Fixed-Combination Halobetasol Propionate and Tazarotene in the Treatment of Psoriasis: Narrative Review of Mechanisms of Action and Therapeutic Benefits

Psoriasis is a lifelong disease associated with cycles of remission and relapse. Topical treatments are the front line of psoriasis therapy for most patients and have antiproliferative, anti-inflammatory, and immunosuppressive mechanisms of action. Novel fixed-dose combinations of topical therapeutic agents are becoming increasingly available, leveraging multiple mechanisms of action to improve safety and efficacy with formulations that are easier to use and may allow for the use of lower doses of active ingredients. A fixed-combination lotion containing the potent-to-super-potent corticosteroid halobetasol propionate (HP) and the retinoid tazarotene (HP 0.01%/TAZ 0.045%) was recently developed using polymeric emulsion technology. This new formulation technology allows for more uniform and efficient delivery of the active ingredients at lower doses than conventional monotherapy formulations of either ingredient while providing enhanced hydration and moisturization. This review provides an up-to-date overview of the therapeutic mechanisms of action of HP and TAZ, the rationale behind the development of HP 0.01%/TAZ 0.045% lotion, and clinical trials data on the efficacy, safety and tolerability, and maintenance of therapeutic effect with HP 0.01%/TAZ 0.045% lotion in the treatment of moderate-to-severe plaque psoriasis

Kate 2006 Winter

Each year, kate seeks to: explore ideas about normative gender, sex, and sexuality work against oppression and hierarchies of power in any and all forms serve as a voice for race and gender equity as well as queer positivity encourage the silent to speak and feel less afraid build a zine and community that we care about and trusthttps://digitalcommons.otterbein.edu/kate/1005/thumbnail.jp

Brodalumab to the Rescue: Efficacy and Safety of Brodalumab in Patients with Psoriasis and Prior Exposure or Inadequate Response to Biologics

Abstract While biologic therapies for psoriasis are effective for many patients, some patients may lose response, have inadequate control of disease, or develop intolerance to certain biologic agents. It may therefore be beneficial for patients whose psoriasis fails to respond to one biologic to switch to a different biologic therapy, in particular one with a different mechanism of action. However, it remains unclear how prior biologic exposure or lack of response affects the efficacy and safety of subsequent biologics in patients with moderate-to-severe psoriasis. Brodalumab, a fully human anti-interleukin-17 receptor A monoclonal antibody, has previously been shown to be efficacious in treating moderate-to-severe psoriasis in three large phase 3 trials (AMAGINE-1, AMAGINE-2, and AMAGINE-3). In this review, we summarize the efficacy and safety of brodalumab in patients with moderate-to-severe psoriasis and a history of biologic exposure. Further, we describe improvements in skin clearance and quality of life measures as well as safety in patients who had inadequate response to ustekinumab and who were rescued with brodalumab therapy. Lastly, we discuss improvements in skin clearance following rescue with brodalumab in patients whose disease failed to respond to secukinumab and ixekizumab. The findings of our review suggest that brodalumab is a safe and efficacious treatment regardless of past biologic use or lack of response to prior biologic therapy

Science for children : a book for teachers

xxx, 494 p.; 24 cm

Fixed-combination halobetasol propionate and tazarotene topical lotion decreases TNF-α and IL-17A levels in psoriatic lesions

Objective Fixed-combination halobetasol propionate (0.01%) and tazarotene (0.045%) lotion (HP/TAZ) is approved for the treatment of plaque psoriasis in adults, with a demonstrated efficacy and safety profile in phase 3 trials. This study examined the effect of HP/TAZ on the reduction of tumor necrosis factor alpha (TNF-α) and interleukin 17 A (IL-17A) and its correlation to psoriasis improvement. Materials and methods Ten adults with mild-to-moderate plaque psoriasis and 2 symmetrical plaques self-applied HP/TAZ (treated plaque) or vehicle lotion (untreated plaque) for 12 weeks. At baseline and each study visit (weeks 2, 4, 8, and 12), Investigator’s Global Assessment (IGA) score and erythema, scaling, and induration were assessed. Additionally, D-squame tape strips were utilized to quantify TNF-α and IL-17A in target lesions by enzyme-linked immunosorbent assay. Results Significant improvements in mean IGA score in HP/TAZ–treated compared with untreated plaques were evident at week 2 and maintained through week 12 (p < 0.003). HP/TAZ significantly reduced TNF-α levels at weeks 4 through 12 (p < 0.03) and IL-17A levels at weeks 2 through 8 (p < 0.05) in treated compared with untreated plaques. Conclusions HP/TAZ was highly effective in treating psoriasis plaques and, although HP/TAZ is not a biologic, effectively reduced cytokine-associated inflammatory markers that drive psoriatic disease

27611 Fixed-combination halobetasol propionate 0.01%/tazarotene 0.045% (HP/TAZ) lotion for the treatment of plaque psoriasis in patients with 3-5% body surface area (BSA) and poor quality of life (QoL)

Use of TAZ with topical steroids, such as superpotent HP, is recommended for mild-to-moderate psoriasis as the combination may provide synergistic efficacy while increasing duration of treatment effect and remission. The objective of this analysis was to investigate HP 0.01%/TAZ 0.045% lotion in patients with relatively low affected BSA and poor QoL, as objective measures such as BSA may underestimate disease severity. Two phase 3, multicenter, double-blind studies enrolled 418 adults with 3-12% BSA and Investigator’s Global Assessment (IGA) score of 3 or 4 (‘moderate’ or ‘severe’) at baseline. Participants were randomized (2:1) to receive HP/TAZ or vehicle lotion once-daily for 8 weeks, with a 4-week posttreatment follow-up. Pooled, post hoc analyses were conducted in a subset of 65 participants with baseline BSA of 3-5% and Dermatology Life Quality Index (DLQI) score ≥11. At week 8, 50.3% of HP/TAZ-treated participants achieved treatment success (≥2-grade reduction from baseline in IGA and score of 0 or 1 [‘clear’ or ‘almost clear’]), vs 14.6% of vehicle-treated participants (P ˂.05). BSA was significantly reduced with HP/TAZ ( 39.2%) vs vehicle lotion (+15.9%; P ˂.05). The percentage of participants experiencing a clinically meaningful ≥4-point reduction in DLQI score was greater for HP/TAZ (85.3%) vs vehicle (55.6%). Numerical improvements with HP/TAZ lotion were maintained 4-weeks posttreatment for efficacy measures and DLQI, consistent with the overall population. Though analyses were limited by the small population, HP/TAZ lotion provided significantly greater efficacy vs vehicle in participants with low BSA and poor QoL, with clinically relevant improvements in QoL

Halobetasol 0.01%/Tazarotene 0.045% Lotion for Moderate-to-Severe Psoriasis: Pooled Phase 3 Analysis of Males and Females

BACKGROUND: Previous results from two phase 3 studies demonstrated efficacy and safety of fixed combination halobetasol propionate 0.01%/tazarotene 0.045% (HP/TAZ) lotion in participants with moderate-to-severe plaque psoriasis. This post hoc analysis evaluated sex-specific efficacy and safety of HP/TAZ lotion. METHODS: In two randomized, double-blind, phase 3 studies, participants were randomized (2:1) to receive HP/TAZ or vehicle lotion once daily for 8 weeks. Male and female participants were evaluated separately in this pooled analysis. Efficacy assessments included treatment success (at least 2‑grade improvement in Investigator\u27s Global Assessment [IGA] score and score of clear/almost clear), impact on individual signs of psoriasis, and affected Body Surface Area (BSA). RESULTS: The analysis included 272 males (HP/TAZ, n=175; vehicle, n=97) and 146 females (HP/TAZ, n=101; vehicle, n=45). Significantly more participants achieved overall treatment success at week 8 with HP/TAZ versus vehicle in both male (38.4% vs 9.8%) and female (44.5% vs 9.9%) subgroups (P\u3c0.001, both). Erythema, plaque elevation, and scaling were also reduced by week 8 in both males and females, with significantly more HP/TAZ-treated participants achieving at least 2‑grade improvement in each sign of psoriasis than vehicle-treated participants (P\u3c0.001 each, both groups). Mean reductions in affected BSA were significantly greater with HP/TAZ versus vehicle lotion in both males and females (P≤0.001, both). The most frequent treatment-related adverse events were contact dermatitis, pruritis, and application site pain (each 4.0%) in females and contact dermatitis (7.6%) in males. CONCLUSION: HP/TAZ lotion was highly effective and safe in both males and females with moderate-to-severe psoriasis over 8 weeks of once-daily use. J Drugs Dermatol. 2020;19(5): doi:10.36849/JDD.2020.5021

Posttreatment maintenance of therapeutic effect with fixed-combination halobetasol propionate 0.01%/tazarotene 0.045% lotion for moderate-to-severe plaque psoriasis

BACKGROUND: The topical corticosteroid halobetasol propionate (HP) and retinoid tazarotene (TAZ) are effective in psoriasis treatment. Fixed-combination HP 0.01%/TAZ 0.045% lotion has demonstrated efficacy and safety in moderate-to-severe plaque psoriasis. OBJECTIVE: To investigate the maintenance of therapeutic effects after cessation of once-daily HP/TAZ treatment. METHODS: In two phase 3 studies (NCT02462070; NCT02462122), adults with moderate-to-severe psoriasis received HP/TAZ for 8 weeks. Data at week 12 were analyzed to evaluate posttreatment maintenance of treatment success (clear/almost clear skin), improvements in signs of psoriasis (erythema, plaque elevation, scaling), and reductions in affected body surface area (BSA). In a 52-week open-label study (NCT02462083), participants stopped HP/TAZ treatment after achievement of treatment success; data were analyzed to assess time to retreatment. RESULTS: Across all studies, most participants who achieved treatment success maintained this effect for at least one month posttreatment. Treatment effects were similarly maintained for improvements in signs of psoriasis and reductions in BSA. Some participants continued to improve after cessation of treatment. Maintenance of treatment success and time to retreatment were greater for participants who achieved clear skin. CONCLUSION: HP/TAZ lotion provides therapeutic effects that persist after treatment cessation, supporting its use in long-term management of plaque psoriasis

Brodalumab: 5-Year US Pharmacovigilance Report.

INTRODUCTION: Brodalumab is a human interleukin-17 receptor A antagonist indicated for the treatment of moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. Although the US prescribing information for brodalumab includes a boxed warning regarding suicidal ideation and behavior, no causal association has been demonstrated. Here, we summarize 5&nbsp;years of pharmacovigilance data, from August 15, 2017, through August 14, 2022, reported to Ortho Dermatologics by US patients and healthcare providers. METHODS: Prevalence of the most common adverse events (AEs) listed in the brodalumab package insert (incidence ≥ 1%) and AEs of special interest are described. Brodalumab exposure was estimated as the time from the first to last prescription-dispensing authorization dates. Data were collected from 4744 patients in the USA, with an estimated exposure of 5815 patient-years. RESULTS: Over 5&nbsp;years, 11 cases of adjudicated major adverse cardiovascular events were reported (0.23 events/100 patients), a rate lower than that experienced by patients in the international Psoriasis Longitudinal Assessment and Registry. There were 106 serious infections. No serious fungal infections were reported. There were 40 confirmed and 2 suspected COVID-19 cases, with no new COVID-19-related deaths. Of 49 reported malignancies among 42 patients, 3 were deemed possibly related to brodalumab. No completed suicides and no new suicidal attempts were reported. CONCLUSION: Five-year pharmacovigilance data are consistent with the established safety profile reported in long-term clinical trials and previous pharmacovigilance reports, with no new safety signals