Triple Combination Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% for Acne: Efficacy and Safety from a Pooled Phase 3 Analysis.

INTRODUCTION: A three-pronged approach to acne treatment combining an antibiotic, antimicrobial, and retinoid may be more efficacious than single/double treatments while potentially reducing antibiotic resistance. This study evaluated the efficacy and safety of the first fixed-dose, triple-combination topical acne product, clindamycin 1.2%/adapalene 0.15%/benzoyl peroxide (BPO) 3.1% gel (CAB) using pooled phase 3 data. METHODS: In two identical phase 3 (N = 183; N = 180), double-blind, 12-week studies, participants aged ≥ 9 years with moderate-to-severe acne were randomized 2:1 to receive once-daily CAB or vehicle gel. Endpoints included ≥ 2-grade reduction from baseline in Evaluator's Global Severity Score and clear/almost clear skin (treatment success) and least-squares mean percent change from baseline in acne lesion counts. Treatment-emergent adverse events (TEAEs) and cutaneous safety/tolerability were evaluated. RESULTS: At week 12, 50.0% of participants achieved treatment success with CAB versus 22.6% with vehicle gel (P < 0.001). CAB resulted in > 70% reductions in inflammatory and noninflammatory lesions at week 12 (77.9% and 73.0%, respectively), which were significantly greater than vehicle (57.9% and 48.2%; P < 0.001, both). Most TEAEs were of mild-moderate severity, and < 3% of CAB-treated participants discontinued study/treatment because of AEs. Transient increases from baseline in scaling, erythema, itching, burning, and stinging were observed with CAB, but resolved back to or near baseline values by week 12. CONCLUSIONS: The innovative fixed-dose, triple-combination clindamycin phosphate 1.2%/adapalene 0.15%/BPO 3.1% gel was efficacious and well tolerated in children, adolescents, and adults with moderate-to-severe acne. Half of participants achieved clear/almost clear skin by 12 weeks, rates not previously seen in clinical studies of other topical acne products. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04214639 and NCT04214652.

Rosacea Core Domain Set for Clinical Trials and Practice: A Consensus Statement.

Importance: Inconsistent reporting of outcomes in clinical trials of rosacea is impeding and likely preventing accurate data pooling and meta-analyses. There is a need for standardization of outcomes assessed during intervention trials of rosacea. Objective: To develop a rosacea core outcome set (COS) based on key domains that are globally relevant and applicable to all demographic groups to be used as a minimum list of outcomes for reporting by rosacea clinical trials, and when appropriate, in clinical practice. Evidence Review: A systematic literature review of rosacea clinical trials was conducted. Discrete outcomes were extracted and augmented through discussions and focus groups with key stakeholders. The initial list of 192 outcomes was refined to identify 50 unique outcomes that were rated through the Delphi process Round 1 by 88 panelists (63 physicians from 17 countries and 25 patients with rosacea in the US) on 9-point Likert scale. Based on feedback, an additional 11 outcomes were added in Round 2. Outcomes deemed to be critical for inclusion (rated 7-9 by ≥70% of both groups) were discussed in consensus meetings. The outcomes deemed to be most important for inclusion by at least 85% of the participants were incorporated into the final core domain set. Findings: The Delphi process and consensus-building meetings identified a final core set of 8 domains for rosacea clinical trials: ocular signs and symptoms; skin signs of disease; skin symptoms; overall severity; patient satisfaction; quality of life; degree of improvement; and presence and severity of treatment-related adverse events. Recommendations were also made for application in the clinical setting. Conclusions and Relevance: This core domain set for rosacea research is now available; its adoption by researchers may improve the usefulness of future trials of rosacea therapies by enabling meta-analyses and other comparisons across studies. This core domain set may also be useful in clinical practice.

Influence of Season on Efficacy and Tolerability of Tazarotene 0.045% Lotion for the Treatment of Acne.

Objective: The condition of the skin can vary due to weather fluctuations. Therefore, this post-hoc analysis evaluated efficacy and safety of tazarotene 0.045% lotion in warmer versus colder months. Methods: In two Phase III, double-blind, 12-week studies, participants aged nine years or older with moderate-to-severe acne were randomized 1:1 to once-daily tazarotene or vehicle lotion. The pooled population (N=1,614) was stratified by randomization date (warmer=May to September; colder=October to April). Evaluations included inflammatory/noninflammatory lesion counts, treatment success, adverse events, and safety/tolerability. Results: Tazarotene 0.045% lotion was similarly efficacious over colder and warmer months. Compared with vehicle, tazarotene demonstrated significantly greater least-squares mean absolute reductions from baseline to Week 12 in inflammatory (colder/warmer tazarotene vs. vehicle: -16.6/-15.8 vs. -13.2/-12.9) and noninflammatory lesions (-23.2/-22.6 vs. -17.5/-15.1); treatment success rates were also significantly higher (30.1/30.8% vs. 18.2/17.6%) (P<0.001, all). No strong seasonal trends in safety were observed, though tazarotene led to slightly more discontinuations (3.4% vs. 1.9%) and related adverse events (12.0% vs. 10.3%) in colder versus warmer months. Transient increases in scaling, erythema, and itching at Weeks 2 to 8 of tazarotene treatment were slightly higher in colder versus warmer months but returned to baseline/improved by Week 12. Limitations: Geographical variation across study sites can lead to varying temperatures and humidity within the same months. Conclusion: Tazarotene 0.045% lotion was efficacious and well tolerated for acne treatment, regardless of season. Year-round tolerability of tazarotene 0.045% lotion may be due to its lower tazarotene concentration and polymeric emulsion technology, which simultaneously delivers moisturizers/humectants/emollients to skin.

Melanin-dependent tissue interactions induced by a 755-nm picosecond-domain laser: complementary visualization by optical imaging and histology.

Fractional picosecond-domain lasers (PSL) induce optical breakdown, which correlates histologically to vacuolization in the epidermis and dermis. In this ex vivo porcine study, we sought to establish a framework for the investigation of laser-tissue interactions and their dependence on melanin density. Light- (melanin index: 24.5 [0-100]), medium- (58.7), and dark-pigmented (> 98) porcine skin samples were exposed to a 755-nm fractional PSL and examined with dermoscopy, line-field confocal optical coherence tomography (LC-OCT), conventional OCT, and subsequently biopsied for digitally stained ex vivo confocal microscopy (EVCM) and histology, using hematoxylin and eosin (HE) and Warthin-Starry (WS) melanin staining. Dermoscopy showed focal whitening in medium- and dark-pigmented skin. Similarly, LC-OCT and OCT visualized melanin-dependent differences in PSL-induced tissue alterations. Vacuoles were located superficially in the epidermis in dark-pigmented skin but at or below the dermal-epidermal junction in medium-pigmented skin; in light-pigmented skin, no vacuoles were observed. Histology confirmed the presence of vacuoles surrounded by areas void of WS staining and disrupted stratum corneum in darker skin. The combined use of optical imaging for multiplanar visualization and histological techniques for examination of all skin layers may mitigate the effect of common artifacts and attain a nuanced understanding of melanin-dependent laser-tissue interactions.

Dermal sensitization, safety, and tolerability of triple-combination clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15% gel from three clinical trials.

BACKGROUND: Using a three-pronged acne treatment approach-combining an antibiotic, antimicrobial agent, and retinoid-may provide greater efficacy than monad or dyad treatments. Herein are the dermal sensitization, irritation, safety, and tolerability results from phase 1 and 2 studies of fixed-dose clindamycin phosphate 1.2%/benzoyl peroxide (BPO) 3.1%/adapalene 0.15% (IDP-126) polymeric mesh gel. METHODS: Two phases 1, single-blind, vehicle-controlled dermal safety studies were conducted in healthy participants aged ≥18 years. One phase 2 (NCT03170388) double-blind, randomized, parallel-group, and vehicle-controlled study was conducted over 12 weeks in participants aged ≥9 years with moderate-to-severe acne. RESULTS: A total of 1,020 participants (IDP-126 gel, vehicle, or 1 of the 3 dyad gels [phase 2 only]) were included across the 3 studies (safety populations: n = 1,004). In the phase 1 studies, IDP-126 had no confirmed sensitization or contact dermatitis. IDP-126 (deemed "moderately irritating") was significantly less irritating than commercially available BPO 2.5%/adapalene 0.3% gel. CONCLUSIONS: The results from these three studies show that the triple-combination IDP-126 had a positive safety profile and was well tolerated in healthy participants and those with moderate-to-severe acne.

Triple-combination clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15% gel for moderate-to-severe acne in children and adolescents: Randomized phase 2 study.

BACKGROUND/OBJECTIVES: Topical clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15% gel (IDP-126) is the first fixed-dose triple-combination formulation in development for acne. This post hoc analysis investigated efficacy and safety of IDP-126 in children and adolescents with moderate-to-severe acne. METHODS: In a randomized, double-blind phase 2 study (NCT03170388), participants ≥9 years of age with moderate-to-severe acne were eligible for randomization (1:1:1:1:1) to once-daily IDP-126, one of three dyad combination gels, or vehicle gel for 12 weeks. This post hoc analysis of pediatric participants (n = 394) included children and adolescents up to 17 years of age. Assessments included treatment success, inflammatory/noninflammatory lesion counts, Acne-Specific Quality of Life (Acne-QoL) questionnaire, treatment-emergent adverse events (TEAEs), and cutaneous safety/tolerability. RESULTS: At Week 12, treatment success rates were significantly greater with IDP-126 (55.8%) than with vehicle (5.7%; p < .001) or any of the dyad combinations (range: 30.8%-33.9%; p < .01, all). Lesion reductions with IDP-126 were also significantly greater than with vehicle (inflammatory: 78.3% vs. 45.1%; noninflammatory: 70.0% vs. 37.6%; p < .001, both) and 9.2%-16.6% greater than with any of the dyad combinations. Increases (improvements) from baseline in Acne-QoL domain scores were generally greater with IDP-126 than in any other treatment group. The most common treatment-related TEAEs across treatment groups were application site pain and dryness. Most treatment-related TEAEs were of mild-to-moderate severity. CONCLUSION: IDP-126 gel-a novel fixed-dose, triple-combination topical formulation for acne-demonstrated superior efficacy to vehicle and three dyad component gels and was well tolerated in children and adolescents with moderate-to-severe acne.

Challenges in Psoriatic Disease Addressed by Fixed-Combination Halobetasol Propionate 0.01% and Tazarotene 0.045% Lotion.

Objective: The fixed-dose corticosteroid/retinoid combination halobetasol propionate (0.01%) and tazarotene (0.045%) lotion (HP/TAZ) is approved for topical treatment of plaque psoriasis in adults. In addition to its current indication for plaque psoriasis, a growing body of clinical data suggests that HP/TAZ may be a beneficial therapy for palmoplantar and scalp psoriasis. Here, we discuss the efficacy and safety of HP/TAZ in various psoriatic phenotypes and related conditions. Methods: Three studies (one post-hoc analysis, two open-label reports) of HP/TAZ were identified for this discussion. Results: A post-hoc analysis demonstrated that once-daily HP/TAZ was associated with sustained efficacy and clinically meaningful quality-of-life improvements in participants with psoriatic disease who had low quality of life and 3% to 5% affected body surface area at baseline. In open-label reports, HP/TAZ was associated with improvement in scalp psoriasis measures, as well as quality of life. Additionally, HP/TAZ was efficacious in patients with palmoplantar psoriasis and in one report of a patient with palmoplantar pustulosis. Limitations: Limitations include the small sample sizes of open-label reports of HP/TAZ; larger studies are needed to confirm findings. Conclusion: Taken together, this evidence suggests that HP/TAZ may address unmet needs in psoriatic disease as a therapy for patients with all levels of psoriasis severity who experience daily challenges associated with their disease and that it may be a candidate for treating a variety of forms of psoriasis.

Improvements in acne and skin oiliness with tazarotene 0.045% lotion in patients with oily skin.

BACKGROUND: Excessive sebum production is a factor in acne development. Tazarotene 0.045% lotion has demonstrated reductions in acne lesions and acne-induced sequelae. OBJECTIVE: Evaluate efficacy, changes in skin oiliness, and safety with tazarotene 0.045% lotion in participants with moderate-to-severe acne and oily skin. METHODS: In two phase 3, double-blind, 12-week studies (NCT03168321; NCT03168334), participants aged ≥ 9 years with moderate-to-severe acne were randomized 1:1 to once-daily tazarotene 0.045% lotion or vehicle lotion (N = 1614). This pooled, post hoc analysis included only participants self-categorized with oily skin at baseline on the Acne-Specific Quality of Life questionnaire item 19 (scores: 0 [extremely oily] to 6 [not at all oily]). Inflammatory/noninflammatory lesion counts, treatment success, skin oiliness, treatment-emergent adverse events (TEAEs), and cutaneous safety/tolerability were evaluated. RESULTS: In all participants with oily skin (n = 793), tazarotene provided greater reductions in inflammatory/noninflammatory lesions (p < 0.001, both) and greater treatment success rates versus vehicle (p < 0.01) at week 12. Over two-thirds of polymeric lotion-treated participants had subjective skin oiliness reductions by week 12, with around a third reporting 'low/not' oily skin. Tazarotene TEAE rates were similar to the overall population. CONCLUSIONS: Once-daily treatment with tazarotene 0.045% polymeric emulsion lotion may help improve patient-perceived skin oiliness in those with moderate-to-severe acne.

SUPPLEMENT INDIVIDUAL ARTICLES: Update on Truncal Acne: A Review of Treatments for a Neglected Disease and the Re-Emergence of Tazarotene.

Acne vulgaris of the trunk carries with it a major psychosocial impact and an unmet need for adequate management. Approximately 50% of patients with facial acne also exhibit involvement of the back, chest, and/or upper arms. The trunk poses a therapeutic challenge given its occlusion by clothing, the tendency for mechanical rubbing, a sebum physiology that differs from the face, as well as the fact that there is a large surface area for topical therapies to cover. Furthermore, truncal acne is underreported for a variety of reasons such as cultural barriers, sentiments of embarrassment, and prioritization of facial acne. To date, few medications have been studied specifically for truncal acne. In this article, an updated review of truncal acne and available therapies is provided. The most recent evidence for tazarotene, a third-generation retinoid previously approved for psoriasis and facial acne vulgaris over two decades ago, is also reviewed and compared to trifarotene, a fourth-generation retinoid that is the only approved tropical retinoid for both facial and truncal acne. J Drugs Dermatol. 2022;21:12(Suppl):s5-14.

Vehicle Formulation Impacts Tolerability and Patient Preference: Comparison of Tretinoin Branded Lotion and Generic Cream.

BACKGROUND: Topical retinoids like tretinoin are a mainstay of acne treatment but associated cutaneous irritation and drying may lead to poor adherence. As vehicle optimization can improve patient preference and adherence, tretinoin 0.05% lotion (Altreno®) was formulated using polymeric emulsion technology for uniform delivery of micronized tretinoin and moisturizing/hydrating excipients. This study compared tolerability and participant preference of a branded tretinoin 0.05% lotion versus generic cream. METHODS: In this single-center, double-blind, split-face study, 25 adult females with acne were randomized to apply lotion and cream to opposite cheeks once daily for 2 weeks. Investigator-assessed skin irritation and appearance, as well as participant ratings of the products and skin sensations, were evaluated immediately after first use and after 2 weeks. RESULTS: At week 2, there was significantly greater erythema, scaling, and dryness (122%–144%; P<0.01 each) and decreased skin softness, smoothness, radiance, and brightness (~40% difference; P<0.01 each) on the cream-treated versus lotion-treated side of the face. More participants agreed that the lotion was gentle, comfortable/soothing, spreadable, absorbent, not sticky, and left minimal residue versus cream (range: 72%–92% vs 8%–36%). Agreement scores on skin sensations (eg, soft, not dry, less dull) were similarly higher for lotion versus cream. Overall, ~70% of participants preferred to take home the lotion over the cream. CONCLUSIONS: After 2 weeks of once-daily use, tretinoin 0.05% lotion was associated with less irritation and superior skin appearance/ sensation versus generic 0.05% cream, with most participants preferring the lotion over cream. These results demonstrate the importance of a well-designed vehicle formulation on tolerability and patient preference. J Drugs Dermatol. 2022;21(8): 875-880. doi:10.36849/JDD.6945.

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.

In Vitro Rheology Predicts Improved Spreadability of Tazarotene 0.045% Lotion Versus Trifarotene 0.005% Cream.

BACKGROUND: Intrinsic properties of vehicles used to deliver topical therapies can profoundly impact drug penetration, efficacy, patient acceptance, and treatment adherence. Therefore, advancements in vehicle technology demand sophisticated, quantitative approaches to describe and differentiate topical formulations. The objective of these studies was to quantitatively evaluate spreadability of two topical formulations for the treatment of acne via in vitro rheological measurement (how a substance’s flow characteristics change under applied stress or force) and spreadability on living skin. METHODS: Rheological characteristics (shear-thinning, rigidity, yield stress, and yield strain) of tazarotene 0.045% lotion and trifarotene 0.045% cream were measured using 5 samples of each product. In a clinical split-body study, each formulation was applied to one side of the back of healthy volunteers, and the extent to which each formulation could be spread was measured. RESULTS: Compared to trifarotene cream, tazarotene lotion demonstrated lower mean viscosity, rigidity, and yield stress, and higher yield strain, suggesting a superior spreadability profile. This finding was confirmed in the split-body study of 30 healthy White adults, in which the average area of spread was significantly larger for tazarotene lotion than trifarotene cream (167.0 vs 130.3 cm2; P<0.001). CONCLUSIONS: Rheological assessment effectively predicted the superior spreadability of tazarotene 0.045% lotion versus trifarotene 0.005% cream on living skin. Given the importance of aesthetics of topical formulations, techniques to quantify these properties may have broad implications when developing novel vehicle formulations for dermatology. J Drugs Dermatol. 2022;21(3):250-257. doi:10.36849/JDD.6703.

Efficacy and Safety of a Fixed-Dose Clindamycin Phosphate 1.2%, Benzoyl Peroxide 3.1%, and Adapalene 0.15% Gel for Moderate-to-Severe Acne: A Randomized Phase II Study of the First Triple-Combination Drug.

BACKGROUND: A three-pronged approach to acne treatment-combining an antibiotic, antibacterial, and retinoid-could provide greater efficacy and tolerability than single or dyad treatments, while potentially improving patient compliance and reducing antibiotic resistance. OBJECTIVES: We aimed to evaluate the efficacy and safety of triple-combination, fixed-dose topical clindamycin phosphate 1.2%/benzoyl peroxide (BPO) 3.1%/adapalene 0.15% (IDP-126) gel for the treatment of acne. METHODS: In a phase II, double-blind, multicenter, randomized, 12-week study, eligible participants aged ≥ 9 years with moderate-to-severe acne were equally randomized to once-daily IDP-126, vehicle, or one of three component dyad gels: BPO/adapalene; clindamycin phosphate/BPO; or clindamycin phosphate/adapalene. Coprimary endpoints were treatment success at week 12 (participants achieving a ≥ 2-grade reduction from baseline in Evaluator's Global Severity Score and clear/almost clear skin) and least-squares mean absolute changes from baseline in inflammatory and noninflammatory lesion counts to week 12. Treatment-emergent adverse events and cutaneous safety/tolerability were also assessed. RESULTS: A total of 741 participants were enrolled. At week 12, 52.5% of participants achieved treatment success with IDP-126 vs vehicle (8.1%) and dyads (range 27.8-30.5%; P ≤ 0.001, all). IDP-126 also provided significantly greater absolute reductions in inflammatory (29.9) and noninflammatory (35.5) lesions compared with vehicle or dyads (range inflammatory, 19.6-26.8; noninflammatory, 21.8-30.0; P < 0.05, all), corresponding to > 70% reductions with IDP-126. IDP-126 was well tolerated, with most treatment-emergent adverse events of mild-to-moderate severity. CONCLUSIONS: Once-daily treatment with the novel fixed-dose triple-combination clindamycin phosphate 1.2%/BPO 3.1%/adapalene 0.15% gel demonstrated superior efficacy to vehicle and all three dyad component gels, and was well tolerated over 12 weeks in pediatric, adolescent, and adult participants with moderate-to-severe acne. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT03170388 (registered 31 May, 2017).

Fixed-Combination Halobetasol Propionate/Tazarotene Lotion for Psoriasis in Patients With 3%-5% Affected Body Surface Area.

INTRODUCTION: Patients with psoriasis and low body surface area (BSA) involvement often experience substantially reduced quality of life and may be candidates for topical therapies. Fixed-combination halobetasol propionate (0.01%) and tazarotene (0.045%) lotion (HP/TAZ) vs vehicle lotion was evaluated in participants with 3% to 5% BSA involvement. METHODS: In two phase 3, multicenter, double-blind, vehicle-controlled, 8-week studies (ClinicalTrial.gov identifiers: NCT02462070/NCT02462122), adults with moderate/severe investigator’s global assessment (IGA) score were randomized 2:1 to once-daily HP/TAZ or vehicle. Pooled post hoc analyses included participants with baseline BSA involvement of 3% to 5%. Measures included treatment success (≥2-grade IGA reduction, clear/almost clear score), reduction in affected BSA, and clinically meaningful improvement (reduction) of ≥4 points on dermatology life quality index (DLQI). RESULTS: Of 418 participants, 232 had baseline BSA involvement of 3% to 5% (HP/TAZ, n=149; vehicle, n=83). At week 8, 42.7% of HP/TAZ-treated participants achieved treatment success, compared with 11.4% of vehicle-treated participants (P< .001). Participants experienced significantly greater reductions in affected BSA at week 8 with HP/TAZ (-36.0%) vs vehicle (-1.6%; P< .001). Larger proportions experienced clinically meaningful DLQI improvements at week 8 with HP/TAZ (64.2%) vs vehicle (47.4%; P< .05). More participants achieved a ≥2-grade improvement in plaque elevation and scaling with HP/TAZ vs vehicle (each comparison, P< .001). Serious adverse events and discontinuations due to treatment-emergent adverse events were rare. CONCLUSIONS: In participants with plaque psoriasis and BSA involvement of 3% to 5%, HP/TAZ provided significantly improved effectiveness after 8 treatment weeks vs vehicle lotion, with clinically meaningful improvements in quality of life. J Drugs Dermatol. 2021;20(8):829-836. doi:10.36849/JDD.6217.

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-superpotent 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.

Tazarotene 0.045% Lotion for Moderate-to-Severe Acne Patients: Pooled Phase 3 Analysis by Age and Sex.

BACKGROUND: Two identical phase 3 trials (NCT03168321 and NCT03168334) and pooled post hoc analyses have established efficacy and safety of a polymeric tazarotene 0.045% lotion formulation in patients with moderate-to-severe acne. Presented here are post hoc analyses that further examine efficacy and safety of tazarotene 0.045% lotion by age and sex. METHODS: Patients aged ≥ 9 years with moderate-to-severe acne (score 3 or 4 on the Evaluator's Global Severity Score [EGSS]) were equally randomized to once-daily tazarotene 0.045% lotion or vehicle lotion for 12 weeks. Efficacy outcomes included inflammatory/noninflammatory lesion counts and treatment success (proportion of participants achieving ≥ 2-grade reduction from baseline in EGSS and score of 0 [clear] or 1 [almost clear]). Adolescent and adult females (n=1,013) and males (n=529) were subdivided into 3 age groups: 13­19, 20­29, and ≥30 years. RESULTS: At week 12, large least-squares mean percent reductions in inflammatory and noninflammatory lesions were observed across all 3 tazarotene-treated age groups in males and females (range, -50.2% to -64.8%). Treatment success rates ranged from 23.6% to 38.4%. Across all efficacy assessments, significant differences between tazarotene and vehicle (P<0.05) were generally observed in the younger male and female participants (13­19 and 20­29). No notable age-related patterns were found for safety outcomes, though tazarotene-treated males of all age groups reported fewer adverse events than females. CONCLUSIONS: Tazarotene 0.045% lotion is efficacious and well tolerated in female and male adolescents and adults with moderate-to-severe acne. J Drugs Dermatol. 2021;20(6):608-615. doi:10.36849/JDD.6070.

Topical Oxymetazoline Hydrochloride Cream 1% for the Treatment of Persistent Facial Erythema of Rosacea in Adults: A Comprehensive Review of Current Evidence.

BACKGROUND: Rosacea is a chronic, multisymptom, inflammatory condition that affects the centrofacial skin. Facial erythema associated with rosacea can negatively impact a patient's quality of life and is often hard to treat. OBJECTIVE: We sought to review the literature on the role of alpha-adrenergic receptors (α-adrenoceptors) in the context of persistent facial erythema in patients with rosacea and the use of oxymetazoline hydrochloride cream 1% as a topical treatment. METHODS: PubMed was searched; search terms included "alpha adrenoceptor," "oxymetazoline," and "rosacea." Additional articles were identified from the reference lists of the results. RESULTS: Some α-adrenoceptor agonists have vasoconstrictive properties and may be used topically to treat persistent facial erythema in rosacea. Oxymetazoline hydrochloride cream 1% is an α1A-adrenoceptor agonist approved for the treatment of persistent facial erythema associated with rosacea. Based on our review, we discuss the role of the α-adrenoceptor in persistent facial erythema; provide an overview of the mechanism of action of α-adrenoceptor agonists, such as oxymetazoline, in the treatment of persistent facial erythema; and summarize the clinical development and data to date demonstrating the efficacy and safety of oxymetazoline in the treatment of persistent facial erythema associated with rosacea. CONCLUSION: The review of available literature suggests that oxymetazoline cream is well-tolerated, safe, and effective for the treatment of persistent facial erythema in rosacea and is an important component of combination treatment regimens, which are likely to become the standard of treatment for rosacea in the future.

Optimized formulation for topical application of a fixed combination halobetasol/tazarotene lotion using polymeric emulsion technology.

BACKGROUND: Successful clinical data on halobetasol propionate 0.01%/tazarotene 0.045% (HP/TAZ) lotion in moderate-to-severe plaque psoriasis are published. This article charts its formulation development. METHODS: Dermal deposition, clinical efficacy, and synergistic effect of HP and TAZ delivered by polymeric emulsion technology was compared to HP 0.05% cream (Ultravate) and TAZ 0.1% cream (Tazorac); skin hydration and barrier maintenance with vehicle lotion through Trans Epidermal Water Loss (TEWL) and corneometry using human cadaver tissue; and steroid potency by vasoconstrictor assay (VCA) in healthy volunteers. Safety and tolerability evaluated in clinical studies and patient preference questionnaire. RESULTS: HP/TAZ lotion, using polymeric emulsion technology demonstrated better active ingredient delivery than HP 0.05% or TAZ 0.1% creams; supported by synergistic clinical data, with high HP potency outcome. Efficacy was rapid and sustained posttreatment. Layering TAZ 0.1% cream onto HP 0.05% cream had a negative effect on receptor phase levels. HP/TAZ lotion provided rapid and sustained increases in skin moisturization and gradually decreases in TEWL. Most subjects responded favorably to questions on the physical attributes of the vehicle lotion. CONCLUSIONS: Fixed combination HP 0.01%/TAZ 0.045% lotion formulation utilizing innovative polymeric emulsion technology and optimal selection of solvents/emollients/humectants, has recently been developed. Features inherent in technology translate into rapid, sustained efficacy, low irritation, and good patient acceptance.

Oxymetazoline and Energy-Based Therapy in Patients with Rosacea: Evaluation of the Safety and Tolerability in an Open-Label, Interventional Study.

BACKGROUND AND OBJECTIVES: The objectives of this study were to evaluate the safety, tolerability, and efficacy of oxymetazoline hydrochloride cream, 1% (oxymetazoline) when used as an adjunctive treatment with energy-based therapy for patients with moderate to severe facial erythema associated with rosacea. STUDY DESIGN/MATERIALS AND METHODS: In this Phase 4, multicenter, interventional, open-label study, eligible patients received one of four energy-based therapies (potassium titanyl phosphate laser, intense pulsed light therapy, pulsed-dye laser Vbeam Perfecta, or pulsed-dye laser Cynergy) on day 1 and day 29 and once-daily application of oxymetazoline on days 3 through 27 and days 31 through 56. Improvement from baseline in Clinician Erythema Assessment (CEA) score, patient satisfaction measures, incidence of treatment-emergent adverse events (TEAEs), and worsening from baseline on dermal tolerability assessments and the Clinician Telangiectasia Assessment (CTA) were assessed. Data were summarized using descriptive statistics. RESULTS: A total of 46 patients (mean age, 51.1 years; 78.3% female) enrolled in this study. Similar numbers of patients received each of the energy-based therapies in addition to oxymetazoline. All patients demonstrated an improvement from baseline in CEA during the study with 39 of 43 evaluable patients (90.7%) demonstrating an improvement 6 hours posttreatment on day 56. Most patients were satisfied or very satisfied with treatment at the end of the study. All TEAEs were mild or moderate in severity. Some patients experienced worsening in dermal tolerability assessment symptoms (range: 4-21 patients; 8.7-45.7%). Worsening in CEA and CTA were each reported by three patients (6.5%) at any time during the study. CONCLUSIONS: Treatment with oxymetazoline as adjunctive therapy with energy-based therapy was safe, well tolerated, and reduced facial erythema in patients with moderate to severe persistent facial erythema associated with rosacea. Lasers Surg. Med. © 2020 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals LLC.

Update on the Management of Rosacea from the American Acne & Rosacea Society (AARS).

Importance: Previous consensus articles on rosacea from the American Acne and Rosacea Society (AARS) have focused on pathophysiology, clinical assessment based on phenotypic expressions of rosacea, management guidelines, discussions of individual medical therapies, and reviews of physical modalities. Pathophysiologic mechanisms believed to be operative in rosacea have been covered extensively in the literature. Objective: This article updates the previously published consensus recommendations from the AARS on the management of rosacea, including systematic literature and evidence-based reviews of available therapeutic agents and physical modalities. Observations: This article includes discussions of available published data on topical ivermectin, topical oxymetazoline, combination therapy approaches, and physical devices for the management of rosacea. Consistent with what many publications on rosacea currently emphasize, clinicians are encouraged to define the clinical manifestations present in the patient and to select therapies that correlate with the optimal treatment of those manifestations. There are less data available on how to optimally integrate therapies; however, it appears that rationally selected medical therapies can be utilized concurrently. Conclusion: Due to the multifactorial pathogenesis of rosacea, its clinical presentation is heterogeneous. Rosacea is a chronic and recurrent inflammatory disorder, and clinical manifestations often vary in nature and severity over time, which might necessitate an adjustment in treatment. As new data become available, rosacea management approaches should be updated.