OBJECTIVE • This post hoc analysis of two randomized phase 3 trials (NCT02462070 and NCT02462122)1 and a 52-week open-label study (NCT02462083)2 evaluated the efficacy and safety of halobetasol propionate (0.01%) and tazarotene (0.045%) lotion (HP/TAZ) in participants achieving ≥75% improvement in the product of investigator’s global assessment and affected body surface area (IGAxBSA-75) at or before week 12 CONCLUSIONS • HP/TAZ was associated with long-term skin clearance in participants who achieved clinically meaningful improvement in psoriasis lesions, as measured by IGAxBSA-75 – These findings suggest that HP/TAZ promotes remission of psoriasis after treatment discontinuation • Clinically meaningful improvement in psoriasis lesions was also associated with decreased signs and symptoms (itch, dryness, and burning/ stinging) and posttreatment maintenance of those improvements SYNOPSIS • Fixed-combination halobetasol propionate (0.01%) and tazarotene (0.045%) lotion (HP/TAZ) is approved to treat plaque psoriasis in adults3 • The product of investigator’s global assessment and affected body surface area (IGAxBSA) is a measure of psoriasis severity4 – ≥75% reduction from baseline (IGAxBSA-75) is considered as clinically meaningful improvement in skin clearance5 METHODS • In the randomized trials, participants were assigned 2:1 to either HP/TAZ once daily or vehicle lotion, with a primary endpoint of treatment success at week 8 (IGA score of clear [0] or almost clear [1]) and follow-up assessment at week 12 (Figure 1A) • Similarly, in the open-label study, all participants received HP/TAZ once daily for 8 weeks – Those who achieved treatment success stopped treatment and were reevaluated monthly through 52 weeks, with retreatment as needed (any time IGA was >1) – Those who did not achieve treatment success at week 8 continued to apply HP/TAZ – Participants were allowed 24 continuous weeks of HP/TAZ if they achieved ≥1-grade improvement in IGA from baseline at week 12 (Figure 1B) • In the randomized phase 3 trials, 276 participants were treated with HP/TAZ and 142 received vehicle, while a total of 550 participants were treated in the long-term open-label study • Participants who achieved IGAxBSA-75 at or before week 12 in the randomized phase 3 and open-label studies of HP/TAZ were included in the analysis • Signs and symptoms of psoriasis were evaluated at each study visit – Itch and stinging/burning were scored on a scale from 0 (none) to 3 (severe) as reported by the participant in the past 24 hours – Dryness was scored on a scale from 0 (none) to 3 (severe) as assessed by the investigator Figure 1. Designs of (A) pivotal phase 3 and (B) open-label studies of HP/TAZ. HP/TAZ, halobetasol propionate (0.01%) and tazarotene (0.045%) lotion; IGA, investigator’s global assessment. aTreatment success defined as IGA score of clear (0) or almost clear (1). bImprovement defined as ≥1-grade improvement from baseline IGA; those demonstrating improvement continued the study and were subsequently managed in 4-week cycles (ie, treated with once-daily HP/TAZ if they did not achieve treatment success or received no treatment until the next evaluation if they achieved treatment success). Maximum continuous exposure was 24 weeks. RESULTS Efficacy Participant characteristics • In a pooled analysis of the phase 3 trials, 140 of 276 participants (50.7%) treated with HP/TAZ and 19 of 142 participants (13.4%) who received vehicle achieved IGAxBSA-75 by week 12 • In the open-label study, 254 of 550 participants (46.2%) achieved IGAxBSA-75 by week 12 • Across all studies, prevalence of moderate-to-severe symptoms at baseline was greater in HP/TAZ-treated participants compared with those receiving vehicle (Table 1) Table 1. Baseline Characteristics of Participants in Clinical Studies of HP/TAZ Who Achieved IGAxBSA-75 at or Before Week 12 IGAxBSA-75 • In the randomized trials, a numerically greater proportion of participants receiving HP/TAZ achieved IGAxBSA-75 versus those receiving vehicle at week 8 and week 12 (4 weeks posttreatment; Figure 2) • In the open-label study, 63.3% of participants who achieved IGAxBSA-75 by week 12 maintained IGAxBSA-75 at week 52 Figure 2. Proportion of participants achieving IGAxBSA-75 at week 8 and week 12 (4 weeks posttreatment) in the randomized phase 3 trials of HP/TAZ. BSA, body surface area; HP/TAZ, halobetasol propionate (0.01%) and tazarotene (0.045%) lotion; IGA, investigator’s global assessment; IGAxBSA-75, ≥75% improvement in product of IGA and BSA. Signs and symptoms of psoriasis • In the phase 3 randomized trials, most participants receiving HP/TAZ or vehicle who achieved IGAxBSA-75 at or before week 12 also reported no itch (71.1% vs 73.7%), dryness (68.1% vs 78.9%), or burning/stinging (85.9% vs 94.7%) at week 8, with similar results at week 12 (4 weeks posttreatment; Figure 3) Figure 3. Proportion of participants achieving IGAxBSA-75 at or before week 12 who were free of itch, dryness, and burning/stinging at week 8 and week 12 (4 weeks posttreatment) in the randomized phase 3 trials of HP/TAZ. BSA, body surface area; HP/TAZ, halobetasol propionate (0.01%) and tazarotene (0.045%) lotion; IGA, investigator’s global assessment; IGAxBSA-75, ≥75% improvement in product of IGA and BSA. • In the open-label study of HP/TAZ, the proportion of participants with moderate-to-severe itch, dryness, and stinging/burning decreased at week 52 from baseline (Table 2) Table 2. Change in Moderate-to-Severe Signs/Symptoms of Psoriasis in the Open-label Study of HP/TAZ Safety • Across all studies, rates of skin atrophy, striae, telangiectasias, and folliculitis were low • At week 12 in the randomized phase 3 trials, only 1 participant (0.7%) in the HP/TAZ group experienced skin atrophy, and all other reactions were absent • In the open-label study, rates of these skin reactions were absent in all participants at week 52 Long-term Safety and Efficacy of Fixed-Combination Halobetasol Propionate and Tazarotene Lotion in Patients With Clinically Meaningful Improvement in Plaque Psoriasis Andrew Alexis,1 James Del Rosso,2 Tina Bhutani,3 Kim Papp,4 Abby Jacobson5 1Department of Dermatology, Weill Cornell Medical College, New York, NY; 2JDR Dermatology Research/Thomas Dermatology, Las Vegas, NV; 3UCSF Psoriasis and Skin Treatment Center, San Francisco, CA; 4Probity Medical Research and K. Papp Clinical Research, Waterloo, Ontario, Canada; 5Ortho Dermatologics (a division of Bausch Health US, LLC), Bridgewater, NJ Acknowledgments: This study was sponsored by Ortho Dermatologics. Medical writing support was provided by MedThink SciCom and funded by Ortho Dermatologics. Ortho Dermatologics is a division of Bausch Health US, LLC. References: 1. Stein Gold et al. J Am Acad Dermatol. 2018;79:287-293. 2. Lebwohl et al. J Eur Acad Dermatol Venereol. 2021;35:1152-1160. 3. Duobrii [package insert]. Bausch Health US, LLC; 2019. 4. Gottlieb et al. Dermatology. 2019;235:348-354. 5. Blauvelt et al. J Drugs Dermatol. 2019;18:297-299. Presented at the Fall Clinical Dermatology Conference • October 21-24, 2021 • Las Vegas, NV, and Virtual Sponsored by Ortho Dermatologics, a division of Bausch Health US, LLC. Baseline parameter Pooled randomized trials (HP/TAZ, n=140) Pooled randomized trials (vehicle, n=19) Open-label study (N=254) IGA 3 119 (85) 19 (100) 221 (87) IGA 4 21 (15) 0 33 (13) Mean BSA, % (SD) 5.8 (2.9) 5 (2.2) 5.5 (2.7) Moderate-to-severe itch 62 (44.3) 3 (15.8) 118 (46.5) Moderate-to-severe dryness 41 (29.3) 3 (15.8) 109 (42.9) Moderate-to-severe stinging/burning 23 (16.4) 3 (15.8) 36 (14.2) All values are n (%) except for mean BSA. BSA, body surface area; HP/TAZ, halobetasol propionate (0.01%) and tazarotene (0.045%) lotion; IGA, investigator’s global assessment; IGAxBSA-75, ≥75% improvement in product of IGA and BSA; SD, standard deviation. 71.1 73.7 70.1 78.9 68.1 78.9 70.9 73.7 85.9 94.7 95.5 100 0 10 20 30 40 50 60 70 80 90 100 HP/TAZ at week 8 HP/TAZ, n=140 Vehicle, n=19 Vehicle at week 8 92n = 96 116 14 15 18 94 95 128 15 14 19 HP/TAZ at week 12 Vehicle at week 12 Sy m pt o m -f re e pa rt ic ip an ts , % Itch Dryness Burning/Stinging 82.1 73.173.7 68.4 0 10 20 30 40 50 60 70 80 90 100 Week 8 Week 12 (4 weeks posttreatment) HP/TAZ (n=140) Pa rt ic ip an ts a ch ie vi ng IG A xB SA -7 5, % Vehicle (n=19) n=115 n=14 n=98 n=13 Randomized, Double-Blind, Vehicle-Controlled Treatment Study 1 (NCT02462070) Posttreatment Follow-Up (No Treatment) Baseline B A 2:1 Week 12 HP/TAZ Lotion (n=135) Vehicle Lotion (n=68) Week 8 Study 2 (NCT02462122) 2:1 HP/TAZ Lotion (n=141) Vehicle Lotion (n=74) 2:1 2:1 Day 0 Week 8 Week 12 Week 24 Week 52Screening Once-daily HP/TAZ for 8 weeks Evaluated for treatment success at week 8a Success Treatment stopped for 4 weeks No success Continued once-daily HP/TAZ for 4 weeks Evaluated for improvement at week 12b No improvement Discontinued from study • • - If 24 weeks of continuous treatment were received at any point in the study and the participant did not achieve an IGA score of 0 or 1, the participant was discontinued from the study. Treatment stopped for 4 weeks Continued once Continued study and managed in 4 1 year, with participants reevaluated every 4 weeks for treatment success -week cycles for up to Success: No success: daily HP/TAZ for 4 weeks Sign/Symptom Participants with sign/symptom at week 52, n (%) Mean change from baseline SD Itch 10 (10.2) -0.70 1.09 Dryness 6 (6.1) -0.70 0.90 Stinging/Burning 4 (4.1) -0.20 0.68 HP/TAZ, halobetasol propionate (0.01%) and tazarotene (0.045%) lotion; SD, standard deviation.