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 adult female subjects with mild-to-moderate facial acne.
Methods: A 12-week, open-label, single-center study was conducted including female subjects aged 25 years and older with mild-to-moderate 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 (p<0.02). Significant reductions in the TIL and TPIL occurred at all visits (p<0.001). The acne lotion was very well-tolerated with mean tolerability scores remaining below mild.
Conclusion: The study suggests that our new acne lotion may provide a comprehensive solution for patients seeking an effective, nondrying treatment for mild-to-moderate acne as well as postinflammatory lesions.
Azelaic Acid Foam, 15% in the Treatment of Papulopustular Rosacea: A Randomized, Double-Blind, Vehicle-Controlled Study
Presenters: Draelos Z, Elewski B, Staedtlerc G, Havlickova B
Affiliations: Draelos Z is from Dermatology Consulting Services, High Point, North Carolina; Elewski B is from University of Alabama, Birmingham, Alabama; Staedtlerc G and Havlickova are from Global Clinical Development Dermatology, Bayer Healthcare, Berlin, Germany.
Background: Rosacea is a chronic inflammatory skin disorder primarily of the facial skin. Papulopustular rosacea—the focus of this study—is characterized by persistent central facial erythema with transient papules or pustules or both in a central facial distribution. Azelaic acid (AzA) has demonstrated clinical efficacy and safety for the treatment of rosacea and is currently approved topical 15% gel formulation. Studies have shown that topical foams may have more rapid penetration and greater total absorption than creams and lotions. Foams may also be preferred by patients over gels and creams because of the ease of application and spread, shorter drying time, and reduced density.
Objective: This study was designed to evaluate the safety and efficacy of a new foam formulation of azelaic acid, 15%, in subjects with papulopustular rosacea in a Phase 2 study.
Methods: This was a randomized, double-blind, vehicle-controlled, multicenter, parallel group, Phase 2 study comparing azelaic acid foam, 15%, with vehicle in the treatment of papulopustular rosacea. Subjects (n=401) were randomly allocated to 12 weeks of treatment with twice daily AzA foam, 15%, or vehicle. The primary efficacy variables assessed were 1) Investigator’s Global Assessment (IGA) scores dichotomized into success and failure and 2) nominal change in inflammatory lesion count (papules and pustules) from baseline to end of treatment.
Results: The group treated with AzA foam, 15%, had a higher IGA-based success rate at the end of treatment than the control group (43.4% vs. 32.5%,P=0.017).
The AzA foam, 15%, group also had a greater reduction in the mean nominal inflammatory lesion count from baseline to end of treatment (13 vs. 9.7 reduction, P<0.001). AzA foam, 15%, was safe and well-tolerated. Drug-related adverse events were reported more frequently for the subjects in the AzA foam, 15%, group than in the vehicle group (10.6% vs. 3.9%) and most frequently included application-site pain and pain. Additionally, drug-related adverse events were predominantly local, cutaneous, of mild intensity, transient, and were resolved at the end of study.
Conclusion: The new foam formulation of azelaic acid is effective in the treatment of papulopustular rosacea. AzA foam, 15%, demonstrated a statistically significant advantage over vehicle in both primary and secondary measures of efficacy. Both AzA foam, 15%, and vehicle were safe and well-tolerated. A larger Phase 3 study is being completed and will further evaluate the safety and tolerability of AzA foam, 15%, compared to vehicle. The development of a new foam formulation of AzA would provide increased therapeutic modalities for the treatment of rosacea.
Overall Tolerability of Adapalene-BPO from a Pooled Data Analysis
Presenters: Kircik L
Affiliations: Kircik L is from Mount Sinai Medical Center, New York, New York.
Background: Adapalene/benzoyl peroxide (stabilized in the Simulgel™ vehicle ) gel 0.1%/2.5% has demonstrated effectiveness in the treatment of acne vulgaris in several clinical trials. To further describe the tolerability of this treatment, data were analyzed from several clinical studies that investigated the effectiveness and safety of adapalene/BPO gel 0.1%/2.5%.
Methods: Data from 14 studies were pooled to evaluate the tolerability of adapale/BPO gel 0.1%/2.5% among acne subjects. A total of 2,358 subjects between 9 and 61 years old were treated with adapalene/BPO gel 0.1%/2.5%. Frequency, percentages, and worst postbaseline scores were summarized for dryness, erythema, scaling, and stinging/burning.
Results: Most subjects experienced a worst post-baseline score of none or mild, 83.2 percent for dryness, 78.6 percent for erythema, 86.1 percent for scaling, and 76.8 percent for stinging/burning. Two percent or fewer subjects had a severe score for dryness, erythema, and scaling, and less than five percent of subjects had a severe score for stinging/burning. Fewer than two percent of subjects discontinued due to an adverse event. Even subjects with moderate and severe scores for the tolerability endpoints had improved Investigator’s Global Assessment scores from baseline to Week 4.
Discussion: In this large pooled analysis, adapalene/BPO gel 0.1%/2.5% was well tolerated and provided benefit even in subjects who had a less favorable tolerability profile.
Financial disclosures/funding: Study funded and poster/editorial support provided by Galderma Laboratories, L.P.
A Meta-analysis to Evaluate the Efficacy and Safety of Adapalene-Benzoyl Peroxide Topical Gel in Black Subjects with Mild or Moderate Acne
Presenters: Alexis AF, Kerrouche N, Callender VD
Affiliations: Alexis AF is Director, Skin of Color Center, St. Luke’s-Roosevelt Hospital, New York, New York; Kerrouche N is from Galderma R&D, Biot, France; Callender VD is from Callender Dermatology & Cosmetic Center, Glenn Dale, Maryland.
Background: Adapalene, a synthetic retinoid analogue, and benzoyl peroxide, an effective antimicrobial agent, are currently available at concentrations of 0.1% and 2.5%, respectively, clS el fixed combination gel (A-BPO) for the treatment of acne. Results from three multicenter, randomized, double-blind, vehicle-controlled, clinical trials of A-BPO gel were analyzed in a prospective subgroup meta-analysis. Subjects were assessed at Weeks 1, 2, 4, 8, and 12 for efficacy and safety. The analysis included 238 self-identified black subjects in the A-BPO and vehicle treatment groups who were treated for 12 weeks. This subgroup comprised primarily women with Fitzpatrick skin types V and VI and a mean age of 21.3 years. After 12 weeks of treatment, significantly more subjects achieved investigator’s global assessment success with A-BPO (n=121; 31.4%) than with vehicle (n=117; 14.5%) (P<0.001). Significant reductions in median total lesions were observed with A-BPO compared to vehicle at all post-baseline visits (P<0.01). Most subjects did not experience cutaneous irritation. Of those who did, their worst tolerability scores were mostly none or mild for all treatment groups. Most reported adverse events (AEs) were mild in severity. Two subjects reported serious AEs that were unlikely related to the study treatment: one AE of worsening depression in the adapalene BPO group and one AE of miscarriage in the vehicle group. Four subjects discontinued treatment due to AEs. In conclusion, treatment with A-BPO in black subjects with mild-to-moderate acne was effective and well-tolerated.
Financial disclosures/funding: Study funded and poster/editorial support provided by Galderma Laboratories, L.P.
Adapalene Gel, 0.3% is Efficacious in Reducing Acne Lesions in Adult Women
Presenters: Berson D, Alexis A
Affiliations: Berson D is from Weill Medical College of Cornell University-New York, Presbyterian Hospital, New York, New York; Alexis A is from St. Luke’s-Roosevelt Hospital, New York, New York.
Acne vulgaris is characterized by comedones, papules, and pustules, as well as secondary lesions including scarring and pigmentation. It affects approximately 30 to 85 percent of adolescents, and recent reports suggest an increasing prevalence in adults, particularly women. Adapalene is a naphthoic acid derivative with potent retinoid and anti-inflammatory properties that was developed for the topical treatment of acne and other retinoid-sensitive dermatoses. Adapalene gel, 0.3%, is a highly effective comedolytic agent, reversing the abnormal follicular keratinization and microcomedo formation, and decreasing inflammatory lesions, which predispose to the secondary lesions. In this analysis, data from two studies comparing adapalene gel, 0.3%, to vehicle gel were combined and evaluated for inflammatory lesion counts, noninflammatory lesion counts, and total lesion counts in female subjects age 18 and older (18-41). The results showed a statistically significant difference favoring adapalene gel, 0.3%, for the mean percent reduction in total lesion count at Week 12 (P=0.045). The median results favored adapalene gel, 0.3%, for all three endpoints. In the adapalene gel, 0.3%, group, the most common treatment-related adverse events (AEs) (occurring in more than 5% of the subjects) were skin discomfort and dry skin, which was equivocal to those seen with adapalene gel, 0.1%. There were no reported serious AEs in any group.
Financial disclosures/funding: Study funded and poster/editorial support provided by Galderma Laboratories, L.P.
Cutaneous Tolerability and Subject Satisfaction of an Over-the-Counter Cleansing and Moisturizing Regimen in Subjects Aged 7 to 11 Years With Acne Prone Skin
Presenters: Hensley DR, Brandt S
Affiliations: Hensley DR is from Metroplex Dermatology, Arlington, Texas; Brandt S is from Galderma Laboratories, L.P., Fort Worth, Texas.
The epidemiology and demographic profile of acne vulgaris has evolved over the past several decades, with a noted earlier onset in patients as young as seven years of age. A commercially available foaming facial wash and moisturizer SPF 30 skin care regimen specifically formulated for acne-prone skin has been shown to be safe and tolerable in subjects 12 years of age and older. In an open-label, single center study, the safety and tolerability of this skin care regimen were assessed in subjects 7 to 11 years of age. Thirty-five subjects applied a foaming facial wash twice daily and a facial moisturizer SPF 30 once daily for 22 days. Subjects were physician assessed for cutaneous tolerability, skin hydration, skin barrier function, and self-assessed for subject satisfaction via a questionnaire. This study group comprised boys and girls who were primarily white (62.9%) with a normal skin type (100%), and a median age of nine years. Most subjects’ cutaneous tolerability scores were “none” when assessed by the investigator (≥85.7%) or the subject (≥88.6%) at Week 1 and at Week 3. Changes in hydration and transepidermal water loss relative to baseline were not clinically meaningful over the course of the study. Eleven subjects reported 13 adverse events (AEs), all mild to moderate in severity. Two subjects reported treatment-related AEs (skin burning sensation and dermatitis contact). In summary, this skin care regimen was well-tolerated during this study and a positive impression for cosmetic acceptability was reported for both products.
Early treatment of Adults with Papulopustular Rosacea with Doxycycline 40mg Modified Release is Associated with Improved Clinical Outcomes
Presenters: Winkelman W
Affiliations: Winkelman W is from Galderma Laboratories, L.P., Fort Worth, Texas.
Rosacea affects millions of people in the United States yearly. While an inflammatory component is known to be associated with rosacea, the mechanisms underlying this process remain unclear. Topical treatments are often prescribed when the symptom presentation is less severe while systemic treatment options are prescribed for the more severe presentations. A multicenter, randomized, double-blind, placebo-controlled study was designed to evaluate clinical markers and biomarker levels in adults ages 18 to 70 years old previously diagnosed with papulopustular rosacea (PPR). One hundred seventy subjects were treated with placebo or doxycycline 40mg modified release (MR) for 12 weeks. Lesion count, investigator’s global assessment (IGA) scores, and rates of clinical treatment successes (defined as IGA score of clear or almost clear) were evaluated at each visit. Doxycycline MR treatment significantly reduced inflammatory lesions of rosacea compared to placebo. The doxycycline MR treatment group’s IGA treatment success rates were significantly higher relative to placebo at Weeks 4, 8, and 12. Post-hoc exploration of the treatment successes revealed that in the subset of subjects who were more recently diagnosed with PPR (defined as ≤5 years since diagnosis), clinical success rates were significantly greater in the doxycycline MR group relative to placebo at Weeks 4 and 8. Subjects with levels of matrix metalloproteinase (MMP) (a biomarker for cutaneous inflammation in rosacea) at or below 0.01 RFU/s and treated with doxycycline MR had improved clinical success rates compared to placebo. Additionally, recently diagnosed subjects with MMP levels at or below 0.01 RFU/s that were in the recently diagnosed group demonstrated even more marked clinical success with doxycycline MR treatment. This study replicates clinical results of doxycycline MR observed in previous studies and extends this line of research by evaluating effects of treatment in the early time period following initial diagnosis. These initial results suggest that early treatment of PPR with doxycycline MR may confer the greatest clinical benefit to patients and suggests that treatment with doxycycline MR should be considered clS el first-line treatment in addition to topical PPR options.
Financial disclosures/funding: Study funded and poster/editorial support provided by Galderma Laboratories, L.P.
ACTINIC KERATOSIS
A Targeted Delivery and Stabilized Retinol Product provides Comparable Efficacy to Tretinoin in a Randomized, Double-Blind, Split-face Comparative Study in Photodamaged Skin
Presenters: Makino ET, Mehta R
Affiliations: Both authors are from SkinMedica, Inc., an Allergan Company, Carlsbad, California.
Objectives: Retinol has been shown to improve the appearance of photodamaged skin when applied topically and is generally considered to be approximately 10 times less potent than tretinoin. To assess this theory, the efficacy and tolerability of a novel retinol complex was compared to tretinoin.
Methods: A randomized, double-blind, split-face study was conducted to compare three concentrations of the targeted delivery retinol formulation (RET; 0.25%, 0.5%, 1.0%) against three strengths of tretinoin (0.025%, 0.05%, and 0.1%) in subjects with moderate-to-severe photodamage. Subjects were randomized into three groups: Group 1 (RET 0.25% vs. tretinoin 0.025%); Group 2 (RET 0.5% vs. tretinoin 0.05%); and Group 3 (RET 1.0% vs. tretinoin 0.1%). Subjects were randomized to apply RET on one half of the face and tretinoin on the other half for 12 weeks. Clinical evaluations for efficacy, tolerability, and standardized digital photographs were conducted.
Results: At Week 12, all groups showed statistically significant improvements from baseline in all efficacy parameters (all p<0.001). There were no significant differences between RET and tretinoin in all efficacy and tolerability parameters.
Conclusion: Results from this comparison study suggest that this novel retinol complex containing multiple agents for optimal delivery to the dermis provides comparable improvements to tretinoin in photodamaged skin.
Efficacy of Sequential Treatment with Ingenol Mebutate Gel 0.015%, Following Cryosurgery for Actinic Keratosis on the Face and Scalp
Presenters: Berman B, Goldenberg G, Hanke CW, Tyring SK, Werschler WP, Knudsen KM, Goncalves J, Larsson T, Swanson N
Affiliations: Berman B is from University of Miami Miller School of Medicine, Miami, Florida, and Center for Clinical and Cosmetic Research, Aventura, Florida; Goldenberg G is from Mount Sinai School of Medicine, New York, New York; Hanke CW is from St. Vincent Hospital, Indianapolis, and the Laser & Skin Surgery Center of Indiana, Carmel, Indiana; Tyring SK is from University of Texas Health Science Center, Houston, Texas; Werschler WP is from Department of Medicine/Dermatology, University of Washington School of Medicine, Seattle, Washington; Knudsen KM and Larsson T are from LEO Pharma A/S, Ballerup, Denmark; Goncalves J is from LEO Pharma Inc, Parsippany, New Jersey; Swanson N is from Oregon Health and Science University, Portland, Oregon.
Background: Cryosurgery effectively treats individual lesions of actinic keratosis (AK), yet recurrence rates are high, and the treatment does not address field cancerization of perilesional skin. We planned to compare complete clearance of AK lesions using cryotherapy followed by field treatment with ingenol mebutate (IngMeb) compared with cryotherapy and vehicle gel. The 12-month efficacy results from our study evaluating sequential treatment of AKs on the face and scalp with cryosurgery followed by IngMeb 0.015% gel versus cryosurgery and vehicle gel are presented.
Methods: This was a Phase 3, multicenter, randomized, two-arm, parallel-group, double-blind, vehicle-controlled, 12-month study (NCTO1541553). Patients with 4 to 8 clinically, typical, and discrete AKs within a contiguous 25cm2 treatment area on the face or scalp were enrolled and received liquid nitrogen cryosurgery to all visible AKs. Patients were randomized to field treatment with IngMeb 0.015% gel or vehicle gel once daily for three consecutive days. Three weeks after cryosurgery, field treatment was applied to patients in both groups. The primary endpoint was complete clearance of AKs in the treatment area at Week 11. Secondary endpoints were percentage reduction in the total number of AKs and partial clearance rate (≥75%) of AKs across the period from Week 11 to 12 months. Patients who withdrew early were classified as non-responders.
Results: A total of 329 patients (80.5% with face and 19.5% with scalp lesions) were randomized to IngMeb 0.015% gel (n=167) or vehicle (n=162) gel following cryosurgery. These patients were all white, predominantly male (82.4%), and had a median age of 67 years (range 34-89); most had Fitzpatrick skin type I (15.2%) or II (48%). In total, 92 percent completed 11 weeks and 88 percent concluded the 12-month period. Complete clearance rates were greater with IngMeb compared with vehicle for all lesions at 11 weeks (60.5% vs. 49.4%; p=0.04) and 12 months (30.5% vs. 18.5%; p=0.01). The relative complete AK clearance achieved by 11 weeks increased at 12 months in the IngMeb group, from a relative ratio of 1.22 (1.01-1.49) to 1.67 (1.12-2.50). In the treatment area surrounding the frozen lesions, only 38.9 percent of patients experienced new emerging lesions in the IngMeb-treated field, while in the vehicle group, 51.9 percent of patients had new lesions emerging from previously not visible subclinical lesions (p=0.01). The mean percent reduction of AKs at 12 months was significantly higher with IngMeb for all lesions (59.5% vs. 44.4%; p=0.004) than with vehicle. Over 12 months, partial (≥75%) AK clearance rates also improved significantly with IngMeb for all lesions (50.9% vs. 37%;p=0.01).
Conclusion: Sequential topical treatment with IngMeb 0.015% gel following cryosurgery significantly enhanced the efficacy of cryosurgery, with a more pronounced relative benefit at 12 months. This difference is derived both from enhancing the effect of cryosurgery with IngMeb on the visible baseline lesions and from a field treatment effect of IngMeb on subclinical lesions not visible at baseline.
Financial disclosures/funding: This study (NCTO 1541553) was funded by LEO Pharma A/S. Medical writing services were provided by Dr. Isabelle Leach of iMed Comms, Macclesfield, United Kingdom, and were funded by LEO Pharma A/S.
Clinical Pearls with Ingenol Mebutate Treatment in Elderly Patients with Actinic Keratosis in a Community Dermatology Practice
Presenters: Bettencourt MS
Affiliations: Bettencourt MS is Medical Director, Bettencourt Skin Center, Henderson, Nevada; Assistant Clinical Professor of Dermatology, University of Nevada, Las Vegas, Nevada
Background: The management of patients with actinic keratosis (AK) includes both lesion-directed and field-directed therapies to target discreet, isolated lesions as well as skin with confluent visible and subclinical AKs. The objective of this investigation was to retrospectively analyze the charts of patients from a community dermatology practice and describe their results with ingenol mebutate treatment of AK.
Methods: The chart review extracted information on the patients’ medical history and demographics, pertinent history of AK and skin cancer, and treatments for those conditions. Analysis of the patients’ current treatment course with ingenol mebutate included data on the size and location of treatment areas, local skin reactions, adverse events, short-term efficacy, and long-term follow-up.
Results: Ingenol mebutate was used to treat AK in 135 patients from January 2012 to January 2013. Sixteen patients treated a second body site, and three patients treated a third site, for a total of 154 treatments. These patients had a prolonged history of AK that included prior treatment with cryosurgery and/or topical agents. Many of these patients also had a history of nonmelanoma skin cancer. In the current course of treatment with ingenol mebutate, 78 percent of patients presented with sun-damaged skin with >15 AKs, including AKs that were recurrent or hyperkeratotic. The majority of patients, 77 percent, received cryosurgery to all visible lesions two weeks before their first ingenol treatment course. Ingenol mebutate gel, 0.015%, was used to treat the face in 77 patients, the scalp in 45 patients, and the chest in one patient; ingenol mebutate gel, 0.05%, was used to treat the forearms and/or hands in 31 patients. Treatment areas were typically >25 cm2 in size and included portions of the face, the entire scalp, or entire forearms. Local skin reactions consisting of mild-to-moderate erythema and flaking/scaling generally resolved within one week and were not treated in most patients. Complete and partial clearance were defined as 100 and ≥75-percent clearance, respectively, of baseline and emergent AKs. At 1 to 4 months after treatment of the face, the rates of complete and partial clearance were 44 and 55 percent, respectively. The rate of complete clearance for patients who treated areas of the face > 100cm2 in size was less than that for patients who treated areas ≤100cm2 in size. At 1 to 4 months after treatment of the scalp, the rates of complete and partial clearance for the scalp were 22 and 67 percent, respectively; for forearm and hand AK, >80 percent of patients demonstrated ≥75-percent improvement. At evaluations up to one year after ingenol mebutate treatment, emergent lesions were recognized in the treated field and treated with cryosurgery. Patients reported high treatment satisfaction and indicated that they would use ingenol mebutate on other body sites with AK.
Conclusion: Dermatology patients treated in a community-based practice achieved substantial clearance of AK on head and body sites following treatment with ingenol mebutate gel. The proportion of patients who achieved 100-percent clearance on the face was higher for treatment areas ≤ 100cm2 than for treatment areas > 100cm2. Ingenol mebutate is an effective, well-tolerated topical treatment for managing the burden of AK in sun-damaged skin.
Clinical Presentation of Local Skin Reactions Associated with Treatment of Actinic Keratosis with Ingenol Mebutate Gel in Elderly, Community Dermatology Patients
Presenters: Bettencourt MS
Affiliations: Bettencourt MS is Medical Director, Bettencourt Skin Center, Henderson, Nevada; Assistant Clinical Professor of Dermatology, University of Nevada, Las Vegas, Nevada
Background: Patients with heavily sun-damaged skin frequently have a substantial burden of actinic keratosis (AK) and subclinical AKs, which are treated with topical therapy to target large areas. All of the topical agents for AK treatment cause a localized inflammatory skin reaction as a consequence of the therapeutic activity that eliminates transformed keratinocytes. These local skin reactions (LSRs) persist during treatment. Since many agents require application for several weeks, patients who are unable to tolerate the prolonged skin reactions may discontinue treatment early and not achieve the expected rates of clearance. Ingenol mebutate gel, 0.05% and 0.015%, is a topical treatment for AK that is applied for only 2 or 3 days. The purpose of this study was to retrospectively analyze the LSRs experienced by community dermatology patients who treated AKs with ingenol mebutate gel.
Methods: Patient charts were reviewed for data on the severity, onset and duration, and treatment of LSRs. The correlation between the intensity of LSRs and clearance of AKs was examined.
Results: Ingenol mebutate was used to treat 135 patients from January 2012 to January 2013. These patients had a prolonged history of AK that included prior treatment with cryosurgery and/or topical agents. In their current treatment course, all patients applied all doses of ingenol mebutate to treatment areas that were generally >25cm2 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-to-Moderate 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 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 well-tolerated. 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.
Maximal Use Systemic Exposure (MUSE) Study Evaluating AN2728, A Novel Boron-Based Small Molecule, for the Treatment of Pediatric and Adolescent Subjects with Mild-to-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 open-label, 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 mild-to-moderate AD, defined as a score of 2 (mild) or 3 (moderate) on the 5-point 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%, maybe 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 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 x1 x 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 (-3.8+0.53x)/ 1+e(-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 moderate-severe 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
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 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<0.001). Negative mycology was achieved in 31.1 percent of patients treated with Tavaborole versus 7.2 percent of vehicle-treated patients in Study 301 and 35.9 percent versus 12.2 percent of patients in Study 302 (for each, p<0.001). In both studies, the proportion of patients with completely clear or almost clear nail was superior with Tavaborole: 26.1 versus 9.3 percent in Study 301; 27.5 versus 14.6 percent in Study 302 (for each, p<0.0001). A superior outcome was also observed for completely clear or almost clear nail with negative mycology with Tavaborole treatment: 15.3 versus 1.5 percent in Study 301; 17.9 versus 3.9 percent for Study 302 (for each, p<0.001). In both Phase 3 trials, Tavaborole Topical Solution, 5% was well-tolerated with no serious treatment-related AEs and a low rate of discontinuation resulting from AEs. Based on these data, the once-daily application of Tavaborole Topical Solution, 5%, appears to be a safe and effective treatment for toenail onychomycosis.
Itraconazole is an Effective Oral Treatment for Onychomycosis: Results from a Phase 3, Randomized, Multicenter, Placebo-Controlled Study
Presenters: Fleischer A, Verma A, Olayinka B, Hardas B
Affiliations: All authors are from Merz Pharmaceuticals, LLC, Greensboro, North Carolina.
Background: Itraconazole, approved for treatment of toenail fungal infection onychomycosis, provides antifungal activity at a dosage requiring once-daily (QD) administration of two lOOmg capsules for 12 weeks. Utilizing the Meltrex® technology delivery system, a novel 200mg formulation of itraconazole was developed delivering the same dosage as two capsules in a single tablet.
Methods: This Phase 3, randomized, placebo-controlled trial investigated the noninferiority of one itraconazole 200mg tablet to two itraconazole lOOmg capsules dosed QD for 12 weeks, with a 40-week follow-up period. Clinical cure (Investigator’s Global Assessment plus mycological examination) was the primary outcome measure and clinical improvement was a secondary endpoint. Safety and efficacy of itraconazole 200mg tablets were also compared with placebo.
Results: Significantly more patients in the intent-to-treat per-protocol populations on itraconazole (200mg tablet or two 10-mg capsules) achieved complete cure and clinical improvement compared with placebo. For both endpoints, itraconazole 200mg tablet QD was noninferior to itraconazole lOOmg capsules and superior to placebo. All treatment groups demonstrated a similar safety profile with no new safety signals identified.
Conclusion: Once-daily itraconazole 200mg was well-tolerated and may be an effective alternative to two itraconazole lOOmg capsules for the treatment of toenail onychomycosis. The convenience of a simpler dosing regimen may help improve patient compliance.
Efinaconazole Topical Solution May Reach the Onychomycosis Infection Site by Spreading Through the Space Between the Nail Plate and Nail Bed
Presenters: Pariser DM, Pollak RA, Pillai R, Olin JT
Affiliations: Pariser DM is from Virginia Clinical Research, Inc., Norfolk, Virginia; Pollak RA is from San Antonio Podiatry Associates, San Antonio, Texas; Pillai R is from Dow Pharmaceutical Sciences Inc., a Division of Valeant Pharmaceuticals New Jersey; Olin JT is from Valeant Pharmaceuticals North America, LLC, Bridgewater, New Jersey
Background: The vehicle formulation of efinaconazole topical solution, 10%, includes ingredients that result in low surface tension, with the development goal being to better penetrate the nail plate.
Objective: To evaluate the ability of the efinaconazole vehicle to reach the site of infection by spreading through the space between the nail plate and nail bed, rather than through the nail plate.
Methods: 11 patients (mean age 48.5 years) were entered with clinically determined onychomycosis. Two separate applications of vehicle formulation (with fluorescein incorporated) were applied distally only to the toe between the nail and nail bed, avoiding application to the surface of the toenail. Affected nails were clipped to reveal the nail bed and examine underside of nail. Spread of formulation was assessed qualitatively under visible and ultraviolet light conditions by photographing target toenails 20 to 30 minutes after vehicle application, and after the nail clippings.
Results: Assessments under visible light conditions showed yellowing of the nail where disease appeared to be present and heavy disposition under the underside of the nail clippings. Fluorescence was observed where disease seemed to be present, and spreading of the formulation to the nail bed and under the nail was visually confirmed post nail clipping.
Conclusion: These qualitative data suggest that this formulation also fosters an additional approach to the infection site, by spreading into the space between the nail and nail bed.
In Vitro Nail Penetration of (14C)-Efinaconazole Topical Solution, 10%
Presenters: Pillai R, Korotzer A, Olin JT
Affiliations: Pillai R is from Pharmaceutical Sciences Inc., a Division of Valeant Pharmaceuticals North America, LLC, Bridgewater, New Jersey; Korotzer A and Olin JT are from Valeant Pharmaceuticals North America, LLC, Bridgewater, New Jersey.
Objective: To evaluate the penetration of efinaconazole topical solution, 10%, through human nail samples.
Methods: Daily applications of (14C)-efinaconazole topical solution, 10%, to human volunteer nail samples (55.1μL/cm2) for 28 days. Radioactivity assessed in receptor fluid and nail plate using Franz-type diffusion cell system. Cumulative permeability into the receptor fluid = concentration of (14C)-efinaconazole x volume of receptor chamber (4.7mL)/application area of nail plate (0.0908cm2). The flux rate through the nail plate = cumulative permeability/time point (day).
Results: Efinaconazole was detected in the receptor phase as early as Day 1. There was a time-dependent increase in the amount of (14C)-efinaconazole topical solution, 10%, penetrating through the nail. The flux rate reached steady state from Day 18 to Day 28 (average rate 1.40μg eq./cm2/day). The concentration of (14C)-efinaconazole in human nails after 28-days application was 3.1 lμg eq./mg (3.11mgeq./g).
Conclusion: Nail penetration of (14C)-efinaconazole topical solution, 10%, was noted from Day 1, was time-dependent, and reached steady state after Day 18.
In Vitro Nail Penetration Study with Ex Vivo Human Nails Demonstrates Penetration of Tavaborole Topical Solution, 5%, Through Nail Polish
Presenters: Coronado D, Chanda S Merchant T, Bu W, Zane LT
Affiliations: The authors are from Anacor Pharmaceuticals, Inc., Palo Alto, California
Onychomycosis causes nails to become thickened and discolored, often leading to social embarrassment. Individuals may wish to use nail polish to mask the appearance of infected nails due to onychomycosis. To be effective, topical antifungal medications must be able to penetrate through the nail plate and into the nail bed. Tavaborole Topical Solution, 5%, for the treatment of onychomycosis has demonstrated the ability to readily penetrate the nail plate. The objective of this study was to evaluate the penetration of Tavaborole Topical Solution, 5%, through nail polish on fingernails obtained from human female cadavers. Five fingernails from four donors (N=20) were divided into two treatment groups. Two nails per donor received one coat of a commercial brand of nail polish. Another two nails per donor received no nail polish. One nail from each donor served as a non-dosed control. Tavaborole Topical Solution, 5%, was applied to each nail (except the non-dosed control) once daily for 20 consecutive days using a positive placement pipette calibrated to deliver 12.5μL/cm2 of solution. Using the Franz Finite dose model, drug penetration was measured by monitoring its rate of appearance in the receptor solution (phosphate buffered saline) bathing the inner surface of the nail. Aliquots of the receptor solution samples were collected over the course of the study and analyzed for the presence of Tavaborole using a qualified liquid chromatography-tandem mass spectrometry (LC/MS/MS) method. The mean (SD) cumulative penetration of tavaborole in the treatment group with nail polish was 3526 (1433) μg/cm2 compared to 2661 (1319) μg/cm2 in the treatment group with no nail polish. The penetration of Tavaborole Topical Solution, 5%, through nails with nail polish was not statistically different from penetration through nails without nail polish. These results demonstrate Tavaborole Topical Solution, 5%, was able to penetrate through one coat of a commercial brand of nail polish using an ex vivo human female fingernail model.
PSORIASIS
Long-Term Safety and Efficacy of Apremilast, an Oral Phosphodiesterase 4 Inhibitor, in Patients With Moderate-to-Severe Psoriasis: Efficacy and Safety Results From a Phase III, Randomized Controlled Trial (ESTEEM 1)
Presenters: Papp K, Reich K, Leonardi C, Kircik L, Chimenti S, Hu CC, Stevens RM, Day RM, Griffiths CEM
Affiliations: Papp K is from Probity Medical Research, Waterloo, Ontario, Canada; Reich K is from SCIderm Research Institute and Dermatologikum Hamburg, Hamburg, Germany; Leonardi C is from Saint Louis University School of Medicine, St. Louis, Missouri; Kircik L is from Physicians Skin Care, PLLC, Louisville, Kentucky; Chimenti S is from University of Rome Tor Vergata, Rome, Italy; Hu CC, Stevens RM, and Day RM are from Celgene Corporation, Warren, New Jersey; Griffiths CEM is from Dermatology Centre, University of Manchester, Manchester, United Kingdom.
Background: Apremilast (APR), an oral phosphodiesterase 4 inhibitor, works intracellularly to regulate inflammatory mediators.
Methods: In ESTEEM 1, patients with moderate-to-severe plaque psoriasis (Psoriasis Area and Severity Index [PASI] ≥12, body surface area [BSA] ≥10%, static Physician’s Global Assessment [sPGA] ≥3) were randomized 1:2 to placebo (PBO) or APR 30mg BID (APR30). At Week 16, PBO patients were switched to APR30 through Week 32. At Week 32 patients treated with APR30 at baseline who achieved ≥75% reduction from baseline in PASI score (PASI-75) were re-randomized (1:1, blinded) to continue APR30 or receive PBO through Week 52. Upon loss of PASI-75, patients who were re-randomized to PBO resumed APR30
Results: 844 patients were randomized (mean psoriasis duration, 19.4 years; mean PASI score, 19.0; mean BSA, 24.7%). At Week 16, significantly more patients receiving APR30 achieved PASI-75 (33.1%) versus PBO (5.3%; P<0.0001); primary endpoint. Mean percent change from baseline in PASI score was 52.1 percent for APR30 versus 16.7 percent for PBO (P<0.0001). At Week 32, 154 patients randomized to APR30 at baseline were PASI-75 responders and were re-randomized to continue APR30 (n=77) or switch to placebo (n=77). In the randomized treatment withdrawal phase, 61.0 percent of 77 patients randomized to continue APR30 at Week 32 had PASI-75 at Week 52; 75.3 percent had ≥70 percent improvement in PASI score; mean percent change from baseline in PASI score at Week 52 was -80.5 percent. Of patients who lost PASI-75 (median time: 5.1 weeks), 70.3 percent regained PASI-75 after restarting APR30. The duration of re-treatment with APR30 through Week 52 ranged from 3.4 to 22.1 weeks.
APR was generally well-tolerated for up to 52 weeks. During the APR exposure period (defined as Weeks 0-52; including all patients who received APR, regardless of when initiated), 804 received ≥1 dose of APR30; adverse events (AEs) in ≥5 percent of patients were diarrhea (18.7%), URTI (17.8%), nausea (15.3%), nasopharyngitis (13.4%), tension headache (9.6%), and headache (6.5%). In APR-treated patients reporting diarrhea and nausea, the majority of the cases occurred within two weeks of the first dose, were predominantly mild in severity, and generally resolved within one month. The exposure-adjusted incident rate for AEs did not appear to increase over time, no new significant AEs emerged with continued exposure, and no clinically meaningful changes in laboratory measurements were reported. AEs were predominantly mild or moderate in severity. The occurrence of serious AEs was 4.2 percent and no specific serious AE was reported for >3 patients during the APR exposure period. Discontinuation rate due to AEs was low during the APR-exposure period (7.3%).
Conclusion: APR30 significantly reduced the severity of moderate-to-severe psoriasis over 16 weeks of treatment. The clinical response for APR30 was generally maintained in patients treated for 52 weeks. APR 30 demonstrated an acceptable safety profile and was generally well tolerated for up to 52 weeks. Most AEs were mild or moderate in severity and did not lead to discontinuation.
Clinical Study Results of Desoximetasone 0.25% Super-Potent Spray in Moderate-to-Severe Plaque Psoriasis for Four Weeks
Presenters: Kircik L
Affiliations: Kircik L is Clinical Associate Professor of Dermatology, Mount Sinai Medical Center, New York, New York; Clinical Associate Professor of Dermatology, Indiana University School of Medicine, Indianapolis, Indiana; Medical Director, Physicians Skin Care, PLLC, Louisville, Kentucky.
Two Phase 3, double-blind, randomized, vehicle-controlled parallel studies evaluated the efficacy and safety of desoximetasone spray 0.25%, a super-potent topical corticosteroid, twice daily versus vehicle spray twice daily for 28 days in adult patients with moderate-to-severe plaque psoriasis. To qualify for study entry, the subject needed to exhibit a PGA score of 3 (moderate) or 4 (severe) for overall disease severity and a target lesion with an area of at least 5cm2 that achieved a combined Total Lesion Severity Score of ≥7, with a plaque elevation score of ≥3 (at least moderate).
In both Phase 3 studies, a statistically significantly greater percentage of subjects in the desoximetasone spray 0.25% compared to vehicle group achieved both clinical success and treatment success at Day 28. These results demonstrated superior efficacy in the active study group for both overall improvement of plaque psoriasis and in the individual psoriasis lesion (by TLSS) designated at baseline as the most severely involved plaque (target lesion).
Tolerability and safety were assessed at all study visits. No statistically significant differences were observed between study arms and no major safety signals related to AEs were noted. No stinging and burning were reported with the spray formulation.
Secukinumab in Patients with Moderate-to-Severe Plaque Psoriasis: Results from the Efficacy of Response And Safety of 2 fixed secUkinumab REgimens in Psoriasis (ERASURE)
Presenters: Elewski B, Lebwohl M, Papp K, Nakagawa H, Sigurgeirsson B, Tsai T, Tyring S, Hampele I, Karpov A, Helou S, Papavassilis C; for the ERASURE Study Group
Affiliations: Elewski B is from the Department of Dermatology, University of Alabama at Birmingham School of Medicine, Birmingham, Alabama; Lebwohl M is from the Department of Dermatology, Mount Sinai School of Medicine, New York, New York; Papp K is from Probity Medical Research, Waterloo, Ontario, Canada; Nakagawa H is from the Department of Dermatology, The Jikei University School of Medicine, Tokyo, Japan; Sigurgeirsson B is from Faculty of Medicine, Department of Dermatology, University of Iceland, Reykjavik, Iceland; Tsai T is from the Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Tyring S is from the Department of Dermatology, The University of Texas Health Science Center at Houston, Houston, Texas; Hampele I, Karpov A, and Papavassilis C are from Novartis Pharma AG, Basel, Switzerland; Helou S is from Novartis Pharmaceuticals Corporation, East Hanover, New Jersey.
Background: IL-17A plays a critical role in the pathogenesis of psoriasis. The goal of the ERASURE study was to evaluate the efficacy and safety of secukinumab, a fully human anti-IL-17A monoclonal antibody, compared to placebo for up to 52 weeks in patients with moderate-to-severe plaque psoriasis.
Methods: This was a double-blind, placebo-controlled, multicenter, Phase 3 trial involving 738 patients. Patients were randomized to 1 of 3 treatment arms: s.c. secukinumab 150mg (n=245) or 300mg (n=245) or placebo (n=248). The co-primary objectives were to demonstrate superior efficacy of secukinumab versus placebo, based on the Psoriasis Area and Severity Index (PASI 75) and Investigator’s Global Assessment (IGA) 0/1 (modified 2011) response rates at Week 12. Key secondary endpoints included the PASI 90 response at Week 12 and maintenance of the PASI 75 and IGA 0/1 response at Week 52, as well as safety and tolerability.
Results: Improvements of at least 75% and 90% in the PASI response score at Week 12 were seen in 81.6 and 59.2 percent, respectively, of patients in the secukinumab 300mg dose group and in 71.6 and 39.1 percent, respectively, of patients in the 150mg dose group, compared with 4.5 and 1.2 percent, respectively, of patients in the placebo group (P<0.0001 for all comparisons with placebo). The percentage of patients with an IGA 0/1 (modified 2011) score (i.e., clear or almost clear) was 65.3 and 51.2 percent with the secukinumab 300mg and 150mg doses, respectively, compared with 2.4 percent with placebo (P<0.0001 for all comparisons with placebo). The secukinumab 300mg dose resulted in improved PASI 75 (P=0.0080) and IGA 0/1 scores at Week 12 (P=0.0016) compared with the 150mg dose. PASI 50 responses with each secukinumab dose differed from placebo as early as Week 2 (P<0.0001), with maximal response rates seen around Week 16 (PASI 90 response rate at Week 16 was 69.8 percent for patients who received secukinumab 300mg). Clinical responses to secukinumab continued to be sustained through 52 weeks. The most common AEs were nasopharyngitis, upper respiratory tract infection, and headache. No new or unexpected safety findings were observed with either dose of secukinumab.
Conclusion: Results from this study show that secukinumab has rapid, high, sustained efficacy and an acceptable safety profile treatment for moderate-to-severe plaque psoriasis. The clinical response rates reported in the secukinumab 300mg dose group were consistently higher than with 150mg dose group.
Financial disclosures/funding: This study was sponsored by Novartis Pharma AG. These results were previously presented at the 22nd Annual Congress of the European Academy of Dermatology and Venereology, October 2-6, 2013, Istanbul, Turkey.
Patient Perspectives in the Management of Psoriasis: US Results From the Population-Based Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) Survey
Presenters: Lebwohl MG; Armstrong AW; Van Voorhees AS; Kalb RE; Kavanaugh A
Affiliations: Lebwohl MG is from The Icahn School of Medicine at Mount Sinai, New York, NY; Armstrong AW is from the Department of Dermatology, University of Colorado at Denver, Aurora, Colorado; Van Voorhees AS is from the Department of Dermatology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania; Kalb RE is from the Department of Dermatology, State University of New York at Buffalo School of Medicine and Biomedical Sciences Medical Group, Buffalo, New York; Kavanaugh A is from the University of California at San Diego, La Jolla, California.
Background: To gain further insight into real-world treatment trends and unmet needs from the patient and physician perspectives, the population-based Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) survey of 3,426 patients and 781 physicians in North America and Europe was conducted. We report results from the subset of US patients participating in the survey.
Methods: Telephone numbers for this household survey were randomly selected by list-assisted random digit dialing. Adults diagnosed with psoriasis and/or psoriatic arthritis (PsA) participated. Patients did not have to be currently under the care of a healthcare provider (HCP), a patient organization member, or receiving treatment.
Results: From 52,926 US households screened, 1,005 adults completed the survey. The US household prevalence of psoriasis was 4.0 percent; the extrapolated population prevalence was 2.2 percent. A diagnosis of psoriasis alone was reported by 73.1 percent of patients; 26.9 percent indicated a diagnosis of PsA (± a separate diagnosis of psoriasis). Severe disease was reported by 29.5 percent of patients with psoriasis and 55.9 percent with PsA. The most important factors contributing to symptom severity in psoriasis patients were itching (36.1%) and location or size of skin lesions (21.8%). In PsA patients, the most important factors were pain or swelling of joints (48.1%) and itching (14.8%). Although most patients had seen an HCP in the past 12 months, ≈20 of patients who had not seen an HCP reported it was because they did not think their HCP could help. About 23 percent of psoriasis patients and 55 percent of PsA patients reported ever having a discussion with their current HCP about conventional oral or biologic therapies. Current or prior conventional oral therapy was reported by 14.8 percent of psoriasis and 52.2 percent of PsA patients; 30.3 percent (psoriasis) and 46.1 percent (PsA) of these patients were taking these medications at the time of the survey, whereas the majority had discontinued therapy. Only 8.6 percent of psoriasis patients reported ever having used biologic therapy versus 42.6 percent of PsA patients; ≈60 percent of these patients were receiving biologies at the time of the survey, whereas the rest had discontinued. At the time of the survey, 21.6 percent of patients reported no current treatment; 9.3 percent of psoriasis and 50.0 percent of PsA patients were receiving systemic therapy. Perceived treatment burden, safety/tolerability concerns, and lack of effectiveness were associated with treatment dissatisfaction and discontinuation.
Conclusion: Psoriasis and PsA remain undertreated in the United States, marked by high treatment dissatisfaction and discontinuation. Several unmet needs are identified and warrant further attention.
Malignancy Events in the Psoriasis Longitudinal Assessment and Registry (PSOLAR) Study: Current Status of Observations
Presenters: Lebwohl M, Fiorentino D, Ho V, Langley R, Fakharzadeh S, Calabro S, Langholff W, Chevrier M, on behalf of the PSOLAR Steering Committee
Affiliations: Lebwohl M is from Mount Sinai Medical Center, New York, New York; Fiorentino D is from Dalhousie University, Halifax, Nova Scotia, Canada; Ho V is from University of British Columbia, Vancouver, British Columbia, Canada; Langley R is from Stanford University, Stanford, California; Fakharzadeh S, Calabro S, Langholff W, and Chevrier M are from Janssen Services, LLC, Horsham, Pennsylvania.
Objective: To report the accrual of malignancies excluding nonmelanoma skin cancers (NMSC) in the PSOLAR study.
Methods: PSOLAR is a multicenter, longitudinal, observational study evaluating long-term safety and clinical outcomes for patients receiving (or eligible to receive) treatment for psoriasis with biologies and/or conventional systemic agents. The accrual of malignancies excluding NMSC (i.e., basal/squamous cell carcinomas) in PSOLAR overall and by exposure sub-groups is reported. Rates of malignancy are assessed using a definition of exposure based on whether patients had ever been exposed to a given therapy at any time prior to the event. In cases of exposure to multiple therapies, malignancies are attributed to treatment groups in the order of ustekinumab first, infliximab/golimumab second, other biologies third, and non-biologic therapy last.
Results: As of the August 23, 2012, data cut, 11,900 of 12,000 patients had enrolled in PSOLAR (22,918 cumulative patient-years of follow-up). Unadjusted rates of malignancy, excluding NMSC, across treatment groups were: ustekinumab 0.53 events per 100 patient years of observation (PYO) [95% CI: 0.35][0.76; 28/5332 PYO], infliximab/golimumab 0.70 per 100 PYO [95% CI: 0.44][1.06; 22/3136], other biologies (almost exclusively etanercept/adalimumab) 0.68 per 100 PYO [95% CI: 0.53][0.87; 69/10093], non-biologic therapy 0.83 per 100 PYO [95% CI: 0.58][1.14; 36/4357], and overall 0.68 per 100 PYO [95% CI: 0.57][0.79; 155/22918]. Limitations: Due to channeling of therapy, there may be differences in subgroup characteristics. Formal comparison will require statistical modeling to adjust for patient characteristics and risks, including consideration of multiple treatments.
Conclusion: Although many patients exposed to biologies have been exposed to multiple prior immunosuppressive therapies, rates of malignancy appear limited overall. Unadjusted rates show a trend toward lower rates in ustekinumab-treated patients, despite the rules of event attribution, compared to other treatment groups. These are preliminary results; PSOLAR will follow patients for up to eight years, providing additional data over time. PSOLAR is a powerful resource for tracking safety events of interest among patients eligible to receive systemic therapies.
Economic And Comorbidity Burden Among Patients With Moderate-To-Severe Psoriasis
Presenters: Feldman S, Zhao Y, Shi L, Tran MH
Affiliations: Feldman S is from Wake Forest Baptist Medical Center, Winston-Salem, North Carolina; Zhao Y and Tran MH are from Novartis Pharmaceuticals Corporation, East Hanover, New Jersey; Shi L is from Tulane University, New Orleans, Louisiana.
Background: Previous studies demonstrated substantial economic and comorbidity burdens associated with psoriasis (PsO) before biologies were available. Biologies have changed PsO treatment paradigms and potentially improved patient outcomes. This study aims to reassess the economic and comorbidity burden of PsO in the biologic era.
Objective and purpose: To compare the comorbidity burden, healthcare resource utilization, and costs between moderate-to-severe PsO patients and matched controls.
Methods: Adults (18-64 years) with at least two distinct PsO diagnoses (ICD-9-CM: 696.1) were identified in the OptumHealth Reporting and Insights claims database (01/2007-03/2012). Moderate-to-severe PsO patients (cases) were selected as those receiving ≥1 systemic or phototherapy during the 12-month study period following the index date (randomly selected date after the first PsO diagnosis). Controls were free of PsO and psoriatic arthritis (PsA) and matched 1:1 with cases on age, gender, and geographic region. All patients had at least 12 months of continuous enrollment after the index date. PsO-related comorbidities, medication use, all cause healthcare utilization, and costs were compared between cases and controls. Multivariate regression models were performed to examine the impact of PsO on comorbidities, medication use, and healthcare costs and utilization adjusting for demographics, index year, insurance type, non-PsO-related comorbidities. Odds ratios were reported for any medication use, hospitalization, emergency room (ER) visit, and outpatient visit, and incidence rate ratios (IRR) were reported for the number of medications filled. Adjusted cost differences between cases and controls were also estimated.
Results: A total of 5,492 matched pairs of moderate-to-severe PsO patients and controls were selected, with mean age 47.6 years and 55.5 percent male. PsO patients were significantly more likely to have almost all comorbidities examined, with the top three most common in both groups being hyperlipidemia (33.3% vs. 27.3%), hypertension (32.8% vs. 23.5%), and diabetes (15.8% vs. 9.7%). Controlling for between-group differences, PsO patients were more likely to have any medication filled [OR=27.5] and more distinct number of prescription medications (IRR=2.1) than controls (both P<0.01). Compared with controls, PsO patients were more likely to have any inpatient admission (OR=1.3), ER (OR=1.3), and outpatient visit (OR=29.3) (all P<0.01). PsO patients also incurred significantly higher total, pharmacy, and medical costs (adjusted annual costs differences: $18,960, $13,990, and $3,895 per patient, respectively, all P<0.01) than controls. Limitations included potential bias resulting from unobserved difference between cases and controls, classification of PsO severity based on treatments rather than clinical measures, potentially underestimated comorbidities based on ICD-9-CM codes, and limited generalizability beyond the commercial health plans and the age groups included.
Conclusion: Compared with PsO-and PsA-free controls, moderate-to-severe PsO patients were more likely to have PsO-related comorbidities and incurred significantly higher healthcare utilization and costs.
First-Line Use of Calcipotriene/Betamethasone Dipropionate Combination Products for the Treatment of Plaque Psoriasis is Associated With Lower Health Care Utilization and Cost
Presenters: Feldman SR; Levi E; Pathak P; Kakatkar S; Balkrishnan R
Affiliations: Feldman SR is from Wake Forest Baptist Medical Center, Winston-Salem, North Carolina; Levi E is from Scientific Advisor, LEO Pharma Inc.; Pathak P and Kakatkar S are from Outcomes Inc.; Balkrishnan R is from University of Michigan, Ann Arbor, Michigan and Outcomes Inc.
Background: Calcipotriene/betamethasone dipropionate combination topical products are an established treatment for patients with plaque psoriasis. In appropriate patients, using the combination products as first-line therapy after the psoriasis diagnosis might be beneficial. This study investigated whether such use might lower the cost impact on health care budgets.
Methods: A retrospective study using Thomson Reuters MarketScan® national claims data from 2006 to 2011 was performed to identify patients who received psoriasis medications following a psoriasis diagnosis (ICD-9 code 696. lx). Patients were continuously enrolled during one-year pre- and post-index date periods. The two study cohorts were cohort A (patients treated with calcipotriene/betamethasone dipropionate combination products immediately post-diagnosis) and cohort B (patients treated with any other topical psoriasis medication immediately post-diagnosis). The frequency of office visits and total health care costs (includes pharmacy costs and costs of inpatient and outpatient services) during the one-year post-index period were assessed. Multiple regression analyses adjusting for baseline demographic and clinical covariates, including a proxy for psoriasis severity, were performed.
Results: In total, 16,977 patients were identified in the two cohorts based on the topical medication prescribed (cohort A = 7,307; cohort B = 9,670). During the one-year follow-up period, mean (± SD) total and psoriasis-related office visits were significantly lower in cohort A (13.36±14.39; 2.79±7.60) than cohort B (16.08±16.68; 4.25±10.23) (both P<0.001). Mean total health care costs were less for cohort A ($7,785.80±$15,255.60; median = $3,411) than cohort B ($11,757.20 ±$19,747.60; median = $5,595.80) (P<0.001). In a generalized linear model adjusted for baseline covariates, cohort A had significantly lower costs than cohort B (β ± SE = 0.041±0.017; P=002).
Conclusion: First-line treatment with calcipotriene/betamethasone dipropionate combination products after psoriasis diagnosis was associated with fewer office visits and lower total health care costs.
Predicting Improvement in Signs and Symptoms of Plaque Psoriasis after 1 Week of Treatment with Clobetasol Propionate 0.05% Spray
Presenters: Feldman S, Baum E, Winkelman W
Affiliations: Feldman S is from Wake Forest University School of Medicine, Winston-Salem, North Carolina; Baum E is from the Department of Dermatology, University of Alabama, Tuscaloosa, Alabama; Winkelman W is from Galderma Laboratories, L.P., Fort Worth, Texas.
Up to 40 percent of patients with plaque psoriasis may not use their topical medicines as directed. Early response to topical therapy, especially for pruritus, may be one important motivator to ensure adherence of patients to their full course of therapy. Clobetasol propionate 0.05% (CP) spray is a topical super-high potent corticosteroid. CP is indicated to treat moderate-to-severe plaque psoriasis in patients with lesions covering 20 percent or less body surface area and has demonstrated efficacy and safety in clinical trials after one week of therapy. A post-hoc analysis was performed on the combined populations of two Phase 3 pivotal trials of CP spray versus vehicle (N=240) in patients with moderate-to-severe plaque psoriasis. Overall disease severity (ODS), erythema, plaque elevation, scaling, and pruritus (all assessed on a 5-point scale of 0 [clear] to 4 [severe/very severe]) were analyzed using a generalized linear model to determine if early response at Week 1 would be predictive of response at Week 4. Subjects on CP spray whose Week 1 ODS or pruritus score was at most mild were treatment successes (clear or almost clear) at Week 4. A negligible number of vehicle-treated patients demonstrated a response at both Week 1 and Week 4 for either ODS or pruritus. Pruritus and disease severity responses to CP spray at 1 week predicted treatment success in both pruritus and the overall disease severity at four weeks.
Effectiveness and Safety of Clobetasol Propionate 0.05% Spray Added on to Regimens Containing Biologic Agents for the Treatment of Moderate to Severe Plaque Psoriasis
Presenters: Feldman SR; Koo JYM
Affiliations: Feldman S is from Wake Forest University School of Medicine, Winston Salem, North Carolina; Koo JYM is from University of California, San Francisco Medical Center, San Francisco, California.
Moderate-to-severe psoriasis often requires systemic treatment, but even biologic medications do not induce complete clearing in the majority of patients. Topical treatments are often used as adjuncts to systemic treatment. A Phase 4, multicenter, open-label trial was conducted to evaluate the effectiveness and safety of twice-daily clobetasol propionate 0.05% spray when added on to an existing stable regimen that included a biologic treatment (3 months duration) in 183 patients with moderate, severe, or very severe plaque psoriasis. By Week 4, 78 percent of patients with moderate or severe disease and 66 percent of patients with very severe disease at baseline were clear or almost clear (P\.0001). Worst skin tolerability response was assessed post-baseline and included erythema (28% mild, 6% moderate, 1% severe), peeling (29% mild, 7% moderate, 1% severe), dryness (35% mild, 9% moderate, 2% severe), and stinging (24% mild, 4% moderate, 1% severe). Telangiectasias and skin atrophy were reported in 1% of patients each at some point during the study (post-baseline). Pruritus was reported in 10 percent of patients, and folliculitis was reported in one percent of patients. Ten patients experienced adverse events that were regarded as probably related to the study regimen, one of whom discontinued treatment. The addition of clobetasol propionate 0.05% spray to a stable regimen including a biologic resulted in clear or almost clear status in the majority of patients and provides an option for additional control of psoriasis plaques when biologic agents as monotherapy are not as effective as physicians and patients require.
Financial disclosures/funding: Study funded and poster/editorial support provided by Galderma Laboratories, L.P.
Clinical Improvement in Psoriasis Observed Over 1 to 4 Weeks of Treatment with Ixekizumab
Presenters: Blauvelt A, Cameron G, Zhu B, Shen W, Heffernan M
Background: Not only are rapid improvements in psoriasis ideal for improving patient quality of life, it has also been shown that early clinical improvements provide valuable information about the longer term effectiveness of a medication. Ixekizumab, a monoclonal antibody neutralizing IL-17A, has previously
been shown to be effective in patients with moderate-to-severe psoriasis through 20 weeks of treatment.
Objective: To evaluate the magnitude of the clinical responses to ixekizumab after 1 to 4 weeks of treatment in a Phase 2 clinical trial.
Methods: Patients diagnosed with moderate-to-severe psoriasis (n=142) were randomized into one of the following treatment arms: 10, 25, 75, or 150mg of ixekizumab, or placebo, administered subcutaneously at 0, 2, 4, 8, and 12 weeks. The 75 and 150mg groups were analyzed here. For improvements in PASI from baseline, comparisons between treatment groups and placebo were calculated using ANCOVA. For the proportions of patients achieving ≥50% or ≥75% improvement in PASI (PASI 50 or PASI 75), comparisons between treatment groups and placebo were made using Fisher’s exact tests.
Results: Significant differences in percent change in PASI from baseline were observed as early as Week 1 in the 75mg (22%) and 150mg (30%) groups compared to placebo (6%, p<0.05). Similarly, significant improvements were observed in the 75 and 150mg groups versus placebo as early as Week 1 in erythema, induration, and scaling as well as across body regions (head, trunk, arms, legs). Psoriasis on the head showed significantly greater (p<0.05) improvements at Week 1 compared to the arms and legs. Significant differences in PASI 50 rate were observed as early as Week 2, in the 75mg (38%) and 150mg (68%) groups versus placebo (8%, p<0.05). PASI 50 rates increased at Week 4 to 69% in the 75mg and 82% in the 150mg groups, respectively, versus 12% in placebo (p<0.05). Significant differences in PASI 75 response rates were observed as early as Week 2 in the 150mg group versus placebo (21% vs. 0%, p<0.05). PASI 75 response rates were 38 and 64% in the 75 and 150mg groups, respectively, at Week 4 versus 0% in placebo (p<0.05).
Conclusion: Ixekizumab treatment resulted in statistically significant improvements in PASI as early as 1 week with greater improvements in psoriasis on the head before other body regions. More patients achieved a PASI 50 as early as Week 2 in the 75 and 150mg groups than in the placebo group. More patients achieved a PASI 75 than placebo at Week 2 in the 150mg group and at Week 4 in the 75 and 150mg groups. Larger trials are needed to fully understand the speed of clinical responses to ixekizumab and how well these early improvements predict long-term outcomes.
Financial disclosures/funding: Study funded by Eli Lilly and Co.
Alphabetical Index
BY ARTICLE TITLE
A Meta-analysis to Evaluate the Efficacy and Safety of Adapalene-Benzoyl Peroxide Topical Gel in Black Subjects with Mild or Moderate Acne.......................7
A Targeted Delivery and Stabilized Retinol Product provides Comparable Efficacy to Tretinoin in a Randomized, Double-Blind, Split-face Comparative Study in Photodamaged Skin...............9
A Topical Non-Drying Acne Treatment provides Rapid Control of Inflammatory Lesions and Reduces Post-Inflammatory Hyperpigmentation and Erythema.......................6
Adapalene Gel, 0.3% is Efficacious in Reducing Acne Lesions in Adult Women.......................8
Assessing the Predictive Probability of Melanoma and Other High-Risk Pigmented Lesions Using Data Provided by a Multispectral Digital Skin Lesion Analysis Device.......................12
Azelaic Acid Foam, 15% in the Treatment of Papulopustular Rosacea: A Randomized, Double-Blind, Vehicle-Controlled Study ..................................7
Clinical Improvement in Psoriasis Observed Over 1 to 4 Weeks of Treatment with Ixekizumab.................21
Clinical Pearls with Ingenol Mebutate Treatment in Elderly Patients with Actinic Keratosis in a Community Dermatology Practice ..............................................10
Clinical Presentation of Local Skin Reactions Associated with Treatment of Actinic Keratosis with Ingenol Mebutate Gel in Elderly, Community Dermatology Patients ..............................................11
Clinical Study Results of Desoximetasone 0.25% Super-Potent Spray in Moderate-to-Severe Plaque Psoriasis for Four Weeks ...................17
Cutaneous Tolerability and Subject Satisfaction of an Over-the-Counter Cleansing and Moisturizing Regimen in Subjects Aged 7 to 11 Years With Acne Prone Skin.......................8
Early Treatment of Adults with Papulopustular Rosacea with Doxycycline 40mg Modified Release is Associated with Improved Clinical Outcomes.......................9
Economic And Comorbidity Burden Among Patients With Moderate-ToSevere Psoriasis.......................19
Effectiveness and Safety of Clobetasol Propionate 0.05% Spray Added on to Regimens Containing Biologic Agents for the Treatment of Moderate to Severe Plaque Psoriasis.......................20
Effectiveness and Safety of Tavaborole, A Novel Boron-Based Molecule for the Topical Treatment of Toenail Onychomycosis: Results From Two Phase 3 Studies.......................14
Efficacy and Safety of Azelaic Acid 15% Gel versus Hydroquinone 4% Cream in the Treatment of Melasma.................13
Efficacy of Sequential Treatment with Ingenol Mebutate Gel 0.015%, Following Cryosurgery for Actinic Keratosis on the Face and Scalp ....................................9
Efinaconazole Topical Solution May Reach the Onychomycosis Infection Site by Spreading Through the Space Between the Nail Plate and Nail Bed.............................................15
First-Line Use of Calcipotriene/Betamethasone Dipropionate Combination Products for the Treatment of Plaque Psoriasis is Associated With Lower Health Care Utilization and Cost ...........................19
In Vitro Nail Penetration of (14C)-Efinaconazole Topical Solution, 10%...15
In Vitro Nail Penetration Study with Ex Vivo Human Nails Demonstrates Penetration of Tavaborole Topical Solution, 5%, Through Nail Polish....15
Itraconazole is an Effective Oral Treatment for Onychomycosis: Results from a Phase 3, Randomized, Multicenter, Placebo-Controlled Study.......................14
Long-Term Safety and Efficacy of Apremilast, an Oral Phosphodiesterase 4 Inhibitor, in Patients With Moderate-toSevere Psoriasis: Efficacy and Safety Results From a Phase III, Randomized Controlled Trial (ESTEEM 1).......................16
Malignancy Events in the Psoriasis Longitudinal Assessment and Registry Study: Current Status of Observations ..18
Maximal Use Systemic Exposure (MUSE) Study Evaluating AN2728, A Novel Boron-Based Small Molecule, for the Treatment of Pediatric and Adolescent Subjects with Mild-to-Moderate Atopic Dermatitis.......................12
Overall Tolerability of Adapalene-BPO from a Pooled Data Analysis.......................7
Patient Perspectives in the Management of Psoriasis: US Results From the Population-Based Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) Survey.......................18
Predicting Improvement in Signs and Symptoms of Plaque Psoriasis after 1 Week of Treatment with Clobetasol Propionate 0.05% Spray.......................20
Safety and Efficacy of AN2728 Topical Ointment, 2% and 0.5%, in a Phase 2 Dose-Ranging Study of Adolescents with Mild-to-Moderate Atopic Dermatitis.......................11
Secukinumab in Patients with Moderateto-Severe Plaque Psoriasis: Results from the Efficacy of Response And Safety of 2 fixed secUkinumab REgimens in Psoriasis (ERASURE).......................17
BY AUTHOR
ALEXIS AF..................7,8
ALY R.......................14
ARMSTRONG AW................18
BALDWIN SL..................14
BALKRISHNAN R...............19
BAUM E......................20
BERMAN B.....................9
BERSON D.....................8
BETTENCOURT MS...........10,11
BLAUVELT A..................21
BRANDTS......................8
BU W........................15
CALABRO S...................18
CALL R......................12
CALLENDER V...............7,13
CAMERON G...................21
CHANDAS.....................15
CHEVRIER M..................18
CHIMENTI S..................16
CORONADO D..................15
DAY RM......................16
DRAELOS Z.................7,12
ELEWSKI BE.............7,14,17
FAKHARZADEH S...............18
FELDMAN S................19,20
FIORENTINO D................18
FLEISCHER A.................14
GOLDENBERG G.................9
GONCALVES J..................9
GONZÁLEZ SOTO R......14
GRIFFITHS CEM...............16
HAMPELE I...................17
HANKE CW.....................9
HARDAS B....................14
HAVLICKOVA B.................7
HEBERT AA...................12
HEFFERNAN M.................21
HELOU S.....................17
HENSLEY DR...................8
HO V........................18
HU CC.......................16
HUGHES M....................11
KAKATKAR S..................19
KALB RE.....................18
KARPOVA.....................17
KAVANAUGH A.................18
KERROUCHE N..................7
KIRCIK L...............7,12,16
KNUDSEN KM...................9
KOO JYM.....................20
KOROTZER A..................15
LANGHOLFF W.................18
LANGLEY R...................18
LARSSON T....................9
LEBWOHL MG...............17,18
LEONARDI C..................16
LEVI E......................19
MAKINO ET..................6,9
MEHTA R....................6,9
MERCHANT T..................15
NAKAGAWAH...................17
OLAYINKA B..................14
OLIN JT.....................15
PAPAVASSILIS C..............17
PAPP K...................16,17
PARISER DM..................15
PATHAK P....................19
PILLAI R....................15
POLLAK RA...................15
REICH K.....................16
RICH P......................14
RIGEL DS....................12
SHEN W......................21
SHI L.......................19
SIGURGEIRSSON B.............17
SPELMAN L...................11
SPELLMAN MC.................11
STAEDTLERC G.................7
STEIN-GOLD L................11
STEVENS RM..................16
SWANSON N....................9
TRAN MH.....................19
TSAIT.......................17
TSCHEN E....................12
TUCKER N....................12
TYRING SK.................9,17
VAN SYOC M..................12
VAN VOORHEES AS.............18
VERMAA......................14
WERSCHLER WP.................9
WILTZ H.....................14
WINKELMAN W...............9,20
YOO J.......................12
YOUNG C.....................13
ZANELT.............11,12,14,15
ZHAO Y......................19
ZHU B.......................21
Biography
