Halobetasol Propionate 0.01%/Tazarotene 0.045% Lotion for Moderate-to-Severe Psoriasis: Pooled Phase 3 Analysis of Lower Extremities

April 2020 | Volume 19 | Issue 4 | Original Article | 389 | Copyright © April 2020


Published online March 20, 2020

Stephen Tyring , Leon H. Kircik , Paul Yamauchi , Abby Jacobson , Tina Lin

aUniversity of Texas Health Science Center, Houston, TX bIndiana University School of Medicine, Indianapolis, IN; Physicians Skin Care, PLLC, Louisville, KY; and Icahn School of Medicine at Mount Sinai, New York, NY cDermatology Institute & Skin Care Center, Inc., Santa Monica, CA dOrtho Dermatologics,* Bridgewater, NJ *Ortho Dermatologics is a division of Bausch Health US, LLC.

sion. Treatment success on these signs were achieved in almost half of participants treated with HP/TAZ compared with <25% of those treated with vehicle; these significant therapeutic effects were observed as early as week 2 and sustained posttreatment. In addition to demonstrating efficacy at psoriasis lesions on the lower extremities, treatment with HP/TAZ also was effective for reducing overall psoriasis severity in this population.

Following 8 weeks of HP/TAZ treatment, a significantly greater percentage of participants achieved overall treatment success, defined as a 2-grade improvement and a score of clear or almost clear on the IGA across all treatment areas. Overall affected BSA levels were also significantly reduced compared with vehicle at week 8. Similar results were also observed using the IGAx- BSA composite tool, with significantly greater mean reductions in IGAxBSA score at week 8 for HP/TAZ- versus vehicle-treated patients. A reduction of ≥75% from baseline IGAxBSA score (IGAxBSA-75) was achieved by approximately 38% of HP/TAZtreated participants versus 13% of vehicle-treated participants at week 8. Effects of HP/TAZ at week 8 were sustained at week 12 for all efficacy measures. The safety and tolerability of HP/TAZ in this subpopulation of participants was consistent with that reported in the overall population from previous studies.10,11 In this subpopulation, the most common treatment-related TEAEs in HP/TAZ-treated participants were contact dermatitis, skin atrophy, folliculitis, and excoriation. Although AEs such as skin thinning are a concern with higher potency topical corticosteroids, 12 skin atrophy was reported in only 4 participants in this study. All cases were mild or moderate in severity and resolved or were resolving at the end of the study with either no change in treatment or a dose reduction.

The lower extremities represent one of the most commonly affected areas associated with chronic plaque psoriasis.3,7 This was found to be the case for the current analysis as well, with over half of participants from the original phase 3 studies having an investigator-identified target lesion on the leg. Of note, the percentage of participants from these studies with psoriasis affecting the lower extremities is likely higher than 52%, as the subpopulation evaluated in this study was limited to only those with a target lesion on the leg and did not necessarily include all patients with psoriasis affecting the lower extremities. Demographic and disease characteristics in this post hoc subpopulation were generally similar to that observed in the overall population, with the exception of a slightly higher target lesion size in patients with a target lesion of the leg (41.5 cm2) versus those in the overall pooled population (37.5 cm2).11

Very few studies have specifically evaluated treatment efficacy by specific body region. However, evidence from a recent observational study of biologic agents in real-world clinical practice suggested that the most common sites of recalcitrant psoriasis include the lower leg and elbows.7 Other studies have similarly found that psoriasis lesions located on lower extremities are often among the slowest areas to respond to biologic treatment. 5,6,8

Evidence for the efficacy of topical treatments for psoriasis of the lower extremities is lacking. Results from the current study demonstrate that HP/TAZ was effective in reducing the signs of psoriasis at lower extremity lesions, and that these effects were rapid, occurring within 2 weeks of initiation of treatment. In addition, effects of HP/TAZ were sustained during the 4-week posttreatment period, which may reflect the benefit of adding tazarotene to the potent effects of halobetasol. Application of this combination lotion formulation is not limited to the 2 consecutive weeks of use common with superpotent topical corticosteroids10 since HP/TAZ has been shown to cause only minimal irritant effects commonly caused by tazarotene, and also minimizes local halobetasol-related AEs.13

There are several limitations to this post hoc analysis that should be considered. While this analysis was able to identify and select patients with a target lesion on the lower extremities, the target lesion was restricted to the leg, had to be between 16-100 cm2 in size, and could not include areas covering bony prominences (eg, knees). As a result, the likelihood exists that some participants with psoriasis affecting the lower extremities may not have been included. Additionally, study criteria limited the population to participants with BSA of 3-12%, and patients with greater severity were not included in the studies. Finally, efficacy data for HP/TAZ in areas other than the leg were not evaluated in this study, so comparisons between body regions are not possible. However, the results of this subanalysis were generally consistent with results reported for the overall population. 11

CONCLUSIONS

Fixed combination halobetasol propionate 0.01% and tazarotene 0.045% lotion provided rapid and sustained efficacy versus vehicle following 8 weeks of therapy in patients where the leg was identified as the target lesion. HP/TAZ was effective at reducing erythema, plaque elevation, and scaling as well as overall IGA scores and affected BSA levels. HP/TAZ was safe and welltolerated and may provide a reasonable treatment option for patients with psoriasis affecting the lower extremities.

DISCLOSURES

Stephen Tyring has acted as an investigator for Ortho Dermatologics. Leon H. Kircik has acted as an investigator, advisor, speaker, and consultant for Ortho Dermatologics. Paul Yamauchi has served as speaker, consultant, and investigator for AbbVie, Amgen, Janssen, Novartis, Lilly, LEO, Ortho Dermatologics, and Sun Pharma. Abby Jacobson and Tina Lin are employees of Ortho Dermatologics and may hold stock and/or stock options in its parent company.