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

Randomized phase 3 evaluation of trifarotene 50 μg/g cream treatment of moderate facial and truncal acne.

BACKGROUND: Acne vulgaris often affects the face, shoulders, chest, and back, but treatment of nonfacial acne has not been rigorously studied. OBJECTIVES: Assess the safety and efficacy of trifarotene 50 μg/g cream, a novel topical retinoid, in moderate facial and truncal acne. METHODS: Two phase III double-blind, randomized, vehicle-controlled, 12-week studies of once-daily trifarotene cream versus vehicle in subjects aged 9 years or older. The primary end points were rate of success on the face, as determined by the Investigator\u27s Global Assessment (clear or almost clear and ≥2-grade improvement), and absolute change from baseline in inflammatory and noninflammatory counts from baseline to week 12. The secondary end points were rate of success on the trunk (clear or almost clear and ≥2-grade improvement) and absolute change in truncal inflammatory and noninflammatory counts from baseline to week 12. Safety was assessed through adverse events, local tolerability, vital signs, and routine laboratory testing results. RESULTS: In both studies, at week 12 the facial success rates according to the Investigator\u27s Global Assessment and truncal Physician\u27s Global Assessment and change in inflammatory and noninflammatory lesion counts (both absolute and percentage) were all highly significant (P \u3c .001) in favor of trifarotene when compared with the vehicle. LIMITATIONS: Adjunctive topical or systemic treatments were not studied. CONCLUSION: These studies demonstrate that trifarotene appears to be safe, effective, and well tolerated in treatment of both facial and truncal acne

Identifying gaps and providing recommendations to address shortcomings in the investigation of acne sequelae by the Personalising Acne: Consensus of Experts panel

Background: The physical sequelae of acne include erythema, hyperpigmentation, and scarring, which are highly burdensome for patients. Early, effective treatment can potentially limit and prevent sequelae development, but there is a need for guidance for and evidence of prevention-oriented management to improve patient outcomes. Objective: To identify unmet needs of acne sequelae and generate expert recommendations to address gaps in clinical guidance. Methods: The Personalizing Acne: Consensus of Experts panel of 13 dermatologists used a modified Delphi approach to achieve a consensus on the clinical aspects of acne sequelae. A consensus was defined as ≥75% of the dermatologists voting agree or strongly agree. All voting was electronic and blinded. Results: The panel identified gaps in current guidance and made recommendations related to acne sequelae. These included identification and classification of sequelae, pertinent points to consider for patient consultations, and management aimed at reducing the development of sequelae. Limitations: The recommendations are based on expert opinion and made in the absence of high-quality evidence. Conclusions: The identified gaps should help inform future research and guideline development for acne sequelae. The consensus-based recommendations should also support the process of consultations throughout the patient journey, helping to reduce the development and burden of acne sequelae through improved risk factor recognition, early discussion, and appropriate management

The Personalised Acne Care Pathway-Recommendations to guide longitudinal management from the Personalising Acne: Consensus of Experts

Background: Acne is a chronic disease with a varying presentation that requires long-term management. Despite this, the clinical guidelines for acne offer limited guidance to facilitate personalized or longitudinal management of patients. Objectives: To generate recommendations to support comprehensive, personalized, long-term patient management that address all presentations of acne and its current and potential future burden. Methods: The Personalising Acne: Consensus of Experts panel consisted of 13 dermatologists who used a modified Delphi approach to reach consensus on statements related to longitudinal acne management. The consensus was defined as ≥75% voting agree or strongly agree. All voting was electronic and blinded. Results: Key management domains, consisting of distinct considerations, points to discuss with patients, and pivot points were identified and incorporated into the Personalised Acne Care Pathway. Long-term treatment goals and expectations and risk of (or fears about) sequelae are highlighted as particularly important to discuss frequently with patients. Limitations: Recommendations are based on expert opinion, which could potentially differ from patients\u27 perspectives. Regional variations in health care systems may not have been captured. Conclusions: The Personalised Acne Care Pathway provides practical recommendations to facilitate the longitudinal management of acne, which can be used by health care professionals to optimize and personalize care throughout the patient journey

Oral Azithromycin for Treatment of Intractable Rosacea

Rosacea is a common chronic cutaneous disorder that primarily occurs on the convex surfaces of the central face and is often characterized by exacerbations and remissions. A case of a 52-yr-old woman visited our clinic in February 2008 complaining typical features of rosacea including multiple pinhead to rice-sized erythematous papules. We applied various conventional treatments including topical benzoyl peroxide and metronidazole as well as oral metronidazole, isotretinoin, and doxycycline. The lesions were not controlled but were rather aggravated by complications from these treatments. Therefore, we prescribed oral azithromycin, which has anti-inflammatory effects and reduces reactive oxygen species. Ten weeks after the administration of oral azithromycin, 500 mg per day for 2 weeks, the lesions had mostly disappeared and no specific side effects related to the azithromycin were noted. Oral azithromycin dosing 500 mg/day for 2 weeks is effective for treatment of intractable rosacea

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 sequalae. 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 = 1,614). This pooled, post hoc analysis included only participants self-categorized with oily skin at baseline on the Acne 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 \u3c 0.001, both) and greater treatment success rates versus vehicle (P \u3c 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 \u27low/not\u27 oily skin. Tazarotene TEAE rates were similar to the overall population. CONCLUSION: Once-daily treatment with tazarotene 0.045% polymeric emulsion lotion may help improve patient-perceived skin oiliness in those with moderate-to-severe acne

The Personalized Acne Treatment Tool - Recommendations to facilitate a patient-centered approach to acne management from the Personalizing Acne: Consensus of Experts

BACKGROUND: Acne, a commonly treated skin disease, requires patient-centered management due to its varying presentations, chronicity, and impact on health-related quality of life. Despite this, evidence-based clinical guidelines focus primarily on clinical severity of facial acne, omitting important patient- and disease-related factors, including ongoing management. OBJECTIVES: To generate recommendations to support patient-centered acne management, which incorporate priority and prognostic factors beyond conventional clinical severity, traditionally defined by grading the appearance and extent of visible lesions. METHODS: The Personalizing Acne: Consensus of Experts consisted of 17 dermatologists who used a modified Delphi approach to reach consensus on statements regarding patient- and treatment-related factors pertaining to patient-centered acne management. Consensus was defined as ≥75% voting agree or strongly agree. RESULTS: Recommendations based on factors such as acne sequelae, location of acne, high burden of disease, and individual patient features were generated and incorporated into the Personalized Acne Treatment Tool. LIMITATIONS: Recommendations are based on expert opinion, which may differ from patients\u27 perspectives. Regional variations in healthcare systems may not be represented. CONCLUSIONS: The Personalizing Acne: Consensus of Experts panel provided practical recommendations to facilitate individualized management of acne, based on patient features, which can be implemented to improve treatment outcomes, adherence, and patient satisfaction

Multidisciplinary Consideration of Potential Pathophysiologic Mechanisms of Paradoxical Erythema with Topical Brimonidine Therapy

Rosacea is a chronic inflammatory disease with transient and non-transient redness as key characteristics. Brimonidine is a selective α2-adrenergic receptor (AR) agonist approved for persistent facial erythema of rosacea based on significant efficacy and good safety data. The majority of patients treated with brimonidine report a benefit; however, there have been sporadic reports of worsening erythema after the initial response. A group of dermatologists, receptor physiology, and neuroimmunology scientists met to explore potential mechanisms contributing to side effects as well as differences in efficacy. We propose the following could contribute to erythema after application: (1) local inflammation and perivascular inflammatory cells with abnormally functioning ARs may lead to vasodilatation; (2) abnormal saturation and cells expressing different AR subtypes with varying ligand affinity; (3) barrier dysfunction and increased skin concentrations of brimonidine with increased actions at endothelial and presynaptic receptors, resulting in increased vasodilation; and (4) genetic predisposition and receptor polymorphism(s) leading to different smooth muscle responses. Approximately 80% of patients treated with brimonidine experience a significant improvement without erythema worsening as an adverse event. Attention to optimizing skin barrier function, setting patient expectations, and strategies to minimize potential problems may possibly reduce further the number of patients who experience side effects. Funding: Galderma International S.A.S., Paris, France