Selected Poster Abstracts from MauiDerm for Dermatologists 2020

May 1, 2020

A message from the Guest Editor and MauiDerm Program Director, George Martin, MD

Dear Colleagues:

The 2020 edition of the MauiDerm for Dermatologists meeting had a variety of clinical and scientific data presented, but not just at the podium. A wide range of clinically relevant material was also presented in poster format. For those of you who were unable to participate in the meeting or were not able to attend the poster sessions, we have compiled abstracts from a select group of research posters presented during the 2020 meeting. It is my hope that you will find the highlighted research informative and thought provoking.

For an alphabetical index organized by poster presenter names and poster titles, please see page 33 of this supplement.

With aloha,

George Martin, MD

MauiDerm 2020 Program Director; Guest Editor, The Journal of Clinical and Aesthetic Dermatology

J Clin Aesthet Dermatol. 2020;12(5 Suppl):S8–S35

Funding for this supplement was provided by Amgen.

CONTENT

ACNE

An open-label extension of two Phase III studies evaluating long-term efficacy of FMX101 4% minocycline foam for the treatment of acne vulgaris
Comparative pharmacokinetic profiles of a novel low-dose, micronized isotretinoin 32mg formulation and lidose-isotretinoin 40mg in fed and fasted conditions: two open-label, randomized, crossover studies in healthy adult participants
Comparison of a novel tazarotene 0.045% lotion to tazarotene 0.1% cream: patient-reported outcomes from a Phase II clinical trial
Efficacy and safety of a novel tazarotene 0.045% lotion in female and male patients with moderate-to-severe acne
Efficacy of a novel tretinoin 0.05% lotion in the treatment of moderate-to-severe acne by gender and race: pooled analysis of two Phase III studies
Successful treatment in acne patients with radiofrequency and intense pulsed light
Twyneo (microencapsulated benzoyl peroxide 3%, tretinoin 0.1%) Phase III efficacy and safety: results from two randomized, controlled clinical trials

ACTINIC KERATOSES

Efficacy of ALA–PDT in the treatment of actinic keratoses on the upper extremities: a post-hoc analysis of a Phase III, randomized, vehicle-controlled trial
Measuring the predictive value of serological quantification of cytokines with the onset of influenza-like signs and symptoms induced by imiquimod 3.75% cream: results of a single center, open-label, proof of concept trial

AESTHETICS

Clinical efficacy of intralesional insulated microneedle electrocoagulation for periorbital syringoma treatment
Collagenase clostridium histolyticum (cch) for the treatment of cellulite: pooled analyses from two Phase III, randomized, double-blind, placebo-controlled trials (release-1 and release-2)
COVE-1: a Phase II open-label study to evaluate the efficacy, safety, and tolerability of vp-102 for the treatment of common warts
Efficacy and tolerability of a retinoid/alpha hydroxy acid-based professional peel system in subjects with mild-to-moderate photodamage
Evaluation of efficacy and tolerance of repairing cream formulated with new biotechnological active ingredient
Ex-vivo human skin assessment of minocycline permeation and penetration into epidermis, dermis, and sebaceous appendages
Protection and rejuvenation against skin damage in a highly air-polluted area from a novel antioxidant dual serum system: a randomized, regimen-controlled study in Beijing, China
Volume and height reduction of fibrotic scars shown with 3-D imaging 12 weeks after noninvasive treatment with a rapid acoustic pulse (rap) device in a proof of concept study

ATOPIC DERMATITIS

Atopic dermatitis disease biomarkers strongly correlate with IL-13 levels, are regulated by IL-13, and are modulated by tralokinumab in vitro
Dupilumab for the treatment of chronic actinic dermatitis: a case series

CUTANEOUS ONCOLOGY

Association between baseline disease characteristics and relapse-free survival (rfs) in patients (pts) with braf v600–mutant resected Stage 3 melanoma treated with adjuvant dabrafenib (d) + ttametinib (t) or placebo (pbo)
CemiplimAb-rwlc Survivorship and Epidemiology (CASE) study in advanced cutaneous squamous cell carcinoma (CSCC)
Development and validation of a nomogram incorporating molecular and clinical factors for accurate prediction of recurrence risk in patients with cutaneous melanoma
Efficacy and safety of sonidegib in patients with aggressive and nonaggressive subtypes of locally advanced basal cell carcinoma: long-term, 42-month results from the BOLT study
Integrating the 40-gene expression profile (40-gep) test into management of high-risk cutaneous squamous cell carcinoma
Practical management of adverse events using dosing strategies for patients receiving sonidegib for advanced basal cell carcinoma
Treatment patterns and outcomes among patients with advanced cutaneous squamous cell carcinoma (CSCC) in a US community oncology setting

MISCELLANEOUS

Evaluation of skin barrier and hydration effects of a new rebalancing, moisturizing treatment cream in a human epidermal skin model
Successful treatment of steatocystoma multiplex using Erbium:YAG laser
Topical sodium thiosulfate as treatment of calcinosis cutis: a case series and systematic review

PSORIASIS

A head-to-head comparison of ixekizumab versus guselkumab in patients with moderate-to-severe plaque psoriasis: 12-week efficacy, safety, and speed of response from a randomized, double-blinded trial
An oral, selective tyrosine kinase 2 inhibitor, bms-986165, improves health-related quality of life in psoriasis: results from a Phase II trial
Characteristics of patients with palmoplantar pustulosis compared to those with psoriasis vulgaris: a claims database study
Clinical efficacy of an at-home, 620 and 660nm red-light treatment on scalp pruritus and irritation
Clinical implications of early PASI responses to tildrakizumab in patients with moderate-to-severe plaque psoriasis
Efficacy and safety of apremilast in patients with moderate-to-severe plaque psoriasis of the scalp: 32-week results from the Phase III style study
Efficacy and safety of brodalumab in patients with inadequate response to ustekinumab: analysis of two phase 3 psoriasis studies
Efficacy and safety of halobetasol propionate 0.01%/tazarotene 0.045% (hp/taz) lotion in the treatment of moderate to severe plaque psoriasis of the lower extremities
Guselkumab demonstrates greater efficacy compared to secukinumab across body weight quartiles and body mass index categories: Week 48 results from the eclipse trial
Ixekizumab demonstrates high sustained efficacy and a favorable safety profile in patients with moderate-to-severe psoriasis through five years of treatment
Long-term efficacy and safety of switching from adalimumab to risankizumab: results from the open-label extension study LIMMitless
Long-term efficacy of certolizumab pegol dosed at 400mg every two weeks in patients with plaque psoriasis: pooled 128-week data from two Phase III trials (CIMPASI-1 and CIMPASI-2)
Long-term safety of tildrakizumab in patients with moderate-to-severe plaque psoriasis: incidence of malignancies through three years (148 weeks) from Resurface 1 and Resurface 2 Phase III trials
Long-term safety of tildrakizumab in patients with moderate-to-severe plaque psoriasis: incidence of severe infections through 3 years (148 weeks) from two Phase III trials
Randomized, double-blind, placebo-controlled, multiple-dose, Phase IIb study to demonstrate the safety and efficacy of tildrakizumab, a high-affinity anti–interleukin-23p19 monoclonal antibody, in patients with active psoriatic arthritis
Safety and efficacy of a fixed combination halobetasol propionate 0.01%/tazarotene 0.045% (hp/taz) lotion in the treatment of female patients with moderate-to-severe plaque psoriasis
Safety of risankizumab in patients with moderate-to-severe psoriasis: analysis of pooled clinical trial data
Safety of tildrakizumab in patients with pre-existing metabolic syndrome: long-term data from the post-hoc analysis of two Phase III clinical studies (reSURFACE 1 and reSURFACE 2)
Secondary efficacy outcomes from a Phase IIb, randomized dose-finding study of tapinarof cream for the treatment of plaque psoriasis
Tapinarof cream for the treatment of plaque psoriasis: efficacy and safety by baseline disease characteristics and skin type in a Phase IIb randomized study
Total healthcare costs and long-term treatment patterns of biologics and apremilast among patients with moderate-to-severe plaque psoriasis by metabolic condition status

ROSACEA

DFD-29, a low-dose oral minocycline, shows early treatment success at Week 4 in papulopustular rosacea

VITILIGO

Efficacy and safety of a 52-week, randomized, double-blind trial of ruxolitinib cream for the treatment of vitiligo
Vitiligo prevalence and patient-perceived concern by vitiligo lesion location in a US population

ACNE

An open-label extension of two Phase III studies evaluating long-term efficacy of FMX101 4% minocycline foam for the treatment of acne vulgaris

Presenters: Gold LS,¹ Dhawan S,² Weiss J,³ Draelos ZD,⁴ Ellman H,⁵ Stuart I⁶

Affiliations: ¹Henry Ford Health System; ²Center for Dermatology Clinical Research, Inc; ³Gwinnett Dermatology; ⁴Dermatology Consulting Services; ⁵Foamix Pharmaceuticals Inc.

Background: The safety, efficacy, and facial tolerability of FMX101 4% topical minocycline foam were evaluated in the 12-week, double-blind phase of two identical Phase III studies (Study 4 and Study 5) of subjects with moderate-to-severe acne vulgaris, followed by a nine-month open-label extension (OLE). The safety and efficacy assessments from the OLE phase of both studies are presented here.

Objective: To assess the long-term safety and efficacy of FMX101 4% for the treatment of moderate-to-severe acne.

Methods: Eligible subjects completing the double-blind phase could continue into the OLE phase for an additional nine months of treatment with FMX101 4%; eligible subjects in the vehicle group were switched to active treatment. Eligibility was determined by an Investigator’s Global Assessment (IGA) score that had not worsened from baseline to the end of the double-blind phase. Treatment was guided by the clinical response of each subject and could be suspended or resumed at the investigator’s discretion. Efficacy assessments in the OLE phase included reduction from baseline to Week 52 in inflammatory and noninflammatory lesion counts and the percentage of subjects achieving IGA treatment success, defined as an IGA score of clear (0) or almost clear (1) and at least a two-grade improvement. Safety assessments included treatment-emergent adverse events (TEAEs), vital signs, tolerability, and laboratory testing. A subject satisfaction questionnaire was administered at
Week 52.

Results: Of the 961 subjects enrolled in the double-blind phases (Study 4, N=466; Study 5, N=495), 657 subjects entered the OLE (Study 4, n=284; Study 5, n=373), and 414 subjects completed the current study (Study 4, n=172; Study 5, n=242). Throughout the OLE phase, both studies demonstrated ongoing reduction in inflammatory and noninflammatory lesion counts from baseline and an increase in the proportion of subjects achieving IGA treatment success. More than 99 percent of the TEAEs that occurred were mild or moderate in severity. No serious TEAEs leading to subject discontinuation were reported in either study. The most frequently observed TEAEs in the OLE were nasopharyngitis (5.0%), headache (3.2%), and elevated creatinine phosphokinase (2.3%), similar to the double-blind phase. Three TEAEs leading to discontinuation (application-site acne, edema, and dermatitis) were potentially related to treatment but were not regarded as serious. At the Week 52 assessment of facial local tolerability, less than 95 percent of subjects reported an absence of or only mild signs and symptoms. The majority of subjects (>80%) reported being satisfied or very satisfied with FMX101 4%.

Conclusion: Overall, FMX101 4% during the OLE phase of Study 4 and Study 5 appeared to be safe, effective, and well tolerated for the long-term treatment of acne.

Financial Disclosures: Dr. Stein Gold is an advisor and investigator for Foamix, Galderma, LEO Pharma, Novartis, and Valeant and is an investigator for Janssen, AbbVie, and Solgel and an advisor and investigator for Novartis. Dr. Dhawan is an investigator for Foamix, AbbVie, Galderma, Lilly, Moberg, Solgel, Incyte, Valeant, Novartis, and Dermira, and a speaker for Pfizer and Dermira. Dr. Weiss is a principal investigator for AbbVie, Aclaris, Endo, Foamix, Galderma, LEO, Moberg, Promius, and Valeant; he is a speaker for AbbVie, Almirall, Dermira and Ortho Dermatologics and a consultant for Aclaris and LEO, as well as an advisor for Foamix, Galderma, and Valeant. Dr. Draelos is a principal investigator and advisor for Foamix. Dr. Ellman is a former employee and stockholder of Foamix. Dr. Iain Stuart is an employee and stockholder at Foamix Pharmaceuticals.

Comparative pharmacokinetic profiles of a novel low-dose micronized-isotretinoin 32mg formulation and lidose-isotretinoin 40mg in fed and fasted conditions: two open-label, randomized crossover studies in healthy adult participants

Presenters: Madan S,¹ Kumar S,² Segal J³

Affiliations: ¹Research and Development Centre, Sun Pharmaceutical Industries Ltd, Gurgaon, Haryana, India; ²Clinical Pharmacology and Pharmacokinetics, Sun Pharmaceutical Industries Ltd, Gurgaon, Haryana, India; ³Sun Pharmaceutical Industries, Inc.,
Princeton, NJ

Background: For treatment of severe acne, lidose-isotretinoin does not require administration with food to optimize efficacy.^1,2 A novel low-dose, micronized, isotretinoin formulation has been developed using technology that substantially increases the surface area per unit mass of the drug in formulation.

Methods: We present data from two open-label, randomized, crossover studies comparing the bioavailability of micronized isotretinoin 32mg with lidose-isotretinoin 40mg under fed and fasted conditions and assessing the effect of food on micronized isotretinoin 32mg bioavailability. The fed bioequivalence and food-effect study was a three-treatment/six-sequence study in which healthy adults received single doses of fed-state micronized-isotretinoin 32mg, fed-state lidose-isotretinoin 40mg, and fasted-state micronized-isotretinoin 32mg. The fasting study was a two-treatment/two-sequence study where healthy adult men received single doses of micronized-isotretinoin 32mg and lidose-isotretinoin 40mg under fasted conditions. Blood samples were collected before dosing and over the 96 hours postdosing. Bioavailability was measured using log-transformed maximum isotretinoin plasma concentration (LnC_max) and log-transformed area under the concentration-time curve from Time 0 to last measurable isotretinoin concentration (LnAUC0–t) and from Time 0 to infinity (LnAUC0–infinity). Adverse events were monitored.

Results: In the fed bioequivalence and food-effect study (n=65), 90-percent confidence intervals for the baseline-adjusted least squares geometric mean ratios for LnAUC0–t¬, LnAUC0–infinity, and LnC_max fell within the 80.0 to 125.0 percent range for bioequivalence for fed-state micronized-isotretinoin versus fed-state lidose-isotretinoin. Taking micronized isotretinoin with a meal, as opposed to under fasted conditions, increased LnAUC0–t and LnAUC0–infinity by 24.8 and 23.2 percent but did not affect LnCmax. In the fasting study (n=18), micronized-isotretinoin had approximately two times higher bioavailability than lidose-isotretinoin. Both isotretinoin formulations were well tolerated with no serious adverse events reported.

Conclusion: Micronized-isotretinoin 32mg is bioequivalent to lidose-isotretinoin 40mg under fed conditions and is twice as bioavailable under fasted conditions. Food has no effect on the rate and a marginal effect on the extent of micronized-isotretinoin 32mg absorption, which is less than the effect on other marketed isotretinoin products.^3,4

Funding: These studies were funded by Sun Pharmaceutical Industries Ltd, Gurgaon, Haryana, India. Analyses were presented at the 2019 Maui Derm NP+PA Summer Meeting.

Comparison of a novel tazarotene 0.045% lotion to tazarotene 0.1% cream: patient-reported outcomes from a Phase II clinical trial

Presenters: Draelos ZD,¹ Cook-Bolden F,²Green L,³ Guenin E,⁴ Martin G,⁵Pillai R⁵

Affiliations: ¹Dermatology Consulting Services, PLLC, High Point, NC; ²Dept. of Dermatology, Mount Sinai Hospital Center, New York, NY;³Dept. of Dermatology, George Washington University School of Medicine, Washington, DC; ⁴Ortho Dermatologics*, Bridgewater, NJ; ⁵Bausch Health US, LLC*,
Petaluma, CA

*Bausch Health US, LLC is an affiliate of Bausch Health Companies Inc. Ortho Dermatologics is a division of Bausch Health US, LLC.

Background: Current gel, foam, and cream tazarotene (TAZ) formulations can cause irritation; thus, a novel TAZ 0.045% lotion was developed utilizing polymeric emulsion technology. This formulation results in a more uniform distribution of the active ingredient and hydrating excipients at the skin’s surface. In a 12-week, double-blind, Phase II study (NCT02938494), TAZ 0.045% lotion was superior to vehicle on inflammatory and noninflammatory lesion count reductions in participants with moderate-to-severe acne. In addition, tazarotene lotion was as effective as the higher concentration tazarotene 0.1% cream (already approved for acne) but with fewer adverse events. Patient-reported outcomes from this Phase II study are presented here.

Methods: In this randomized, double-blind study, patients aged 12 years or older were randomized (2:2:1:1) to receive TAZ 0.045% lotion, TAZ 0.1% cream, lotion vehicle, or cream vehicle. Outcomes included: oily/shiny skin, Acne-Specific Quality of Life Questionnaire (Acne-QoL), and Subject Self-Assessment (SSA). Data were analyzed descriptively in participants with available data at Week 12. Lotion and cream vehicles were combined for this analysis.

Results: The intent-to-treat population included 210 participants. At Week 12, the percentages of participants reporting “no oily or shiny skin on face” was slightly higher with TAZ 0.1% cream (31.3% [20/64]) than TAZ 0.045% lotion (27.7% [18/65]) and both were greater than combined vehicle (18.0%). Among participants with any oily/shiny skin, the percentage who were “not bothered at all” was higher with TAZ 0.045% lotion (31.3% [15/48]) than with TAZ 0.1% cream (25.0% [11/44]) or vehicle (24.0% [12/50]). Mean changes from baseline to Week 12 in Acne-QoL domains generally indicated greater improvement with both TAZ formulations versus vehicle: self-perception (8.2, 8.4, and 6.1, respectively), role-emotional (7.2, 7.4, and 5.7), role-social (5.0, 5.7, and 4.5), and acne symptoms (7.4, 6.1, and 6.3). Per SSA, the percentages of participants reporting 90 to 100 percent clear skin were slightly higher with TAZ 0.045% lotion (38.5% [25/65]) than TAZ 0.1% cream (35.9% [23/64]); both were greater than vehicle (24.6% [15/61]).

Conclusion: Consistent with clinician-assessed primary endpoints, patient-reported skin oiliness, acne severity, and QoL were improved with TAZ 0.045% lotion versus vehicle. Taken together with the improved tolerability and similar efficacy of TAZ 0.045% lotion versus TAZ 0.1% cream, this lower-dose, novel lotion formulation of TAZ might be a viable new treatment option that is as effective as TAZ 0.1% cream with fewer adverse events.

Financial Disclosures: This study was supported by Ortho Dermatologics, Inc., Bridgewater, NJ. Ortho Dermatologics is a division of Bausch Health US, LLC. ZD received funding from Ortho Dermatologics to conduct the research presented in this poster. FCB has served as consultant, speaker, and/or investigator for Galderma, LEO Pharma, Almirall, Cassiopea, Ortho Dermatologics, Investigators Encore, Foamix, Hovione, Aclaris, and Cutanea. LG has served as consultant, speaker, and/or investigator for Arcutis, Abbvie, Amgen, Celgene, Dermavant, Jannsen, Lilly, MC2, Novartis, Ortho Dermatologics, Sienna, SunPharma, UCB. EG is an employee of Ortho Dermatologics and might hold stock and/or stock options in its parent company. GM and RP are employees of Bausch Health US, LLC and might hold stock and/or stock options in its parent company.

Efficacy and safety of a novel tazarotene 0.045% lotion in female and male patients with moderate-to-severe acne

Presenters: Baldwin H,¹ Green L,² Kircik LH,³
Guenin E⁴

Affiliations: ¹The Acne Treatment and Research Center, Morristown, NJ; ²Department of Dermatology, George Washington University School of Medicine, Washington, DC; ³Indiana University School of Medicine, Indianapolis, IN; Physicians Skin Care, PLLC, Louisville, KY; and Icahn School of Medicine at Mount Sinai, New York, NY; ⁴Ortho Dermatologics*, Bridgewater, NJ

*Ortho Dermatologics is a division of Bausch Health US, LLC.

Background: Acne is a common dermatologic issue that occurs more often in female patients than in male patients. A novel tazarotene 0.045% lotion formulation was developed utilizing polymeric emulsion technology, resulting in a more uniform distribution of the active ingredient and hydrating excipients at the skin’s surface. In a 12-week, randomized, double-blind, Phase II study (NCT02938494), tazarotene 0.045% lotion was superior to vehicle on inflammatory/noninflammatory lesion count reductions in patients with moderate-to-severe acne. In addition, tazarotene 0.045% lotion was as effective as the higher concentration tazarotene 0.1% cream (already approved for acne) but with fewer adverse events (AEs). Efficacy and safety for female and male patients are presented in post-hoc analysis.

Methods: Patients aged 12 years or older were randomized (2:2:1:1) to receive tazarotene 0.045% lotion, tazarotene 0.1% cream, lotion vehicle, or cream vehicle. Efficacy assessments included reductions in inflammatory/noninflammatory lesion counts and treatment success, defined as the percent of patients achieving at least a two-grade reduction in Evaluator Global Severity Scores [EGSS] and a clear/almost clear score. AEs were also assessed. For this post-hoc analysis, lotion vehicle and cream vehicle were combined.

Results: The intent-to-treat population included 210 participants (male, n=94; female, n=116). At Week 12, tazarotene 0.045% lotion-treated female and male patients had greater mean percent reductions from baseline in inflammatory and noninflammatory lesion counts versus combined vehicle (female: 70.1% vs. 53.6%, 59.2% vs. 40.9%; male: 56.5% vs. 48.7%, 54.1% vs. 28.2%). Tazarotene 0.045% lotion-treated female and male patients also had significantly greater absolute least-squares mean reductions from baseline versus vehicle in noninflammatory lesion counts (p<0.05, both); only female patients had significant mean reductions versus vehicle in inflammatory lesion counts (p<0.05). A larger percentage of tazarotene 0.045% lotion-treated female and male patients achieved treatment success versus vehicle (female: 24.3% vs. 10.5%; male: 12.5% vs. 9.7%), although this difference was not significant. There were no significant differences between the sexes on inflammatory/noninflammatory lesion counts or treatment success at Week 12, regardless of treatment with tazarotene 0.045% lotion or tazarotene 0.1% cream. Treatment-emergent AE (TEAE) rates were higher in male patients than in female patients for both tazarotene 0.045% lotion (19.4% and 10.8%, respectively) and tazarotene 0.1% cream (30.0% and 24.4%); there were no differences with vehicle (13.3% and 13.5%).

Conclusion: Tazarotene 0.045% lotion was effective versus vehicle in reducing inflammatory and noninflammatory lesion counts in female patients and noninflammatory lesion counts in male patients. Taken together with the improved tolerability of tazarotene 0.045% lotion versus tazarotene 0.1% cream, this novel lotion formulation is a viable new treatment option that is as effective as cream with fewer AEs.

Financial Disclosures: This study was supported by Ortho Dermatologics, Inc., Bridgewater, NJ. Ortho Dermatologics is a division of Bausch Health US, LLC. HB has served as advisor, investigator, and on speakers’ bureau for Almiral, Foamix, Galderma, and Ortho Dermatologics. LG has served as consultant, speaker, and/or investigator for Arcutis, Abbvie, Amgen, Celgene, Dermavant, Jannsen, Lilly, MC2, Novartis, Ortho Dermatologics, Sienna, SunPharma, and UCB. LHK has acted as an investigator, advisor, speaker, and consultant for Ortho Dermatologics. EG is an employee of Ortho Dermatologics and might hold stock and/or stock options in its parent company.

Efficacy of a novel tretinoin 0.05% lotion in the treatment of moderate-to-severe acne by sex and race: pooled analysis of two Phase III studies

Presenters: Lain E,¹ Day D,² Harper J,³ Guenin E⁴

Affiliations: ¹Austin Institute for Clinical Research, Austin, TX; ²Day Dermatology and Aesthetics, New York, NY; ³Dermatology and Skin Care Center of Birmingham, Birmingham, AL; ⁴Ortho Dermatologics*, Bridgewater, NJ

*Ortho Dermatologics is a division of Bausch Health US, LLC.

Background: Acne is the most common dermatologic issue in patients with skin of color. Additionally, the prevalence of acne in adults is increasing, and it occurs more often in women than in men. The first lotion formulation of tretinoin, developed by utilizing novel polymeric emulsion technology, has been evaluated in two Phase III studies in patients with moderate-to-severe acne (NCT02932306, NCT02965456). This post-hoc analysis was conducted to assess efficacy of this novel tretinoin 0.05% lotion in patients by sex as well as black or white race.

Methods: In two Phase III, multicenter, double-blind studies, patients with moderate-to-severe acne were equally randomized to tretinoin 0.05% lotion or vehicle lotion once daily for 12 weeks. A pooled post-hoc analysis was conducted to evaluate the effect of sex and race on the efficacy of tretinoin 0.05% lotion. Efficacy assessments included reductions in inflammatory/noninflammatory lesion counts and percentage of patients achieving treatment success, defined as a two-grade or greater reduction in the Evaluator Global Severity Score (EGSS) and a clear/almost clear score.

Results: A total of 1,640 patients were included in the pooled analysis. At Week 12, all tretinoin-treated women and men had significantly greater mean percent reduction from baseline versus vehicle in inflammatory (female: 56.9% vs. 47.1%; male: 53.4% vs. 39.4%; p less than or equal to 0.001, all) and noninflammatory lesion counts (51.7% vs. 34.9%; 46.1% vs. 29.7%; p<0.001, all) and a larger percentage achieved treatment success versus vehicle (p less than or equal to 0.001, both). Compared to the men, tretinoin-treated women had greater mean percent reductions in noninflammatory lesion counts at Week 12 (p<0.05) and a larger percentage achieved treatment success (p<0.05). There were significant reductions in inflammatory lesion counts in tretinoin-treated white women and men (female: 56.3% vs. 45.4%; male: 51.9% vs. 40.1%; p=0.001 vs. vehicle, both) and in tretinoin-treated black men at Week 12 (58.6% vs. 40.9%; p<0.05 vs. vehicle). All tretinoin-treated patients except the black female patients had significant reductions in noninflammatory lesion counts at Week 12 (p<0.01 vs. vehicle, all). Compared with vehicle, significantly more tretinoin-treated white female and male patients achieved treatment success (p<0.01, both). The percentages of tretinoin-treated black men and women achieving treatment success were greater than vehicle, but these differences were not significant.

Conclusion: Tretinoin 0.05% lotion has been shown to be effective in patients with moderate to severe acne, including females and males overall and within White and Black racial subgroups.

Financial Disclosures: This study was supported by Ortho Dermatologics, Inc., Bridgewater, NJ. Ortho Dermatologics is a division of Bausch Health US, LLC. EL has nothing to disclose. DD has participated in speaker programs for Bausch Health. JH has received honoraria from Aclaris, Almirall, BioPharmX, Cassiopea, Cutanea, Dermira, Foamix, Galderma, LaRoche-Posay, Ortho Dermatologics, and Sun. EG is an employee of Ortho Dermatologics and might hold stock and/or stock options in its parent company.

Successful treatment in acne patients with radiofrequency and intense pulsed light

Presenters: Jung YJ, Song CH, Ko YW, Koh WS, Kim JE, Ro YS, Ko JY

Affiliation: Department of Dermatology, Hanyang University College of Medicine, Seoul, Korea

Objectives: Acne is a common disorder of pilosebaceous units, resulting from interplay of follicular hyperkeratinization, seborrhea, Cutibacterium acnes colonization, and release of inflammatory mediators. Prevalence is estimated at 85 percent of 12- to 25-year-olds, and acne can persist from adolescence into adulthood. Among different treatment modalities of acne vulgaris, radiofrequency (RF) and intense pulsed light (IPL) could act as an efficient additional treatment modality to topical and systemic medications. A RF and IPL combined device (dermaAKNE®, Huons, Korea) was recently introduced for the additional benefits of decreased sebaceous gland volume and immunomodulatory effect. Therefore, it could potentially be used as an effective treatment modalities for the acne.

Methods: A total of 44 patients, aged 19 to 44, with moderate-to-severe acne vulgaris were included. Our study design was a split-face design using a combined device of RF and IPL. One side of the face of each participant served as control and the other side was treated by RF and IPL for two treatments at two-week intervals. Comedone extraction was perfomed on both sides of the face. We evaluated the efficacy of the treatment using clinical photos to assess the number of acne lesions, adverse effects, and the number of scarring lesions after eight and 12 weeks. Additionally, patient satisfaction was assessed using a seven-point grading scale.

Results: The study included 44 patients with acne vulgaris (27 male, 17 female). Their ages ranged from 19 to 39 years. At 12 weeks, after Visit 1, acne lesion reduction percentages were 34.80 percent (±33.45) for treated side and 13.76 percent (±37.58) for control side. The difference of reduction rate between the treated side and control side was 21.03 percent (±25.09) indicating the treated side showed more significant improvement (p<.05). In the assessment of adverse events, one patient experienced mild erythema which spontaneously improved.

Conclusion: Monopolar RF has been used to treat active cystic scarring acne. RF has inhbits sebaceous gland activity and promote dermal contouring. IPL has a photodynamic effect that leads to generation of reactive oxygen species and to photothermolysis of blood supplies of sebaceous glands. Therefore, in combination, the two have an additive effect to treat acne lesions, suggesting it would be an effective therapeutic option for acne. A larger, randomized trial with a greater variety of subjects would be needed.

Twyneo (microencapsulated benzoyl peroxide 3%, tretinoin 0.1%) Phase III efficacy and safety: results from two randomized controlled clinical trials

Presenters: Del Rosso J,¹ Sugarman J,² Levy-Hacham O,³ Mizrahi R³

Affiliations: ¹JDR Research, Las Vegas, NV; ²University of California – San Francisco, San Francisco, CA; ³Sol-Gel Technologies Ltd, Ness Ziona, Israel

Background: Benzoyl peroxide and tretinoin are widely prescribed and considered to be highly effective in the treatment for acne vulgaris. However, benzoyl peroxide causes degradation of tretinoin, reducing its effectiveness. Twyneo is an investigational, antibiotic-free, fixed-dose combination of microencapsulated tretinoin 0.1% and microencapsulated benzoyl peroxide 3% cream. The use of Sol-Gel’s microencapsulation technology platform provides a stable combination of benzoyl peroxide and tretinoin, extending drug delivery time and reducing potential irritation caused by direct application of the drugs to the skin.

Methods: In two multicenter, randomized, double-blind, parallel-group, vehicle-controlled trials (SGT-65-04 and SGT-65-05) at 63 sites across the United States, 858 patients, aged nine years or older, with moderate-to-severe acne were enrolled. Patients were randomized in a 2:1 ratio to 12 weeks of once-daily treatment with either Twyneo (n=571) or vehicle cream (n=287). The coprimary endpoints for both trials were the proportion of patients who achieved at least a two-grade reduction from baseline and clear (Grade 0) or almost clear (Grade 1) at Week 12 on a five-point Investigator Global Assessment (IGA) scale; absolute change from baseline in inflammatory lesion count at Week 12; and absolute change from baseline in noninflammatory lesion count at Week 12.

Results: Twyneo was significantly superior to vehicle for all primary endpoints in both Phase III trials. In trial SGT-65-04, 38.5 percent of patients treated with Twyneo achieved success in IGA versus 11.5% for vehicle (p<0.001). The respective values in trial SGT-65-05 were 25.4 percent and 14.7 percent (p=0.017). In trial SGT-65-04, the absolute change from baseline in inflammatory lesion count for Twyneo was -21.6 versus -14.8 for vehicle (p<0.001). In trial SGT-65-05, the absolute change from baseline of inflammatory lesion count for Twyneo was -16.2 versus -14.1 for vehicle (p=0.021). In trial SGT-65-04, the absolute change from baseline in noninflammatory lesions for Twyneo was -29.7 versus -19.8 for vehicle (p<0.001). The respective values in study SGT-65-05 were -24.2 and -17.4 (p<0.001). Twyneo was well-tolerated in both Phase III studies. The majority of local skin reactions and other adverse events were mild in severity. There were no treatment-related serious adverse events and four unrelated serious adverse events (1 Twyneo, 3 vehicle). Less than five percent of patients discontinued Twyneo due to adverse events.

Conclusions: Twyneo combines two of the safest and most effective topical agents available for the treatment of acne into a single application. Results from the two Phase III trials of Twyneo demonstrated that this new microencapsulated formulation of benzoyl peroxide and tretinoin provided statistically significant and clinical meaningful improvements in IGA and corresponding reductions in both inflammatory and noninflammatory lesions in patients with moderate to severe acne. Twyneo was safe and well tolerated with generally mild adverse events and no treatment-related serious adverse events.

Financial Disclosures. Not provided.

ACTINIC KERATOSES

Efficacy of aminolevulinic acid (ALA) 20% solution photodynamic therapy (PDT) in the treatment of actinic keratoses on the upper extremities: a post-hoc analysis of a Phase III, randomized, vehicle-controlled trial

Presenters: Berman B,^1,2 Bhatia N,³ Piacquadio D,⁴Houlihan A,⁵ Siegel D^6,7

Affiliations: ¹Center for Clinical and Cosmetic Research, Aventura, FL; ²Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL; ³Therapeutics Clinical Research, San Diego, CA; ⁴Therapeutics, Inc., San Diego, CA; ⁵DUSA Pharmaceuticals, Inc., Wilmington, MA; ⁶Department of Dermatology, The State University of New York Downstate Health Sciences University, Brooklyn, NY; ⁷Dermatology Service, Veterans Affairs New York Harbor Healthcare System, Brooklyn, NY, USA.

Background/Objective: Aminolevulinic acid 20% solution photodynamic therapy (ALA-PDT) is indicated for targeted treatment of actinic keratosis (AK) on the face, scalp, and upper extremities. In a Phase III study of 135 subjects (NCT02137785), ALA-PDT at baseline and Week 8 using lesion-targeted treatment and a three-hour occluded incubation was superior to vehicle (VEH)-PDT for AK clearance of the upper extremities. Results of that study assessed response of the entire field to treatment, including new AKs present at follow-up, in calculations of clearance rates. This ancillary analysis assesses treated AKs only, since treatment was delivered as targeted treatment rather than field directed.

Methods: Analyses include mean AK clearance rate compared to baseline, cumulative disease area clearance, and subgroup analysis of complete clearance rate by lesion size.

Results: The mean AK clearance rate for ALA-treated lesions of all sizes was 81 percent at 12 weeks (after up to two treatments), compared with 45 percent for lesions receiving VEH (p<0.0001, linear mixed model). At Week 12, 71 and 60 percent of patients experienced complete clearance of AKs between 25mm² to 35mm² in size and 36mm² or greater in size, respectively. Mean cumulative disease area at baseline was 149mm² and 154mm²for ALA and VEH-treated AKs, respectively; 82 percent of the cumulative disease area was cleared at Week 12 after ALA-PDT compared to 43 percent after VEH-PDT.

Conclusions: ALA-PDT resulted in high clearance rates of treated AKs, including good response of large AKs and high mean cumulative area clearance rates.

Funding: This study was supported by DUSA Pharmaceuticals, Inc.

Measuring the predictive value of serological quantification of cytokines with the onset of influenza-like signs and symptoms induced by imiquimod 3.75% cream: results of a single center, open-label, proof of concept trial

Presenter: Bhatia N

Affiliation: Therapeutics Clinical Research, San Diego, CA

Background: Imiquimod is an immune-response modifier that is FDA approved for the treatment of actinic keratosis (AKs), external genital warts, and superficial basal cell carcinoma. It is a potent inducer of interferon (IFN)-alpha and other proinflammatory cytokines. Some patients treated with topical imiquimod develop influenza-like symptoms (e.g., myalgia, malaise, headache, low-grade fever, and fatigue) that might be related to elevated levels of proinflammatory cytokines associated with application of the drug.

Objective: This study was carried out to assess correlations between influenza-like symptoms and cytokine levels in patients who applied imiquimod cream to their skin for 14 days. Other variables that might influence emergence and severity of symptoms included age, severity of local skin reactions, and the amount of surface area involved. Change from baseline at subsequent study visits (Days 8, 15, 43, and 57 [end of study]) in cytokines (interleukin [IL]-6, IL-8, IL-12, IL-13, IL-2 receptor [R], tumor necrosis factor-alpha [TNF], IFN-alpha, and IFN-gamma) as well as the area of the body exposed to the treatment and clearance of AKs were evaluated.

Methods: In this single-center, open-label study, 15 men and seven women, ages 30 to 89 years, with 5 to 20 AKs cleansed their designated treatment areas (i.e., entire face and balding scalp or chest or upper extremities) with an approved cleanser and, after the skin was dry, applied imiquimod 3.75% over the course of 14 days.

Results: All but one subject experienced either complete clearance or partial clearance of actinic keratoses with no more than three remaining in the treatment field. The occurrence (n) of systemic symptoms characteristic of influenza was infrequent during the treatment period, including: fever (n=1), myalgia (n=1), fatigue (n=0), malaise (n=1), headache (n=4), gastrointestinal symptoms (n=3), dizziness (n=3), and arthralgia (n=3) with no apparent relationship between clearance on the occurrence of symptoms. Subjects that experienced systemic symptoms during treatment had a baseline AK count mean of 14.0 (14.0) at the end of treatment and a 2.9(0.0) change from baseline regarding cytokine levels. Those who did not experience systemic symptoms had a 13.7 (14.0) AK count mean at the end of treatment and 2.4 (1.0) change in cytokine levels from baseline. Twelve subjects had elevations in at least one cytokine at one or more post-baseline visits. For Visits 1 and 2, Subject 4 remained at IL-2, with an elevation to IL-3 at Visit 2 and then to IL-2R, IL-13 at Visit 4. Subject 7 did not experience an elevation until Visits 3 and 4 (IL-13). Subject 8 remained at IFN-gamma for all four visits. At Visit 2, Subject 10 was IL-2, IL-12, just IL-13 at Visit 3, and IL-2, IL-12, IFN-gamma by Visit 4. For the first three visits, Subject 11 remained at IL-6, IL-2R, IL-13. Subject 12 experienced an elevation during Visit 3 (IL-13), while Subject 13 did at Visits 1 and 3 (both at IL-13). At Visit 3, Subjects 15 and 23 had an elevation of IL-8, IL-13 (for 15) and IL-13 (for 23). Subject 18 had an elevation of IL-13 at Visit 1, Subject 20 had the same elevation at Visits 2 and 4, and Subject 21 had an elevation of IL-13 at Visit 1 and then IL-12 at Visit 2. There were no apparent relationships between the occurrences of cytokine elevations and either of the occurrence of influenza-like symptoms or local skin reactions. Some subjects experienced more than one symptom scored at 2 or more or from Visits 2 to 4, while others did not have symptoms with a score of 2 or more throughout all four visits.

Conclusion: Treatment on the face led to more incidence of flu-like symptoms in younger patients. Elevations in proinflammatory cytokines did not appear to predict the development of either systemic symptoms or local skin reactions. Of the four groups, elderly patients treated on the body were less likely to develop reactions.

Disclosures: The author would like to recognize the contributions of AraMed Strategies Inc for scientific analysis and editorial support.

Funding: Study funding was provided by Ortho Dermatologics.

AESTHETICS

Clinical efficacy of intralesional insulated microneedle electrocoagulation for periorbital syringoma treatment

Background: Syringoma is a benign neoplasm. However, it causes cosmetic problems for patients. This study presents the results of periorbital syringoma treatment with intralesional insulated microneedle electrocoagulation.

Objectives: To evaluate the clinical effect of intralesional insulated microneedle electrocoagulation in treating periorbital syringoma.

Methods: Eighteen patients treated with intralesional insulated microneedle electrocoagulation were analyzed retrospectively. A physician compared the pre- and post-treatment photographs to evaluate and score the clinical results. The results were rated using Global Improvement Scale, using Grade 0 (worsened), Grade 1 (0–25%, minimal improvement or steady-state), Grade 2 (26%–50%, moderate response), Grade 3 (51%–75%, marked improvement), and Grade 4 (near-total improvement of >75%).

Results: Nine patients (50%) showed near-total improvement (>75%), five patients (27.8%) showed marked response (51%–75%), and four patients (22.2%) showed Grade 2 (26–50%) improvement. Overall, 14 patients (77.8%) showed an improvement of over 51 percent. There were no patients with Grade 0 or Grade 1 responses.

Conclusion: Intralesional insulated microneedle electrocoagulation showed promising results for periorbital syringoma treatment. We believe it can be an effective and safe therapeutic modality for the treatment of periorbital syringoma.

**Collagenase Clostridium histolyticum (CCH) for the treatment of cellulite: pooled analyses from two Phase III, randomized, double-blind, placebo-controlled trials (RELEASE-1 and RELEASE-2)**

Presenters: Fabi SG,¹ Kaminer MS, ² Bass LS,³ Joseph JH,⁴ Davis M, ⁵ Hurley D,⁵ Liu G,⁵ McLane MP,⁵ Vijayan S,⁵ Diab D,⁵ Gold M,⁶ Kaufman J⁷

Affiliations: ¹Cosmetic Laser Dermatology, San Diego,CA,and University of California-San Diego, San Diego,CA; ²SkinCare Physicians, Chestnut Hill, MA; ³Bass Plastic Surgery PLLC, New York, NY; ⁴John H. Joseph Facial, Plastic, and Reconstructive Surgery, Beverly Hills, CA;⁵Endo Pharmaceuticals Inc., Malvern, PA; ⁶Tennessee Clinical Research Center, Nashville, TN; ⁷Skin Associates of South Florida, Coral Gables, FL.

Background/Objectives: CCH has been submitted to the FDA for the treatment of moderate-to-severe cellulite of the buttocks in adult women. We aimed to assess the efficacy of CCH in the treatment of cellulite on the buttocks in women using pooled data from two identically designed Phase III, double-blind, randomized, controlled trials (RCTs) and to assess the safety and tolerability of CCH.

Methods: In the study, 843 women with moderate-to-severe cellulite (Score, 3–4 on Patient Reported Photonumeric Cellulite Severity Scale [PR-PCSS] and Clinician Reported PCSS [CR-PCSS]) of the buttocks were treated (Days 1, 22, 43) with subcutaneous CCH 0.84mg (n=424) or placebo (n=419) per treatment area. The primary efficacy endpoint was the percentage of two-level composite responders (greater than or equal to 2-level improvement in PR-PCSS and CR-PCSS) at Day 71. The clinical meaningfulness of PR-PCSS change was evaluated using anchor-based analyses, one-way ANOVAs included Subject Global Aesthetic Improvement Scale (S-GAIS), subject satisfaction (independent variables), and PR-PCSS (dependent variable).

Results: More women treated with CCH versus placebo were two levels or greater (odds ratio [95% CI], 5.88 [2.25–15.38]; p<0.001) and greater than or equal to 1-level (3.84 [2.73-5.40]; p<0.001) composite responders at Day 71. More women treated with CCH versus placebo had at least a one-level S-GAIS improvement (61.6% vs. 30.5%; p<0.001) and reported being satisfied or very satisfied (49.1% vs. 19.4%). Anchor-based analyses indicated PR-PCSS score change of one or greater was clinically meaningful. More women had one-level PR-PCSS improvement or greater with CCH versus placebo (56.1% vs. 32.9%; p<0.001). Most adverse events in the CCH group were transient, mild to moderate and injection-site-related (i.e., bruising, pain, nodule, pruritus, erythema). Only one patient in each of the pooled CCH and placebo groups experienced a serious treatment-emergent adverse event. None were deemed related to treatment by the investigator.

Conclusion: In this pooled analysis, CCH provided statistically significant improvements in cellulite severity, patient satisfaction scores, and was generally well tolerated

Funding: Information not provided.

Disclosures: SGF reports serving as a consultant and clinical trial investigator for Endo Pharmaceuticals Inc. MSK reports serving as a clinical investigator and consultant for Endo Pharmaceuticals Inc. LSB reports being a clinical investigator for Endo Pharmaceuticals Inc., Merz North America Inc, and Cynosure; and serving as a consultant for Cynosure. JHJ reports serving as a clinical investigator for Endo Pharmaceuticals Inc and a shareholder of Endo PharmaceuticalsInc. DH, GL, MD, MPM, and SV are employees of Endo Pharmaceuticals Inc. JK reports serving as a clinical investigator and consultant for Endo Pharmaceuticals Inc. MG reports being a consultant and clinical investigator for Endo Pharmaceuticals Inc.

COVE-1: a Phase II, open-label study to evaluate the efficacy, safety and tolerability of VP-102 for the treatment of common warts

Presenters: Guenthner S,¹ McFalda W, ² Kwong P, ³ Eads K,¹ d’Arnaud P, ⁴ Willson C,⁵ Burnett P⁵

Affiliation: ¹The Indiana Clinical Trials Center, Plainfield, IN; ²Clarkston Skin Research, Clarkston, MI; ³Solutions Through Advanced Research, Jacksonville, FL; ⁴Instat Consulting, Chatham, NJ, ⁵Verrica Pharmaceuticals Inc., West Chester, PA

Background: Studies have shown variable effectiveness of compounded cantharidin in the treatment of common warts (i.e., verruca vulgaris) due to a lack of standardized treatment regimens, quality of ingredients and formulations, and large-scale clinical trials.

Objective: The objective of this Phase II study was to evaluate the efficacy, safety, tolerability, and optimal regimen of VP-102 in the treatment of common warts. VP-102 is a proprietary drug delivery combination containing a topical formulation with 0.7% (w/v) cantharidin in a single-use delivery device.

Methods: This study included subjects with up to six common warts (less than or equal to 10mm in diameter, <3mm in height, excluding genital, palmar/plantar and subungual warts) in two treatment cohorts. Cohort 1 (n=20) included subjects, aged two years or older, for dermal application of VP-102 occluded with transparent surgical tape for 24 hours to all treatable wart sites once every 14 days until complete clearance or up to four treatments, followed by wart clearance and safety assessments at Day 84. Cohort 2 (n=35) included subjects, 12 years or older, who received wart paring to remove thick scale prior to application of VP-102 with occlusive tape for 24 hours, with clinic visits to measure safety and efficacy assessments and apply VP-102 every 21 days for up to four treatments, followed by a safety and efficacy assessment at Day 84. Safety and efficacy of warts treated prior to Day 84 was also measured during follow up visits on Days 105, 126, and 147 in Cohort 2.

Results: The percentage of subjects with complete clearance of all treatable common warts at Day 84 was 19 percent (4/21) for Cohort 1 and 51 percent (18/35) for Cohort 2. Percentages of complete clearance for follow-up visits for Cohort 2 were 45.7 percent, 40 percent, and 40 percent for Days 105, 126 and 147, respectively. The most common treatment-emergent AEs included application site vesicles, pain, pruritus, erythema, and scab; most AEs were mild or moderate in severity. AEs listed were considered related to pharmacodynamic action of the active ingredient, cantharidin, a topical vesicant.

Conclusion: VP-102 showed favorable tolerability and an acceptable safety profile, as well as efficacy in complete clearance of common warts from baseline to Day 84 and follow up visits. Due to the higher percentage of patients with complete clearance, the treatment regimen for Cohort 2 will be utilized in future studies.

Funding: Studies were sponsored by Verrica Pharmaceuticals Inc.

Disclosures: Information not provided.

Efficacy and tolerability of a retinoid/alpha hydroxy acid-based professional peel system in subjects with mild to moderate photodamage

Presenters: Price CJ,¹ Taylor A,¹ Tisbert K,¹ Nelson DB²

Affiliations: ¹SkinScience M.D., Phoenix, AZ; ²Skinbetter science, LLC, Phoenix, AZ

Background: Chemical peels accelerate natural exfoliation and help diminish the visible signs of aging. Patients seek treatments that require minimal downtime and maximum results. Alpha and beta hydroxy acids (AHA and BHA, respectively) have been mainstay ingredients of superficial peels. Here, we describe a study evaluating a new professional peel system (AHA-Ret Peels 30/50) that incorporates AHAs and BHA in combination with a double-conjugated retinoid.

Objective: To evaluate the tolerability and efficacy of AHA-Ret Peels 30/50 in subjects with mild-to-moderate photodamage following three peel treatments over 12 weeks.

Methods: Eligible subjects were 25 to 60 years of age, with Fitzpatrick Skin Type (FST) II to IV with mild-to-moderate photodamage who did not exhibit a severe response to patch testing following product application. Subjects were assigned to receive three peel treatments, once every four weeks, with AHA-Ret 30 or AHA-Ret 50, based on photodamage severity. In conjunction with AHA-Ret 30/50, subjects utilized an at-home skincare regimen that included a gentle cleanser, a comprehensive topical antioxidant, a rebalancing moisture treatment cream, and a retinoid/AHA-based overnight cream and sun protection factor (SPF) 30+. Using digital imagery, the investigator assessed changes from baseline in the appearance of erythema, fine lines/wrinkles, skin tone, skin texture, and pore size using a six-point grading scale (0=None to 5=Severe). Subjects completed tolerability and satisfaction self-assessments. Evaluation and collection of AEs occurred throughout the study.

Results: All subjects (N=28) were eligible for full face application of AHA-Ret 30/50 peels following patch testing. Thirteen subjects (mean age: 35 years) received the AHA-Ret 30 Peel; the majority were FST II with mild photodamage. After one treatment, subjects demonstrated a 43-percent average improvement in skin tone and a 40-percent average improvement in erythema from baseline. Following three peel treatments, improvements from baseline were demonstrated in the appearance of erythema (58%), skin tone, (52%), skin texture (49%), fine lines/wrinkles (48%), and pore size (45%). All (100%) subjects agreed that their skin improved in all categories evaluated, and that their pores were less visible following each peel. Fifteen subjects (mean age: 51 years) received the AHA-Ret 50 Peel. Subjects were FST II (60%), III (13%) or IV (27%) with moderate photodamage. After one treatment, subjects demonstrated an average 33-percent improvement in skin tone and a 30-percent improvement in erythema from baseline, with continued improvements in erythema (35%), skin tone (36%), skin texture (38%), fine lines/wrinkles (27%), and pore size (41%) after three treatments. All (100%) subjects agreed that the overall condition of their skin had improved from baseline as early as the first peel, and that their skin was clearer, smoother and brighter after three treatments. No subjects discontinued due to an AE. Subjects in both groups reported mild, transient stinging, tingling, and itching immediately following application with mild flaking/peeling resolving within 7 to 10 days.

Conclusion: A new double-conjugated, retinoid/AHA/BHA professional peel system (AHA-Ret 30/50), in conjunction with an at-home skincare regimen demonstrated progressive improvements in the appearance of photodamage from baseline after three peel treatments. Most mild, transient adverse events occurred immediately following application with peeling/flaking resolving within 7 to 10 days.

Evaluation of efficacy and tolerance of repairing cream formulated with new biotechnological active ingredient

Presenters: Beziat Monteil C, Noizet M, Galliano MF

Affiliation: Pierre-Fabre Dermo-Cosmétique, Toulouse, France

Background: Skin healing is greatly influenced by the human microbiome. Epithelial cells can communicate with bacteria via toll-like receptors, and it has been shown that stimulation of these receptors by bacteria can accelerate skin healing. A new biotechnological ingredient derived from nonpathogenic bacteria, Aquaphilus dolomiae, has shown regenerative skin healing properties.

Objective: This clinical study aimed to evaluate the efficacy and tolerance of the new repairing cream.

Methods: In this open, monocentric study, 88 participants aged three months to 70 years were treated with the new repairing cream twice a day for indications that included postpeeling (n=5), postlaser treatment (n=6), postcryotherapy (n=11), irritation in adults (n=11), irritation in children/infants (n=22), irritation in intimate areas of women (n=11), and rash (n=11). Dermatologists, pediatricians, and gynecologists evaluated the repairing efficacy and safety at Days 1, 3, 8, and 22. Pictures were taken at these periods, and a satisfaction questionnaire was given to the patients at the end of the study. Overall, the new formula showed very good skin and gynecological tolerance.

Results: At Day 22, 100 percent of patients felt an improvement starting after the first application. Repair efficacy also steadily increased from Day 1 to Day 22. On Day 3, physicians noted that the cream was working in 78 percent of patients, and by Day 22, 90 percent showed improvement. More than 90 percent of the subjects reported that the cream had a protective texture, did not sting, and it did not leave white stains on clothes or on the skin. Eighty-nine percent of patients noted rapid repair, high quality of skin repair, and less visible marks.

Conclusion: Due to extensive and progressive research regarding the microbiome and skin healing, the new repairing cream was created with a new biotechnological ingredient. It is safe and effective for all age ranges and can be used for numerous indications from post treatment irritation to general rashes. Almost complete unanimous satisfaction was seen among patients regarding efficacy and tolerability. There are no concerns in safety or quality regarding this product.

Financial Disclosure: This study was supported by Pierre Fabre Dermo-Cosmétique, Toulouse, France.

Ex-vivo human skin assessment of minocycline permeation and penetration into epidermis, dermis, and sebaceous appendages

Presenters: Elliott R¹ Lawrence G,¹ Stakias V,¹
Stuart I¹

Affiliations: ¹Foamix Pharmaceuticals Inc., Bridgewater, NJ

Background: Two novel foam formulations of minocycline with differing concentrations of antibiotic have been developed for potential use in dermal conditions. Permeation and penetration of minocycline into the epidermis, dermis, and sebaceous appendage with these formulations have yet to be characterized.

Objective: To perform an ex-vivo permeation and penetration assessment for two prototype foam formulations of minocycline, FMX101 4% and FMX103 1.5%.

Methods: A flow-through diffusion cell (MedFlux-HT™) was used to assess drug delivery between donor and receptor compartments across dermatomed human skin. The extraction solvent was 90/9/1 methanol/water/formic acid, and the receptor solution was 35mM EDTA in 130mM sodium acetate, pH 5.0, with 0.01% Brij-O20. LC-MS/MS was used for quantification of minocycline from receptor solution and skin tissue homogenates. Human skin from a single donor was initially stored at -80 degrees Celsius and thawed at room temperature prior to placement into the diffusion cells. Ex-vivo skin permeation and penetration experiments consisted of two active (FMX101 4% and FMX103 1.5%) and two placebo formulations. Minocycline penetration was examined by extracting drug from epidermis, dermis, and the sebaceous appendage.

Results: At 12 hours after skin application, the amount of minocycline permeating into receptor solution ranged from 24 to 417ng/cm² for FMX101 4% and from 55 to 129ng/cm² for FMX103 1.5% (differences not statistically significant). Penetration of minocycline into the sebaceous appendage was 3,539ng (0.67% of applied dose) for FMX101 4% and 909ng (0.52%) for FMX103 1.5% (p<.001). Approximately half of the minocycline delivered to the epidermis was recovered from the sebaceous appendages for both formulations. When the sebaceous appendages were removed, similar percentages of the applied minocycline dose were delivered to the epidermis, 0.28% for FMX101 4% and 0.29% for FMX103 1.5%. With intact sebaceous appendages, delivery was 1.02% (4818ng) and 1.54% (2838ng), respectively. Dermis delivery was 1680 to 2407ng for FMX101 4% and 676 to 1419ng for FMX103 1.5% (p<.05). A post-hoc analysis was conducted to convert the observed amounts of minocycline to concentration of minocycline (µg/mL) for each layer. With intact sebaceous appendages, minocycline delivery to the epidermis was 560.21ug/mL for FMX101 4% and 329.94ug/mL for FMX103 1.5%; delivery to the dermis was 17.50ug/mL and 14.79ug/mL. After removal, respective delivery to the epidermis was 165.64ug/mL and 59.03ug/mL, and to the dermis it was 25.07ug/mL and 7.05ug/mL.

Conclusion: FMX101 4% and FMX103 1.5% delivered similar, high concentrations of minocycline to the epidermis and sebaceous appendage, but much lower concentrations to the dermis skin layer.

Financial Disclosers: Drs. Elliot, Lawrence, Stakias, and Stuart are employees of Foamix Pharmaceuticals Inc.

Protection and rejuvenation against skin damage in a highly air polluted area from a novel antioxidant dual serum system: a randomized, regimen-controlled study in Beijing, China

Presenters: Liu W,¹ Krutmann J,² Jie L,³ Liu D,³ Makino ET,⁴ Mehta RC⁴

Affiliations: ¹Department of Dermatology, General Hospital of Air Force, Beijing, China; ²IUF-Leibniz Research Institute for Environmental Medicine, Duesseldorf, Germany; ³Air Force Medical Center, Beijing China; ⁴SkinMedica, Inc., an Allergan Company, Irvine, CA

Background/Objective: Environmental effects, such as air pollution, have been increasingly linked to the aged appearance of the skin. Exposure to air pollution has been shown to increase proinflammatory mediators and induce gene expression related to dark spot and wrinkle formation.^{1, 2} A novel antioxidant dual serum system (LVS), consisting of a day serum (LVD) and a night serum (LVN), was developed based on circadian rhythm of the skin to provide protective and reparative effects against environmental damage by combining a unique blend of antioxidants and peptides.

Method: A 12-week, randomized, regimen-controlled clinical study was conducted to assess the effects of LVS on subjects who were occupationally exposed to an excessively high concentration of air pollution. Female Chinese subjects (N=105), ages 33 to 60 years, completed the 12-week study (active: n=52, control: n=53). Active subjects received LVS and a basic moisturizer, and control subjects received only the basic moisturizer. At all visits (baseline, Days 28, 56 and 84), objective instrumentation measuring skin color, wrinkles, moisture loss, elasticity, sebum, pH, and hydration were taken from the facial skin.

Results/Conclusion: Despite high levels of air pollution during the study, significant improvements over control were observed for both skin brightness (L*) and redness (a*) at all follow-up visits (all p<0.03; independent sample t-test). The active group also showed significant improvements at all follow-up visits in skin hydration, elasticity, moisture loss, and skin wrinkles compared to baseline (all p<0.05; paired t-test). Results from this study suggest that LVS might provide protection and rejuvenation effects to skin exposed to air pollution.

Volume and height reduction of fibrotic scars shown with three-dimensional (3D) imaging 12 weeks after noninvasive treatment using a Rapid Acoustic Pulse (RAP) device in a proof-of-concept study

Presenters: LaTowsky B,¹ Capelli CC,² Robertson DW²
Affiliations: ¹Clear Dermatology and Aesthetics Center, Scottsdale, AZ; ²Soliton, Inc., Houston, TX

Objective/Background: The objective of this single-site, proof-of-concept, international review board (IRB)-approved, human clinical study was to evaluate the safety, tolerability, and efficacy of the RAP device for the temporary improvement in the appearance of fibrotic scars. The RAP device produces high intensity acoustic shock waves at a rapid rate of 50 pulses per second. It has the potential to improve the appearance of scars through both microdisruption of the scar tissue matrix and downregulation of fibrotic fibroblasts leading to scar remodeling. The RAP device has been successfully used in two IRB-approved human clinical trials to accelerate laser-based tattoo removal and in a proof-of-concept trial to improve the appearance of cellulite.

Method: A single six-minute RAP session was used to treat 11 fibrotic scars (e.g., keloid or hypertrophic scars) in 10 participants. Immediately post-treatment, unexpected adverse events (UAEs) and treatment tolerability were recorded. Assessment of scar dimensions and appearance was performed using before and after photos taken with a 3D multispectral camera (Antera 3D Pro, Miravex, Dublin, Ireland). Images acquired with the 3D multispectral camera were analyzed using proprietary software for changes in scar volume and height from pretreatment to the 12-week follow-up. At the 12-week follow-up, participants were asked to fill out a patient satisfaction survey.

Results: The 3D scar assessment of pre- and post-treatment photographs of 11 treated scars demonstrated an average reduction in volume of 29.6 percent (p< 0.01) (range: 2% to -48%), and an average reduction in height of 14.6 percent (p< 0.005) (range 0% to -34%). Except for mild erythema and pinpoint bleeding, no UAEs occurred from the RAP treatment. The treatment sessions were considered tolerable by all subjects. The average pain score was 2.2 on a 0 to 10 pain score, with 10 being the worst possible pain. Seven of the10 participants agreed or strongly agreed that their scar(s) was improved, while two were neutral, and one disagreed. Eight of 10 agreed or strongly agreed that they would do the treatment again, while one was neutral, and one disagreed. Finally, 6 of 10 agreed or strongly agreed that they would recommend the treatment to a friend, while three were neutral, and one disagreed.

Conclusions: The treatment of fibrotic scars using the RAP device is safe and tolerable. Follow-up at 12 weeks demonstrated that RAP provides significant improvements in the appearance of fibrotic scars from a single, short-duration, noninvasive treatment with minimal pain, and most patients expressed satisfaction with the treatment outcomes.

ATOPIC DERMATITIS

Atopic dermatitis disease biomarkers strongly correlate with IL-13 levels, are regulated by IL-13, and are modulated by tralokinumab in vitro

Presenters: Weidinger S, Tollenaere MAX, Drerup K, Litman T, Norsgaard H

Background: Atopic dermatitis (AD) is a chronic pruritic skin disease characterized by immune-mediated inflammation and skin barrier dysfunction. The immune-mediated inflammation is associated with Type 2 pathway activation. Even in nonlesional skin, subclinical inflammation and impaired skin barrier function is present. In a recent large-scale RNA-seq based transcriptomic study of AD, psoriasis, and matched control samples, it was found that the Type 2 cytokine IL-13 was the most distinctive¹ marker for AD. Increased expression levels of IL-13 were found in both lesional and nonlesional skin affected by AD. Expression levels of IL-13 in lesional AD skin correlated with disease severity. In contrast, expression of the Type 2 cytokine IL-4 was undetectable or barely detectable in the AD skin samples.

Objective: We aimed to evaluate the correlation of IL-13 expression with AD disease biomarkers in lesional skin samples from the same AD patient cohort. In addition, we investigated IL-13 mediated regulation of AD disease biomarkers in vitro and their modulation by tralokinumab, a monoclonal antibody in Phase III development for AD that specifically neutralizes IL-13.

Methods: A correlation analysis was performed between the expression levels of IL-13 and all other genes in nonlesional and lesional skin biopsies from 27 cases¹with moderate-to-severe AD. In-vitro cultures of human primary keratinocytes and dermal fibroblasts were stimulated with recombinant human IL-13 in the absence or presence of tralokinumab in a concentration range of 0.1-100nM. Gene expression was analyzed by qPCR using Taqman gene expression assays.

Results: In the AD patient cohort, a high correlation was found in lesional skin between gene expression levels of IL-13 and genes related to epidermal differentiation/lipid synthesis/skin barrier function (FLG: corr. -0.55; FLG2: corr. -0.61; LOR: corr. -0.59; ELOVL6: corr. -0.73), chemokines involved in attraction of immune cells (CCL2: corr. 0.69; CCL17: corr. 0.81; CCL22: corr. 0.78), and to pruritus and hyperproliferation (NTRK1: corr. 0.82; coding for the NGF receptor TrkA).

Conclusion: Using in-vitro cultures of human primary keratinocytes and dermal fibroblasts, we showed that the expression of disease biomarkers was regulated by IL-13, mimicking the expression in AD, and normalized by tralokinumab.

Funding: The study was funded by LEO Pharma.

Disclosures: Information not provided.

Dupilumab for the treatment of chronic actinic dermatitis: a case series

Presenters: Konda S,¹ Patel N,² Lim HW¹

Affiliations: ¹Department of Dermatology, Henry Ford Health System, Detroit, MI; ²School of Medicine, Tulane University, New Orleans, LA

Background: Chronic actinic dermatitis (CAD) is an immune-mediated photodermatosis characterized by chronic, pruritic, eczematous, and often lichenified plaques distributed primarily upon sun-exposed skin. The pathophysiology is believed to involve a delayed-type hypersensitivity reaction to an endogenous, photoinduced, cutaneous antigen, which has been speculated to be deoxyribonucleic acid (DNA). First-line management options include strict photoprotection, topical corticosteroids (TCS), and topical calcineurin inhibitors (TCI). However, these are rarely sufficient on their own. Thus, many systemic therapies are often utilized with varying degrees of success. Dupilumab is a human monoclonal antibody that was initially approved in the United States for moderate-to-severe atopic dermatitis, which is similarly characterized by chronic, eczematous, pruritic skin lesions. Only one case using dupilumab for the treatment of CAD has previously been reported. Here, we present four therapeutically challenging cases of CAD that were successfully managed with dupilumab.

Methods: Four patients with clinicopathologically diagnosed CAD were evaluated and treated in the dermatology clinic of a hospital-based tertiary care center. In all cases, traditional topical and systemic therapies failed to induce a significant reduction in disease activity.

Following discussion with each patient, the decision was made to initiate dupilumab 600mg subcutaneously followed by 300mg every other week. All other systemic medications were ceased, but strict photoprotective measures and topical therapies were continued. Monitoring of clinical response, as demonstrated by cutaneous findings and symptomatology, was continued from the time of treatment initiation, ranging between months to years depending upon the patient in question.

Results: All four patients experienced marked improvement in disease control within one month of starting dupilumab, and this effect was found to be durable in nature. Of note, one patient underwent phototesting in 2015 that revealed 24-hour minimal erythema dosages for ultraviolet A (UVA) at 3J/cm2 and ultraviolet B (UVB) at 12mJ/cm². This same patient was initiated on dupilumab in January 2018, and repeat phototesting in February 2019 revealed 24-hour minimal erythema dosages for UVA at 12J/cm² and UVB at 12mJ/ cm². No significant adverse effects of therapy were noted.

Conclusion: Effective, long-term treatments for CAD are lacking, and the course of the disease tends to be unpredictable. Our case series suggests that dupilumab might be a viable option for CAD that has proven refractory to standard therapies. All four patients in our cohort exhibited sustained improvement in skin findings and associated symptoms within one month of initiation of therapy. Our observations support further investigation of dupilumab as an alternative or adjunctive treatment for CAD. In particular, studies with larger patient cohorts and longer follow-up periods are necessary to ascertain whether dupilumab maintains long-term disease remission.

CUTANEOUS ONCOLOGY

Association between baseline disease characteristics and relapse-free survival (RFS) in patients (pts) with BRAF V600-mutant resected Stage III melanoma treated with adjuvant dabrafenib (D) + ttametinib T) or placebo (PBO)

Presenters: Schadendorf D,¹ Dummer R,² Hauschild A,³ Santinami M,⁴ Atkinson V,⁵ Mandalà M,⁶ Chiarion-Sileni V,⁷ Larkin J,⁸ Nyakas M,⁹ Dutriaux C,¹⁰ Haydon A,¹¹ Mortier L,¹² Robert C,¹³ Schachter J,¹⁴ Ortmann CE,¹⁵ de Jong E,¹⁵ Gasal E,¹⁶ Kefford R,¹⁷ Kirkwood JM,¹⁸ Long GV¹⁹

Affiliations: ¹University Hospital Essen, Germany; ²University Hospital Zürich Skin Cancer Center, Switzerland; ³University Hospital Schleswig-Holstein, Germany; ⁴Fondazione Istituto Nazionale Tumori, Italy; ⁵Princess Alexandra Hospital, Australia; ⁶Papa Giovanni XXIII Cancer Center, Italy; ⁷Veneto Institute of Oncology, Italy; ⁸Royal Marsden NHS Foundation Trust, United Kingdom; ⁹Oslo University Hospital, Norway; ¹⁰Centre Hospitalier Universitaire de Bordeaux, France; ¹¹Alfred Hospital, Australia; ¹²Université de Lille, France; ¹³Institut Gustave Roussy and Paris-Sud University, France; ¹⁴Ella Lemelbaum Institute for Immuno-Oncology and Melanoma, Israel; ¹⁵Novartis Pharma AG, Switzerland; ¹⁶Novartis Pharmaceuticals Corporation, NJ; ¹⁷Macquarie University, Australia; ¹⁸University of Pittsburgh, PA; ¹⁹Melanoma Institute Australia

Objective: In the COMBI-AD trial (NCT01682083), 12 months of adjuvant D+T led to significant improvement of RFS versus PBO (hazard ratio [HR], 0.47; p< .001) in patients with resected BRAF V600–mutant Stage III melanoma; three- and four-year RFS rates were 59 percent and 54 percent, respectively. Previous results showed consistent treatment benefit across baseline disease stage according to AJCC Edition 7/8. Here, we explored the association between baseline disease characteristics and RFS to identify patient subgroups likely to benefit from adjuvant treatment.

Methods: Randomized patients with completely resected BRAF V600E/K–mutant Stage III melanoma received 12 months of adjuvant D (150mg BID)+T (2mg QD) orally or PBO. Within each subgroup, predictive value was explored using Kaplan-Meier analysis, and HRs were calculated using a Pike estimator.

Results: Minimum follow-up was 40 months for 870 enrolled patients (D+T, 438; PBO, 432). Kaplan-Meier analysis demonstrated treatment benefit across all subgroups analyzed. Assessment of RFS by extent of primary tumor (T-stage) showed consistent benefit favoring D+T vs. PBO (HR [95% CI]; T1, 0.42 [0.25–0.70]; T2, 0.51 [0.34–0.76]; T3, 0.55 [0.39–0.77]; T4, 0.42 [0.29–0.60]). HRs by nodal burden (N-stage) showed consistent treatment benefit (N1, 0.52 [0.37–0.72]; N2, 0.38 [0.28–0.53]; N3, 0.58 [0.41–0.83]). Substantial treatment benefit was observed in pts with baseline in-transit metastases (HR, 0.45 [95% CI, 0.24–0.82]) and those with no in-transit metastases detected at baseline (HR, 0.49 [95% CI, 0.40–0.60]). When RFS was assessed according to melanoma presentation, treatment benefit favoring D+T versus PBO was observed in patients with superficial spreading melanoma (HR, 0.48 [95% CI, 0.35–0.66]) and those with nodular melanoma (HR, 0.53 [95% CI, 0.37-0.75]).

Conclusion: These results confirm earlier findings showing that treatment benefit of adjuvant D+T versus PBO is independent of baseline factors.

Funding: This study was sponsored by GlaxoSmithKline. Dabrafenib-trametinib are assets of Novartis AG as of 2 March 2015. This abstract was accepted and previously presented at the American Society of Clinical Oncology 2019 Annual Meeting. All rights reserved.

Disclosure: Information not provided.

Cemiplimab-rwlc Survivorship and Epidemiology (CASE) study in advanced cutaneous squamous cell carcinoma (CSCC)

Presenters: Chandra S,¹ Rabinowits G,² Migden MR,³ Chen CI,⁴ Desai J,⁴ Seluzhytsky A,⁵ Sasane M,⁵ Campanelli B,⁴ Chen Z,⁴ Freeman ML,⁶ Ibrahim SF,⁷ Khushalani NI,⁸ Ruiz E,⁹ Andria M⁴

Affiliations: ¹Division of Hematology Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL; ²Hematology/Oncology, Miami Cancer Institute/Baptist Health South Florida, Miami, FL; ³Departments of Dermatology and Head and Neck Surgery, University of Texas, MD Anderson Cancer Center, Houston, TX; ⁴Regeneron Pharmaceuticals Inc., Tarrytown, NY; ⁵Sanofi, Bridgewater, NJ; ⁶Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA; ⁷Department of Dermatology, Rochester Medical Center, Rochester, NY; ⁸Department of Cutaneous Oncology, Moffitt Cancer Center, Tampa, FL; ⁹Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA.

Background: Cemiplimab, a PD-1 monoclonal antibody, demonstrated substantial antitumor activity, growing evidence of durable responses, and an acceptable safety profile in patients with advanced CSCC (metastatic [m] and locally advanced [la] CSCC) in Phase I and II studies (NCT02383212; NCT02760498). In 2018, cemiplimab-rwlc became the first FDA-approved systemic therapy for patients with M or laCSCC who are not candidates for curative surgery or curative radiation. In 2019, the EMA granted a conditional approval for the same indication. No data exist on the clinical characteristics, disease progression, and survivorship of patients with advanced CSCC receiving cemiplimab in real-world clinical practice.

Objectives: 1) Describe the effectiveness of cemiplimab in eligible patients, including A) patients who are immunosuppressed or immunocompetent, B) after prior exposure to radiotherapy, and C) as a first-line or later systemic treatment regardless of disease etiology; 2) evaluate safety; 3) describe patients receiving cemiplimab in real-world setting; 4) describe real-world use patterns of cemiplimab; and 5) describe patient experience, including quality of life and functional status, and clinician-reported performance status.

Methods: CASE, a prospective Phase IV, noninterventional, survivorship and epidemiology cohort study (NCT03836105) will include patients with advanced CSCC, in a real-world setting, who have begun treatment or for whom treatment with cemiplimab is planned. Enrollment of approximately 350 patients is planned in up to 100 study sites in the US within a 24-month recruitment period. Duration of follow-up is up to 36 months. Evaluable patients will be those who received one or more dose of cemiplimab in the real-world setting and are assessed for response by a physician. Data will be summarized descriptively and will primarily fall into 1) patient and tumor characteristics; 2) treatment effectiveness; 3) safety; 4) treatment patterns; and 5) patient experience. This study is open for enrollment.

Funding: Sponsored by Regeneron Pharmaceutical, Inc. and Sanofi.

Disclosures: S Chandra reports institutional research funding from Bristol-Myers Squibb, consulting/advisory role for Bristol-Myers Squibb, EMD Serono, Biodesix, and Regeneron Pharmaceuticals, Inc., and other conflicts with Bristol-Myers Squibb, EMD Serono, Biodesix, and Regeneron Pharmaceuticals, Inc. G Rabinowits reports institutional research funding from Eselixis, EMD Serono, and Millennium, consulting/advisory role for EMD Serono Pfizer, Sanofi, Regeneron Pharmaceuticals Inc., and Merck and stock/other ownership interests from Syros Pharmaceuticals and Regeneron Pharmaceuticals, Inc. MR Migden reports honoraria from Regeneron Pharmaceuticals, Inc., Novartis, Genentech, Eli Lilly, and Sun Pharma. C Chen is an employee and shareholder of Regeneron Pharmaceuticals, Inc. J Desai is an employee and shareholder of Regeneron Pharmaceuticals, Inc. A Seluzhytsky is an employee and shareholder of Sanofi Genzyme. M Sasane is an employee and shareholder of Sanofi Genzyme. B Campanelli is an employee and shareholder of Regeneron Pharmaceuticals, Inc. Z Chen is an employee and shareholder of Regeneron Pharmaceuticals, Inc. ML Freeman reports consulting/advisory role for Bristol-Myers Squibb, Merck, Sanofi and Regeneron Pharmaceuticals, Inc., and speakers’ bereau for Bristol-Myers Squibb, Merck, Sanofi, Regeneron Pharmaceuticals, Inc., and Novartis. SF Ibrahim reports research funding from Regeneron Pharmaceuticals, Inc. and Castle, speakers’ bureau from Genentech, and travel and accommodation expenses from Regeneron Pharmaceuticals, Inc. and Genentech. NI Khushalani reports grants from Regeneron Pharmaceuticals, Inc.; grants and advisory board fees from Bristol-Myers Squibb and HUYA Bioscience International; advisory board fees from EMD Serono, Regeneron Pharmaceuticals, Inc., Genentech, AstraZeneca (data safety monitoring committee), Merck, ARRAY Biopharma, and Immunocore; grants from Merck, Novartis, GlaxoSmithKline, Cellgene, and Amgen; and common stock ownership of Bellicum Pharmaceuticals, Mazor Robotics, Amarin, and Transenetrix. E Ruiz declares no conflict of interest. M Andria is an employee and shareholder of Regeneron Pharmaceuticals, Inc.

Development and validation of a nomogram incorporating molecular and clinical factors for accurate prediction of recurrence risk in patients with cutaneous melanoma

Presenters: Thorpe R,¹ Caruso H,² Monzon F,² Covington KR,² Brodland D,³ Zitelli J³

Affiliations: ¹Ada West Dermatology; ²Castle Biosciences, Inc.;³Zitelli and Brodland, P.C.

Background: Patients with cutaneous melanoma (CM) have an individual recurrence risk impacted by clinical, pathological, and genetic features. The 31-gene expression profile (31- GEP) is a prognostic test for CM that accurately predicts patient five-year recurrence risk, distant metastasis, and melanoma-related death. The 31-GEP is a significant and independent predictor of metastatic risk, as demonstrated in both prospective and retrospective studies. As patient risk is determined by both clinical and genetic features, we developed a nomogram combining 31-GEP class and clinicopathologic features for predicting CM recurrence.

Methods: A prospective cohort of 685 patients with minimum one-year follow-up or recurrence from nine dermatology centers was included in nomogram development. Most patients (n=655/685) did not undergo sentinel lymph node biopsy (SLNB); therefore, the nomogram was developed from noninvasive clinical and molecular features to predict recurrence risk in patients without SLNB information. The cohort had median follow-up time of three years, median age 67 years, and median Breslow thickness (BT) of 0.5mm (82% T1), representing a melanoma patient population typically seen by a dermatology practice. Ulceration was present in seven percent of patients, and elevated mitotic rate (greater than or equal to 2 mitoses/mm²) in 18 percent of patients. A logistic regression model was fitted on clinical and pathological data to determine relative predictive value for recurrence risk. Covariate inclusion for the model was selected by the lowest Bayesian information criteria value with fewest clinical features. Independent validation was completed for recurrence prediction in an archival cohort of 901 CM patients with a median of 5.8 years follow up.

Results: The nomogram with the best fit for recurrence prediction included T stage (BT and ulceration) and 31-GEP results. The 31-GEP was a strong, significant predictor of recurrence in this cohort (coefficient 1.7, p=0.003), and the relative added risk from a Class 2B result compared to a Class 1A result was the same relative risk of a T3a melanoma compared to a T1a melanoma. Patients in Class 1A had improved recurrence-free survival (RFS) when compared to patients in Class 2B (98.9% [95% CI: 98.0-99.8%] vs. 67.4% [95% CI: 54.3-83.7%]). The independent archival cohort validated the nomogram and demonstrated an increasing nomogram score strongly correlated with risk of recurrence (p<0.00001). In a multivariate Cox regression model including 31-GEP and clinical features, only BT and 31-GEP results were significant predictors for RFS (HR 1.26, p=0.0004; HR 9.95, p<0.00001, respectively). In this cohort, SLN status was not a significant predictor of recurrence.

Conclusion: This nomogram combines the 31-GEP with clinical features, creating a clinically useful, accurate tool for optimized outcome consideration. A future aim of this study is to generate a mobile application for expedited conversion of clinical and molecular data to a patient’s individual recurrence risk.

Funding: This study was sponsored by Castle Biosciences, Inc., which developed and validated the 31-GEP test.

Disclosures: Information not provided.

Efficacy and safety of sonidegib in patients with aggressive and nonaggressive subtypes of locally advanced basal cell carcinoma: long-term 42-month results from the BOLT study

Presenters: Lewis KD,¹ Squittieri N,² Migden MR³

Affiliations: ¹University of Colorado Denver, School of Medicine, Division of Medical Oncology, Denver, CO;²Sun Pharmaceutical Industries, Inc., Princeton, NJ; ³University of Texas MD Anderson Cancer Center, Departments of Dermatology, Division of Internal Medicine, and Head and Neck Surgery, Division of Surgery, Houston, TX

Background: Sonidegib, a hedgehog inhibitor (HHI) that selectively targets Smoothened and is approved in the US, the European Union, Switzerland, and Australia for the treatment of adult patients with locally advanced basal cell carcinoma (laBCC) not amenable to curative surgery or radiation therapy. Sonidegib is also approved for the treatment of metastatic BCC (mBCC) in Switzerland and Australia. Through 42 months of the Phase II BOLT (Basal Cell Carcinoma Outcomes with LDE225 [sonidegib] Treatment) trial (NCT01327053), sonidegib 200mg per day demonstrated durable efficacy and consistent/manageable toxicity.

Objective: Here, we report final BOLT 42-month efficacy and safety results—the longest follow-up data available for an HHI—according to aggressive versus nonaggressive tumor histology among patients with laBCC receiving sonidegib 200mg daily.

Methods: BOLT was a randomized, double-blind, Phase II clinical trial conducted in 58 centers across 12 countries. Patients were grouped based on laBCC (aggressive and nonaggressive) and received sonidegib 200mg daily, or mBCC and recieved sonidegib 800mg daily. Eligible patients had either histologically confirmed laBCC (not amenable to curative surgery or radiation) or mBCC (for which all other treatment options had been exhausted). Patients previously treated with sonidegib or other HHI were excluded, and stratification was based on stage, disease histology for patients with laBCC (nonaggressive vs. aggressive) and geographic region. Treatment was continued until disease progression, unacceptable toxicity, death, study termination, or withdrawal of consent. Tumor response by central and investigator review was evaluated using the stringent modified Response Evaluation Criteria in Solid Tumors (mRECIST) for patients with laBCC, including assessment by magnetic resonance imaging (MRI) complemented by color photography and histology of multiple biopsy samples, and complete response was defined as negative histology with complete disappearance of target lesions by all image modalities. For analysis by tumor histology, aggressive histological subtypes included micronodular, infiltrative, multifocal, basosquamous, and sclerosing; nonaggressive histological subtypes included nodular and superficial. Safety/tolerability were assessed through monitoring and recording adverse events (AEs); regular monitoring of hematology, clinical chemistry, and electrocardiograms; and routine monitoring of vital signs and physical condition. Data presented were based on the FDA-approved 200mg dose at 42 months.

Results: At baseline, 58 percent of patients with laBCC receiving sonidegib 200mg daily were male, and the median age was 67 years. The majority of patients had an aggressive histologic subtype (56.1%) and two or more lesions (54.5%), with 43.9 percent having nonaggressive histologic subtype and 45.5 percent having one lesion or less. Among all patients with laBCC who received sonidegib 200mg per day, objective response rate (ORR) by central review was 56.1 percent.

ORR by central review was numerically higher for aggressive (59.5%) versus nonaggressive histology (51.7%) at Month 42. ORR by investigator review was numerically higher overall relative to central review and similar for aggressive (70.3%) versus nonaggressive histology (72.4%). After 42 months, 64 out of 66 (97.0%) patients with laBCC receiving sonidegib 200mg daily experienced an AE. The most frequent AEs in this population were muscle spasms (56.1%), alopecia (51.5%), dysgeusia (47.0%), and nausea (37.9%), with fatigue (31.8%), weight loss (31.8%), increased creatine kinase (28.8%), and diarrhea (27.3%) occurring as well.

Conclusions: After 42 months, sonidegib 200mg per day demonstrated clinically meaningful responses in patients with laBCC evaluated by the stringent mRECIST criteria. Sonidegib 200mg per day was effective in patients with aggressive and nonaggressive tumor histology. AEs were consistent with the known safety profile of sonidegib.

Acknowledgments: Writing and editorial assistance was provided by Jennifer Meyering, RN, MS, CMPP of AlphaBioCom, LLC, King of Prussia, PA, and supported by Sun Pharmaceutical Industries, Inc.

Disclosures: KL has participated on advisory boards for Genentech and Sun Pharmaceutical Industries, Inc., and consulted for Regeneron. NS is an employee of Sun Pharmaceutical Industries, Inc. MM has participated on advisory boards and received honoraria from Genentech, Novartis Pharmaceuticals Corporation, Sun Pharmaceutical Industries, Inc., and Regeneron Pharmaceuticals.

Integrating the 40-gene expression profile (40-GEP) test into management of high-risk cutaneous squamous cell carcinoma

Presenters: Farberg AS,^1,2 Hall MA,³ Douglas L,⁴ Covington KR,³ Kurley SJ,³ Cook RW,³ Dinehart SM¹

Affiliations: ¹Icahn School of Medicine at Mount Sinai, New York, NY; ²Arkansas Dermatology Skin Cancer Center, Little Rock, AR; ³Castle Biosciences, Inc., Friendswood, TX; ⁴Baylor College of Medicine, Houston, TX

Background: As the second most common form of skin cancer, cutaneous squamous cell carcinoma (cSCC) occurs in approximately one million people per year in the US. The incidence of cSCC has been rising rapidly over the last several decades, due partly to an aging population and enhanced detection methods. Associated morbidity and mortality continue to rise. Although most cSCC patients do not develop metastasis (<6%), survival rates are poor for those who do develop regional or distant metastatic lesions. Deaths from cSCC are estimated to rival those from melanoma. Therefore, predicting cSCC metastatic risk is essential for improving patient management and outcomes. The National Comprehensive Cancer Network (NCCN) provides guidelines for low- and high-risk cSCC patient management. The American Joint Committee on Cancer (AJCC) and Brigham and Women’s Hospital (BWH) tumor classification systems better identify patients at high risk for metastasis relative to NCCN guidelines, but their positive predictive values (PPV) are low (14%–38%). Thus, for improved stratification of cSCC patient risk for metastasis, we recently validated a 40-gene expression profile (40-GEP) test in a prospectively planned archival cohort study of 321 patients with primary cSCC and known clinical outcomes, 93 percent of whom were NCCN high risk.

Objective: Here, we report on integration of the 40-GEP test for cSCC metastasis risk into management decision making for risk-appropriate management of NCCN high-risk cSCC patients.

Methods: Medical records, including pathology reports, were reviewed and cases were categorized by NCCN guidelines and staged per AJCC and BWH criteria. The 40-GEP test identified three risk groups having low (Class 1), high (Class 2A), or highest risk (Class 2B) for metastasis at three years postdiagnosis, respectively. For the NCCN high-risk patients (n=300), the numbers of patients in each Class/T stage combination along with metastasis rates were reported and used to align each patient group with risk-appropriate management recommendations. Metastasis rates of less than 10 percent, 10 to 50 percent, and greater than 50 percent were aligned with low, moderate, and high intensity management recommendations, respectively.

Results: Risk-aligned management recommendations based on 40-GEP results and T-stage were developed for low-, moderate-, and high-intensity management within the boundaries of acceptable NCCN patient management approaches for patients with high-risk localized disease. Integration of the 40-GEP test into risk-directed management plans for NCCN high-risk cSCC patients identified a group of patients (Class 1, T1/T2) with risk approaching that of the general population, thereby warranting a low-intensity management strategy and sparing these patients unnecessary procedures and potential adverse effects. Conversely, those patients with rates of metastasis surpassing 50 percent (Class 2B) warrant a high-intensity strategy that increases follow-up visits, utilizes imaging and/or biopsies for nodal assessment, and considers adjuvant treatments and clinical trials for probable metastatic events. These data support integration of the 40-GEP into management of NCCN high-risk cSCC patients for implementation of risk-appropriate treatment plans for these patients.

Funding: This study was sponsored by Castle Biosciences, Inc. which provided funding for tissue and clinical data retrieval for most studies above. This work was previously submitted for consideration at the 2020 Winter Clinical Dermatology Conference.

Disclosures: Information not provided.

Practical management of adverse events using dosing strategies for patients receiving sonidegib for advanced basal cell carcinoma

Presenters: Lear J,¹ Squittieri N,² Guminski A^3,4

Affiliations: ¹Manchester Academic Health Science Centre, MAHSC, Manchester University and Salford Royal NHS Trust, Manchester, UK; ²Sun Pharmaceutical Industries, Inc., Princeton, NJ; ³Department of Medical Oncology, Royal North Shore Hospital, Sydney, Australia; ⁴University of Sydney, Sydney, Australia

Background: Sonidegib, a hedgehog pathway inhibitor (HPI), is approved in the US, European Union, Switzerland, and Australia for the treatment of adult patients with locally advanced basal cell carcinoma (laBCC) not amenable to curative surgery or radiotherapy. BOLT study results with sonidegib 200mg once daily (QD) demonstrated durable efficacy and consistent tolerability through 42 months (NCT01327053). Here, we present and evaluate strategies to manage adverse events (AEs) and possibly reduce discontinuations throughout treatment.

Methods: BOLT was a randomized, double-blind, multicenter Phase II study. HPI-treatment naïve patients with laBCC not amenable to curative surgery/radiotherapy or metastatic BCC (mBCC) were randomized 1:2 to sonidegib 200 or 800mg QD, respectively. Tumor responses were assessed using mRECIST for laBCC and RECIST v1.1 for mBCC. The primary end point was objective response rate (ORR) per central review, as well as safety and tolerability.

Results: Based on the approved BOLT protocol, clinical strategies were developed for managing AEs, including the following for patients receiving sonidegib 200mg QD: for patients with normal creatine kinase (CK) and muscle-related Grade 1 to 2 symptoms, continue sonidegib; for those with Grade 2 or greater, measure CK weekly until symptoms resolve to Grade 1 or less; for those with Grade 3 or greater, symptoms interrupt treatment. For those with asymptomatic Grade 1 to 2 CK elevation, continue same dose; for those with Grade 2, monitor CK weekly until resolved to Grade 1 or less. If symptomatic Grade 1 to 2 CK elevation, continue same dose and monitor CK weekly until CK returns to normal or symptoms resolve. For Grade 3 to 4 CK elevation, interrupt dose, monitor lab values/CK weekly until resolution to Grade 1 or less; consider electromyography, MRI, and muscle biopsy.

At 42 months, ORR (95% confidence interval [CI]) for all patients receiving sonidegib 200mg QD (laBCC and mBCC, n=79) was 48.1 percent (36.7%–59.6%) overall, 48.5 percent (36.0%–61.1%) for patients without dose reduction/delay (n=66), and 46.2 percent (19.2%–74.9%) for patients with 1 or greater dose reduction/delay (n=13). For patients with laBCC (n=66), ORR (95% CI) was 56.1 percent (43.3%–68.3%) overall, 57.4 percent (43.2%–70.8%) for patients without dose reduction/delay (n=54), and 50.0 percent (21.1%–78.9%) for patients with one dose or greater reduction/delay (n=12).

Conclusions: These results support long-term efficacy of sonidegib at the approved dose of 200mg daily and demonstrate that clinical strategies for AE management do not undermine efficacy and might play a role in optimizing sonidegib treatment.

Funding: This study was sponsored by Novartis Pharmaceuticals Corporation.

Disclosures: JL has received personal fees from Novartis Pharmaceuticals Corporation and Sun Pharmaceutical Industries, Inc. NS is an employee of Sun Pharmaceutical Industries, Inc.; and receives honoraria from Galderma, Leo Pharma, Pierre Fabre, Novartis, and Roche; consulting fees from Galderma, Leo Pharma, Pierre Fabre, Novartis, and Roche; patents, royalties, or other intellectual property from Genentech/F. Hoffmann-La Roche, Ltd.; and travel, accommodations, or expenses from Galderma, Leo Pharma, and Roche. AG has participated on advisory boards for Bristol-Myers Squibb; Pfzer, Inc.; and Sanofi; received honoraria from Novartis Pharmaceuticals Corporation; and received travel support from Astellas and Bristol-Myers Squibb.

Treatment patterns and outcomes among patients with advanced cutaneous squamous cell carcinoma (CSCC) in a US community oncology setting

Presenters: Cowey CL,¹ Robert NJ,² Espirito JL,² Davies K,² Frytak J,² Lowy I,³ Fury MG³

Affiliations: ¹Baylor University Medical Center, Sammons Cancer Center, Texas Oncology, PA, Dallas, TX; ²Data, Evidence & Insights, McKesson Life Sciences, The Woodlands, TX; ³Regeneron Pharmaceuticals, Inc., Tarrytown, NY

Background: Advanced CSCC is a term that encompasses patients with locally advanced CSCC (laCSCC) who are not candidates for curative surgery or curative radiation, and patients with metastatic CSCC (mCSCC). Prior studies of conventional chemotherapy or epidermal growth factor receptor inhibitors each enrolled 40 patients or less. This study assessed real-world treatment patterns and clinical outcomes in patients with unresectable laCSCC or mCSCC.

Methods: This retrospective, observational electronic health records study included patients with advanced CSCC who initiated first-line (1L) systemic treatment 1/1/2008 to 12/31/2015, with follow-up to 9/30/2017. Duration of therapy (DOT) and overall survival (OS) were analyzed by Kaplan-Meier method. Response rate was calculated as proportion of patients who achieved physician-assessed-response.

Results: Eighty-two patients were identified (laCSCC: 17, mCSCC: 65; median age at 1L treatment initiation: 75 years; male: [85%]; Caucasian: [79%]; Eastern Cooperative Oncology Group Performance Status of 1: 88%; had received prior radiotherapy: 84%). The most common 1L regimens were carboplatin+paclitaxel (27% of patients) and cetuximab monotherapy (24%). The median 1L DOT was 2.4 months for the overall population, 4.1 months for laCSCC, and 2.3 months for mCSCC. The physician-assessed response rate for 1L therapy was 18.3 percent overall; 17.6 percent for laCSCC, and 18.5 percent for mCSCC. The median OS from 1L treatment initiation was 15.3 months (95% CI, 10.4–21.0) overall; 16.2 months for laCSCC, and 15.3 months for mCSCC. Only 24 patients (29%) received 2L therapy.

Conclusions: This is the largest retrospective data set regarding patients with advanced CSCC treated with anticancer systemic therapy prior to the approval of cemiplimab. Efficacy was low in both laCSCC and mCSCC. These data provide historic benchmarks for outcomes in patients with advanced CSCC prior to the FDA approval of cemiplimab-rwlc.

Funding: Sponsored by Regeneron Pharmaceutical, Inc. and Sanofi and funded by Regeneron Pharmaceuticals, Inc., and Sanofi. Medical writing support and typesetting was provided by Bu Reinen of Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc., and Sanofi.

Disclosures: CL Cowey reports honoraria from Regeneron Pharmaceuticals, Inc. and institutional research funding from Regeneron Pharmaceuticals, Inc., Merck, Novartis, BMS, Genentech, Celldex, Array BioPharma, and Amgen. NJ Robert reports research funding from Side-Out Foundation; consulting or advisory roles with New Century Health, Bristol-Myers-Squibb, and Boehringer Ingelheim; employee and shareholder of McKesson Corporation. JL Espirito and K Davies are employees and shareholders of McKesson Corporation. J Frytak reports travel expenses from Bristol-Myers-Squibb and is and employee and shareholder of McKesson Corporation. MG Fury and IL are employees and shareholders of Regeneron Pharmaceuticals, Inc.

MISCELLANEOUS

Evaluation of skin barrier and hydration effects of a new rebalancing moisturizing treatment cream in a human epidermal skin model

Presenters: McDaniel DH,¹ Wortzman M,² Nelson DB²

Affiliations: ¹McDaniel Institute of Anti-Aging Research, Virginia Beach, VA; ²skinbetter science, LLC, Phoenix, AZ

Background: Extrinsic and intrinsic factors compromise and overwhelm the natural ability of healthy skin to renew itself and maintain its barrier protective function. Three critical elements of skin moisturization and optimal skin barrier health include enhancing skin’s natural lipid bilayer, natural moisturizing factors (NMF) and hyaluronic acid (HA).

Objective: The study described here evaluated skin barrier and hydration effects of a new rebalancing moisturizing treatment (TRMT) cream versus a leading moisturizer utilizing a human epidermal skin model.

Methods: The hydration evaluation consisted of the topical application of 25uL of TRMT (N=5) and 25uL of a market-leading moisturizer (MLM; N=5) to human skin tissue. Five tissues were left untreated (NC). Following 60 minutes of exposure, residual product was removed from tissue surfaces. At zero, 15, and 30 minutes postexposure, epidermal hydration was measured using electrical impedance (Nova Meter DPM9003, Nova Technologies). Following the measurement of epidermal hydration, test formulations were re-applied to tissues and tissues were incubated at 37°C/5%CO2 for 24+/-2 hours. Tissues were harvested for mRNA gene expression (qPCR) analysis of Claudin (CLD [tight junction barrier protein]), Aquaporin (AQP [protein that transports water, urea and glycerol]), Hyaluronic Acid Syntheses (HAS [enzyme responsible for hyaluronan synthesis]), and Hyaluronidase (HYAL [enzyme that degrades HA]).

Results: At zero, 15, and 30 minutes, TRMT and MLM demonstrated statistically significant increased hydration versus NC (p<0.005). TRMT demonstrated greater hydration effects than MLM at each timepoint, with two times greater hydration at 15 minutes. After 24 hours of exposure, tissues treated with TRMT demonstrated substantially greater expression of CLD, AQP, and HA compared to untreated tissues and tissues treated with MLM. TRMT also demonstrated substantially reduced expression of HYAL compared to untreated and MLM-treated tissues. Expression of key biomarkers evaluated for MLM-treated tissues were comparable to untreated tissues.

Conclusion: A new rebalancing moisture treatment cream demonstrated significant effects on skin hydration versus untreated tissues, and greater and longer retention of hydration versus a market-leading moisturizer in a human epidermal skin model. TRMT-treated tissues demonstrated increased expression of key biomarkers associated with beneficial effects on skin barrier and hydration versus untreated tissues and tissues treated with a market-leading moisturizer.

Successful treatment of steatocystoma multiplex using Erbium: YAG laser

Presenters: Ricardo JW,¹ Sebaratnam DF^1,2,3

Affiliations: ¹The Children’s Hospital Westmead, Sydney Australia; ²Department of Dermatology, Liverpool Hospital, Sydney, Australia; ³Faculty of Medicine, University of New South Wales, Sydney, Australia

Background: A 47-year-old man presented with a 20-year progressive history of papules over the torso. He had no palmoplantar keratoderma, nail changes, or hoarse voice and was otherwise in good health. His primary concern was the cosmetic burden of the papules. Examination demonstrated hundreds of soft fluctuant papules over the trunk and limbs. Biopsy demonstrated a cyst lined with squamous epithelium with a prominent eosinophilic cuticle. Sebaceous glands were identified at the wall of the cysts, and his clinical presentation was in keeping with steatocystoma multiplex (SM). Trials of topical corticosteroids, tetracycline antibiotics, and isotretinoin had been unsuccessful. Based on the reported efficacy of simvastatin in pachyonychia congenita, a four-month trial of simvastatin 20mg daily was also pursued with no clinical improvement noted. Having exhausted medical options, the patient proceeded to a trial of ablative laser. There is small volume data regarding the use of laser in SM, with most articles focusing on ablative carbon dioxide laser. Fully ablative carbon dioxide has become less readily available with the advent of fractionated ablative laser and other platforms, such as the erbium: yttrium aluminium garnet (Er:YAG) gaining popularity. The patient received Er:YAG (Sciton) using a 4mm spot, 150um, 50-percent coagulation to each papule to the end point of cyst rupture with the contents manually expressed. Treatment led to resolution of the cysts with no recurrence at three months. This case constitutes the first use of ablative Er:YAG laser in the treatment of SM.

Topical sodium thiosulfate as treatment of calcinosis cutis: a case series and systematic review

Presenters: Ricardo JW,¹ Sebaratnam DF^1,2,3

Affiliations: ¹The Children’s Hospital Westmead, Sydney Australia;²Department of Dermatology, Liverpool Hospital, Sydney, Australia; ³Faculty of Medicine, University of New South Wales, Sydney, Australia

Background: Calcinosis cutis is characterized by the deposition of calcium within the skin and subcutaneous tissue and occurs secondary to multiple cutaneous and systemic disease processes. Reported treatment options include diltiazem, minocycline, colchicine, biphosphates, warfarin, ceftriaxone, aluminum hydroxide, and probenecid, as well as procedural interventions, such as excision, extracorporeal shock wave lithotripsy, and ablative laser. Treatment options are generally disappointing, and literature regarding management is often based on small case series with significant heterogeneity, encumbering an evidence-based approach to management. Topical sodium thiosulfate (TST) has shown some promise in treating calcinosis cutis.

Methods: We conducted a systematic review of the literature according to recommended PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The review employed combinations and variations of the search terms calcinosis cutis, sodium thiosulfate, and sodium metabisulfite. PubMed, MEDLINE, Embase, SCOPUS, ScienceDirect, and Google Scholar were searched in addition to review of reference lists and grey literature. The review was registered on the PROSPERO database (record CRD42019129818) prior to the initiation of the search strategy. Inclusion criteria required studies reporting patients in any age group with a diagnosis of calcinosis cutis made either histologically or radiographically, treated with TST at any concentration, for any given time.

Results: Literature review yielded 20 publications. After screening for duplicates, one publication was removed with eleven more omitted after applying our inclusion and exclusion criteria. The remaining eight publications—six case reports and two case series—reporting on 44 patients were included. We also report on three novel cases of patients treated with TST. The quality of evidence was low as expected, categorised as Level 4 (case series) and Level 5 (case reports). Among the 44 patients, a variety of etiologies were reported, most commonly connective tissue disease. A range of STS formulations was employed. The most commonly employed formulations were 25 percent STS in 40 (91%) patients and nine percent STS in four (10%) patients. Of the 44 patients included in our review, 18 percent had complete resolution with TST, 57 percent demonstrated a partial response, 20 percent had no response, and 5 percent had an unknown response. The mean duration to improvement was 3.6 months, and the mean total duration of treatment was 4.7 months. Seventy-five percent of patients reported an improvement in symptoms, and 20 percent reported no improvement. Nine percent of patients had minor adverse effects, including irritation, pain, and pruritus.

Conclusion: To our knowledge, this is the largest systematic review summarizing the efficacy and safety profile of TST in treating calcinosis cutis. Independent of etiology, an improvement in clinical findings was observed in the majority (75%) of cases. Further, tolerability and safety profile for this medication was favorable, with only minor cutaneous adverse effects reported. Despite these results being based on small-volume case series, they are promising. Calcinosis cutis is often a stubborn condition to treat, and TST might offer a topical treatment that is effective and safe. Further studies comparing it to standard treatments would be of merit.

PSORIASIS

A head-to-head comparison of ixekizumab versus guselkumab in patients with moderate to severe plaque psoriasis: 12-week efficacy, safety, and speed of response from a randomized, double-blind trial

Presenters: Blauvelt A,¹ Papp K,² Jarel A,³ Reich K,⁴ Gottlieb AB,⁵ Lima RG,⁶ Elmaraghy H,⁶ Gallo G,⁶ Renda L,⁶ Park SY,⁶ and Bagel J⁷

Affiliations: ¹Oregon Medical Research Center, Portland, OR, USA; ²Probity Medical Research, Inc., Waterloo, Ontario, Canada; ³Northeast Dermatology Associates, Portsmouth, NH; ⁴Translational Research in Inflammatory Skin Diseases, Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf, and Skinflammation® Center, Hamburg, Germany; ⁵Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY; ⁶Eli Lilly and Company, Indianapolis, IN; ⁷Psoriasis Treatment Center of Central New Jersey, East Windsor, NJ

Background: Biologics targeting the interleukin (IL)-17/IL-23 pathway have demonstrated benefits to patients with high levels of skin improvement. As these drugs have come to market, there is an increasing need to directly compare efficacy and safety between new products to better inform dermatologists and patients regarding drug selection. Comparing speed of response is also important, as this has been identified as a key drug attribute by physicians and patients when choosing a therapeutic option. Ixekizumab (IXE), a high-affinity monoclonal antibody that selectively targets IL-17A, has demonstrated greater skin clearance than etanercept and ustekinumab with consistent long-term efficacy and safety for up to five years of continuous treatment. Here, we report 12-week results of IXORA-R (NCT03573323), which compared the efficacy and safety of IXE versus guselkumab (GUS), an IL-23p19 inhibitor, as well as the speed of response in patients with moderate to severe plaque psoriasis.

Methods: IXORA-R, a 24-week, randomized, double-blinded trial, included adults with moderate to severe plaque psoriasis (sPGA greater than or equal to 3, PASI greater than or equal to 12, BSA greater than or equal to 10%). Patients were randomized (1:1) to IXE or GUS (dosing per label). The primary end point assessed whether IXE was superior to GUS, as measured by PASI 100 at Week 12. Major secondary end points included PASI 100 at Weeks 4, 8, and 24, sPGA [0] at Week 12, PASI 90 at Weeks 4 and 8, PASI 75 at Week 2, and PASI 50 at Week 1. Comparisons in the ITT population were made using Cochran-Mantel-Haenszel test adjusted by pooled site using nonresponder imputation for missing data. Safety analyses included all patients who received one dose or greater of either drug. IXORA-R is still blinded for investigators, sponsor’s study team, and patients; thus, not all efficacy and safety data are disclosed here to maintain study blinding and integrity.

Results: Of 1027 patients randomized (520 to IXE and 507 to GUS), 488 IXE and 482 GUS patients remained in the study through Week 12. Baseline demographics and disease characteristics were generally well balanced between groups. All primary and key secondary, multiplicity-adjusted efficacy end points up to Week 12 were met. IXE was superior to GUS for PASI 100 response at Week 12 (41.3% vs. 24.9%, p<0.001). In addition, more patients on IXE versus GUS achieved PASI 100 and PASI 90 at Weeks 4 and 8, PASI 75 at Week 2, PASI 50 at Week 1 and sPGA (0) at Week 12. No unexpected safety signals were observed.

Conclusion: IXE was superior to GUS in achieving complete skin clearance (PASI 100) at Week 12. More patients on IXE showed improvement over GUS as early as Week 1 for PASI 50, Week 2 for PASI 75, and Week 4 for sPGA (0), PASI 90, and PASI 100. Both drugs demonstrated safety data consistent with their known safety profiles.

Disclosures: A Blauvelt has served as scientific advisor or clinical study investigator for AbbVie, Aclaris, Allergan, Almirall, Amgen, Arena, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermavant, Dermira, Eli Lilly and Company, FLX Bio, Forte, Galderma, Genentech/Roche, GlaxoSmithKline, Janssen, LEO Pharma, Meiji, Merck Sharp & Dohme, Novartis, Pfizer, Purdue Pharma, Regeneron, Revance, Sandoz, Sanofi Genzyme, Sienna Pharmaceuticals, Sun Pharma, UCB Pharma, Valeant, and Vidac, and as a paid speaker for AbbVie, Regeneron, and Sanofi Genzyme. K Papp has received grant support and personal fees from AbbVie, Amgen, Celgene, Eli Lilly and Company, Janssen, Merck, Novartis, and Pfizer, and personal fees from Boehringer Ingelheim. A Jarell has served as scientific advisor or clinical study investigator for AbbVie, Asana Biosciences, Castle Biosciences, Inc., Bristol-Myers Squibb, Celgene, Dermira, Eli Lilly and Company, Galderma, Genentech/Roche, GlaxoSmithKline, LEO Pharma, Novartis, Pfizer, Purdue Pharma, Regeneron, Sanofi Genzyme, Sienna Pharmaceuticals, Sun Pharma, UCB Pharma, and as a paid speaker for Castle Biosciences, Inc., Eli Lilly and Company, Novartis, Regeneron, and Sanofi Genzyme. K Reich served as an advisor and paid speaker and has participated in clinical trials for AbbVie, Affibody, Almirall, Amgen, Avillion, Biogen, Boehringer Ingelheim, Celgene, Covagen, Forward Pharma, Fresenius Medical Care, GlaxoSmithKline, Janssen, Janssen-Cilag, Kyowa Kirin, LEO Pharma, Eli Lilly, Medac, Merck Sharp & Dohme, Novartis, Miltenyi Biotech, Ocean Pharma, Pfizer, Regeneron, Samsung Bioepis, Sanofi, Sun Pharma, Takeda, UCB, Valeant, XBiotech, and Xenoport. A Gottlieb has served as a consultant or speaker for Janssen Inc., Celgene Corp., Bristol Myers Squibb Co., Beiersdorf, Inc., Abbvie, UCB, Novartis, Incyte, Eli Lilly and Company, Reddy Labs, Valeant, Dermira, Allergan, Sun Pharmaceutical Industries, Xbiotech, Leo, and Avotres Therapeutics, and received research/educational grants from Janssen, Incyte, UCB, Novartis, Lilly Xbiotech, and Boeringer Ingelheim. H Elmaraghy, S Y Park, R Gontijo Lima, L Renda, and G Gallo own stock and are employees of Eli Lilly and Company. J Bagel is a speaker and investigator for AbbVie, Celgene, Eli Lilly and Company, Janssen, Novartis and Ortho Dermatologics. He is an investigator for Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, and LEO Pharma.

Characteristics of patients with palmoplantar pustulosis compared with those with psoriasis vulgaris: a claims database study

Presenters: Kotowsky N,¹ Feldman SR,² Garry EM,³ Valdecantos WC,¹ Gao R,¹ Golembesky AK⁴

Affiliations: ¹Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT; ²Department of Dermatology, Wake Forest School of Medicine, Winston-Salem, NC; ³Aetion, Boston, MA; ⁴Boehringer Ingelheim International GmbH, Ingelheim, Germany

Background: Palmoplantar pustulosis (PPP) is a chronic, debilitating, and painful inflammatory skin disease characterized by localized sterile pustules on the palms of the hands and soles of the feet. There is little real-world evidence characterizing patients with PPP.

Objective: This study examined demographics, comorbidities, and concurrent medication use for patients with PPP compared to those with psoriasis vulgaris (PsO) in a real-world setting.

Methods: Patients with PPP or PsO were identified if they had at least one inpatient or two outpatient ICD-10 diagnosis codes (L40.3 or L40.0, respectively) separated by at least 30 days but within 365 days. All analyses were conducted via the Aetion Evidence Platform™, v3.17, using Optum® Clinformatics™ Data Mart, a US administrative claims database. The study period was from October 1, 2015 to March 31, 2019, with the first qualifying diagnosis date (first inpatient or second outpatient claim) after at least six months of continuous baseline enrollment marking the start of follow-up. For comorbidities, a non-psoriasis cohort comprising persons without a history of any psoriasis (but allowing psoriatic arthritis) was provided for context. This group was matched on age and sex to each patient with PPP.

Results: 1,291 patients with PPP and 60,419 with PsO were identified at baseline, with 708 PPP and 32,665 PsO patients having more than 12 months of follow-up. Patients with PPP tended to be female (73.4%; 50.7% for PsO) and had a mean age of 60.0 years (56.4 years for PsO). Compared to patients with PsO and the non-psoriasis group, patients with PPP were more likely to have a diagnosis of hyperlipidemia (PPP: 48.4%; PsO: 39.4%; non-psoriasis: 29.8%), anxiety (PPP: 13.7%; PsO: 10.3%; non-psoriasis: 8.4%), and depression (PPP: 12.7%; PsO: 8.8%; non-psoriasis: 7.3%) at baseline. Of the 708 patients with PPP, 391 (55.2%) were treated with a systemic therapy (either a biologic, an oral non-biologic medication, or both) during the 12-month follow-up: 16 (2.3%) were treated with a biologic only and 319 (45.1%) were treated with an oral systemic therapy. More than half (54.8%) of patients with PPP were treated with a topical steroid medication, 22.7 percent with a topical non-steroid medication, and 34.3 percent with systemic steroids. Methotrexate (16.5%) and acitretin (8.8%) were the most commonly used oral systemic therapies, while adalimumab (6.5%) and ustekinumab (6.2%) were the most commonly used biologics. During the follow-up period, nearly a third (32.1%) of patients with PPP had a prescription for an opioid pain medication (ATC N02AJ or N02AX) compared with 24.8 percent of patients with PsO.

Conclusions: Patients with PPP have more comorbidities than patients with PsO and non-psoriasis patients and receive more pain management than those with PsO. Patients with PPP are more commonly treated with systemic therapies, including biologics and nonbiologic oral medications, than patients with PsO.

Funding: This study was funded by Boehringer Ingelheim.

Disclosures: AK Golembesky, WC Valdecantos, and N Kotowsky are full-time employees of Boehringer Ingelheim. EM Garry is a full-time employee of Aetion, Inc. with stock options, and contracted by Boehringer Ingelheim. S Feldman received research, speaking and/or consulting support from Galderma, GSK/Stiefel, Almirall, Alvotech, Leo Pharma, BMS, Boehringer Ingelheim, Mylan, Celgene, Pfizer, Ortho Dermatology, AbbVie, Samsung, Janssen, Lilly, Menlo, Merck, Novartis, Regeneron, Sanofi, Novan, Qurient, National Biological Corporation, Caremark, Advance Medical, Sun Pharma, Suncare Research, Informa, UpToDate, and the National Psoriasis Foundation. He is founder and majority owner of www.DrScore.com and founder and part owner of Causa Research, a company dedicated to enhancing patient adherence to treatment.

Clinical efficacy of an at-home, 620- and 660-nm red light treatment on scalp pruritus and irritation

Presenters: Nestor MS,¹ Berman B,² Sinclair R,³ Medendorp N,⁴ Womble M,⁴Stasko N⁴

Affiliations: ¹Center for Clinical and Cosmetic Research, Department of Surgery, Division of Plastic and Reconstructive Surgery, Department of Dermatology and Cutaneous Surgery, University of Miami Miller School Of Medicine, Miami, FL; ²Center for Clinical and Cosmetic Research, Department of Dermatology and Cutaneous Surgery, University of Miami Miller School Of Medicine, Miami, FL; ³Department of Dermatology, University of Melbourne, East Melbourne, Australia; ⁴PhotonMD Inc., Durham, North Carolina

Background: Scalp burning, stinging, and pruritus are common patient complaints in the dermatological setting and can be frustrating for both the patient and the dermatologist. Indeed, the prevalence of pruritus of the scalp is up to 45 percent in patients with chronic pruritus. These symptoms are often associated with conditions such as seborrheic dermatitis and scalp psoriasis, where up to 80 percent of patients with psoriasis report scalp itch with a positive correlation between the severity of the lesions and severity of itch, but these symptoms might also appear without any clinical findings. Treatment options for scalp disorders and associated symptoms include topical corticosteroids and, in some cases, antifungals, but the majority of underlying disease pathologies and limited adherence with dosing regimens hinder their clinical benefit. Patients with androgenetic alopecia often report scalp itch and irritation and might also have concomitant seborrheic dermatitis. Based on this, the symptoms of pruritus, irritation, and burning of the scalp were measured in an ongoing multicenter study evaluating the safety and efficacy of a dual wavelength LED light device in subjects being treated with androgenetic alopecia.

Methods: Eighty-one subjects were randomized to either a dual wavelength 620-nm and 660-nm light therapy device paired with a Bluetooth-connected mobile app (REVIAN RED System) or to a sham comparator device with a similar user experience through the mobile app to track daily treatment adherence between both groups. Device usage was fixed at once daily, 10-minute treatment durations for a period of 26 weeks. The trial population consisted of adult men and women between 18 and 65 years of age with a diagnosis of androgenetic alopecia, consistent with men who have Norwood Hamilton Classification IIa to V patterns of hair loss and women who have Ludwig-Savin Scale I-1 to I-4, II-1, II-2 or frontal, both with Fitzpatrick Skin Types I–IV. The Hair Specific Skindex-29 Quality of Life Questionnaire (HSSQOL) was used to assess itching, burning/ stinging, irritation, and other patient reported outcomes. Participants scored each question on a scale from 1 (never) to 5 (all the time).

Results: Secondary efficacy assessment–Hair Specific Skindex-29 QOL at Week 16. The Hair Specific Skindex 29 Quality of Life Questionnaire (HSSQOL) is a 29-item questionnaire with three domains: seven questions for symptoms domain, 10 questions for emotion domain, and 12 questions for function domain. Specifically, for the symptom of “my scalp burns or stings,” at the end of the 16-week trial, 100 percent of the active treated group showed never or rarely having the symptom versus 66.6 percent of the sham group, and 0 percent of the active group reported the symptoms sometime or often versus 33.4 percent of the sham-treated group (p=0.007). For the symptom of “my scalp itches” (i.e., pruritus), 77.8 percent of the active treatment group and 44 percent of the sham-treated group reported the symptom never or rarely versus 16.7 percent of the active group, and 57.6 percent of the sham-treated group reporting the symptom sometime or often (p=0.02) Finally, regarding “my scalp is irritated,” 83.4 percent of the active treatment group and 55.5 percent of the sham-treated group reported the symptom never or rarely versus 16.6 percent of the active treated group, and 44.5 percent of the sham-treated group reported the symptoms sometime or often (p=0.07. Red and Infrared Low Level Light Therapy (LLLT) has previously been shown to have anti-inflammatory effects in patients with plaque psoriasis, leading to clearance of recalcitrant lesions and reductions in plaque desquamation, induration, and erythema. The addition of 620nm LED light results in increased release of nitric oxide (NO) in the skin and provides a complimentary mechanism to reduce inflammation, irritation, and pruritis.

Conclusion: The FDA-cleared dual wavelength device was found to be safe and well tolerated, with statistically significant differences observed in patient-reported pruritus and burning/stinging compared to sham after 16 weeks of once daily, at-home treatment. The MOA for improved scalp symptoms is proposed to be a combination of the benefits of traditional anti-inflammatory and antipruritic effects of red (660nm) LLLT and the anti-inflammatory effects of nitric oxide (NO) released with 620nm light. The authors are unaware of any previous reports of a reduction in scalp pruritis with traditional LLLT devices used to treat androgenetic alopecia. Independent, well-controlled studies are warranted to confirm these findings for the broader population of individuals suffering from itch and irritation symptoms associated with scalp conditions, such as seborrheic dermatitis or psoriasis.

Funding: This trial was sponsored by REVIAN, Inc.

Disclosures: Information not provided.

Clinical implications of early PASI responses to tildrakizumab in patients with moderate to severe plaque psoriasis

Presenters: Feldman SR,¹ Merola JF,² Pariser DM,³ Zhang J,⁴ Zhao Y,⁴ Parno J,⁴ Mendelsohn AM,⁴ Lowry S,⁴ Gottlieb AB⁵

Affiliations: ¹Wake Forest School of Medicine, Winston-Salem, NC; ²Brigham and Women’s Hospital, Harvard Medical School, Boston, MA; ³Eastern Virginia Medical School and Virginia Clinical Research, Inc., Norfolk, VA; ⁴Sun Pharmaceutical Industries, Princeton, NJ; ⁵Icahn School of Medicine at Mount Sinai, New York, NY

Background: Tildrakizumab, a humanized, IgG1/kappa monoclonal antibody selectively inhibiting the p19 subunit of IL-23, is approved for the treatment of adult patients with moderate to severe plaque psoriasis. Psoriasis Area Severity Index (PASI) improvements from baseline differed between tildrakizumab nonresponders (PASI less than 50), responders (PASI greater than or equal to 75), and super-responders (PASI greater than or equal to 90) as early as Week 4.

Objective: To evaluate whether early improvements in PASI scores potentially identify Week 28 PASI responders and nonresponders.

Methods: This analysis included patients from the pooled Phase III trials of tildrakizumab in plaque psoriasis (reSURFACE 1 [NCT01722331] and reSURFACE 2 [NCT01729754]) who were randomized to receive tildrakizumab 100mg at Weeks 0, 4, 16, and 28. Four mutually exclusive groups were created based on each patient’s Week-28 PASI response: PASI 50 or less, PASI 50–74, PASI 75–89, and PASI 90–100 (observed data). Percent of PASI improvements from baseline at Weeks 4 and 16 were analyzed for each of the Week 28 PASI response groups. Additionally, improvements in PASI scores from baseline at Weeks 4 and 16 were examined to identify Week-28 PASI response groups.

Results: Overall, 575 patients (mean age: 45.6 years, male: 69.5%) treated with tildrakizumab 100mg from baseline to 28 weeks were included. The proportions of patients achieving PASI 50 or less, PASI 50–74, PASI 75–89, and PASI 90–100 at Week 28 were 8.3 percent, 14.3 percent, 23.8 percent, and 53.5 percent, respectively. Eighty-five percent of patients with PASI 50 or less at Week 16 did not achieve Week-28 PASI responder status, while 58 percent of the Week-28 nonresponders did not achieve at least a PASI 50 response at Week 16. Forty-one percent of patients achieved PASI 50 or greater at Week 4: two-thirds became super-responders and over 85 percent were responders at Week 28. Among the Week-28 super-responders and responders, 50 percent and 45 percent achieved PASI 50 or greater at Week 4, respectively.

Conclusion: The majority of patients with moderate to severe psoriasis treated with tildrakizumab 100mg achieved PASI 75 responder status at Week 28. PASI improvements as early as Week 4 can be used to potentially identify Week-28 PASI improvement status of patients. By Week 16, few patients were nonresponders and did not become responders by Week 28. In comparison, patients achieving PASI 50 or greater at Week 4 were more likely to become responders and even super-responders by Week 28.

Funding: This study was sponsored by Sun Pharmaceutical Industries, Inc.

Disclosures: Information not provided.

Efficacy and safety of apremilast in patients with moderate to severe plaque psoriasis of the scalp: 32-week results from the Phase III STYLE study

Presenters: Voorhees AV,¹ Gold LS,²Lebwohl M,³ Strober B,^4,5 Gordon KB,⁶ Sofen H,⁷ Papp K,^5,8 Bagel J,⁹ Zhang Z,¹⁰ Paris M,¹⁰ Shah N,¹⁰ Zhang W,¹⁰ Wang Y¹⁰

Affiliations: ¹Eastern Virginia Medical School, Norfolk, VA; ²Henry Ford Health System, West Bloomfield, MI; ³Icahn School of Medicine at Mount Sinai, New York, NY; ⁴University of Connecticut, Farmington, CT; ⁵Probity Medical Research, Waterloo, Ontario, Canada; ⁶Medical College of Wisconsin, Milwaukee, WI; ⁷Dermatology Research Associates, Los Angeles, CA; ⁸K Papp Clinical Research, Waterloo, Ontario, Canada; ⁹Psoriasis Treatment Center of Central New Jersey, East Windsor, NJ; ¹⁰Celgene Corporation, Summit, NJ

Background: The STYLE study (NCT03123471) evaluated efficacy and safety of apremilast in patients with moderate to severe plaque psoriasis of the scalp through Week 32.

Methods: This was a Phase III, multicenter, randomized, double-blind, placebo (PBO)-controlled study in patients with moderate to severe plaque psoriasis of the scalp (Scalp Physician Global Assessment [ScPGA] 3 or greater [moderate or greater]; and psoriasis-involved scalp surface area [SSA] 20% or greater) with inadequate response/intolerance to one or more topical therapy and moderate to severe plaque psoriasis (Psoriasis Area and Severity Index 12 or greater; psoriasis-involved body surface area [BSA] 10% or greater; static PGA [sPGA] 3 or greater [moderate or greater]). Patients were randomized (2:1) to receive either apremilast 30mg BID (APR) or PBO through Week 16 and then continued APR (APR/APR) or were switched to APR (PBO/APR) through Week 32 (APR extension phase). The primary end point was the proportion of patients achieving ScPGA response at Week 16 (score of 0 [clear] or 1 [almost clear] with at least a 2-point reduction from baseline) with APR versus PBO. Secondary end points included proportion of patients with at least a 4-point reduction from baseline in Scalp Itch NRS and Whole Body Itch NRS scores at Week 16 and change from baseline at Week 16 in Dermatology Life Quality Index (DLQI) total score. End points were evaluated at Week 16 using the Cochran-Mantel-Haenszel method for binary end points and analysis of covariance model for continuous end points, with missing values imputed using multiple imputation. From Week 16 to Week 32, continuous variables were summarized using descriptive statistics; categorical variables were summarized with frequency tabulations.

Results: Intent-to-treat adult patients (n=303) were randomized (PBO n=102, APR n=201); 249 patients entered the APR extension phase (PBO/APR n=84, APR/APR n=165). Baseline demographics and disease characteristics were generally comparable between PBO and APR patients (mean [SD]: age, 46.7 [15.2] and 47.0 [15.0] years; disease duration, 14.8 [11.3] and 15.7 [12.4] years; SSA, 58.2 percent [26.4] and 61.9 percent [27.2]; Scalp Itch NRS, 6.7 [2.4] and 6.6 [2.5]; BSA, 21.2% [14.8] and 19.0% [10.8]; Whole Body Itch NRS, 7.2 [2.0] and 7.2 [2.3]; and DLQI, 12.6 [7.2] and 12.6 [7.0]). At Week 16, significantly more patients treated with APR versus PBO achieved ScPGA response, Scalp Itch NRS response, and Whole Body Itch NRS response; mean improvement in DLQI score was significantly greater with APR versus PBO. At Week 32, improvements in efficacy end points and DLQI were maintained in APR/APR patients continuing treatment and emerged in PBO/APR patients after switching to APR (Table). The most common AEs (occurring in 5 or less percent of patients, either group) through Week 16 were diarrhea, nausea, headache, and vomiting. None of the most common AEs were serious, and most AEs were mild to moderate in severity. From Week 16 through Week 32, the most common AEs were diarrhea and nausea. No deaths were reported in the study.

Conclusions: APR demonstrated clinically and statistically significant efficacy versus PBO in patients with moderate to severe plaque psoriasis of the scalp; response was sustained with continued treatment through Week 32. AEs were consistent with the known safety profile of APR.

Efficacy and safety of brodalumab in patients with inadequate response to ustekinumab: analysis of two Phase III psoriasis studies

Presenters: Blauvelt A,¹ Tyring SK,² Langley RG,³ Jacobson A,⁴ Pillai R,⁵ Israel RJ⁶

Affiliations: ¹Oregon Medical Research Center, Portland, OR; ²University of Texas Health Science Center, Houston, TX; ³Dalhousie University, Halifax, NS; ⁴Ortho Dermatologics,* Bridgewater, NJ; ⁵Bausch Health US, LLC,* Petaluma, CA; ⁶Bausch Health US, LLC,* Bridgewater, NJ

*Bausch Health US, LLC is an affiliate of Bausch Health Companies Inc; Ortho Dermatologics is a division of Bausch Health US, LLC.

Objective: Brodalumab, a fully human anti–interleukin-17 receptor A (IL-17RA) monoclonal antibody, antagonizes inflammatory cytokines involved in psoriasis pathogenesis. This post-hoc analysis of two Phase III psoriasis studies (AMAGINE-2/-3) evaluated the efficacy and safety of brodalumab in patients initially randomized to ustekinumab (an anti–IL-12/-23 monoclonal antibody) who were rescued with brodalumab after an inadequate clinical response to ustekinumab.

Methods: After a 12-week (wk) induction phase during which patients were randomized 2:2:1:1 to brodalumab 210mg or 140mg every two weeks (Q2W), ustekinumab (45mg for patients 100kg or less or 90mg for pts >100kg on Day 1 and Week 4), or placebo, patients received maintenance treatment as follows: brodalumab-treated patients were rerandomized to brodalumab 210mg Q2W, 140mg Q2W, 140mg Q4W, or 140mg Q8W, ustekinumab-treated patients continued to receive ustekinumab, and those receiving placebo switched to brodalumab 210mg Q2W. At Week 16, patients with inadequate response (single sPGA score 3 or greater or persistent sPGA score of 2 over 4 weeks or more) were eligible for rescue with brodalumab 210mg Q2W. After Week 16, patients on ustekinumab with an inadequate response remained on ustekinumab.

Results: A total of 590 patients were randomized to ustekinumab during the induction phase, of which 124 were rescued with brodalumab at Week 16 due to an inadequate response. Prior to rescue (at Week 12), Psoriasis Area and Severity Index 75 percent, 90 percent, and 100 percent response rates (PASI 75, 90, and 100) in patients randomized to ustekinumab who were eventually rescued with brodalumab were 24 percent, 5 percent, and zero percent, respectively. After rescue with brodalumab 210mg, PASI 75, 90, and 100 response rates in these patients increased to 73 percent, 58 percent, and 36 percent, respectively, at Week 52. Similarly, the sPGA of 1 or less response rate increased from 2.4 percent at Week 12 to 60.5 percent at Week 52. In ustekinumab-treated patients rescued with brodalumab, rate of treatment-emergent adverse events (TEAEs) through Week 52 was 377.3 events per 100 patient-years, and the rate of serious AEs was 4.3 per 100 patient-years. No life-threatening or fatal adverse events were reported in these patients.

Conclusion: In patients with an inadequate response to ustekinumab, brodalumab might be a safe and effective alternative treatment.

Efficacy and safety of halobetasol propionate 0.01%/tazarotene 0.045% (HP/TAZ) lotion in the treatment of moderate to severe plaque psoriasis of the lower extremities

Presenters: Tyring SK,¹ Kircik LH,² Yamauchi PS,³ Anbalagan N,⁴ Lin T,⁴

Affiliation: ¹University of Texas Health Science Center, Houston, TX; ²Indiana University School of Medicine, Indianapolis, IN; Physicians Skin Care, PLLC, Louisville, KY; and Icahn School of Medicine at Mount Sinai, New York, NY; ³Dermatology Institute & Skin Care Center, Inc., Santa Monica, CA; ⁴Ortho Dermatologics*, Bridgewater, NJ

*Ortho Dermatologics is a division of Bausch Health US, LLC.

Background: Topical treatments as part of combination therapy for moderate to severe psoriasis are becoming increasingly common. While psoriasis commonly affects lower extremities, treatment can be more problematic and burden of disease heightened. Recent Phase III clinical data have demonstrated that a fixed combination of halobetasol propionate 0.01% and tazarotene 0.045% (HP/TAZ) lotion was significantly more effective than vehicle after eight weeks of treatment in patients with moderate to severe localized plaque psoriasis, though efficacy in specific locations has not been reported.

Objective: To evaluate once daily, fixed combination halobetasol propionate 0.01% and tazarotene 0.045% (HP/TAZ) lotion versus vehicle in participants with moderate to severe plaque psoriasis of lower extremities.

Methods: In two Phase III, multicenter, double-blind studies, participants were randomized (2:1) to receive HP/TAZ or vehicle lotion for eight weeks. This pooled post-hoc analysis included a subset of participants who had a target lesion on the leg (HP/TAZ, n=148; vehicle, n=71). Efficacy assessments included treatment success (2-grade improvement or greater) in each individual sign of psoriasis (erythema, plaque elevation, scaling) at the target lesion, and overall treatment outcomes, including overall treatment success (2-grade improvement or greater in Investigator Global Assessment [IGA] score and a score of “clear” or “almost clear”), decrease in Body Surface Area (BSA) affected, and reduction in IGAxBSA.

Results: Psoriasis signs were reduced by Week 8, with more HP/TAZ treated participants achieving improvements in erythema (41.6%), plaque elevation (58.5%), and scaling severity (59.5%) on the leg compared to vehicle (12.5%, 19.2%, and 21.0%, respectively; p<0.001 all). Significantly more participants achieved treatment success (IGA) at Week 8 with HP/TAZ compared to vehicle (36.4% vs. 10.4%; p<0.001). Significant differences versus vehicle were observed by Week 4. The HP/TAZ group had a mean 32.7-percent reduction in BSA at Week 8 versus 1.0% with vehicle (p<0.001). Change from baseline in IGAxBSA score was also improved with HP/TAZ compared to vehicle (-47.3% vs. -4.5%; p<0.001).

Conclusion: HP/TAZ lotion provided significantly improved efficacy following eight weeks of therapy compared to vehicle in patients where the leg was identified as the target lesion.

Funding: This study was supported by Ortho Dermatologics, Inc., Bridgewater, NJ. Ortho Dermatologics is a division of Bausch Health US, LLC.

Disclosures: SKT has acted as an investigator for Ortho Dermatologics. LHK has acted as an investigator, advisor, speaker, and consultant for Ortho Dermatologics. PSY has served as speaker, consultant, and investigator for AbbVie, Amgen, Janssen, Novartis, Lilly, LEO, Ortho Dermatologics, and Sun Pharma. TL is an employee of Ortho Dermatologics and might hold stock and/or stock options in its parent company.

Guselkumab demonstrates greater efficacy compared to secukinumab across body weight quartiles and body mass index categories: Week 48 results from the ECLIPSE trial

Presenters: Armstrong A,¹ Blauvelt A,² Flavin S,³ Hsu MC,³ Randazzo B,^3,4 Reich K,⁵ Langley RG⁶

Affiliations: ¹Keck School of Medicine, University of Southern California, Los Angeles, CA; ²Oregon Medical Research Center, Portland, OR; ³Janssen Research & Development, LLC, Spring House, PA;⁴University of Pennsylvania, Philadelphia, PA; ⁵Translational Research in Inflammatory Skin Diseases, Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf, and Skinflammation® Center, Hamburg, Germany; ⁶Dalhousie University, Halifax, NS, Canada

Background: Psoriasis is a chronic disease requiring long-term treatment. Differences in body weight and body mass index (BMI) of patients can impact the efficacy of fixed-dose biologic therapies.

Objective: We aim to evaluate efficacy results from the Phase III ECLIPSE Trial 4 of guselkumab versus secukinumab by baseline body weight quartiles and BMI categories.

Methods: Patients were randomized to receive guselkumab 100mg administered by subcutaneous (SC) injection at Weeks 0, 4, and 12, then every eight weeks through Week 44 (N=534) or secukinumab 300mg SC at Weeks 0, 1, 2, 3, and 4, then every four weeks through Week 44 (N=514). Placebo was administered to guselkumab patients to mimic the dosing of secukinumab and to maintain the blind. There were no body weight restrictions for enrollment in the trial. The primary end point was the proportion of patients achieving a Psoriasis Area and Severity Index (PASI) 90 response at Week 48. Analyses were performed describing PASI 90, PASI 100, Investigator’s Global Assessment (IGA) score of 0 (cleared), and IGA score of 0/1 (cleared/ minimal) responses at Week 48 by baseline body weight quartile (Q1, less than or equal to 74kg; Q2, greater than 74 to less than or equal to 87kg; Q3, greater than 87 to less than or equal to 100kg; and Q4, greater than 100kg), and BMI category (normal, less than 25kg/m²; overweight, 25 or greater to <30kg/m²; and obese, 30kg/m²or greater). All end points by body weight quartile and IGA 0/1 by BMI category were post-hoc analyses. Data were analyzed using nonresponder imputation (i.e., patients with missing data were considered as nonresponders) after applying treatment failure rules (i.e., patients were considered nonresponders after discontinuing treatment for lack of efficacy, or an adverse event of psoriasis worsening, or after initiating a prohibited psoriasis treatment).

Results: Of the 1,048 total patients, 41.8 percent in the guselkumab group and 44.0 percent of patients in the secukinumab group had obesity (n=223), 33.0 percent in the guselkumb group and 34.6 percent in the secukinumab group had overweight (n=176), and 25.1 and 21.3 percent of patients in each had a “normal” (n=134) BMI. The average body weight was 89kg in both treatment groups. Four primary end point results for the overall trial population showed superior efficacy with guselkumab compared to secukinumab based on PASI 90 response rates at Week 48 of 84.5 percent versus 70.0 percent, respectively (p<0.001). For PASI 90, Q1, 74kg or less was 86.7% vs. 75.6% (11.1 [0.9, 21.3]), and PASI 100 was 58.7% vs. 56.1% (2.6 [–10.0, 15.3]), for Q2, >74 to 87kg or less, PASI 90 was 89.1% vs. 73.0% (16.0 [6.0, 26.0]) and PASI 100 was 66.4% vs. 51.8% (14.6 [2.0, 27.2]), PASI 90 Q3, >87 to 100kg or less was 80.3% vs. 71.0% (9.3 [–1.9, 20.6]) and PASI 100 was 59.1% vs. 47.6% (11.5 [–1.4, 24.4]), and PASI 90 Q4, >100kg was 82.1% vs. 61.3% (20.9 [9.4, 32.3]) and PASI 100 50.0% vs. 38.7% (11.3 [–1.4, 24.0]). The percentage of patients achieving an IGA 0/1 response at Week 48 by baseline body weight quartile included: 84.6 percent for Guselkumab 100mg and 78 percent for Secukinumab 300mg for Q1, 89.9 percent and 78.7 percent for Q2, 83.3 percent and 80.6 percent for Q3, and 82.9 percent and 62.9 percent for Q4. The percentage of patients achieving an IGA 0 response at Week 48 included 61.5 percent for guselkumab 100mg and 58.5 percent for secukinumab 300mg for Q1, 71.4 percent and 53.9 percent for Q2, 61.4 percent and 50.0 percent for Q3, and 55.7 percent and 39.5 percent for Q4. The percentage of patients achieving an IGA 0/1 response at Week 48 for the normal BMI category was 85.8 percent (guselkumab 100mg) and 77.1 percent (secukinumab 300mg), 86.9 percent and 81.9 percent for the overweight category, and 83 percent and 69.3 percent for the obese category. The percentage of people who achieved an IGA 0 response at Week 48 for the normal BMI category was 68.7 percent (guselkumab 100mg) and 60.6 percent (secukinumab 300mg), overweight was 64.2 and 54.2 percent, and the obese category was 57 percent and 43.1 percent.

Conclusions: Efficacy outcome response rates at Week 48 were consistently numerically higher for guselkumab compared to secukinumab across all baseline body weight quartiles and BMI categories.

Funding: This poster was supported by Janssen Research & Development, LLC.

Disclosures: Information not provided.

Long-term efficacy and safety of switching from adalimumab to risankizumab: results from the open-label extension LIMMitless

Presenters: Reich K,¹ Ryan C,² Crowley J,³ Szepietowski JC,⁴ Zeng J,⁵ Valdes J,⁵ Photowala H,⁵ Kaufmann C,⁵ Gooderham M⁶

Affiliations: ¹Translational Research in Inflammatory Skin Diseases, Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf, Skinflammation® Center, Hamburg, Dermatologikum Berlin, Berlin Germany; ²Charles’ Institute of Dermatology, University College Dublin, Ireland; ³Bakersfield Dermatology and Skin Cancer Medical Group, Bakersfield, CA; ⁴Department of Dermatology, Venereology and Allergology, Wroclaw Medical University, Wroclaw, Poland; ⁵AbbVie Inc., North Chicago, IL; ⁶School of Medicine, Queen’s University, Kingston, ON and SKIN Centre for Dermatology and Probity Medical Research, Peterborough, ON, Canada

Background: We evaluated the long-term efficacy and safety of switching to risankizumab (RZB) in patients who were initially randomized to adalimumab (ADA) and switched to RZB either before or upon entering the open-label extension, LIMMitless.

Methods: Patients were initially treated with ADA 40mg every other week or RZB 150mg at Weeks 0 and 4. At Week 16, patients in the ADA arm with Psoriasis Area Severity Index (PASI) 50 or less were defined as ADA nonresponders (ADA NR) and switched to RZB every 12 weeks, while patients in the ADA arm with intermediate response (ADA IR; PASI 50 <90) were rerandomized 1:1 to RZB every 12 weeks or ADA every other week. Patients who responded to ADA at Week 16 (ADA R; PASI >90) continued ADA treatment. Regardless of their response to ADA at Week 44, all patients continuing ADA throughout IMMvent were switched at Week 44 to RZB every 12 weeks without a drug washout period upon entering LIMMitless.

Results: In IMMvent, 304 patients were initially randomized to ADA with 276 completing IMMvent and 260 continuing into the open-label extension trial. Patients who switched from ADA to RZB at Week 16 maintained high efficacy at Week 56. Patients who were on ADA until Week 44 and then switched to RZB showed improved efficacy (PASI 90 and sPGA 0/1) after only 12 weeks of RZB treatment compared to their efficacy after 44 weeks of continuous ADA treatment.

Preliminary rates of serious adverse events (AE) and AEs leading to discontinuation across groups were two or less patients per group after their switch to RZB. No events of malignant tumors (including nonmelanoma skin cancers), active tuberculosis, opportunistic infections, serious hypersensitivity reactions, or death were reported while receiving RZB across all treatment groups.

Conclusions: In patients switching to RZB from ADA without a drug washout, RZB provided improved and durable efficacy, and was well tolerated.

Long-term safety of tildrakizumab in patients with moderate to severe plaque psoriasis: incidence of malignancies through three years (148 weeks) from resurface 1 and resurface 2 Phase II trials

Presenters: Reich K,¹ Griffiths CEM,² Iversen L,³ Peserico A,⁴ Pau-Charles I,⁵Blauvelt A,⁶ Thaçi D⁷

Affiliations: ¹University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Skinflammation®, Hamburg, Germany; and Dermatologikum Berlin, Berlin, Germany; ²Centre for Dermatology Research, The University of Manchester, Manchester, UK; ³Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark; ⁴Clinica Dermatologica, Department of Medicine-DIMED University of Padua, Padua, Italy; ⁵Almirall R&D, Barcelona, Spain; ⁶Oregon Medical Research Center, Portland, OR; ⁷Institute and Comprehensive Centre for Inflammation Medicine, University of Lübeck, Lübeck, Germany

Background: Tildrakizumab (TIL) is a high-affinity anti-IL-23p19 monoclonal antibody approved for the treatment of moderate to severe plaque psoriasis.

Objective: The objective of this study was to evaluate malignancies in the Phase III reSURFACE 1 (NCT01722331) and reSURFACE 2 (NCT01729754) trials.

Methods: This was a post-hoc pooled analysis of adult patients with moderate to severe plaque psoriasis from two three-part, parallel-group, double-blind, randomized controlled trials: reSURFACE 1 (64 week) and reSURFACE 2 (52 week). Safety data over 148 weeks, pooled across trials and treatment groups, were included. Groups were defined as TIL 200mg (200mg in at least one part of the study), TIL 100mg (100mg only in at least one part of the study), etanercept (until Week 28), and placebo. Exposure-adjusted incidence rates (EAIR) for malignancies (excluding nonmelanoma skin cancer [NMSC]) and for NMSC were calculated.

Results: Overall, 928 patients receiving TIL 200mg, 872 receiving TIL 100mg, 313 receiving etanercept, and 543 receiving a placebo were included. The EAIR of malignancies was 0.39/100 subject years for TIL 200mg, 0.45 for TIL 100mg, 0.65 for etanercept, and zero for placebo. The EAIR of NMSC was 0.49/100 subject years for TIL 200mg, 0.50 for TIL 100mg, 1.30 for etanercept, and 0.97 for placebo.

Conclusions: Tildrakizumab had a favorable long-term safety profile as demonstrated by a low rate of malignancies (comparable to etanercept and placebo) in patients with moderate to severe plaque psoriasis.

Funding: Studies were funded by Merck Sharp & Dohme Corp; analyses were funded by Sun Pharmaceutical Industries, Inc.

Disclosures: Information not provided.

Long-term safety of tildrakizumab in patients with moderate to severe plaque psoriasis: incidence of severe infections through three years (148 weeks) from two Phase III trials

Presenters: Thaçi D,¹ Reich K,² Iversen L,³ Peserico A,⁴ Pau-Charles I,⁵ Blauvelt A,⁶ Griffiths CEM⁷

Affiliations: ¹Institute and Comprehensive Center for Inflammation Medicine, University of Lübeck, Lübeck, Germany; ²University Medical Center Hamburg-Eppendorf, Hamburg; Skinflammation®, Hamburg; and Dermatologikum Berlin, Berlin, Germany; ³Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark; ⁴Clinica Dermatologica, Department of Medicine-DIMED University of Padua, Padua, Italy; ⁵Almirall R&D, Barcelona, Spain; ⁶Oregon Medical Research Center, Portland, OR, USA; ⁷Dermatology Centre, The University of Manchester, Manchester, UK

Background: Tildrakizumab (TIL) is a high-affinity anti-IL-23p19 monoclonal antibody approved for the treatment of moderate to severe plaque psoriasis.

Objective: The objective of this study was to evaluate severe infections in the Phase III reSURFACE 1 (NCT01722331) and reSURFACE 2 (NCT01729754) trials.

Methods: This is a post-hoc pooled analysis from two three-part, parallel-group, double-blind, randomized, controlled trials; reSURFACE 1 (64 weeks) and reSURFACE 2 (52 weeks). Safety data over 148 weeks, pooled across trials and treatment groups, were included. Patients were stratified by treatment received, defined as TIL 200mg (in at least one part of the study), TIL 100mg (in at least one part of the study), etanercept (until Week 28), and placebo. Severe infections were defined as any infection meeting the regulatory definition of a serious adverse event (SAE) or requiring intravenous antibiotics, irrespective of whether it was reported as an SAE. Exposure-adjusted incidence rates (EAIR) were reported.

Results: Overall, 928 patients receiving TIL 200mg, 872 receiving TIL 100mg, 313 receiving etanercept, and 543 receiving a placebo were included. The EAIR of severe infections was 1.12/100 patient years for TIL 200mg, 1.14 for TIL 100mg, 1.96 for etanercept and 0.97 for placebo. The most commonly reported types of severe infections included appendicitis, cellulitis, diverticulitis, and sinusitis.

Conclusions: Tildrakizumab had a favorable long-term safety profile as demonstrated by a low rate of severe infections (lower than etanercept and comparable to placebo) in patients with moderate to severe plaque psoriasis.

Funding: Studies were funded by Merck Sharp & Dohme Corp. Analyses were funded by Sun Pharmaceutical Industries, Inc.

Disclosures: Information not provided.

Ixekizumab demonstrates high sustained efficacy and a favorable safety profile in patients with moderate to severe psoriasis through five years of treatment

Presenter: Leonardi C,¹ Foley P,² Torii H,³ Gerdes S,⁴ Elmaraghy H,⁵ Gallo G,⁵ Shrom D,⁵ Leung A,⁶ Papp K⁷

Affiliations: ¹Central Dermatology, St. Louis, MO; ²The University of Melbourne and Skin & Cancer Foundation, Melbourne, Australia; ³Division of Dermatology, Tokyo Yamate Medical Center, Tokyo, Japan; Oregon Medical Research Center, Portland, OR; ⁴Psoriasis-Center at the Department of Dermatology, University Medical Center Schleswig-Holstein, Campus Kiel, Kiel, Germany; ⁵Eli Lilly and Company, Indianapolis, IN; ⁶Syneos Health, Raleigh, NC; ⁷K. Papp Clinical Research and Probity Medical Research Inc., Waterloo, Canada

Background: Ixekizumab (IXE), a high-affinity monoclonal antibody targeting interleukin-17A, is approved for moderate to severe plaque psoriasis and active psoriatic arthritis.

Objective: The objective of the study was to evaluate long-term efficacy and safety through five years of treatment with IXE.

Methods: We report the results from the extension period of UNCOVER-1 (NCT01474512) through five years for patients who continuously received the labeled dose of IXE through Week 60 (160mg starting dose, 80mg IXE every 2 weeks [Q2W] through Week 12, and every 4 weeks [Q4W] thereafter). Patients who were static Physician’s Global Assessment (sPGA) 0/1 responders at Week 12 and who completed 60 weeks of treatment could enter the extension period (n=110). Efficacy outcomes included the proportion of patients achieving sPGA 0/1 or at least 75 percent, 90 percent, or 100 percent improvement from baseline in the Psoriasis Area and Severity Index (PASI 75/90/100). During Weeks 60 to 264, patients and investigators could elect to escalate to IXE Q2W dosing through end of study to achieve or maintain efficacy. Efficacy is summarized by observed case. Safety is summarized by incidence rate (IR) per 100 patient-years.

Results: At the start of the extension period (Week 60), the PASI 75/90/100 response rates were 92.7 percent, 82.7 percent, and 56.4 percent, respectively. These response rates were maintained through Week 264, at which point PASI 75/90/100 response rates were 94.3 percent, 81.8 percent, and 46.6 percent, respectively. Overall, 23 (20.9%) patients escalated to IXE Q2W dosing; clinical response was consistent regardless of whether visits with escalated dosing were included in analyses. During Weeks 60 to 264, treatment-emergent adverse events occurred in 99 (IR=31.0) patients, serious adverse events occurred in 24 (IR=7.5) patients, and no deaths occurred (319.4 total patient-years).

Conclusion: Patients receiving IXE maintained high rates of improvement in plaque psoriasis with no unexpected safety outcomes for up to five years of treatment.

Funding: This study was sponsored by Eli Lilly and Company.

Disclosures: C Leonardi has been a consultant, and/or investigator, and/or has received honoraria/other financial benefit from: AbbVie, Amgen, Boehringer-Ingelheim, Celgene, Corrona, Dermira, Eli Lilly and Company, Galderma, Janssen, Leo Pharma, Merck, Novartis, Pfizer, Sandoz, Sienna Tribute, UCB, and Vitae. P Foley has been a investigator, and/or speaker, and/or advisor, and/or received travel/grant/research support from: 3M/iNova/Valeant, Abbott/AbbVie, Actilion, Amgen, Anacor, Ascent, Aspen, Australian Ultraviolet Services, Biogen Idec, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Celtaxsys, Clinuvel, CSL, Cutanea, Dermira, Eli Lilly and Company, Galderma, GSK/Stiefel, Janssen-Cilag, Leo Pharma/Peplin, Mayne Pharma, MedyTox, Merck Serono, Novartis, Regeneron, Roche, Sanofi, Schering-Plough/MSD, Sun Pharma, UCB, and Wyeth/Pfizer. H Torii has been a consultant, and/or received research and/or educational support from: AbbVie, Eli Lilly and Company, Celgene, Janssen, Novartis, Kyowa Hakko Kirin, and Mitsubishi Tanabe Pharma. S. Gerdes has been a consultant, and/or speaker, and/or received grant/research support from: Abbott/AbbVie, Almirall-Hermal, Amgen, Biogen Idec, Celgene, Dermira, Eli Lilly and Company, Forward Pharma, Galderma, Janssen-Cilag, Leo Pharma, Medac, Merck Serono, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Sandoz Biopharmaceuticals, Schering-Plough, Takeda, Teva, UCB, VBL therapeutics, and Wyeth Pharma. H Elmaraghy, G Gallo, and D.Shrom are employees and shareholders of Eli Lilly and Company. A Leung is an employee of Syneos Health. KA Papp has been a consultant, and/or scientific adviser, and/or investigator, and/or scientific officer, and/or speaker for: Amgen, Anacor, AbbVie, Akros Pharma, Allergan, Astellas, AstraZeneca, Baxalta, Baxter, BMS, Boehringer Ingelheim, Can-Fite, Celgene, Coherus, Dermira, Dow Pharma, Eli Lilly and Company, Forward Pharma, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa Hakko Kirin, Leo Pharma, MedImmune, Meiji Seika Pharma, Merck Sharp & Dohme, Merck-Serono, Mitsubishi Tanabe Pharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Roche, Sanofi/Genzyme, Takeda, UCB, and Valeant.

An oral, selective tyrosine kinase 2 inhibitor, BMS-986165, improves health-related quality of life in psoriasis: results from a Phase II trial

Presenters: Thaçi D,¹Papp K,² Gordon KB,³ Morita A,⁴ Gooderham M,⁵ Foley P,⁶ Alemao E,⁷ Kisa R,⁷ Elbez Y,⁸ Ren H,⁷Banerjee S⁷

Affiliations: ¹University of Lübeck, Lübeck, Germany; ²K Papp Clinical Research and Probity Medical Research, Waterloo, ON, Canada; ³Medical College of Wisconsin, Milwaukee, WI; ⁴Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan; ⁵Skin Centre for Dermatology, Queen’s University and Probity Medical Research, Peterborough, ON, Canada; ⁶The University of Melbourne, St Vincent’s Hospital Melbourne & Probity Medical Research, Skin & Cancer Foundation Inc, Melbourne, Victoria, Australia; ⁷Bristol-Myers Squibb, Princeton, NJ;⁸Excelya, Boulogne-Billancourt, France

Background: Health-related quality of life (HRQoL), as measured by the Dermatology Life Quality Index (DLQI), is an important patient-reported outcome in psoriasis trials. BMS-986165 is an oral, selective tyrosine kinase 2 inhibitor that blocks Type I interferon and IL-23 signaling pathways central in psoriasis pathophysiology.

Objective: In a 12-week Phase II trial (NCT02931838), BMS-986165 demonstrated dose-dependent efficacy with acceptable safety in patients with psoriasis. Here, we report DLQI responses over time.

Methods: Patients were randomly assigned to receive placebo or BMS-986165 orally at 3mg every other day, 3mg once daily (QD), 3mg twice daily (BID), 6mg BID, or 12mg QD (n=44–45/group). The primary efficacy end point was a 75-percent or greater reduction from baseline in the psoriasis area and severity index (PASI 75) at Week 12. DLQI overall scores of 0/1 (no impact on patient’s HRQoL)³ were assessed at prespecified time points. Scores of zero (suggestive of no psoriasis skin symptoms) on DLQI Question 1 (Q1), reflecting the effect on HRQoL of the most relevant symptoms of psoriasis (itching, soreness, skin pain, stinging), were assessed.

Results: Baseline DLQI scores were similar across groups. A dose-dependent improvement was observed in the proportion of patients attaining scores of 0/1 on the DLQI overall and a score of 0 on DLQI Q1. Patients receiving BMS-986165 at doses 3mg or greater BID attained DLQI 0/1 as early as Week 4 (earliest time point evaluated). At Week 12, the proportion of patients with a score of 0/1 on the DLQI overall and 0 on Q1 was 64 and 59 percent, respectively, in the BMS-986165 groups versus four and nine percent with placebo. Improvements in scores of 0/1 on the DLQI overall or 0 on DLQI Q1 occurred concordantly with PASI 75 improvements with each dose over time.

Conclusion: BMS-986165 improved HRQoL, as measured by the proportions of patients for whom psoriasis had no impact on HRQoL and those without bothersome subjective psoriasis symptoms. Improvements were seen as early as Week 4 and were concordant with PASI 75 responses. Phase III trials in psoriasis (NCT03624127, NCT03611751, NCT04167462, NCT03924427) are ongoing to assess BMS-986165 in larger patient groups.

Disclosures: D Thaçi: Research Support/P.I. (clinical trials): AbbVie, Almiral, Amgen, Biogen-Idec, Bioskin, Boehringer-Ingelheim, BMS, Celgene, Chugai, Dermira, Dignity, Elli-Lilly, Forward-Pharma, Glaxo-Smith-Kline, Leo Pharma, Janssen-Cilag, Maruho, MSD, Mitsubishi Pharma, Novartis, Pfizer, Regeneron, Roche, Sanofi, Sandoz-Hexal, UCB; consultant: AbbVie, Almiral, Biogen-Idec, Bioskin, BMS, Celgene, Dignity, Galapagos, Leo-Pharma, Maruho, Mitsubishi, Novartis, Pfizer, Xenoport; lectures: AbbVie, Almiral, Amgen, Biogen-Idec, Bioskin, Celgene, Dignity, Janssen, Leo-Pharma, Pfizer, Roche-Possay, Novartis, Mundipharma, MSD, USB, Sanofi, Sandoz-Hexal; Scientific Advisory Board: AbbVie, Amgen, Biogen-Idec, Bioskin, BMS, Celgene, Dignity, Eli-Lilly, GSK, Galapagos, Leo-Pharma, Janssen-Cilag, Morphosis, Novartis, Pfizer, Mundipharma, MSD, Sandoz, Sanofi, UCB. KA Papp: speakers bureau: AbbVie, Amgen, Astellas, Celgene, Eli Lilly, Galderma, Janssen, Kyowa Hakko Kirin, LEO Pharma, Merck (Merck Sharp & Dohme), Novartis, Pfizer, Valeant; grant/research support: AbbVie, Akros, Allergan, Amgen, Anacor, Arcutis, AstraZeneca, Baxalta, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Coherus, Dermira, Dow Pharma, Eli Lilly, Galderma, Genentech, GlaxoSmithKline, Janssen, Kyowa Hakko Kirin, LEO Pharma, MedImmune, Meiji Seika Pharma, Merck Serono, Novartis, Pfizer, Regeneron, Roche, Sanofi-Aventis/Genzyme, Takeda, UCB, Valeant; consultant: AbbVie, Akros, Amgen, Arcutis, Astellas, AstraZeneca, Baxalta, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, CanFite, Celgene, Coherus, Dermira, Dow Pharma, Eli Lilly, Forward Pharma, Galderma, Genentech, Janssen, Kyowa Hakko Kirin, LEO Pharma, Meiji Seika Pharma, Merck (Merck Sharp & Dohme), Merck Serono, Mitsubishi Pharma, Novartis, Pfizer, Regeneron, Roche, Sanofi-Aventis/Genzyme, Takeda, UCB, Valeant; honoraria: AbbVie, Akros, Amgen, Baxter, Boehringer Ingelheim, Celgene, Coherus, Eli Lilly, Forward Pharma, Galderma, GlaxoSmithKline, Janssen, Kyowa Hakko Kirin, Merck (Merck Sharp & Dohme), Merck Serono, Novartis, Pfizer, Takeda, UCB, Valeant; Scientific Officer/Steering Committee/Advisory board: AbbVie, Akros, Amgen, Anacor, Astellas, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dow Pharma, Eli Lilly, Galderma, Janssen, Kyowa Hakko Kirin, Merck (Merck Sharp & Dohme), Merck Serono, Novartis, Pfizer, Regeneron, Sanofi-Aventis/Genzyme, Valeant. K Gordon: grant/research support, consultant: AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermira, Eli Lilly, Janssen, Novartis, Pfizer, Sun, UCB. A Morita: grant/research support, consultant, speakers bureau: AbbVie, Eli Lilly, Janssen, Kyowa Hakko Kirin, LEO Pharma, Maruho, Mitsubishi-Tanabe, Novartis. M Gooderham: speakers bureau, consultant, investigator/advisor: AbbVie, Akros, Amgen, Arcutis, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermira, Eli Lilly, Galderma, GlaxoSmithKline, Incyte, Janssen, Kyowa Hakko Kirin, LEO Pharma, Merck, MedImmune, Novartis, Pfizer, Regeneron, Roche, Sanofi Genzyme, Takeda, UCB, Valeant. P Foley: speakers bureau, consultant, investigator, advisor, travel grants: 3M/iNova/Valeant, Abbott/AbbVie, Amgen, Biogen Idec, Boehringer Ingelheim, Botanix, Bristol-Myers Squibb, Celgene, Celtaxsys, CSL, Cutanea, Dermira, Eli Lilly, Galderma, GlaxoSmithKline/Stiefel, Janssen, LEO Pharma/Peplin, Novartis, Regeneron, Sanofi Genzyme, Schering-Plough/Merck Sharp & Dohme, Sun Pharma, UCB, Wyeth/Pfizer. E Alemao, R Kisa, H Ren, and S Banerjee: Employees of Bristol-Myers Squibb and might own stock options. Y Elbez: consultant: Bristol-Myers Squibb.

Long-term efficacy of certolizumab pegol dosed at 400mg every two weeks in patients with plaque psoriasis: pooled 128-week data from two Phase III trials (CIMPASI-1 and CIMPASI-2)

Presenters: Gordon KB,¹ Warren RB,² Gottlieb AB,³ Blauvelt A,⁴Thaçi D,⁵ Leonardi C,⁶ Poulin Y,⁷ Boehnlein M,⁸ Kavanagh S,⁹ Arendt C,¹⁰ Reich K¹¹

Affiliations: ¹Medical College of Wisconsin, Milwaukee, WI, USA;²Dermatology Centre, Salford Royal NHS Foundation Trust, Manchester NIHR Biomedical Research Centre, The University of Manchester, UK;³Icahn School of Medicine at Mount Sinai, New York, NY, USA; ⁴Oregon Medical Research Center, Portland, OR, USA; ⁵Institute and Comprehensive Center for Inflammation Medicine, University Hospital of Lübeck, Lübeck, Germany; ⁶Central Dermatology and Saint Louis University School of Medicine, St Louis, MO, USA; ⁷Centre de Recherche Dermatologique du Québec Métropolitain, Québec, Canada; ⁸UCB Pharma, Monheim, Germany; ⁹UCB Pharma, Raleigh, NC, USA; ¹⁰UCB Pharma, Brussels, Belgium; ¹¹Translational Research in Inflammatory Skin Diseases, Institute for Health Services Research in Dermatology and Nursing, University Medical Center Hamburg-Eppendorf, Germany and Skinflammation® Center, Hamburg, Germany

Objective: Certolizumab pegol (CZP), an Fc-free, PEGylated anti-tumor necrosis factor (TNF), has FDA and European Medicines Agency (EMA) approval for the treatment of moderate to severe plaque psoriasis (PSO).^1,2We present long-term clinical responses for patients with PSO who received CZP dosed at 400mg every two weeks (Q2W) for up to 128 weeks.

Methods: Data were pooled from the CIMPASI-1 (NCT02326298) and CIMPASI-2 (NCT02326272) Phase III trials. Included patients were adults with PSO for six or more months (Psoriasis Area and Severity Index [PASI] 12 or greater, 10 percent or greater body surface area affected, Physician’s Global Assessment [PGA] 3 or higher on a 5-point scale), and were randomized 2:2:1 to CZP 400mg Q2W: CZP 200mg Q2W (400mg loading dose at Weeks 0, 2 and 4): placebo (PBO). We report patients initially randomized to PBO at Week 0 who did not achieve PASI 50 (50% or greater improvement from baseline in PASI) at Week 16, and subsequently entered the open-label escape arm and received CZP 400mg Q2W for up to 128 weeks. Patients who completed Week 48 in the escape arm continued receiving CZP 400mg Q2W, although Week 48 PASI 75 responders could dose de-escalate to 200mg Q2W at the investigator’s discretion. Subsequent dose adjustment was permitted based on PASI response or at the investigator’s discretion. We report PASI 75, PASI 90, Dermatology Life Quality Index (DLQI) 0/1, and PGA 0/1 over 128 weeks CZP 400mg Q2W treatment in the open-label escape arm. Responder rates reflect the simple, average response across multiply imputed data sets, with missing data imputed using Markov Chain Monte Carlo (MCMC) methodology.

Results: After 16 weeks of treatment with PBO, 72 patients entered the CZP 400mg Q2W open-label escape arm. Following 16 weeks’ CZP 400mg Q2W treatment, 77.2 percent of patients achieved PASI 75 and 50.2 percent achieved PASI 90. Responder rates were maintained or improved to Week 128 (75.5% achieved PASI 75 and 57.8% achieved PASI 90). Similar trends were reported for DLQI 0/1 and PGA 0/1. Of the patients who achieved PASI 75 after 16 weeks of CZP treatment, 83.9 percent still reported PASI 75 after 128 weeks.

Conclusion: These data demonstrate durable, long-term efficacy of CZP 400mg Q2W in moderate to severe PSO. Patients who achieved PASI 75 after 16 weeks of CZP treatment showed durability of response to Week 128.

Funding: This study was funded by UCB Pharma

Disclosures: Information not provided.

Randomized, double-blind, placebo-controlled, multiple-dose, Phase IIb study to demonstrate the safety and efficacy of tildrakizumab, a high-affinity anti-IL-23p19 monoclonal antibody, in patients with active psoriatic arthritis

Presenters: Mease PJ,¹ Chohan S,² García Fructuoso FJ,³ Gottlieb AB,⁴ Chou RC,⁵ Mendelsohn AM,⁶ Ballerini R,⁶ Luggen ME^7,8

Affiliations: ¹Swedish Medical Center/Providence St. Joseph Health and University of Washington, Seattle, WA; ²Arizona Arthritis and Rheumatology Research, PLLC, Phoenix, AZ; ³Hospital CIMA Sanitas, Barcelona, Spain; ⁴Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY; ⁵Division of Allergy, Immunology and Rheumatology, University at Buffalo School of Medicine and Biomedical Sciences, Buffalo, NY; ⁶Sun Pharmaceutical Industries, Inc., Princeton, NJ; ⁷Cincinnati Rheumatic Disease Study Group, Inc., Cincinnati, OH; ⁸University of Cincinnati College of Medicine, Cincinnati, OH

Objective: This randomized, double-blind, placebo-controlled, multiple-dose, Phase IIb study (NCT02980692) evaluated the efficacy and safety of tildrakizumab (TIL)—a high-affinity anti–IL-23p19 monoclonal antibody—in patients with active psoriatic arthritis (PsA) to Week 24 (W24).

Methods: Patients with active PsA were randomized 1:1:1:1:1 to receive TIL (200mg every four weeks [Q4W], 200mg every 12 weeks [Q12W], 100mg Q12W, 20mg Q12W) or placebo Q4W. Assessments included: proportion of patients who achieved a 20/50/70-percent reduction from baseline by American College of Rheumatology response criteria (ACR20/50/70) and proportion of patients with baseline body surface area of three percent or more who achieved Psoriasis Area and Severity Index (PASI) 75/90/100, Leeds Enthesitis Index (LEI), 66 swollen and 68 tender joint counts (SJC, TJC), patient pain (0–100mm visual analogue scale), and treatment-emergent adverse event (TEAE) monitoring.

Results: Overall, 391 out of 500 patients met inclusion criteria. At Week 24, 79.5 percent/52.6 percent/28.2 percent, 77.2 percent/50.6 percent/29.1 percent, 71.4 percent/45.5 percent/22.1 percent, 73.1 percent/39.7 percent/16.7 percent, and 50.6 percent/24.1 percent/10.1 percent patients receiving TIL 200 Q4W, TIL 200 Q12W, TIL 100 Q12W, TIL 20 Q12W, and placebo, respectively, achieved ACR20/50/70 (p<0.01/0.05/0.05 versus placebo [except TIL 20 Q12W ACR70]); and 64.2 percent/47.2 percent/30.2 percent, 79.6 percent/50.0 percent/25.0 percent, 55.6 percent/38.9 percent/25.9 percent, and 46.3 percent/36.6 percent/22.0 percent versus 16.7 percent/7.1 percent/4.8 percent achieved PASI 75/90/100, respectively (p<0.01/0.01/0.05 vs. placebo). At Week 24, the least squares (LS) mean (standard error [SE]) reduction from baseline in SJC was 8.3 (0.5), 7.7 (0.5), 8.2 (0.5), and 7.6 (0.5) in TIL arms vs. 6.5 (0.5) in the placebo arm, and was statistically significant in TIL 100mg Q12W and 200mg Q4W vs. placebo (p=0.0189 and 0.0111, respectively). LS mean (SE) reduction in TJC was 11.9 (1.0), 12.6 (1.0), 13.0 (1.0), and 12.0 (1.0) in TIL arms versus 9.4 (1.0) in the placebo arm and was statistically significant for TIL 100 and 200mg Q12W versus placebo (p=0.0140 and 0.0234). TIL 200 Q4W significantly improved LEI by 71.2 percent (p<0.05). All TIL arms improved patient pain from baseline (LS mean reduction 28.9–35.2, p<0.05 vs. placebo except TIL 20 Q12W). The most frequent TEAEs for TIL versus placebo included nasopharyngitis (5.4% vs. 6.3%) and diarrhea (1.3% vs. 0). No candidiasis, inflammatory bowel disease, major adverse cardiac events, or malignancies were reported.

Conclusion: By Week 24, TIL was significantly more efficacious than placebo in treating joint and skin manifestations of PsA, with a low rate of TEAEs.

Funding: The studies were funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ. Analyses were funded by Sun Pharmaceutical Industries, Inc., Princeton, NJ.

Disclosures: Information not provided.

Safety and efficacy of a fixed combination halobetasol propionate 0.01%/tazarotene 0.045% (HP/TAZ) lotion in the treatment of female participants with moderate to severe plaque psoriasis

Presenters: Gold LS,¹ Elewski B,² Draelos ZD,³ Lin T,⁴

Affiliations: ¹Henry Ford Hospital, Detroit, MI; ²University of Alabama at Birmingham School of Medicine, Birmingham, AL; ³Dermatology Consulting Services, PLLC, High Point, NC; ⁴Ortho Dermatologics*, Bridgewater, NJ

*Ortho Dermatologics is a division of Bausch Health US, LLC.

Background: Topical therapy is an integral part of the management of psoriasis. Studies suggest that disease characteristics and optimal treatment strategies might differ between male and female patients with psoriasis. Further, female patients might have an increased burden of disease compared to male patients, as they have been shown to have higher levels of stress, stigmatization, and loneliness due to psoriasis. Previously published results from two Phase III studies have demonstrated the efficacy and safety of a fixed combination halobetasol propionate 0.01%/tazarotene 0.045% (HP/TAZ) lotion in the treatment of moderate to severe plaque psoriasis.

Objective: The objective of this post-hoc analysis was to evaluate efficacy and safety of HP/TAZ lotion in female patients with psoriasis.

Methods: In two Phase III, multicenter, double-blind studies (NCT02462070 and NCT02462122), participants were randomized (2:1) to receive HP/TAZ or vehicle lotion once-daily for eight weeks, with a four-week posttreatment follow-up. Data from these two studies were pooled and analyzed post hoc in a subset of female participants. Efficacy assessments included treatment success (2-grade improvement or greater from baseline in the Investigator Global Assessment [IGA] score and score of “clear” or “almost clear” [primary end point]), impact on individual signs of psoriasis at the target lesion and change in affected Body Surface Area (BSA). TEAEs were evaluated.

Results: The analysis population included 146 female participants (HP/TAZ, n=101; vehicle, n=45). At Week 8, the percentage of participants with treatment success was significantly greater in the HP/TAZ group (44.5%) than the vehicle group (9.9%; p<0.001); significant differences were observed by Week 2 and maintained posttreatment. Significantly more HP/TAZ-treated participants achieved at least a two-grade improvement in erythema (52.9%), plaque elevation (63.8%), and scaling (65.5%) at Week 8 compared to vehicle (17.0%, 18.9%, and 24.7%, respectively; p<0.001 all). The mean reduction from baseline to Week 8 in BSA was 34.2 percent for HP/TAZ versus 8.7 percent with vehicle (p=0.001). The most frequently reported treatment-related TEAEs in the HP/TAZ group were contact dermatitis, pruritis, and application site pain (all 4.0%); pruritis was more common with vehicle (7.0%).

Conclusion: HP/TAZ lotion was associated with significant reductions in disease severity in female patients with moderate to severe psoriasis, with good tolerability and safety over eight weeks of once-daily use.

Funding: This study was supported by Ortho Dermatologics, Inc., Bridgewater, NJ. Ortho Dermatologics is a division of Bausch Health US, LLC.

Disclosures: LSG has served as investigator/consultant or speaker for Ortho Dermatologics, LEO, Dermavant, Incyte, Novartis, AbbVie, and Lilly. BE has provided clinical research support (research funding to University) for Abbvie, Anaptys- Bio, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Incyte, Leo, Lilly, Merck, Menlo, Novartis, Pfizer, Regeneron, Sun, Ortho Dermatologics, Vanda and as a consultant (received honorarium) from Boehringer Ingelheim, Celgene, Leo, Lilly, Menlo, Novartis, Pfizer, Sun, Ortho Dermatologics, Verrica. ZD received funding from Ortho Dermatologics to conduct the research presented in this poster. TL is an employee of Ortho Dermatologics and might hold stock and/or stock options in its parent company.

Safety of risankizumab in patients with moderate to severe psoriasis: analysis of pooled clinical trial data

Presenters: Bachelez H,¹ Gordon KB, ² Blauvelt A,³ Strober B,⁴ Harbers S,⁵ Valdes J,⁶ Waterhouse B,⁶ Sinvhal R,⁶Lebwohl M,⁷ Reich K⁸

Affiliations:¹Saint-Louis Hospital, Sorbonne Paris Cité University Paris Diderot, Paris, France; ²Medical College of Wisconsin, Milwaukee, WI; ³Oregon Medical Research Center, Portland, OR; ⁴Yale University, New Haven, and Central Connecticut Dermatology, Cromwell, CT; ⁵AbbVie Inc., Rungis, France; ⁶AbbVie Inc., North Chicago, IL; ⁷Icahn School of Medicine at Mount Sinai, New York, NY; ⁸University Medical Center Hamburg-Eppendorf and Skinflammation® Center, Hamburg, Germany

Objective: Here, we report short- and long-term safety in patients with moderate to severe psoriasis treated with risankizumab (RZB).

Methods: Safety was evaluated (vs. adalimumab [ADA], ustekinumab [UST], and placebo [PBO]) through Week 16 of RZB treatment from five Phase II to III trials and in larger all-RZB data set from 11 Phase I to III completed and ongoing trials as of September 26, 2018.

Results: Week 16 data included patients receiving RZB 150mg (n=1306), ADA (n=304), UST (n=239), and PBO (n=300), representing 402.2, 95.0, 75.9, and 92.0 patient-years [PY]). All-RZB data set (treatment duration up to 52.5 months) included 2502 patients receiving one dose or greater of RZB, representing 4401.8 PY. Through Week 16, adverse events (AEs) occurred in 48.9 percent, 56.9 percent, 52.3 percent, and 48.3 percent of patients receiving RZB 150mg, ADA, UST, and PBO; serious AE (SAE) rates were 2.4 percent, 3.0 percent, 5.0 percent, and 4.0 percent, respectively. In general, AEs through Week 16 were comparable across treatment groups, and most were mild to moderate in severity. Most frequent SAEs reported with RZB 150mg through Week 16 were cellulitis (n=2; 0.2%) and squamous cell carcinoma (n=2; 0.2%). Overall infection rates through Week 16 were similar for RZB, UST, and ADA. Upper respiratory infections were the most common infections among RZB-treated patients. Through Week 16, malignant tumors occurred in six (0.5%) RZB patients, one (0.3%) ADA patient, no UST patients, and one (0.3%) PBO patient. In general, exposure-adjusted rates of treatment-emergent AEs (TEAE) and TEAEs of safety interest did not increase over time. With long-term exposure of RZB, the SAE rate remained consistent (9.9 and 8.9 events (E)/100PY through Week 16 and long-term, respectively), and rates of infection did not increase (90.8 and 63.6 E/100PY through Week 16 and long-term, respectively). Rates of serious infections remained consistent over time (1.7 and 1.4 E/100PY), with most commonly reported serious infections being sepsis, cellulitis, and pneumonia. The Week 16 and long-term rates of nonmelanoma skin cancer (NMSC, 0.7 and 0.7 E/100PY) and malignant tumors excluding NMSC (0.7 and 0.6 E/100PY) in RZB-treated patients were consistent. There were no cases of active tuberculosis in the short- or long-term analysis.

Conclusion: Week 16 AE rates with RZB were low and similar to comparator groups and to AE rates with long-term RZB treatment up to 52.5 months. Pooled safety data encompassing 4401.8 PY of exposure from the clinical trial program support that RZB treatment is safe and well tolerated in patients with moderate to severe psoriasis.

Acknowledgments/Funding: AbbVie funded this research, participated in data collection, analysis and interpretation of the data, and in writing, review, and approval of the publication. Medical writing support was provided by Madhura Mehta, PhD, Mayur Kapadia, MD, and Janet Matsuura, PhD, of Complete Publication Solutions, LLC (North Wales, PA) and was funded by AbbVie Inc.

Disclosures: H Bachelez has received honoraria or fees for serving on advisory boards, as a speaker, and as a consultant, and grants as an investigator from AbbVie, Almirall, Amgen, Bayer, Baxalta, Biocad, Boehringer Ingelheim, Celgene, Dermavant, Eli Lilly, Janssen, Leo Pharma, Menarini, MSD, Novartis, Pfizer, Pierre Fabre, Sandoz, Sun Pharmaceuticals, and UCB. KB Gordon has received honoraria for serving as a consultant and/or grants as an investigator from AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Dermira, Eli Lilly, GlaxoSmithKline, Janssen, Leo Pharma, Novartis, Pfizer, Regeneron, Sanofi-Aventis, Sun, and UCB. A Blauvelt has served as a scientific advisor and/or clinical study investigator for AbbVie, Aclaris, Almirall, Arena, Athenex, Boehringer Ingelheim, Bristol-Myers Squibb, Dermavant, Dermira, Eli Lilly and Company, FLX Bio, Forte, Galderma, Janssen, Leo, Novartis, Ortho, Pfizer, Regeneron, Sandoz, Sanofi Genzyme, Sun Pharma, and UCB Pharma, and as a paid speaker for AbbVie. B Strober has received honoraria for serving as a consultant and on advisory boards of AbbVie, Almirall, Amgen, Boehringer Ingelheim, Bristol-Myers-Squibb, Celgene, Dermavant, Dermira, Eli Lilly, GlaxoSmithKline, Janssen, Leo, Medac, Meiji Seika Pharma, Menlo Therapeutics, Novartis, Ortho Dermatologics/Valeant, Pfizer, Regeneron, Sanofi-Genzyme, Sebela Pharmaceuticals, Sirtris, Sun Pharma, and UCB Pharma; served as an investigator and received funding to the University of Connecticut from AbbVie, Boehringer Ingelheim, Galderma, GlaxoSmithKline, Novartis, Eli Lilly, Janssen, Merck, Pfizer, Sienna, and Celgene; received consulting fees for serving as a scientific director of the CORRONA Psoriasis Registry; and received grant support to the University of Connecticut for Fellowship Program from AbbVie and Janssen. S Harbers, J Valdes, B Waterhouse, and R Sinvhal are full-time salaried employees of AbbVie and might own stock/options. M Lebwohl has received grants as an investigator from Abbvie, Amgen, AstraZeneca, Boehringer Ingelheim, Celgene, Eli Lilly, Incyte, Janssen/Johnson & Johnson, Kadmon, LEO Pharma, MedImmune, Novartis, Pfizer, Sciderm, UCB, Ortho-dermatologics, and ViDac and has received honoraria for serving as a consultant for Allergan, Almirall, Arcutis, Boehringer Ingelheim, Bristol-Myers Squibb, Castle Biosciences, LEO Pharma, Menlo, Mitsubishi Pharma, Neuroderm LTD, Pfizer, Promius/Dr. Reddy, Theravance Biopharma, and Verrica. K Reich has served as advisor and/or paid speaker for and/or participated in clinical trials sponsored by AbbVie, Affibody, Almirall, Amgen, Biogen, Boehringer Ingelheim, Celgene, Centocor, Covagen, Forward Pharma, Fresenius Medical Care, GlaxoSmithKline, Janssen-Cilag, Kyowa Kirin, LEO Pharma, Lilly, Medac, Merck Sharp & Dohme, Miltenyi Biotec, Novartis, Ocean Pharma, Pfizer, Regeneron, Samsung Biopepis, Sanofi, Takeda, UCB, Valeant, and Xenoport.

**Safety of tildrakizumab in patients with preexisting metabolic syndrome: long-term data from the post-hoc analysis of two Phase III clinical studies (reSURFACE 1 and reSURFACE 2)**

Presenters: Lebwohl MG,¹ Mehta NN,² Gottlieb AB,³ Mendelsohn AM,⁴ Parno J,⁴ Rozzo SJ,⁴ Menter AM⁵

Affiliations: ¹Department of Dermatology, Mount Sinai Hospital, New York, NY; ²National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD; ³Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY; ⁴Sun Pharmaceutical Industries, Inc., Princeton, NJ; ⁵Division of Dermatology, Baylor Scott & White, and Texas A&M College of Medicine, Dallas, TX

Objective: We present long-term safety data for tildrakizumab (TIL)—a high-affinity, humanized, immunoglobulin G1kappa, anti–interleukin-23p19 monoclonal antibody approved for treatment of moderate to severe plaque psoriasis—in patients with versus without metabolic syndrome (MetS).

Methods: In the Phase III, double-blind, randomized, controlled, 64/52 week reSURFACE 1/2 base studies (NCT01722331/NCT01729754) and their long-term extensions, adults with moderate to severe chronic plaque psoriasis received TIL 100 or 200mg. This post-hoc analysis of pooled safety data evaluated treatment-emergent adverse events (TEAEs), stratified by MetS status, through up to five years of exposure.

Results: Of patients who continuously received TIL 100/200mg (n=369/330) in the base studies, 79/67 (21.4%/20.3%), respectively, met MetS criteria at baseline. Base period TEAE incidence rates were generally comparable between patients with and without MetS; the most frequent TEAE was infections (TIL 100mg, 50.6% vs. 53.1%, n=40 vs. 154; TIL 200mg, 62.7% vs. 52.9%, n=42 vs. 139). Of 335/305 patients who continuously received tildrakizumab 100/200mg throughout base and extension periods (total 1401.5/1362.3 patient years [PY]), 70/64 (20.9%/21%), respectively, had MetS. Overall exposure-adjusted rates (number of patients with events/100 PY) of Tier 1 TEAEs were comparable between patients with versus without MetS (TIL 100 mg, 2.4 vs. 2.7 per 100 PY; 200mg, 1.5 vs. 2.6 per 100 PY). No reports of diabetes worsening by MetS status were noted, and only one myocardial infarction event was reported.

Conclusion: Tildrakizumab safety did not vary by MetS status over up to five years of treatment.

Funding: The studies were funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ. Analyses were funded by Sun Pharmaceutical Industries, Inc., Princeton, NJ.

Disclosures: Information not provided.

Secondary efficacy outcomes from a Phase IIb, randomized dose-finding study of tapinarof cream for the treatment of plaque psoriasis

Presenters: Gold LS,¹ Bhatia N,² Tallman AM,³ Rubenstein D⁴

Affiliations: ¹Henry Ford Health System, Detroit, MI; ²Therapeutics Clinical Research, San Diego, CA; ³Dermavant Sciences, Inc., New York, NY; ⁴Dermavant Sciences, Inc., Durham, NC

Background/Objective: Despite available options for treating psoriasis, there is a need for effective topical therapies that can be used without concerns about body surface area (BSA) restrictions or long treatment duration. Tapinarof is a therapeutic aryl hydrocarbon receptor modulating agent (TAMA) under investigation for the treatment of psoriasis and atopic dermatitis.

Method: This Phase IIb, double-blind, six-arm, vehicle-controlled randomized study (NCT02564042) assessed the efficacy and safety of tapinarof cream in subjects with plaque psoriasis. Subjects (aged 18–65 years) with 1 to 15 percent BSA involvement and Physician Global Assessment (PGA) score of at least 2 at baseline were randomized 1:1:1:1:1:1 to tapinarof cream 0.5% or 1% once (QD) or twice daily (BID) or vehicle QD or BID for 12 weeks with a four-week follow-up. The primary end point was the proportion of subjects achieving PGA score 0 or 1 and 2-grade or greater improvement in PGA score from baseline to Week 12, which has been reported elsewhere. Secondary efficacy outcomes reported here include a 50-percent or greater reduction in Psoriasis Area and Severity Index (PASI50), PASI90, mean change in PGA scores and total target lesion grading scores from baseline, and pruritus numeric rating scale (NRS) response.

Results: Of 227 randomized subjects, 174 completed the study. Most subjects (80%) had a baseline PGA score of 3 (moderate). Mean PASI was 8.8. Higher PASI50 (all p<0.001) and PASI90 (p<0.01 except for the tapinarof 0.5% QD group) response rates were observed in all tapinarof groups versus vehicle at Week 12 and were maintained for four weeks after the end of study treatment. Mean improvements in PGA scores (all p<0.001) and total target lesion grading scores (all p<0.001) from baseline to Week 12 were significantly greater in all tapinarof groups versus vehicle and were maintained for four weeks after the end of study treatment (all p<0.01). In subjects with a baseline pruritus NRS item score of 4 or greater, pruritus NRS response at Week 12 (4 improvement or greater in pruritus NRS score from baseline) was 55 to 73 percent (tapinarof 1% groups) and 56 to 57 percent (tapinarof 0.5% groups) versus 33 to 60 percent (vehicle groups). Most treatment-emergent adverse events were mild or moderate, and the most common (5% or greater) across all groups were folliculitis (9%) and contact dermatitis (5%). Most incidences of folliculitis and contact dermatitis were mild or moderate.

Conclusion: These results support the primary analysis showing that tapinarof cream was efficacious and well tolerated in adults with psoriasis.1 A Phase III study of tapinarof cream 1% QD in psoriasis is ongoing (NCT03956355).

Tapinarof cream for the treatment of plaque psoriasis: efficacy and safety by baseline disease characteristics and skin type in a Phase IIb randomized study

Presenters: Lebwohl M,¹ Del Rosso J,² Hong CH,³ Tallman AM,⁴ Kircik LH^1,5

Affiliations: ¹Icahn School of Medicine at Mount Sinai, New York, NY; ²JDR Dermatology Research/Thomas Dermatology, Las Vegas, NV; ³University of British Columbia and Probity Medical Research, Surrey, BC, Canada; ⁴Dermavant Sciences, Inc., New York, NY; ⁵Skin Sciences, PLLC, Louisville, KY

Background: Tapinarof is a therapeutic aryl hydrocarbon receptor-modulating agent (TAMA) in development for the treatment of psoriasis and atopic dermatitis. In a previously reported Phase IIb efficacy and safety study (NCT02564042), Physician Global Assessment (PGA) responses (0 or 1 and 2-grade or greater improvement from baseline) at Week 12 were significantly higher in all tapinarof cream groups versus vehicle. Tapinarof cream demonstrated durable PGA responses through four weeks after the end of study treatment.¹

Method: A post-hoc analysis of PGA response stratified by baseline percentage body surface area (BSA) affected, psoriasis duration, and Fitzpatrick Skin Type was conducted to evaluate the efficacy and safety of tapinarof cream versus vehicle across subgroups.

Results: Overall, mean baseline disease characteristics were comparable across groups. Most subjects (80%) had a baseline PGA score of 3 (moderate). Mean baseline Psoriasis Area and Severity Index score was 8.8. Stratified by baseline BSA, PGA response at Week 12 in subjects treated with tapinarof 1% twice daily (BID), 1% once daily (QD), 0.5% BID, and 0.5% QD vs. vehicle BID and vehicle QD was: 67 percent, 60 percent, 33 percent, and 35 percent versus 13 percent and 6 percent, respectively (1 to <10% BSA affected; n=102); and 64 percent, 40 percent, 75 percent, and 38 percent versus zero percent and 0 percent, respectively (10% or greater BSA affected; n=39). Stratified by psoriasis duration, PGA response at Week 12 in subjects treated with tapinarof 1% BID, 1% QD, 0.5% BID, and 0.5% QD versus vehicle BID and vehicle QD was: 50 percent, 80 percent, 50 percent, and 29 percent versus 0 percent and 0 percent, respectively (6 months to <5 years; n=27); 67 percent, 50 percent, 20 percent, and 50 percent versus 25 percent and 0 percent (5 years to <10 years; n=32); and 73 percent, 50 percent, 53 percent, and 33 percent versus eight percent and eight percent (10 years or greater; n=82). Stratified by Fitzpatrick Skin Type, PGA response at Week 12 in subjects treated with tapinarof 1% BID, 1% QD, 0.5% BID, and 0.5% QD versus vehicle BID and vehicle QD was: 60 percent, 67 percent, 50 percent, and 25 percent versus zero percent and 10 percent, respectively (Fitzpatrick Skin Type I/II; n=41); 54 percent, 47 percent, 60 percent, and 44 percent versus 18 percent and 0 percent (Fitzpatrick skin type III/IV; n=73); and 100 percent, 75 percent, 25 percent, and 25 percent versus 0 percent and 0 percent (Fitzpatrick Skin Type V/VI; n=27). Incidence and type of adverse events were generally comparable across groups and consistent with those observed in the overall population.

Conclusions: Tapinarof cream was efficacious and well tolerated across subgroups regardless of baseline percentage BSA affected, psoriasis duration, or Fitzpatrick Skin Type. A Phase III study of tapinarof cream 1% QD in psoriasis is ongoing (NCT03956355).

Total healthcare costs and long-term treatment patterns of biologics and apremilast among patients with moderate to severe plaque psoriasis by metabolic condition status

Presenters: Feldman SR,¹ Zhang J,² Martinez DJ,³ Lopez-Gonzalez L,³ Marchlewicz EH,³ Shrady G,³ Mendelsohn AM,² Zhao Y²

Affiliations: ¹Wake Forest School of Medicine, Winston-Salem, NC; ²Sun Pharmaceutical Industries, Princeton, NJ; ³IBM Watson Health, Washington, DC

Background: Patients with metabolic conditions incur significant economic burden. However, long-term healthcare costs and treatment patterns of psoriasis patients with metabolic conditions are not well characterized.

Objective: This study examined the healthcare costs and treatment patterns of patients with psoriasis who newly initiated a biologic or apremilast (APR) by metabolic condition status.

Methods: Adult patients with psoriasis were selected into five mutually exclusive cohorts based on their initial index medication (secukinumab [SEC], adalimumab [ADA], ustekinumab [UST], etanercept [ETA], or APR) filled between 01/01/2015 and 08/31/2018 using a large US claims database. Eligible patients had no index medication use in the 12-month pre-index period, and had continuous medical and pharmacy benefits in the 12-month pre-index and 24-month post-index periods. Subgroups were stratified by a metabolic condition (obesity, hypertension, hyperlipidemia, diabetes, or metabolic syndrome) diagnosis captured in the 12-month pre-index period. Total costs were compared between patients with and without metabolic conditions within each treatment cohorts. Adjusted costs were estimated via multivariate analyses controlling for patient demographics and comorbidities. Adherence (measured by proportion of days covered), discontinuation, and switching were also examined.

Results: Out of the 7,773 patients included, the proportions of patients with metabolic conditions were: SEC: 56.7 percent; ADA: 50.6 percent; UST: 47.5 percent; ETA: 52.5 percent; and APR: 55.2 percent. Over the 24-month follow-up period, patients with metabolic conditions incurred significantly higher adjusted total costs (SEC: $128,126 vs. $120,808; ADA: $113,788 vs. $96,375; UST: $130,190 vs. $109,958; ETA: $110,390 vs. $101,746; APR: $80,647 vs. $68,720; all p<0.05 except SEC). Adherence ranged 0.42 to 0.57 over the 24-month follow-up, and switching was 25.3 to 53.6 percent. Overall discontinuation was high (35.1%–53.9%), with patients with metabolic conditions having higher discontinuation except for APR.

Conclusion: Many moderate to severe psoriasis patients who initiated biologics or APR had metabolic conditions. Patients with metabolic conditions generally incur significantly higher healthcare costs and had higher discontinuation rates than those without metabolic conditions. Overall adherence was poor, and switching was high regardless of metabolic condition status. There is still a significant unmet need for long-term psoriasis management, especially in patients with comorbid metabolic conditions.

Funding: Sponsored by Sun Pharmaceutical Industries, Inc.

Disclosures: Information not provided.

ROSACEA

DFD-29, a low dose oral minocycline, shows early treatment success at Week 4 in papulopustular rosacea

Presenters: Gold LS¹Alikunju S,² Shenoy S,³ Singh P,³ Sidgiddi S³

Affiliations: ¹Henry Ford Medical Center, Detroit, MI; ²Dr Reddy’s Laboratories Ltd., Hyderabad, India; ³Dr Reddy’s Laboratories Inc., Princeton, NJ

Background: Rosacea is a chronic facial skin disease, primarily involving the central face. DFD-29, a low dose oral minocycline, is being evaluated as an anti-inflammatory treatment option for papulopustular rosacea.

Methods: This Phase II, randomized, double-blind trial enrolled adults with mild, moderate, or severe papulopustular rosacea. Subjects were randomized to receive DFD-29 (minocycline HCl) 40mg or 20mg extended release capsules, Oraycea® (doxycycline HCl) 40mg capsules, or placebo, one capsule a day for 16 weeks. A key end point in the study was to assess proportion of subjects with IGA (modified scale without erythema) treatment success, defined as an IGA grade of 0 or 1, with at least a two-grade reduction from baseline, at Weeks 4, 8, 12 and 16.

Results: The Full Analysis Set (FAS) included 200 subjects. Of these, 53 subjects were in the DFD-29 (40mg) group, 47 in DFD-29 (20mg), 48 in doxycycline (40mg), and 52 in the placebo group. At Week 4, treatment success was observed for six subjects (11.32%) following treatment with DFD-29 (40mg), for one subject (2.13%) following treatment with DFD-29 (20mg), for zero subjects following treatment with Oraycea® (40mg), and with placebo. Statistically significant difference was observed for DFD-29 (40mg) versus placebo (p=0.026) as well as compared to Oraycea® (40mg) (p=0.027). At Week 8, treatment success was observed for 21 subjects (39.62%) with DFD-29 (40mg), for 11 subjects (23.40%) following treatment with DFD-29 (20mg), for seven subjects (14.58%) with Oraycea® (40mg), and for three subjects (5.77%) with placebo. Highly statistically significant treatment difference (p<0.0001) was observed for DFD-29 (40mg) versus placebo. Furthermore, statistically significant treatment difference was observed for DFD-29 (40mg) compared to Oraycea® (40mg) (p=0.005). At Week 12, treatment success was observed for 31 subjects (58.49%) with DFD-29 (40mg), for 16 subjects (34.04%) with DFD-29 (20mg), for 11 subjects (22.92%) with Oraycea® (40mg), and for nine subjects (17.31%) with placebo. Highly statistically significant treatment difference (p<0.0001) was seen for DFD-29 (40mg) versus placebo. Furthermore, statistically significant treatment difference was observed for DFD-29 (40mg) compared to Oraycea® (40mg) (p=0.0003). At Week 16, treatment success was observed for 35 subjects (66.04%) with DFD-29 (40mg), for 15 subjects (31.91%) with DFD-29 (20mg), for 16 subjects (33.33%) with Oraycea® (40mg), and for six subjects (11.54%) with placebo. Highly statistically significant treatment difference (p<0.0001) seen for DFD-29 (40mg) versus placebo and statistically significant treatment difference was observed for DFD-29 (40mg) compared to Oraycea® (40mg) (p=0.001).

Conclusion: Treatment with DFD-29 shows statistically significant treatment success as early as Week 4 against both placebo and Oraycea, and the treatment success continues to improve gradually for 16 weeks. At all-time points, DFD-29 (40mg) was found to be statistically superior to Oraycea and placebo, while it was statistically highly significant (p<0.0001) to placebo from Week 8 onwards.
Funding: This study was funded and sponsored by the Dr Reddy’s Laboratories group of companies.

Disclosures: Information not provided.

VITILIGO

Efficacy and safety of a 52-week, randomized, double-blind trial of ruxolitinib cream for the treatment of vitiligo

Presenters: Harris JE,¹ Pandya AG,² Lebwohl M,³ Grimes P,⁴ Hamzavi I,⁵ Gottlieb AB,⁶ Butler K,⁷ Kuo F,⁷ Sun K, ⁷ Rosmarin D⁸

Affiliations: ¹University of Massachusetts Medical School, Worcester, MA; ²University of Texas Southwestern Medical Center, Dallas, TX; ³Mount Sinai Hospital, New York, NY; ⁴The Vitiligo & Pigmentation Institute of Southern California, Los Angeles, CA; ⁵Henry Ford Medical Center, Detroit, MI;⁶Icahn School of Medicine at Mount Sinai, New York, NY; ⁷Incyte Corporation, Wilmington, DE; ⁸Tufts Medical Center, Boston, MA

Background: Vitiligo is a chronic autoimmune disease resulting in patches of skin depigmentation and reduced quality of life. Disease pathogenesis is driven by Janus kinase (JAK) 1 and JAK2 signaling. This randomized controlled study investigated the therapeutic potential of a cream formulation of ruxolitinib, a JAK1/JAK2 inhibitor, in patients with vitiligo after 52 weeks of treatment.

Methods: This 52-week, double-blind component of a three-part, 156-week, Phase II study (NCT03099304) enrolled patients, aged 18 to 75 years, with vitiligo—with depigmentation of 0.5 percent or greater facial body surface area (BSA) and three percent or greater nonfacial BSA. Patients were equally randomized to receive ruxolitinib cream (1.5% twice daily [BID], or 1.5%, 0.5%, or 0.15% once daily [QD]) or vehicle BID for 24 weeks (Part 1) for treatment of lesions constituting 20 percent or less of BSA. In Part 2, patients maintained their original dose until Week 52 or were rerandomized (vehicle or 0.15% QD) to one of the three higher ruxolitinib cream doses if they did not achieve 25 percent or greater improvement from baseline in facial Vitiligo Area Scoring Index (F-VASI25) at Week 24.

Results: Patients (n=157) (mean [SD] age, 48.3 [12.9] years) were randomized (30–32 patients per group). Baseline mean (SD) facial and total BSA involvement were 1.48 percent (0.86%) and 22.1 percent (18.4%), respectively; disease duration was 17.4 (13.5) years. F-VASI50 at Week 24 (primary end point) was achieved by significantly more patients treated with ruxolitinib cream (1.5% BID, 45.5% [P<0.001]; 1.5% QD, 50.0% [p<0.001]; 0.5% QD, 25.8% [p<0.05]; 0.15% QD, 32.3% [p<0.01]) than vehicle (3.1%). F-VASI75 and F-VASI90 at Week 24 were achieved by 9.7 to 30.3 percent and 3.2 to 13.3 percent of patients across ruxolitinib cream doses (vehicle, 0%). At Week 52, patients treated with 1.5 percent BID attained the highest F VASI50 (57.6%), F VASI75 (51.5%), and F-VASI90 (33.3%) responses. Total VASI50 (T VASI50) at Week 52 (key secondary end point) was achieved by 25.8 to 36.4 percent of patients across the three higher ruxolitinib cream doses in a dose-dependent manner and by 45.0 percent of patients treated with 1.5 percent BID who had baseline total BSA 20 percent or less (n=20). No clinically significant application site reactions or serious treatment-related adverse events (AEs) were associated with ruxolitinib cream.

Conclusion: Ruxolitinib cream monotherapy produced substantial facial and total body repigmentation of vitiligo lesions after Week 24 with continued improvement through 52 weeks of treatment (highest responses with 1.5% BID). All doses of ruxolitinib cream were well tolerated, and no treatment-related serious AEs were reported.

Disclosures: JEH has served as a consultant for AbbVie, Aclaris Therapeutics, BiologicsMD, EMD Serono, Genzyme/Sanofi, Janssen, Pfizer, Rheos Medicines, Sun Pharmaceuticals, TeVido BioDevices, The Expert Institute, 3rd Rock Ventures, and Villaris Therapeutics; has served as an investigator for Aclaris Therapeutics, Celgene, Dermira, EMD Serono, Genzyme/Sanofi, Incyte Corporation, LEO Pharma, Pfizer, Rheos Medicines, Stiefel/GSK, Sun Pharmaceuticals, TeVido BioDevices, and Villaris Therapeutics; holds equity in Rheos Medicines, TeVido BioDevices, and Villaris Therapeutics; is a scientific founder of Villaris Therapeutics; and has patents pending for IL-15 blockade for treatment of vitiligo, JAK inhibition with light therapy for vitiligo, and CXCR3 antibody depletion for treatment of vitiligo. AGP has served as an investigator for Aclaris Therapeutics, Immune Tolerance Network, Incyte Corporation, and Pfizer; a consultant for Incyte Corporation and Pfizer; and a board member who also holds stock options for Clarify Medical. ML is an employee of Mount Sinai Hospital, which receives research funds from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Celgene, Eli Lilly and Company, Incyte Corporation, Janssen/Johnson & Johnson, Kadmon, LEO Pharma, MedImmune, Novartis, Ortho Dermatologics, Pfizer, Sciderm, UCB, and ViDac, and is a consultant for Allergan, Almirall, Arcutis, Avotres, BirchBioMed, Boehringer Ingelheim, Bristol-Myers Squibb, Cara Therapeutics, Castle Biosciences, Dermavant Sciences, Encore, Inozyme, LEO Pharma, Meiji, Menlo, Mitsubishi Pharma, Neuroderm Ltd, Pfizer, Promius Pharma/Dr. Reddy, Theravance Biopharma, and Verrica Pharmaceuticals. PG has served as a consultant for Aclaris Therapeutics, Clarify Medical, DermaForce, Incyte Corporation, Proctor & Gamble, and Versicolor Technologies and a principal investigator for Aclaris Therapeutics, Allergan/SkinMedica, Clinuvel Pharmaceuticals, Incyte Corporation, Johnson & Johnson, L’Oreal, Merz Pharma, Pfizer, Thync Global Inc., and VT Cosmetics. IH has served as an advisory board member for AbbVie; a consultant for Incyte Corporation, Pfizer, and UCB; a principal investigator for AbbVie, Allergan, Bayer, Clinuvel Pharmaceuticals, Estée Lauder, Ferndale Laboratories, Galderma Laboratories LP, GE Healthcare, Incyte Corporation, Janssen, Janssen Biotech, Johnson & Johnson, Lenicura, LEO Pharma, Pfizer, and Unigen; a subinvestigator for Amgen, Bristol-Myers Squibb, Foamix Pharmaceuticals, and Janssen; president of the HS Foundation; and co-chair of the Global Vitiligo Foundation. ABG has received research or educational grants from Boehringer Ingelheim, Incyte Corporation, Janssen, Novartis, UCB, and Xbiotech and has served as a consultant or advisory board member for AbbVie, Avotres Therapeutics, Beiersdorf, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Incyte Corporation, Janssen, LEO Pharma, Novartis, Sun Pharmaceutical Industries, UCB, Valeant, and Xbiotech. KB, FK, and KS are employees and shareholders of Incyte Corporation. DR has received honoraria as a consultant for AbbVie, Celgene, Dermavant Sciences, Dermira, Eli Lilly and Company, Janssen, Novartis, Pfizer, Regeneron Pharmaceuticals, Sanofi, and Sun Pharmaceuticals; received research support from AbbVie, Bristol-Myers Squibb, Celgene, Dermira, Eli Lilly and Company, Incyte Corporation, Janssen, Merck, Novartis, Pfizer, and Regeneron Pharmaceuticals; and served as a paid speaker for AbbVie, Celgene, Eli Lilly and Company, Janssen, Novartis, Pfizer, Regeneron Pharmaceuticals, and Sanofi.

Vitiligo prevalence and patient-perceived concern by vitiligo lesion location in a US population

Presenters: Harris JE,¹ Bibeau K,² Jones H,² Pandya AG³

Affiliations: ¹University of Massachusetts Medical School, Worcester, MA; ²Incyte Corporation, Wilmington, DE; ³University of Texas Southwestern Medical Center, Dallas, TX

Background: Vitiligo is a disease characterized by patches of skin depigmentation and is associated with significant quality-of-life impairments in routine activities and psychosocial well being. Global vitiligo prevalence is approximately 0.5 to 2 percent, with reported rates varying geographically.

Objective: The objectives of this study were to estimate the prevalence of self-reported vitiligo signs in the US population as well as to determine the distribution and extent of vitiligo lesions and associated patient-perceived concern.

Methods: An online global survey was fielded in Europe, Japan, and the United States to participants aged 18 years or older. Participants were asked to identify whether they had ever been formally diagnosed with vitiligo and, if not, whether they had signs consistent with vitiligo (i.e., loss of color or patches of pale or white skin). Vitiligo prevalence was calculated using the sum of participants who self-reported diagnosed vitiligo, undiagnosed vitiligo, and vitiligo signs. Participants with physician-diagnosed vitiligo were asked to report the location of current lesions and their corresponding level of concern with each lesion location. Level of concern was scored from 0 to 10 on an 11-point Likert scale, with scores of 8, 9 or 10 indicating very high concern.

Results: A total of 35,694 participants responded to the survey, including 8,517 from the United States. Among US respondents, reported vitiligo prevalence was 1.4 percent (diagnosed vitiligo, 0.6%; undiagnosed vitiligo, 0.4%; vitiligo signs, 0.4%). There were 48 American patients with formally diagnosed vitiligo. Of these, 29 were female, 18 were male, and one chose not to report sex. Most physician-diagnosed patients were younger than 45 years old (n=29, 60.4%) and White (n=37, 77.1%); the most frequently reported Fitzpatrick Skin Type was light brown skin (Skin Type 3; n=18, 37.5%). Among the reported sites of vitiligo lesions, the hands and/or wrists (39.6%), the back and front of legs (35.4% and 33.3%, respectively), head (29.2%), top of arm (29.2%), chest and/or abdomen/stomach (29.2%), and buttocks (29.2%) were most commonly affected. The highest levels of concern were seen with lesions on the armpits (72.7%), buttocks (71.4%), underside of arms (69.2%), back (66.7%), and head (64.3%). Although lesions on the hands and/or wrists were more prevalent than those on the head (39.6% vs. 29.2%), hand and/or wrist lesions were of less concern than lesions on the head (47.4% vs. 64.3%).

Conclusion: The highest levels of concern for vitiligo in visible areas were reported for lesions on the head. Aside from the head, areas of greatest concern for patients with vitiligo (i.e., armpits, arms, buttocks, and back) can largely be hidden by clothing. Further research is warranted to examine the relationship of quality of life with patient concern regarding the location of vitiligo lesions.

Acne, Actinic Keratoses, Atopic Dermatitis, cutaneous oncology, Psoriasis, Rosacea, vitiligo