ACKNOWLEDGEMENTS: Medical writing support was provided by Prescott Medical Communications Group (Chicago, IL) with financial support from Ortho Dermatologics; Ortho Dermatologics is a division of Bausch Health US, LLC | Presented at Winter Clinical Dermatology Conference 2020 • January 17-22, 2020 • Kohala Coast, HI SYNOPSIS ◾ Topical corticosteroids are the mainstay of psoriasis treatment, particularly for mild disease,1 though topical treatments as part of combination therapy for moderate-to-severe psoriasis is becoming increasingly common ◾ However, continuous use of topicals may be limited due to application-site adverse events (AEs)1 ◾ Recent phase 3 clinical data have demonstrated efficacy and tolerability of a fixed combination lotion containing halobetasol propionate 0.01% and tazarotene 0.045% (HP/TAZ; Duobrii® Ortho Dermatologics, Bridgewater, NJ) in patients with moderate-to-severe localized plaque psoriasis2,3 OBJECTIVE ◾ To investigate AEs and local skin reactions following long-term use of HP/TAZ lotion METHODS ◾ This was a 1-year multicenter, open-label study (NCT02462083) in patients with moderate-to-severe plaque psoriasis ◾ Participants were treated with HP/TAZ lotion once-daily for 8 weeks and intermittently as needed in 4-week intervals (Figure 1) • At week 8, treatment was stopped for participants that achieved treatment success; those who did not reach treatment success were treated for 4 additional weeks • All participants were re-evaluated at week 12; those demonstrating ≥1-grade improvement in baseline Investigator’s Global Assessment (IGA) continued the study and were subsequently managed in 4-week cycles, either treated with HP/TAZ lotion once-daily if they had not achieved treatment success or receiving no treatment until the next evaluation if they had achieved treatment success ◾ Maximum continuous exposure was 24 weeks FIGURE 1. Open-Label Study Design Once- daily HP/TAZ Successa Treatment stopped for 4 weeks Improvementb Continued study and managed in 4-week cycles for up to 1 year, with patients re-evaluated every 4 weeks for treatment successa No improvement Discontinued from study No success Continued once-daily HP/TAZ for 4 weeks Day 0 Week 8 Evaluated for treatment successa Week 12 Evaluated for ≥1-grade improvement from baseline IGA Week 24 If continuous treatment was received, IGA score of 0 or 1 needed to continue study 1 Year Maximum continuous exposure was 24 weeks. aTreatment success defined as score of 0 or 1 on IGA. bImprovement defined as ≥1-grade improvement from baseline IGA. HP/TAZ, halobetasol propionate 0.01%/tazarotene 0.045%; IGA, Investigator’s Global Assessment. Safety and Tolerability of Fixed Combination Halobetasol Propionate 0.01% and Tazarotene 0.045% (HP/TAZ) Lotion in Patients With Moderate-to-Severe Plaque Psoriasis: Results From a 1-Year, Open-Label Study FIGURE 2. Local Skin Reactions Over Time, By Severity (Safety Population) 100% 80% 60% 40% 20% 0% None Mild Moderate Severe P e rc e n ta g e o f P a rt ic ip a n ts Baseline Week 12 Week 24 Week 36 Week 52 Itching Baseline Week 12 Week 24 Week 36 Week 52 Dryness Baseline Week 12 Week 24 Week 36 Week 52 Burning/Stinging FIGURE 3. Incidence of Local Skin Reactions Over Time (Safety Population) 3% 2% 1% 0% P e rc e n ta g e o f P a rt ic ip a n ts 0.5% 1.7% 1.4% 0.9% 0% 1.1% 1.3% 0.8% 0.9% 0.7% 0.2% 0.8% 0.6% 0% 0% 0.4% 1.5% 1.1% 0.4% 0% Baseline Week 12 Week 24 Week 36 Week 52 Skin Atrophy Baseline Week 12 Week 24 Week 36 Week 52 Striae Baseline Week 12 Week 24 Week 36 Week 52 Telangiectasias Baseline Week 12 Week 24 Week 36 Week 52 Folliculitis Skin Reactions ◾ Select local signs/symptoms showed marked improvements in severity of itching, dryness, and burning/stinging over the study course; greatest improvement was for itching (Figure 2) ◾ Incidence of treatment-emergent Grade 3 local skin reactions was 22.2% for itching, 6.9% for dryness, and 9.8% for burning/stinging ◾ Incidence of other local skin reactions are shown in Figure 3 • Incidence peaked at 2.3% for skin atrophy (week 8), 2.7% for folliculitis (week 8), and 1.5% for striae and telangiectasias (week 28) ◾ Local skin reactions most frequently reported as AEs were application site folliculitis (14 participants [2.5%]; 1 discontinued) and application site atrophy (4 participants [0.7%]; 1 discontinued); no participant reported striae or telangiectasias AEs ◾ Most local skin reactions were transient and resolved prior to end of dosing CONCLUSIONS ◾ No clinically meaningful trends in local skin reactions were observed following long-term use of a fixed combination HP 0.01%/TAZ 0.045% lotion ◾ The types of TEAEs were consistent with those of a corticosteroid and retinoid product, but occurred at lower- than-anticipated frequencies, suggesting a favorable long-term safety profile for HP/TAZ lotion REFERENCES 1. Menter A, et al. J Am Acad Dermatol. 2009;60(4):643-659. 2. Stein Gold L, et al. J Am Acad Dermatol. 2018;79(2):287-293. 3. Sugarman JL, et al. J Drugs Dermatol. 2018;17(8):855-861. AUTHOR DISCLOSURES Dr. Mark G Lebwohl is an employee of Mount Sinai and receives research funds from AbbVie, Amgen, Arcutis, AstraZeneca, Boehringer Ingelheim, Celgene, Clinuvel, Eli Lilly, Incyte, Janssen Research & Development LLC, Kadmon Corp LLC, Leo Pharmaceuticals, Medimmune, Novartis, Ortho Dermatologics, Pfizer, Sciderm, UCB Inc, and ViDac.; is a consultant for Allergan, Almirall, Arcutis Inc, Avotres Therapeutics, BirchBioMed Inc, Boehringer-Ingelheim, Bristol-Myers Squibb, Cara Therapeutics, Castle Biosciences, Corrona, Dermavant Sciences, Foundation for Research and Education in Dermatology, Inozyme Pharma, LEO Pharma, Meiji Seika Pharma, Menlo, Mitsubishi, Neuroderm, Pfizer, Promius/Dr. Reddy’s Laboratories, Theravance, and Verrica. Dr. Jeffery Sugarman is a consultant for Ortho Dermatologics, Bausch Health, Regeneron, Sanofi, and Pfizer. Dr. David M Pariser has served as consultant to Atacama Therapeutics, Bickel Biotechnology, Biofrontera AG, Celgene, Dermira, LEO, Regeneron, Sanofi, TDM SurgiTech, TheraVida, and Ortho Dermatologics; investigator for Abbott Laboratories, Almirall, Amgen, AOBiome, Asana Biosciences, Bickel Biotechnology, Celgene, Dermavant, Dermira, Eli Lilly, LEO, Menlo Therapeutics, Merck & Co., Novartis, Novo Nordisk A/S, Ortho Dermatologics, Pfizer, Regeneron, and Stiefel; on advisory board for Pfizer; and on the data monitoring board for BMS. Dr. Jerry Bagel is an investigator and speaker for Ortho Dermatologics. Dr. Tina Lin is an employee of Ortho Dermatologics and may hold stock and/or stock options in its parent company. Dr. Robert Israel is an employee of Bausch Health US, LLC and may hold stock and/or stock options in its parent company. RESULTS Participants and Exposure ◾ A total of 550 participants were included in the safety population • Mean age was 51.9 years (range: 19 to 87 years); 65.6% were male and 86.0% were white • Baseline IGA was moderate (3; 86.5%) or severe (4; 13.5%); median affected Body Surface Area was 5% ◾ Median amount of study drug used was 256.5 g, median length of exposure was 172 days, and median number of applications was 164 Treatment-Emergent Adverse Events ◾ Over half of participants experienced treatment-emergent adverse events (TEAEs) during the year-long study, primarily during the first 12 weeks (Table 1) • Most TEAEs were mild or moderate • None of the serious adverse events (SAEs) were related to treatment ◾ The most common TEAEs related to study drug were application site reactions (Table 1) TABLE 1. Treatment-Emergent Adverse Event Summary (Safety Population) 0-12 Weeks (n=527) >12-24 Weeks (n=392) >24-36 Weeks (n=239) >36 Weeks-EOS (n=219) Total (N=550) Number of TEAEs, No. 395 194 98 71 758 Participants with ≥1 TEAE, n (%) 223 (42.3) 130 (33.2) 61 (25.5) 43 (19.6) 314 (57.1) Discontinued study drug due to TEAE, n (%) 30 (5.7) 9 (2.3) 2 (0.8) 0 41 (7.5) Participants with ≥1 SAE,a n (%) 6 (1.1) 5 (1.3) 5 (2.1) 2 (0.9) 18 (3.3) Treatment-related TEAE, n (%) 120 (22.8) 43 (11.0) 18 (7.5) 8 (3.7) 161 (29.3) TEAEs by severity, n (%) Mild 99 (18.8) 67 (17.1) 28 (11.7) 22 (10.0) 122 (22.2) Moderate 101 (19.2) 55 (14.0) 26 (10.9) 16 (7.3) 151 (27.5) Severe 23 (4.4) 8 (2.0) 7 (2.9) 5 (2.3) 41 (7.5) Most common treatment-related TEAEs,b n (%) Application site dermatitis 38 (7.2) 20 (5.1) 6 (2.5) 2 (0.9) 56 (10.2) Application site pruritus 22 (4.2) 6 (1.5) 4 (1.7) 2 (0.9) 33 (6.0) Application site pain 24 (4.6) 2 (0.5) 1 (0.4) 1 (0.5) 28 (5.1) Application site irritation 10 (1.9) 4 (1.0) 3 (1.3) 1 (0.5) 13 (2.4) aNone of the SAEs were deemed related to treatment; bIn >2% of total participants. EOS, end of study; SAE, serious adverse event; TEAE, treatment-emergent adverse event. Mark G Lebwohl, MD1; Jeffrey Sugarman, MD, PhD2; David M Pariser, MD3; Jerry Bagel, MD4; Tina Lin, PharmD5; Robert Israel, MD6 1Icahn School of Medicine at Mount Sinai, New York, NY; 2University of California, San Francisco, CA; 3Virginia Clinical Research Center, Norfolk, VA; 4Psoriasis Treatment Center of Central New Jersey, East Windsor, NJ; 5Ortho Dermatologics*, Bridgewater, NJ; 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.