Efficacy of a Once-Daily Fixed Combination Halobetasol (0.01%) and Tazarotene (0.045%) Lotion in the Treatment of Localized Moderate-to-Severe Plaque Psoriasis

March 2019 | Volume 18 | Issue 3 | Features | 297 | Copyright © March 2019

Andrew Blauvelt MD MBA,a Lawrence J. Green MD,b Mark G. Lebwohl MD,c Paul S. Yamauchi MD PhD,d Tina Lin PharmD,e Gina Martin MOT,f Radhakrishnan Pillai PhDf

aOregon Medical Research Center, Portland, OR bDepartment of Dermatology, George Washington University School of Medicine, Washington, DC cIcahn School of Medicine at Mount Sinai, New York, NY dClinical Science Institute, Santa Monica, CA eOrtho Dermatologics, Bridgewater, NJ fBausch Health Americas, Inc., Petaluma, CA

Abstract
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Recently, clinical data on 8 weeks’ once-daily treatment of localized moderate-to-severe psoriasis with a novel fixed combination halobetasol propionate 0.01%/tazarotene 0.045% (HP/TAZ) lotion were published.1,2 HP/TAZ lotion was significantly more effective than individual active ingredients or vehicle, based on improvements in Investigator’s Global Assessment (IGA), body surface area (BSA) involvement, and signs and symptoms of psoriasis (erythema, plaque elevation, and scaling) at the target lesion as well as a synergistic benefit over individual active ingredients, and good tolerability.To address recognized limitations of Psoriasis Area and Severity Index (PASI), IGA, and BSA, alternative disease severity assessments have been developed. The product of IGA and BSA involvement (IGAxBSA) is a simple validated alternative for assessing treatment response that provides a more representative overview of psoriasis by considering both plaque qualities and disease extent. It also correlates well with PASI.3-5Here, we further investigate the efficacy of HP/TAZ lotion through a post hoc analysis of two large multicenter, double-blind studies (N=418) using the IGAxBSA assessment tool to evaluate improvement in disease severity and achievement of a clinically meaningful outcome in patients with localized moderate-to-severe psoriasis.Detailed trial methodology has been presented elsewhere,2 and is briefly described here. Patients with a clinical diagnosis of moderate-to-severe psoriasis (IGA 3 or 4) and 3-12% BSA (N=418) were randomized (2:1) to receive HP/TAZ lotion or vehicle applied topically to affected areas once-daily for 8 weeks, with a 4-week post-treatment follow-up. IGAxBSA scores were calculated at baseline, and weeks 2, 4, 6, 8, and 12. A clinically meaningful outcome was defined as achievement of ≥75% reduction in IGAxBSA score from baseline (IGAxBSA-75).Improvement in disease severity following treatment with HP/TAZ lotion was rapid and statistically significant compared to vehicle from week 2 (P less than 0.001) and at all subsequent evaluations (all P less than 0.001). At week 8, mean percent changes in IGAxBSA score from baseline were 51.9% and 9.21% for HP/TAZ lotion and vehicle (P less than 0.001) (Figure 1). Efficacy was sustained over the 4-week post-treatment period. At Week 12, mean percent changes in IGAxBSA score from baseline were 46.6% and 7.92% respectively (P less than 0.001).At week 8, IGAxBSA-75 was achieved by 41.7% of patients treated with HP/TAZ lotion and 9.9% treated with vehicle (P<0.001), see Figure 2. This clinically meaningful improvement was maintained 4 weeks post-treatment (week 12) with 41.4% of HP/TAZ lotion patients achieving IGAxBSA-75 compared with 10.7% treated with vehicle (P less than 0.001).In both phase 3 studies, IGAxBSA scores for patients treated with HP/TAZ lotion correlated strongly with BSA (r=0.90 and 0.95 at week 8). Improvements in baseline IGAxBSA scores were similar in patients stratified by baseline disease severity (assessed by either BSA or IGA). In patients treated with HP/TAZ lotion who had a baseline BSA >5% or ≤5%, percent changes in mean baseline IGAxBSA scores by week 8 were 49.0% and 54.3% (P=0.379 between group comparison). In patients who had severe (IGA = 4) or moderate (IGA = 3) disease at baseline, percent changes in mean baseline IGAxBSA scores at week 8 were 52.9% and 51.7% (P=0.747 between group comparison).In this post hoc analysis of two phase 3 vehicle-controlled studies of localized moderate-to-severe plaque psoriasis treated with once-daily HP/TAZ lotion or vehicle for 8 weeks, we demonstrate a rapid reduction in IGAxBSA scores and mean change from baseline of 52% with HP/TAZ lotion, similar to results reported for apremilast by week 16 (48%).6 Comparable