Efficacy and Safety of Tazarotene Lotion, 0.045% in the Treatment of Truncal Acne Vulgaris.

BACKGROUND: Although truncal acne is thought to have the same pathophysiology as facial acne, treatment response may differ based on body area involvement. Traditionally, prescribers have relied on oral therapies for the management of truncal acne, possibly because oral therapy has been considered more convenient than topical application of medication to the chest and back. A lotion formulation may be particularly well-suited for the treatment of truncal acne. Tazarotene lotion, 0.045% is FDA approved for treatment of acne vulgaris in individuals 9 years of age or older. This pilot study was designed to investigate the efficacy and safety of Arazlo lotion for the treatment of truncal acne. STUDY FINDINGS: A total of 19 subjects ranging in age from 12 to 58 years completed the 12-week study. There were significant reductions in truncal IGA (the primary endpoint) at each of the study follow-up visits. At week 12, 89% of subjects were clear or almost clear, as assessed by truncal IGA score. There were statistically significant reductions in inflammatory, non-inflammatory, and total lesion counts from baseline to week 12. Treatment with tazarotene lotion 0.045% was well-tolerated, with erythema, dryness, peeling, oiliness, pruritis, and burning generally rated as trace or mild. Most subjects (64% or more) rated the lotion as “Good” or “Excellent” in general and in comparison to their prior medications. CONCLUSIONS: Tazarotene lotion, 0.045% is shown to be effective and well-tolerated for the management of truncal acne in this pilot study. Further studies with placebo control and larger populations are warranted. J Drugs Dermatol. 2022;21(7):713-716. doi:10.36849/JDD.6967.

Tazarotene 0.045% Lotion for Females With Acne: Analysis of Two Adult Age Groups.

BACKGROUND: Females aged ≥25 years may have acne with different etiology, presentation, burden, and treatment response than females 18–24 years. This post hoc analysis investigated efficacy and safety of tazarotene 0.045% lotion in females ≥18 years or ≥25 years of age. METHODS: In two phase 3 double-blind studies, participants 9 years of age and older with moderate-to-severe acne were randomized (1:1) to once-daily tazarotene 0.045% lotion or vehicle lotion for 12 weeks. Pooled data were analyzed for females aged ≥18 years (n=744) or ≥25 years (n=335). Assessments included inflammatory/noninflammatory lesion counts, treatment success (≥2-grade reduction from baseline in Evaluator’s Global Severity Score and score of 0 [clear] or 1 [almost clear]), Acne-Specific Quality of Life (Acne-QoL) questionnaire, treatment-emergent adverse events (TEAEs) and cutaneous safety/tolerability. RESULTS: At week 12, tazarotene-treated females in both age groups had greater reductions from baseline versus vehicle in inflammatory (≥18 years: 60.6% vs 53.7% [P<0.01]; ≥25 years: 60.9% vs 57.3% [P>0.05]) and noninflammatory lesions (59.0% vs 48.4% and 61.1% vs 48.8%; P<0.01, both). Rates of treatment success were greater with tazarotene versus vehicle; this difference was significant for females ≥18 years. Acne-QoL improvements were similar across age groups and generally greater with tazarotene than vehicle. TEAEs were mostly mild to moderate in severity. No age-related trends for safety or tolerability were observed. CONCLUSIONS: Tazarotene 0.045% lotion demonstrated comparable efficacy, improvement in quality of life, and safety in adult females aged ≥18 or ≥25 years with moderate-to-severe acne. This cosmetically elegant lotion is a well-studied and important treatment option for all patients, particularly adult females. J Drugs Dermatol. 2022;21(5):587-595. doi:10.36849/JDD.6876.

Halobetasol Propionate 0.01% Lotion for Plaque Psoriasis and Corticosteroid-Responsive Dermatoses.

A novel topical corticosteroid, halobetasol propionate (HP) 0.01% lotion (Bryhali™), has recently been introduced for the treatment of plaque psoriasis and corticosteroid-responsive dermatoses in adults. Once daily application of HP 0.01% lotion is indicated for use up to 8 weeks. Treatment success for plaque psoriasis in the pivotal phase 3 clinical trials (defined as an Investigator Global Assessment [IGA] of clear/almost clear [IGA 0/1] with ≥2-grade improvement from baseline) occurred in over one-third of patients by week 8. Treatment-emergent adverse events were typically mild-to-moderate in intensity and usually limited to the application site(s). No treatment-related cases of skin atrophy have been reported from the studies. Counselling should be considered to optimize treatment outcomes.

Molecular Mechanisms of Malignant Transformation of Oral Submucous Fibrosis by Different Betel Quid Constituents-Does Fibroblast Senescence Play a Role?

Betel quid (BQ) is a package of mixed constituents that is chewed by more than 600 million people worldwide, particularly in Asia. The formulation of BQ depends on a variety of factors but typically includes areca nut, betel leaf, and slaked lime and may or may not contain tobacco. BQ chewing is strongly associated with the development of potentially malignant and malignant diseases of the mouth such as oral submucous fibrosis (OSMF) and oral squamous cell carcinoma (OSCC), respectively. We have shown recently that the constituents of BQ vary geographically and that the capacity to induce disease reflects the distinct chemical composition of the BQ. In this review, we examined the diverse chemical constituents of BQ and their putative role in oral carcinogenesis. Four major areca alkaloids-arecoline, arecaidine, guvacoline and guvacine-together with the polyphenols, were identified as being potentially involved in oral carcinogenesis. Further, we propose that fibroblast senescence, which is induced by certain BQ components, may be a key driver of tumour progression in OSMF and OSCC. Our study emphasizes that the characterization of the detrimental or protective effects of specific BQ ingredients may facilitate the development of targeted BQ formulations to prevent and/or treat potentially malignant oral disorders and oral cancer in BQ users.

Tazarotene/Betamethasone Dipropionate Cream in Patients with Plaque Psoriasis: Results of a Prospective, Multicenter, Observational Study.

BACKGROUND: Topical agents are still the mainstay for the treatment of mild-to-moderate plaque psoriasis, in which fixed combinations play an important role. Tazarotene/betamethasone dipropionate (Taz/BD) cream is a novel fixed combination approved for treating plaque psoriasis in China, but its efficacy and safety have not been verified in a real-world environment. OBJECTIVES: The primary objective was to investigate the efficacy and safety of Taz/BD cream in treating plaque psoriasis. The secondary objectives were to assess its relapse after discontinuation and the efficacy and safety profiles during retreatment. METHODS: A prospective, multicenter, large-scale observational study was conducted. Adult patients with chronic plaque psoriasis involving <20% of the body surface area were enrolled. Taz/BD cream was applied once daily for 4 weeks. Patients who achieved ≥90% improvement in the Psoriasis Area and Severity Index (PASI) from baseline to week 4 were followed up to investigate relapse after drug withdrawal. Relapsed patients underwent another 4-week treatment. RESULTS: In total, 2,299 eligible patients were enrolled, and 2,095 patients (91.1%) completed the 4-week study. The mean PASI improvement at week 4 was 53.7%, and the PASI 50/75 response rates were 62.5 and 26.8%, respectively. The mean PASI reduction in plaque induration, desquamation and erythema were 58.3, 61.0 and 40.0%, respectively (p < 0.001). Adverse reactions occurred in 445 patients (20.8%) at week 4. The most frequently reported adverse reactions were local skin irritation, including pruritus (10%), pain (6.7%), erythema (6.1%) and desquamation (1.8%). During the post-treatment period, 47 patients (24.0%) relapsed within 8 weeks after drug discontinuation. Forty-five patients were retreated for another 4 weeks, and the PASI 50/75 response rates were 72.7 and 40.9%, respectively. There were no unexpected safety signals during retreatment. CONCLUSION: Taz/BD cream is effective and well tolerated in treating mild-to-moderate plaque psoriasis under near real-world conditions and demonstrates efficacy and safety during retreatment.

Treating Psoriasis With Halobetasol Propionate and Tazarotene Combination: A Review of Phase II and III Clinical Trials.

Objective: To review phase II and III clinical trial data to evaluate the efficacy and safety of the halobetasol propionate/tazarotene (HP/TAZ) combination lotion (Duobrii), a medication approved by the Food and Drug Administration in April 2019 for adults with plaque psoriasis. Data Sources: A systematic search (January 2005 to July 2019) of MEDLINE (PubMed) and EMBASE databases was performed using the terms halobetasol, tazarotene, halobetasol/tazarotene, Duobrii, and IDP-118. Study Selection and Data Extraction: Relevant English-language articles reporting on phase II and phase III clinical trials were included. Data from the individual trials were extracted independently and then cross-checked to ensure accuracy. Data Synthesis: HP/TAZ was safe and efficacious compared with HP alone, TAZ alone, or vehicle. More patients achieved treatment success, described as a ≥2-grade improvement on Investigator Global Assessment Scale, over 8 weeks of treatment and at the 4-week follow-up after treatment cessation. The most common adverse events were dermatitis, pain, and pruritus, which occurred more often in the TAZ groups compared with the HP/TAZ cohorts. Relevance to Patient Care and Clinical Practice: The once-daily HP/TAZ combination lotion simplifies psoriasis treatment and may facilitate adherence, which may improve psoriasis outcomes. Conclusions: HP/TAZ combination lotion is efficacious and safe for plaque psoriasis treatment, with more patients achieving end points and fewer side effects than in HP, TAZ, or vehicle-treated controls. Drug synergy may play a role. Importantly, patient adherence to a once-daily combinational therapy is likely to contribute to efficacy.

Once-Daily Polymeric Tazarotene 0.045% Lotion for Moderate-to-Severe Acne: Pooled Phase 3 Analysis by Sex.

Background: Two identical phase 3 randomized, double-blind, vehicle-controlled, 12-week studies (NCT03168321 and NCT03168334) demonstrated the efficacy and safety of tazarotene 0.045% lotion in participants with moderate-to-severe acne. Data from these studies were pooled and analyzed post hoc to evaluate outcomes by sex. Methods: Patients aged ≥9 years with moderate-to-severe acne (score 3 or 4 on the Evaluator's Global Severity Score [EGSS]) were randomized (1:1) to once-daily tazarotene 0.045% lotion or vehicle lotion for 12 weeks. Outcomes comprised inflammatory/noninflammatory lesion counts, treatment success (proportion of participants achieving ≥2-grade reduction from baseline in EGSS and score of 0 ["clear"] or 1 ["almost clear"]), and treatment-emergent adverse events (TEAEs). Results: A total of 1,064 females and 550 males were included in this analysis. For both sexes, least-squares mean percent changes from baseline to week 12 in lesion counts were significantly greater with tazarotene 0.045% lotion versus vehicle (inflammatory: females, -60.1% vs -52.1%; males, -53.6% vs -39.8%; noninflammatory: females, -57.6% vs -44.9%; males, -52.9% vs -36.5%; P<0.001, all). The percentage of participants achieving treatment success at week 12 was also significantly higher with tazarotene 0.045% lotion versus vehicle in females and males (P<0.001, both). Compared with tazarotene-treated males, tazarotene-treated females had significantly greater changes from baseline in inflammatory and noninflammatory lesions and a greater proportion achieved treatment success at week 12 (P<0.05, all). TEAE rates were similar between tazarotene- and vehicle-treated males; rates were higher for tazarotene-treated females than vehicle-treated females. Conclusions: Tazarotene 0.045% lotion was efficacious and well tolerated in the treatment of moderate-to-severe acne in female and male participants. J Drugs Dermatol. 2020;19(8): doi:10.36849/JDD.2020.5249

Tazarotene 0.045% Lotion for the Once-Daily Treatment of Moderate-to-Severe Acne Vulgaris in Adult Males

BACKGROUND: There has been an increasing interest in gender differences both in the pathogenesis and treatment of acne vulgaris (acne). However, while acne prevalence among adolescents is comparable across sexes, acne is much more common in adult women than in adult men which has been largely ignored. Acne is likely less common in adult men because of the declining rate of sebum secretion observed with increasing age, and yet it can be more severe than in adult women. In addition, adherence to topical medications is especially poor in adult men where tactile and sensory perceptions are low. The first lotion formulation of tazarotene was developed using polymeric emulsion technology to provide an important alternative option to treat these acne patients, especially those who may be sensitive to the irritant effects of other tazarotene formulations. OBJECTIVE: To evaluate the efficacy and safety of a new tazarotene 0.045% lotion formulation based on polymeric emulsion technology in treating adult male subjects with moderate or severe acne, in comparison with adolescent males treated with the same tazarotene 0.045% lotion. METHODS: Post hoc analysis of two multicenter, randomized, double-blind, vehicle-controlled phase 3 studies in moderate-or-severe acne. Subjects (aged 10 and older, N=1614) were randomized (1:1) to receive tazarotene 0.045% lotion or vehicle, once-daily for 12 weeks. Efficacy assessments included changes in baseline inflammatory and noninflammatory lesions and treatment success (at least 2-grade reduction in Evaluator's Global Severity Score [EGSS] and clear or almost clear). Quality of Life was assessed using the validated Acne-QoL scale. Safety, adverse events (AEs) were evaluated throughout; cutaneous tolerability (using a 4-point scale where 0=none and 3=severe) at each study visit. RESULTS: A total of 268 male subjects (85≥18 years old and 183<18 years old) were treated with tazarotene 0.045% lotion once-daily for 12 weeks. At week 12, percent reductions in inflammatory and noninflammatory lesions with tazarotene 0.045% lotion were 62.3% and 59.5% in the adult male population, compared with 49.4% (P=0.001) and 49.5% (P=0.016) in the adolescent male population. Treatment success was achieved by 33.0% of adult male subjects treated with tazarotene 0.045% lotion, compared with 21.6% in the adolescent male population (P=0.059). Quality of life (as assessed by Acne-QoL domain scores) was better in adolescent males at baseline. Improvements in QoL domain scores were similar to those seen in the overall study population, with greater absolute change in domain scores in the adult males. Improvement in acne symptom scores was significantly greater in adult males (P=0.029). Tazarotene 0.045% lotion was well-tolerated. The number of subjects reporting any AE in the adult male population was 11 (13.6%) compared with 39 (21.4%) in the adolescent male population. There was only one (1.2%) treatment-related AE (application site pain) reported in the adult males compared with 11 (6.0%) in the adolescent males, where the most common treatment-related AEs were application site pain (3.3%), dryness (1.1%), and erythema (1.1%). Mean scores for hyper- and hypopigmentation were very low at baseline in both groups with no appreciable change with treatment. CONCLUSIONS: Tazarotene 0.045% lotion provides greater efficacy and better tolerability in adult males (above 18 years old) than the adolescent male population with moderate-to-severe acne patients. J Drugs Dermatol. 2020;19(1):78-85. doi:10.36849/JDD.2020.3979

Effects of Tazarotene 0.045% Lotion on Quality of Life in Patients With Moderate-to-Severe Acne.

BACKGROUND: In two phase 3 trials (NCT03168334, NCT03168321), participants with moderate-to-severe acne had significant symptom improvements after 12 weeks of treatment with tazarotene 0.045% lotion. Given the negative psychosocial effects of acne on patients, data from these studies were analyzed to evaluate quality of life in various subgroups. METHODS: Mean changes from baseline to week 12 in Acne-Specific Quality of Life (Acne-QoL) domain and item scores were analyzed in the pooled intent-to-treat (ITT) population and in participants who were categorized as follows: Evaluator's Global Severity Score (EGSS) score=3 (“moderate”) or score=4 (“severe”) at baseline; Acne-QoL total score ≥60 (better quality of life) or <60 (worse quality of life), based on the median score at baseline. Exploratory analyses based on sex and race were also performed. RESULTS: In the pooled ITT population (N=1614), Acne-QoL improvements were greater with tazarotene 0.045% lotion versus vehicle lotion, with significant differences in the acne symptoms domain, 3 acne symptom items, 2 self-perception items, 1 role-emotional item, and 1 role-social item (all P<0.05). Acne-QoL improvements with tazarotene 0.045% lotion were comparable between the EGSS subgroups. However, participants who self-reported worse quality of life at baseline (Acne-QoL total score <60) had notably greater improvements than those with better quality of life. Female and Black participants had greater Acne-QoL improvements than male and White participants. CONCLUSIONS: Participants treated with tazarotene 0.045% lotion had significant quality-of-life improvements. Clinician-rated symptom severity appeared to have a smaller effect on Acne-QoL outcomes than participants’ own assessments of quality of life. J Drugs Dermatol. 2020;19(11): doi:10.36849/JDD.2020.5457.

Novel Polymeric Lotion Formulation of Once-Daily Tazarotene (0.045%) for Moderate-to-Severe Acne: Pooled Phase 3 Analysis.

Background: As current tazarotene formulations indicated for acne (0.1%) can cause irritation, a new tazarotene 0.045% lotion formu-lation was developed using polymeric emulsion technology. The objective was to assess efficacy, safety, and tolerability of tazarotene 0.045% lotion in patients with moderate-to-severe acne in a pooled analysis of data from two identical phase 3, double-blind, random-ized, vehicle-controlled 12-week clinical studies. Methods: Patients aged ≥9 years with moderate-to-severe acne were randomized (1:1) to tazarotene 0.045% lotion or vehicle lotion applied once daily. Inflammatory and noninflammatory lesion counts and Evaluator's Global Severity Score (EGSS) were assessed. Treatment success was defined as a ≥2-grade improvement in EGSS and a score of 'clear'/'almost clear'. Adverse events (AEs) and cutaneous safety and tolerability were also assessed. Results: In total, 1614 patients (mean age: 20.5 years) were randomized to tazarotene 0.045% lotion (n=799) or vehicle (n=815). At week 12, tazarotene 0.045% lotion demonstrated statistically significant superiority versus vehicle in reducing inflammatory and non-inflammatory lesion counts (least-squares mean percent changes from baseline: inflammatory, -57.9% vs -47.8% [P<0.001]; noninflam-matory, -56.0% vs -42.0% [P<0.001]). Treatment success at week 12 was also greater with tazarotene 0.045% lotion versus vehicle (30.4% vs 17.9%; P<0.001). The most frequent treatment-emergent AEs related to tazarotene treatment were application site pain (5.3%), dryness (3.6%), and exfoliation (2.1%). Conclusions: The new tazarotene 0.045% lotion formulated with polymeric emulsion technology demonstrated statistically signifi-cantly superior efficacy versus vehicle and was well tolerated in pediatric and adult patients with moderate-to-severe acne in this pooled analysis of 2 vehicle-controlled phase 3 studies. J Drugs Dermatol. 2020;19(3):272-279. doi:10.36849/JDD.2020.4869.

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 2­grade improvement in Investigator's 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<0.001, 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 2­grade improvement in each sign of psoriasis than vehicle-treated participants (P<0.001 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.

The microvascular response in the skin to topical application of methyl nicotinate: Effect of concentration and variation between skin sites.

BACKGROUND: Methyl nicotinate (MN) induces a local cutaneous erythema in the skin and may be used as a local provocation in the assessment of microcirculation and skin viability. The aims were to measure the effects of increasing doses of MN, to find the concentration that yields the most reproducible effect from day to day and between sites, and to study the variation between skin sites. METHODS: Microvascular responses to topically applied MN at different concentrations were measured in 12 subjects on separate days and on contralateral sides, using laser speckle contrast imaging (LSCI). MN effects were measured in four different body sites. RESULTS: At 20 mmol/L, the response to MN was most reproducible day-to-day and site-to-site, and resulted in a plateau response between 5 and 20 min after application. The skin region of the lower back had a lower perfusion value compared to the epigastric region (p = 0.007). When responses were compared to nearby, unprovoked areas, a significantly larger increase in perfusion was seen in the forearm, compared to all other anatomical sites (p < 0.03). CONCLUSION: A concentration of 20 mmol/L MN generated the most reproducible microvascular response in the skin. The response varies between different body sites.

Halobetasol 0.01%/Tazarotene 0.045% Lotion in the Treatment of Moderate-to-Severe Plaque Psoriasis: Maintenance of Therapeutic Effect After Cessation of Therapy

BACKGROUND: Psoriasis is a chronic, immune-mediated disease that varies widely in its clinical expression. Topical corticosteroids (TCS) are the mainstay of treatment. Long-term safety remains a concern, limiting use and recurrence is common. Tazarotene has also been shown to be effective in psoriasis, with efficacy maintained several weeks posttreatment. Fixed combination therapy with TCS and tazarotene may improve psoriasis signs and maintain efficacy between treatment sessions. OBJECTIVE: To investigate the maintenance of effect posttreatment with a once-daily application of halobetasol propionate 0.01%/tazarotene 0.045% (HP/TAZ) lotion in comparison with vehicle in patients with moderate or severe plaque psoriasis. METHODS: Two multicenter, randomized, double-blind, vehicle-controlled Phase 3 studies in moderate or severe psoriasis (N=418). Patients randomized (2:1) to receive HP/TAZ lotion or vehicle, once-daily for 8 weeks with a 4 week posttreatment follow-up. Efficacy assessments included treatment success (defined as at least a 2-grade improvement from baseline in the IGA score, and 'clear' or 'almost clear'), impact on individual signs of psoriasis (erythema, plaque elevation, and scaling) at the target lesion, and maintenance of improvements in Body Surface Area (BSA), IGAxBSA and clinically meaningful benefit (IGAxBSA-75). RESULTS: At week 8, 40.7% of patients achieved treatment success with HP/TAZ lotion, compared with 9.9% treated with vehicle (P<0.001). Four weeks posttreatment, 33.3% of patients achieved treatment success. Two thirds of patients (63%) who were treatment successes at week 8 remained treatment successes posttreatment. In addition, up to 20% of patients who were not treatment successes at week 8 became treatment successes by the end of the study. Three-quarters of patients maintained BSA improvements or reported further reductions in BSA that seemed to be unrelated to baseline BSA severity. At the end of the 4 week posttreatment period, patients who had been treated with HP/TAZ lotion achieved a 46.6% reduction in IGAxBSA, compared with 7.9% on vehicle. 41.7% of patients achieved a clinically meaningful effect at week 8 and this was maintained posttreatment. LIMITATIONS: The studies only had a 4 week follow-up period. CONCLUSIONS: In conclusion, HP 0.01%/TAZ 0.045% lotion provides effective maintenance of efficacy over a 4 week posttreatment period.

Efficacy, Safety, and Tolerability of a Halobetasol 0.01% /Tazarotene 0.045% Fixed Combination in the Treatment of Severe Localized Plaque Psoriasis: Post Hoc Analysis of Two Phase III Randomized Controlled Trials

Background: The use of topical therapy is a key component in the management of almost all psoriasis patients. Topicals are considered first-line therapy for mild disease and are having an increasing role in moderate or severe psoriasis as an integral part of combination therapy. Halobetasol has been shown be effective in moderate or severe localized plaque psoriasis, and tazarotene affords important effects on epidermal hyperproliferation that may be important in more severe disease. Objective: To investigate the efficacy, safety and tolerability of a once-daily application of a fixed combination halobetasol propionate 0.01% and tazarotene 0.045% (HP/TAZ) lotion in comparison with its vehicle in patients with severe localized plaque psoriasis (as defined by an Investigator Global Assessment (IGA) of 4 and Body Surface Area (BSA) of 3%-12%. Methods: Post hoc analysis of two multicenter, randomized, double-blind, vehicle-controlled phase 3 studies. Sixty-two patients with severe localized psoriasis (mean BSA 7.4) randomized (2:1) to receive HP/TAZ lotion or vehicle, once-daily for 8 weeks, with a 4-week posttreatment follow-up. Efficacy assessments included treatment success (defined as at least a 2-grade improvement from baseline in the IGA score and a score of 'clear' or 'almost clear'), impact on individual signs of psoriasis (erythema, plaque elevation, and scaling) at the target lesion, BSA, reduction in mean baseline IGAxBSA and achievement of a clinically meaningful response (number of patients who achieved at least a 75% improvement in IGAxBSA). Safety and treatment emergent adverse events (TEAEs) were evaluated throughout. Results: By week 8, 34.8% of patients were treatment successes compared with 0.0% on vehicle (P=0.004). HP/TAZ lotion was also significantly superior in reducing psoriasis signs and symptoms and improving BSA. At week 8, 47.4% (erythema), 66.4% (plaque elevation), and 65.4% (scaling) subjects achieved at least a 2-grade improvement, compared with 14.0% (P=0.016), 14.8% (P<0.001) and 14.7% (P<0.001) respectively with vehicle. Patients treated with HP/TAZ lotion achieved a 32.8% reduction in baseline mean BSA, compared with a 39.6% increase with vehicle (P=0.013). HP/TAZ lotion achieved a statistically significant superior reduction in mean IGAxBSA compared to vehicle from week 2 (P<0.001 versus vehicle). By week 8, almost half of the patients treated with HP/TAZ lotion achieved a clinically meaningful response (IGAxBSA-75) and a 52.9% reduction in mean IGAxBSA score compared with a 17.5% increase in those patients treated with vehicle (P<0.001). One patient (2.6%) treated with HP/TAZ lotion discontinued due to AE. Most frequently reported treatment related AEs were application site pain (7.9%), contact dermatitis (5.3%) and pruritus (5.3%). Conclusions: HP/TAZ lotion provides significantly greater efficacy than vehicle that is both rapid and sustained, in patients with severe localized plaque psoriasis, with good tolerability and safety over 8 weeks' once-daily use. J Drugs Dermatol. 2019;18(10):1012-1018.

A Phase 2, Multicenter, Double-Blind, Randomized, Vehicle-Controlled Clinical Study to Compare the Safety and Efficacy of a Novel Tazarotene 0.045% Lotion and Tazarotene 0.1% Cream in the Treatment of Moderate-to-Severe Acne Vulgaris

Background: Tazarotene has been extensively studied in clinical trials and is widely used to treat acne vulgaris (acne). Irritation potential has limited its use. Objective: To compare efficacy, safety, and tolerability of a novel formulation tazarotene 0.045% lotion based on polymeric emulsion technology, and tazarotene 0.1% cream in patients with moderate-to-severe acne. Methods: A total of 210 patients, 12 years and older were randomized to receive tazarotene 0.045% lotion, tazarotene 0.1% cream, or respective vehicle in double-blind, randomized, vehicle-controlled, 12-week study evaluating safety and efficacy (inflammatory and noninflammatory lesion counts and using Evaluator Global Severity Scores [EGSS]). In addition, patients completed a patient satisfaction survey (PSS), and acne-specific quality of life (QoL) questionnaire. Safety and cutaneous tolerability were assessed throughout. Results: A novel tazarotene 0.045% lotion demonstrated statistically significant superiority to vehicle in reducing inflammatory and noninflammatory lesion counts (P=.006 and P<.001) and clearly more effective in treatment success at week 12. In addition, at less than half the concentration, tazarotene 0.045% lotion was numerically more effective than tazarotene 0.1% cream. Mean percent reductions in inflammatory and noninflammatory lesions were 63.8% and 56.9%, compared with 60.0% and 54.1% with tazarotene 0.1% cream at week 12. Treatment success assessed by the investigator or patients' self-assessment was also numerically greater with tazarotene 0.045% lotion. There were no significant differences in patient satisfaction or QoL between the two active treatments. Both were well-tolerated, however, there were more treatment-related adverse events with tazarotene 0.1% cream (5.6% versus 2.9%); most common being application site pain. Limitations: This study was primarily designed to direct the phase 3 program and some of the results are post hoc analyses. Conclusions: A novel tazarotene 0.045% lotion provides statistically significant greater efficacy than vehicle in terms of lesion reduction, and numerically better treatment success than tazarotene 0.1% cream; with a highly favorable safety and tolerability profile in moderate-to-severe acne patients. J Drugs Dermatol. 2019;18(6):542-548.

Safety and efficacy of a fixed combination of halobetasol and tazarotene in the treatment of moderate-to-severe plaque psoriasis: Results of 2 phase 3 randomized controlled trials.

BACKGROUND: Topical corticosteroids are the mainstay of psoriasis treatment, with long-term safety considerations limiting their use. Combining them with tazarotene may optimize their efficacy and minimize safety and tolerability concerns. OBJECTIVE: To investigate the safety and efficacy of halobetasol propionate 0.01% plus tazarotene 0.045% (HP/TAZ) lotion in moderate-to-severe plaque psoriasis. METHODS: Two multicenter, randomized, double-blind, vehicle-controlled phase 3 studies (N = 418) were conducted. Subjects were randomized (2:1) to HP/TAZ lotion or vehicle once daily for 8 weeks with a 4-week follow-up. The primary efficacy assessment end point was treatment success (at least a 2-grade improvement from baseline in Investigator's Global Assessment score and a score of clear or almost clear). Safety and treatment-emergent adverse events were evaluated throughout. RESULTS: HP/TAZ lotion demonstrated statistically significant superiority over vehicle within as few as 2 weeks. By week 8, 35.8% (study 1) and 45.3% (study 2) of subjects were treatment successes compared with 7.0% and 12.5% of those treated with vehicle (P < .001). HP/TAZ lotion was also superior in reducing signs and symptoms of psoriasis and body surface area affected by psoriasis. The most frequently reported treatment-related adverse events were contact dermatitis (6.3%), application site pain (2.6%), and pruritus (2.2%). LIMITATIONS: Studies did not include subjects with more than 12% of their body surface area affected by psoriasis. CONCLUSIONS: HP/TAZ lotion was associated with significant reductions in the severity of the clinical signs of psoriasis, with no safety concerns.

Genotoxicity and 28-day oral toxicity studies of a functional food mixture containing maltodextrin, white kidney bean extract, mulberry leaf extract, and niacin-bound chromium complex.

Steady-fiber granule (SFG) is a functional food mixture that is composed of four major ingredients, resistant maltodextrin, white kidney bean (Phaseolus vulgaris) extract, mulberry leaf (Morus alba L.) extract, and niacin-bound chromium complex. This study focused on determining the safety of SFG. Genotoxicity and 28-day oral toxicity were evaluated. SFG did not induce mutagenicity in the bacterial reverse mutation assay using five Salmonella typhimurium strains (TA98, TA100, TA102, TA1535, and TA1537) in the presence or absence of metabolic activation (S9 system). SFG also did not induce clastogenic effects in Chinese hamster ovary cells with or without S9 treatment. Similarly, SFG did not induce genotoxicity in a micronucleus test conducted with mice. A dose-dependent 28-day oral toxicity assessment of SFG for rats revealed no significant effects on mortality, body weight, selected organ weights, and behavior. Evaluations of hematology, clinical biochemistry, and histopathology showed no adverse effects in rats treated with SFG. These results suggest that SFG has no significant mutagenic or toxic properties, and the no observed adverse effect level of SFG was defined as at least 5000 mg/kg/day orally for 28 days for male and female rats.

Tazarotene Revisited: Safety and Efficacy in Plaque Psoriasis and Its Emerging Role in Treatment Strategy

Background: Psoriasis is a chronic, immune-mediated disease that varies widely in its clinical expression. Treatment options focus on relieving symptoms, reducing inflammation, induration, and scaling, and controlling the extent of the disease. While significant data on tazarotene in psoriasis has been available for over 20 years, its main utility is in acne. Objective: To review the clinical studies with tazarotene in psoriasis and establish its future role in the management of this chronic, incurable condition. Methods: An English language literature review was performed utilizing Medline, EMBASE, and the Web of Science to identify relevant articles, both clinical trials and reviews. Results: Tazarotene is a very effective treatment for plaque psoriasis, with significant reductions in both plaque elevation and scaling after 12 weeks. Efficacy appears to be dose and formulation dependent, and erythema less responsive. Tazarotene sustains clinical response posttreatment and may have an important role in maintenance therapy. The most common side effect is mild-to-moderate local irritation, which limited its role as a single agent for psoriasis. Efficacy is enhanced through combination with topical corticosteroids (TCS). Tazarotene may circumvent the problem of TCS tachyphylaxis, due to its sustained efficacy and provide tolerability benefits; tazarotene increases epidermal thickness and may reduce the risk of steroid-induced atrophy. In addition, tazarotene-induced irritation is reduced by the anti-inflammatory effect of TCS. A new fixed combination, well-tolerated tazarotene/halobetasol topical formulation is now available, which provides synergistic efficacy that is both rapid and sustained posttreatment. Conclusions: Tazarotene is a highly effective psoriasis treatment whose efficacy and tolerability can be enhanced through combination therapy with TCS, and a new fixed combination topical formulation of tazarotene and halobetasol may provide an optimal management approach. J Drugs Dermatol. 2018;17(12):1280-1287.

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.

BACKGROUND: Topical corticosteroids (TCS) are the mainstay of psoriasis treatment. Safety concerns may limit use. Combination with tazarotene may optimize efficacy and minimize safety and tolerability concerns. OBJECTIVE: Investigate safety and efficacy of halobetasol propionate 0.01%/tazarotene 0.045% (HP/TAZ) lotion in moderate-to-severe plaque psoriasis. METHODS: Two multicenter, randomized, double-blind, vehicle-controlled phase 3 studies (N=418). Subjects randomized (2:1) to HP/TAZ lotion or vehicle once-daily for 8 weeks, 4-week follow-up. Primary efficacy assessment: treatment success (at least a 2-grade improvement from baseline in IGA score and 'clear' or 'almost clear'). Safety and treatment emergent AEs evaluated throughout. RESULTS: HP/TAZ lotion demonstrated statistically significant superiority over vehicle as early as week 2 (P equals 0.002). By week 8, 40.6% of subjects were treatment successes compared with 9.9% on vehicle (P less than 0.001). A third of subjects remained treatment successes post-treatment. HP/TAZ lotion was also superior in reducing psoriasis signs and symptoms, and Body Surface Area (BSA) involvement. Most frequently reported treatment related AEs were contact dermatitis (6.3%), application site pain (2.6%), and pruritus (2.2%). LIMITATIONS: No data were collected beyond the 4-week follow-up. CONCLUSIONS: HP/TAZ lotion provides synergistic efficacy that is both rapid and sustained, with good tolerability and safety over 8 weeks use. J Drugs Dermatol. 2018;17(8):855-861.

A Phase 2, Multicenter, Double-Blind, Randomized, Vehicle Controlled Clinical Study to Assess the Safety and Efficacy of a Halobetasol/Tazarotene Fixed Combination in the Treatment of Plaque Psoriasis.

BACKGROUND: Psoriasis is a chronic, immune-mediated disease that varies widely in its clinical expression. Treatment options focus on relieving symptoms, reducing inflammation, induration, and scaling, and controlling the extent of the disease. Topical corticosteroids are the mainstay of treatment, however long-term safety remains a concern, particularly with the more potent formulations. Combination therapy with a corticosteroid and tazarotene may improve psoriasis signs at a lower corticosteroid concentration providing a superior safety profile. OBJECTIVE: To investigate the efficacy and safety of a once-daily application of a fixed combination halobetasol propionate 0.01% and tazarotene 0.045% (HP/TAZ) lotion in comparison with its monads and vehicle in subjects with moderate-to-severe plaque psoriasis. METHODS: Multicenter, randomized, double-blind, vehicle-controlled Phase 2 study in moderate or severe psoriasis (N=212). Subjects randomized (2:2:2:1 ratio) to receive HP/TAZ, individual monads, or vehicle, once-daily for 8 weeks. Efficacy assessments included treatment success (defined as at least a 2-grade improvement from baseline in the IGA score and a score of 'Clear' or 'Almost Clear'), and impact on individual signs of psoriasis (erythema, plaque elevation, and scaling) at the target lesion. Safety and treatment emergent adverse events (TEAEs) were evaluated throughout. RESULTS: HP/TAZ lotion demonstrated statistically significant superiority over vehicle as early as 2 weeks. At week 8, 52.5% of subjects had treatment success compared with 33.3%, 18.6%, and 9.7% in the HP (P=0.033), TAZ (P less than 0.001), and vehicle (P less than 0.001) groups, respectively. HP/TAZ lotion was superior to its monads and vehicle in reducing the psoriasis signs of erythema, plaque elevation, and scaling at the target lesion. At week 8, a 2-grade improvement in IGA was achieved by 54.2% of subjects for erythema, 67.8% for plaque elevation, and 64.4% for scaling. Most frequently reported TEAEs were application site reactions, and were more likely associated with the tazarotene component. Side effects such as skin atrophy were rare. CONCLUSIONS: HP/TAZ lotion was consistently more effective than its monads or vehicle in achieving treatment success and reducing psoriasis signs of erythema, plaque elevation, and scaling at the target lesion. Safety data were consistent with the known safety profile of halobetasol propionate and tazarotene, and did not reveal any new safety concerns with the combination product.

J Drugs Dermatol. 2017;16(3):197-204.