Safety and Efficacy of a Fixed Combination Halobetasol and Tazarotene Lotion in the Treatment of Moderate-to-Severe Plaque Psoriasis: A Pooled Analysis of Two Phase 3 Studies

August 2018 | Volume 17 | Issue 8 | Original Article | 855 | Copyright © August 2018

Jeffrey L. Sugarman MD PhD,a Jonathan Weiss MD,b Emil A. Tanghetti MD,c Jerry Bagel MD,d Paul S. Yamauchi MD,e Linda Stein Gold MD,f Tina Lin, PharmD,g Gina Martin MOT,h Radhakrishnan Pillai PhD,h Robert Israel MDi

aUniversity of California, San Francisco, CA bGwinnett Dermatology, PC, and Gwinnett Clinical Research Center, Inc, Snellville, GA cCenter for Dermatology and Laser Surgery, Sacramento, CA dPsoriasis Treatment Center of Central New Jersey, East Windsor, NJ eDavid Geffen School of Medicine at UCLA, Los Angeles, CA fHenry Ford Hospital, Detroit, MI gOrtho Dermatologics, Bridgewater, NJ hDow Pharmaceutical Sciences Inc. (a division of Valeant Pharmaceuticals, North America, LLC.), Petaluma, CA iBausch Health, Bridgewater, NJ

Table 1 Table 2center, and baseline BSA as a covariate. Subgroup analyses for IGA and BSA did not include analysis center as a factor.The primary safety analysis was conducted at week 8 using the Safety analysis set which is all subjects who are randomized,received at least 1 confirmed dose of study drug, and have at least 1 post-baseline safety assessment. Adverse events were recorded and classified using the Medical Dictionary for Regulatory Activities (MedDRA, Version 18.0). All reported treatment-emergent adverse events (TEAEs), defined as any AE with an onset on or after the date of first drug application, were summarized by treatment group and relationship to study drug. Each subject was counted only once within a system organ class or a preferred term using the event with the greatest severity or causality, respectively. A post-hoc Wilcoxon Rank-Sum test was conducted to compare itching, dryness, and burning/stinging scores at week 8 for HP/TAZ lotion vs vehicle.


Subject Disposition

Overall, 418 subjects from 32 study centers in the United States were randomized to HP/TAZ lotion or vehicle (Figure 1) andincluded in the ITT population. Across the two studies, 85.5% (N=236) and 83.8% (N=119) of subjects treated with HP/TAZ lotion or vehicle completed treatment. Main reasons for discontinuation with HP/TAZ lotion were subject request (6.2%, N=17), AEs (4.0%, N=11), or lost to follow-up (3.3%, N=9). Subject request (8.5%, N=12) was also the main reason for discontinuation in the vehicle arms. A total of 410 subjects were included in the safety population,with no post-baseline safety evaluation in 8 subjects.

Subject Demographics and Baseline Characteristics

Demographic data were comparable across the two studies. Mean age was 50.3 years (SD 13.84). Overall, the majority of subjects were male (65.1%, N=272) and Caucasian (85.6%, N=358; Table 1). Baseline disease characteristics were also comparable across the treatment groups. At baseline, subjects had moderate (85.2%, N=356) or severe (14.8%, N=62) disease, with a mean BSA of 5.9 (SD 2.76). Mean size of target lesion was 37.5cm2 (SD 22.85). The majority of subjects had moderate (erythema [79.2%], plaque elevation [76.6%], and scaling [72.5%]) or severe (erythema [12.2%], plaque elevation [12.9%], and scaling [13.6%]) signs of psoriasis at the target lesion site (Table 2).

Efficacy Evaluation

Investigator’s Global Assessment (IGA) of Disease Severity HP/TAZ lotion was consistently more effective than its vehicle in achieving at least a 2-grade improvement from baseline