT are from Anacor Pharmaceuticals, Inc., Palo Alto, California. Purpose: AN2728 is a novel oxaborole compound and phosphodiesterase-4 inhibitor with anti-inflammatory activity. A clinical dose-ranging study was conducted to determine the safety and efficacy of AN2728 Topical Ointment, 2% and 0.5%, administered once daily (QD) or twice daily (BID), in the treatment of mild-to-moderate atopic dermatitis (AD) in adolescents. Methods: This multi-center, randomized, double-blind, bilateral, dose-ranging, Phase 2 study enrolled 86 patients (40% male) aged 12 to
[NOVEMBER 2014 • VOLUME 7 • NUMBER 1 1] SUPPLE MENT T O T H E J O U R N A L O F C L I N I C A L A N D A E S T H E T I C D E R M AT O L O G Y
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17 years with AD involving up to 35 percent of body surface area. Enrolled patients had two target lesions of similar severity based on AD severity index (ADSI) score of 6 to 12, a maximum 1-point difference in ADSI score between the two lesions, and an erythema subscore of at least 2 (moderate). The index comprises the sum of scores ranging from 0 (none) to 3 (severe) for erythema, pruritus, exudation, excoriation, and lichenification. Patients were randomly assigned to a QD or BID treatment frequency. In addition, patients treated one target lesion with AN2728 Topical Ointment, 2%, and the other with AN2728 Topical Ointment, 0.5%. Patients were evaluated on Days 1, 8, 15, 22, and 29. Disease severity was determined based on the ADSI score on Days 8, 15, 22, and 29. The primary endpoint was the change from baseline in ADSI score. Results: AN2728 Topical Ointment, 2% and 0.5%, were found to be generally safe and welltolerated. No serious adverse events (AEs) were reported and no treatment discontinuation occurred due to AEs. Application-site symptoms were uncommon. Based on improved ADSI scores relative to baseline, a clear dose-response was seen across the four dosing regimens. The greatest improvement in ADSI score was noted with treatment with AN2728 Topical Ointment, 2% BID, which yielded a 71-percent improvement in ADSI score from baseline after 28 days, with 62 percent of lesions in this treatment group achieving total or partial clearance. This treatment group also demonstrated the greatest improvement across all five signs and symptoms of AD after 28 days, including a notable 79-percent reduction in pruritus severity. Conclusion: Of the four dosing regimens examined in this Phase 2 study of adolescents with AD, AN2728 Topical Ointment, 2% BID produced the greatest improvements in disease severity and was generally safe and well-tolerated.
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Maximal Use Systemic Exposure (MUSE) Study Evaluating AN2728, A Novel Boron-Based Small Molecule, for the Treatment of Pediatric and Adolescent Subjects with Mildto-Moderate Atopic Dermatitis Presenters: Kircik L, Call R, Tschen E, Draelos ZD, Van Syoc M, Zane L, Hebert AA Affiliations: Kircik L is from DermResearch, PLLC, Louisville, Kentucky; Call R is from Clinical Research Partners, LLC, Henrico, Virginia; Tschen E is from Academic Dermatology Associates, Albuquerque, New Mexico; Draelos ZD is from Dermatology Consulting Services, High Point, North Carolina; Van Syoc M and Zane L are from Anacor Pharmaceuticals, Inc., Palo Alto, California; Hebert AA is from Dermatology Clinical Research Unit, University of Texas Health Science Center, Houston, Texas. AN2728 is a novel boron-based compound that inhibits phosphodiesterase-4 activity and reduces the production of proinflammatory cytokines that may be associated with atopic dermatitis (AD). The objective of this openlabel, maximal use study was to evaluate the systemic exposure, pharmacokinetics, and safety of AN2728 Ointment, 2%, applied twice daily for 28 days for the treatment of AD in children and adolescents. The study enrolled 34 subjects with mildto-moderate AD, defined as a score of 2 (mild) or 3 (moderate) on the 5point Investigator’s Static Global Assessment (ISGA) scale in three patient cohorts based on age and minimum percent of treatable body surface area (%BSA) affected: 2 to 5 years old (≥35%), 6 to 11 years old (≥35%), and 12 to 17 years old (≥25%). During the first eight days when pharmacokinetic assessments were performed, subjects were dosed in the clinic; dosing was performed at home thereafter. Disease severity was measured using ISGA (0, clear to 4, severe), signs/symptoms score (0, none to 3, severe), and %BSA affected. At Day 29, 65 percent of
subjects achieved ISGA scores of clear or almost clear and 47 percent of subjects achieved scores of clear or almost clear with a >2-grade improvement from baseline. Marked reductions from baseline were observed across all the individual signs and symptoms of AD (pruritus, erythema, lichenification, excoriation, and exudation) throughout the treatment period. Notably, mean pruritus scores improved by approximately 60 percent from baseline as early as five days into treatment. The mean %BSA affected decreased by an average of 78 percent across all subjects after four weeks of treatment. The most common treatment-related adverse events were application-site reactions (occurring in 12 subjects), which generally were mild or moderate in severity and resolved spontaneously. One patient withdrew from the study due to application-site pain. Pharmacokinetic results demonstrated low blood levels of AN2728 similar to those previously observed in adults after adjusting for %BSA treated. These results generated under maximal use conditions suggest that AN2728 Ointment, 2%, may be safe and effective in subjects two years of age and older with mild-to-moderate AD.
MELANOMA Assessing the Predictive Probability of Melanoma and Other High-Risk Pigmented Lesions Using Data Provided by a Multispectral Digital Skin Lesion Analysis Device Presenters: Yoo J, Tucker N, Rigel DS Affiliation: Yoo J is from the Department of Dermatology, Albert Einstein School of Medicine, Bronx, New York; Tucker N is from MelaSciences, Irvington, New York; Rigel DS is Clinical Professor of Dermatology, NYU School of Medicine, New York, New York. Background: Risk prediction models are often used as research
SUPPLEMENT TO THE JOURNAL OF CLINICAL AND AESTHETIC DERMATOLOGY [NOVEMBER 2014 • VOLUME 7 • NUMBER 11]
tools to help identify individuals at high risk of specific cancers in the general population. Developing statistical models that evaluate the probability of developing cancer over a defined period of time allows for earlier or more frequent screening and counseling as well as earlier intervention and treatment. While many different diagnostic tools for melanoma have emerged in the past decade, very few have quantified their predictive capacity for melanoma or other high-risk pigmented lesions. Methods: Data from 1,632 pigmented lesions analyzed by a Multispectral Digital Skin Lesion Analysis device (MSDSLA) (MelaFind®, MelaSciences, Inc., Irvington, New York) were used to perform a logistical regression analysis. The MDSLA device assigns classifier scores to pigmented lesions. Final pathological diagnoses were assigned to four distinct categories: high grade dysplastic nevus, atypical melanocytic hyperplasia, malignant melanoma, or other and used as the dependent variable. Using the MSDSLA-derived classifier score (a numerical value based on analytical values from lesion’s level of structural disorder), we derived logistical regression models to determine the probability distribution for malignant melanoma and for lesions that might be considered suitable for biopsy (melanoma or atypical melanocytic hyperplasia or high grade dysplastic nevus). The logistic regression model used was: logit(p) =a + b1 x1+ b2 x2 + ….+ bixi
where p is the calculated probability of melanoma and x1x 2 xi are explanatory variables. The model logit(p)=a+bx is equivalent to p=probability of melanoma (or of lesion considered for biopsy) = e^(a+bx) / 1+e^(a+bx) Results: For the melanoma model: p=probability of melanoma = e (-3.1+0.49x) / 1+e (-3.1+0.49x)
or p / 1-p=odds of melanoma
For every one increase in unit in the MSDLA classifier score, the odds of favoring the presence of melanoma increased by 1.3. For the melanoma/AMH/HGDN model: p=probability of MM/AMH/HGDN = e / 1+e (-3.8+0.53x)
(-3.8+0.53x)
or p/1-p=odds of MM/AMH/HGDN
For every one unit increase the MSDLA classifier score, the odds of favoring the presence of MM/AMH/HGDN increased by 1.7. Conclusion: By performing a multifactorial logistical regression analysis, we were able to calculate the predictive probability of a pigmented lesion for melanoma or for consideration for biopsy based on data obtained from a multispectral digital skin lesion analysis device. This is the first study, to our knowledge, that has evaluated a dermatological technological instrument for its potential quantitative predictive capacity for presence of melanoma and other high-risk pigmented lesions.
MELASMA Efficacy and Safety of Azelaic Acid 15% Gel versus Hydroquinone 4% Cream in the Treatment of Melasma Presenters: Callender V, Young C Affiliations: The authors are from Callender Center for Clinical Research, LLC, Glenn Dale, Maryland. Background: Melasma is a chronic hyperpigmentation of the face for which there are few effective treatments. Hydroquinone (HQ) 4% is often employed as monotherapy or in combination with other agents such as corticosteroids and/or retinoids. Azelaic acid (AA) is a naturally occurring dicarboxylic acid for which several mechanisms of action have been demonstrated, including inhibition of tyrosinase and decreased abnormal melanocyte
synthesis. A previous study of AA 20% cream showed promise versus HQ in melasma treatment. This study is the first to compare the efficacy and safety of AA 15% gel with HQ 4% cream in the treatment of moderatesevere melasma. Methods: Adults of any skin type with stable moderate-severe melasma were enrolled. Exclusion criteria included solely dermal melasma; use of HQ, corticosteroids, or other depigmenting agents within three months; use of a tetracycline or other photosensitizing agent or hormonal medication within three months; or facial procedures within six months. Subjects were randomized 1:1 in double-blind fashion to either treatment. Study medication was applied twice daily for six months. Monthly evaluations included Mexameter M & E readings, Melasma Area & Severity Index (MASI), Physician Global Assessment (PGA), Patient Global Assessment Score (PtGAS), and adverse event reports and laboratory measures. Results: Thirty subjects were enrolled, 15 randomized to each treatment with comparable baseline demographics. Twelve AA-treated subjects (80%) completed the study, while 10 (67%) of HQ subjects completed. Reasons for not completing the study included adverse events (2), lost to follow-up (3), and withdrawal of consent (3). PGA improved significantly for HQ subjects at Months 3, 4, and Final Visit. However, scores were significantly higher for AA versus HQ subjects at Months 1, 2, and 4. PtGAS improved significantly for AA subjects at Months 1, 4, 5, and 6 while HQ treated subjects were significantly better than Baseline at Months 3, 4,and 5. MASI scores improved significantly for AA-treated subjects at Months 1, 2, 3, 4, and Final Visit. HQ subjects showed significant improvement at the Final Visit. Mexameter M mean scores improved significantly from Baseline for AA at Months 5 and 6, and a significant improvement over HQ at Month 5. Significant mean
[NOVEMBER 2014 • VOLUME 7 • NUMBER 1 1] SUPPLE MENT T O T H E J O U R N A L O F C L I N I C A L A N D A E S T H E T I C D E R M AT O L O G Y
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Mexameter E score improvement from Baseline for AA at Month 1, and versus HQ at Month 6. Safety/ tolerability was comparable between treatments. Conclusion: This randomized, double-blind study is the first study to evaluate AA 15% gel versus HQ 4% cream in melasma treatment. While neither product produced substantial improvement, each treatment showed significant improvements from baseline at several time points for the different efficacy parameters. Mean MASI scores were significantly improved at five visits for AA and one visit for HQ. Azelaic acid 15% gel is shown to be a reasonable therapeutic option for the treatment of melasma. Financial disclosures/funding: This study was supported by a grant from Bayer HealthCare.
ONYCHOMYCOSIS Effectiveness and Safety of Tavaborole, A Novel Boron-Based Molecule for the Topical Treatment of Toenail Onychomycosis: Results From Two Phase 3 Studies Presenters: Elewski BE, Rich P, Wiltz H, Aly R, Baldwin SL, Zane LT, González Soto R Affiliation: Elewski BE is from the Department of Dermatology, University of Alabama, Birmingham, Alabama; Rich P is from Oregon Dermatology and Research Center, Portland, Oregon; Wiltz H is from FXM Research Miramar, Miramar, Florida; Aly R is from the Department of Dermatology, University of California, San Francisco, California; Baldwin SL and Zane LT are from Anacor Pharmaceuticals, Inc., Palo Alto, California; González Soto R is from Centro de Dermatologia de Monterrey, Monterrey, Nuevo Leon, Mexico. Onychomycosis is caused primarily by dermatophytes that invade the nail plate and nail bed causing nails to deform, discolor, thicken, split, and separate from the nail bed. Limitations with oral
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treatment options include potential drug interactions and systemic adverse events. Currently approved topical agents are limited by their relatively lower efficacy and the need for adjunctive debridement. Two double-blind, randomized, vehicle-controlled, Phase 3 trials assessed the effectiveness and safety of Tavaborole Topical Solution, 5%, for the treatment of toenail onychomycosis. Both studies enrolled adults with distal subungual onychomycosis affecting 20 to 60 percent of the target great toenail. Study 301 enrolled patients in the United States and Mexico (N=594) and Study 302 enrolled patients in the United States and Canada (N=604). Patients were randomized 2:1 to apply Tavaborole Topical Solution, 5%, or vehicle solution to the affected toenails once daily for 48 weeks. Nail debridement was not permitted. The primary efficacy endpoint was complete cure defined as completely clear nail (no clinical evidence of onychomycosis) and negative mycology (negative KOH and fungal culture). Secondary endpoints included completely clear or almost clear nail, defined as ≤10 percent clinical involvement, negative mycology, and completely clear or almost clear nail with negative mycology. Primary and secondary endpoints were assessed at Week 52. Safety assessments included recording adverse events (AEs), local tolerability, clinical laboratory testing, physical examinations, vital signs, and electrocardiograms. The complete cure rates for tavaborole and vehicle in Study 301 were 6.5 percent and 0.5 percent, respectively (p=0.001), and 9.1 percent and 1.5 percent in Study 302, respectively (p
