Patient- and Clinician-Reported Outcomes for Tirbanibulin in Actinic Keratosis in Clinical Practice Across the United States (PROAK).

BACKGROUND: The Patient-Reported Outcomes in Actinic Keratosis (PROAK) study evaluated patient- and clinician-reported outcomes (PRO; ClinRO) during 24 weeks of follow-up among adult patients with actinic keratosis (AK) on the face or scalp who were administered tirbanibulin 1% ointment in real-world community practices in the United States.  Methods: Quality of life (QoL) was assessed by Skindex-16 at week (W) 8. Additionally, effectiveness (Investigator Global Assessment [IGA]), PRO and ClinRO (Treatment Satisfaction Questionnaire for Medication and Expert Panel Questionnaire), safety, and tolerability were assessed at W8 and W24. RESULTS: The safety population included 300 patients; the full analysis set included 290 patients (278 patients at W24). At W8, a statistically significant difference (P<0.03) was observed for Skindex-16 domains in all assessed subgroups. Clinicians and patients reported high global satisfaction (mean [SD] scores of 74.9 [23.9] and 72.0 [24.6], respectively) at W24. Overall skin appearance improved from baseline to W24 (83.6% clinicians; 78.5% patients). IGA success (IGA score of 0-1) was achieved by 71.9% of patients at W24 with a similar % at W8 (73.8%) suggesting a stable effectiveness over time. About 5% of patients reported at least one adverse event, 4% reported at least one serious adverse event and no patients reported serious adverse drug reactions. At W8, the most frequently reported local skin reactions were mild/moderate erythema (47.6%) and flaking/scaling (49.6%). CONCLUSIONS: Treatment with tirbanibulin demonstrated effectiveness in the management of AK lesions and a favorable safety and tolerability profile. Furthermore, QoL was improved as early as W8, and both patients and clinicians reported high levels of treatment satisfaction, independently of patients' characteristics. J Drugs Dermatol. 2024;23(5):338-346. doi:10.36849/JDD.8264.

Putting the Formulation Back in Foam: Optimizing Seborrheic Dermatitis Treatment Across Diverse Hair Types.

Seborrheic dermatitis (SD) is a chronic inflammatory skin condition that commonly involves the scalp, and thus, affects a diverse demographic with varying hair care needs. Current SD treatments are limited based on optimized formulation, efficacy, adverse events, and lack of placebo-controlled trials. A novel roflumilast foam formulation has emerged as a promising therapeutic option optimally designed for use on the scalp and other hair-bearing areas. We conducted a comprehensive assessment of beauty industry standards, confirming the foam formulation's alignment with industry guidelines and exclusion of potentially harmful ingredients. In addition, consultation with an expert dermatologist panel yielded a strong endorsement, underscoring a high level of confidence in prescribing the foam across diverse hair and skin types.

INDIVIDUAL ARTICLE: Real-World Patient Cases Using Botanical Serum-Containing Corrective Gel as an Adjunct to Aesthetic Facial Laser or Microneedling Radiofrequency (MRF) Treatment.

Integrated skin care is defined as the complementary use of topical treatments to nonsurgical facial rejuvenation procedures, such as lasers and radiofrequency microneedling devices, to produce pleasing aesthetic results. Real-world experience from expert dermatologists is invaluable in guiding patient treatment plans, as there are limited clinical trials on the efficacy of integrated skincare regimens. The SkinCeuticals (New York, NY) Phyto Corrective gel (botanical serum-containing corrective gel) contains a lightweight botanical serum that hydrates, calms, and soothes skin. It contains antioxidant and anti-inflammatory ingredients derived from plant and fruit extracts, making it an appealing option for adjunctive treatment of post-procedure erythema and swelling.  J Drugs Dermatol. 2024;23:3(Suppl 2):s3-s14.

Promoting a Healthy Skin Barrier Using Skin Care in People With Mature Skin Xerosis.

INTRODUCTION: Most people are living into their sixties and beyond. Fundamental changes in chronologically aged skin have significant and widespread dermatological implications. This review discusses aging-associated alterations in epidermal function leading to xerosis and related pruritus and the benefits of maintaining or restoring a healthy skin barrier using skincare, specifically ceramide-containing skincare.   Methods: A panel of 7 dermatologists convened for a meeting to review aspects of xerosis in mature skin, skin barrier changes, and nuances in the treatment and maintenance of mature skin using gentle cleansers and moisturizers. From the selected literature, 13 statements were drafted. During the meeting, the draft statements underwent the panel's evaluation at a workshop, followed by a plenary discussion adopting 5 statements using evidence from the literature coupled with the panel's opinions and experiences. RESULTS: The exact etiology of xerosis is not entirely understood and likely depends on several genetic and environmental mechanisms. Aging-associated changes in epidermal function include a marked reduction in total lipids in the stratum corneum relative to young skin due to reduced epidermal lipid synthesis. In aging skin, xerosis is significantly associated with pruritus. Studies have shown that lipid-containing skin care, such as a gentle ceramide-containing cleanser and moisturizer, promotes a healthy barrier reducing xerosis and pruritus in individuals with mature skin.  Conclusions: The development of xerosis in mature skin involves several genetic and environmental mechanisms. Skincare, including gentle cleansers and moisturizers, has reduced xerosis and pruritus in mature skin individuals.     J Drugs Dermatol. 2024;23(1):1253-1259.     doi:10.36849/JDD.7560.

A Review of the Diagnostic and Therapeutic Gaps in Rosacea Management: Consensus Opinion.

Rosacea is a common, chronic inflammatory disease characterized by both fluctuating and fixed heterogeneous signs such as facial erythema, papules/pustules, telangiectasia, acute vasodilation (flushing), and phymatous changes, and symptoms such as cutaneous stinging and burning. The shift to a phenotype-based approach to rosacea management has improved the consistency of recommendations across recent published guidelines. Consistent and thorough guidance for the classification, diagnosis, and management of the disease is difficult, as the mechanisms underlying the development of rosacea are still not completely understood nor universally accepted. Here, we provide a critical review of current published guidance, and gaps in the knowledge and management of rosacea. We present the recently approved microencapsulated benzoyl peroxide as an effective topical treatment option for papulopustular rosacea. Benzoyl peroxide (BPO) has been used in acne management for many years; however, many clinicians perceive treatment of rosacea with any BPO formulation to be counterintuitive because of concerns of potential skin irritation, while the lack of an accepted mechanism of action on rosacea pathophysiology means that others may be hesitant to use BPO as a treatment. Minocycline foam 1.5% is also an option for the treatment of inflammatory lesions in rosacea, with a decreased risk of systemic adverse events compared with oral minocycline.

Higher Responder Rates Observed With Live Participant Assessment Versus Photographic Assessment After VYC-20L Hyaluronic Acid Treatment for Chin Augmentation.

BACKGROUND: In an evaluator-blinded, randomized controlled trial, the hyaluronic acid soft-tissue filler VYC-20L injectable gel was safe and effective for correcting volume deficits and retrusion in the chin. OBJECTIVES: The objective of this subanalysis was to compare responder rates obtained with photographic vs live assessments. METHODS: Participants were randomized 3:1 to VYC-20L treatment or a 6-month, no-treatment control period followed by optional treatment. Responder rates (≥1-point improvement from baseline on the validated Allergan Chin Retrusion Scale [ACRS]) obtained with photographic assessments and live assessments at Month 6 were compared. Prespecified subgroup analyses compared responder rates by baseline ACRS severity, filler volume, cannula usage, and investigation site. RESULTS: VYC-20L was effective for chin augmentation as evaluated with both live and photographic assessments. The ACRS responder rates at Month 6 were 91.8% with live assessments and 56.3% with photographic assessments. Consistently higher response rates were observed by live vs photographic assessment regardless of baseline ACRS severity, filler volume, cannula usage, and investigation site. CONCLUSIONS: Live assessment of ACRS response after VYC-20L treatment resulted in higher responder rates than photographic assessment, supporting the use of live assessment for this indication to approximate real-world clinical practice.

Field Therapy for Actinic Keratosis: A Structured Review of the Literature on Efficacy, Cost, and Adherence.

BACKGROUND: Although there are evidence-based guidelines for actinic keratosis management, selecting a cost-effective field therapy is challenging because of limited studies comparing cost, efficacy, and adherence among treatments. OBJECTIVE: To review the literature on field-directed therapies for actinic keratosis, comparing efficacy, cost, and adherence data for topical and in-office treatments. MATERIALS AND METHODS: PubMed, Embase, Web of Science, and Google Scholar databases were searched from October 2020 to March 2021 for articles on field therapy for actinic keratosis. Total cost per regimen was estimated using wholesale acquisition cost package prices and Medicare coverage rates for May 2021. Effective cost was approximated by dividing total cost by complete response rate. RESULTS: Efficacy data for various field therapies range widely, and long-term follow-up is limited. Cross-study comparisons are challenging because of heterogeneity of studies. Field-directed therapy with topical 5-fluorouracil and photodynamic therapy have similar effective cost. Adherence may significantly affect real-world efficacy and long-term clearance; this would favor shorter duration topical regimens or in-office procedures. CONCLUSION: Standardization of future studies examining efficacy of field treatments for actinic keratosis will allow comparison across treatments. In-office treatments such as photodynamic therapy represent a cost-effective alternative to topical therapies with comparable efficacy.

Multicenter, prospective feasibility study of Nano-Pulse Stimulation™ technology for the treatment of both nodular and superficial low-risk basal cell carcinoma.

Background: Nano-Pulse Stimulation™ (NPS™) therapy is a new, non-thermal bioelectric modality that applies ultrashort pulses of electric energy to trigger regulated cell death (RCD) in treated tissues. Instead of initiating necrosis by heating or freezing, NPS therapy permeabilizes intracellular organelles to activate the cell's own self-destruct pathway of programmed or regulated cell death. Unlike cryotherapeutic procedures that can both damage structural tissues and diffuse into the periphery beyond the margins of the lesion, NPS therapy only affects cells within the treated zone leaving surrounding tissue and acellular components unaffected. Methods: In this study we treated 37 basal cell carcinoma lesions on 30 subjects (NCT04918381). The treated lesions were photographed on 3-, 7-, 14-, 30- and 60-days after treatment. All subjects then underwent surgical excision for histological examination of the treated tissue. Results: 92% of the BCC lesions (34 of 37) showed complete histological clearance of BCC. Histologic analysis of the 3 cases where residual BCC was noted indicated that full energy coverage was not achieved, which could be remedied with an improved treatment guide to standardize and optimize the CellFX® procedure based on NPS technology. Conclusion: The CellFX procedure was shown to be safe and effective for the treatment of low-risk nodular and superficial BCC lesions.

Tirbanibulin for Actinic Keratosis: Insights into the Mechanism of Action.

Actinic keratosis (AK) is a common pre-neoplastic skin lesion constituted by uncontrolled proliferation of atypical keratinocytes that may evolve to squamous cell carcinoma. With global prevalence increasing, AK is expected to be the most common carcinoma of the skin. Tirbanibulin is a reversible tubulin polymerization inhibitor with potent anti-proliferative and anti-tumoral effects. In-vivo and in-vitro studies have shown that tirbanibulin significantly inhibits cell proliferation, tumor growth and downregulates Src signaling with no overt toxicity. Early phase and Phase III trials have shown high lesion clearance, compliance, and few side effects of once daily tirbanibulin treatment. This review discusses tirbanibulin anti-cancer activity, focusing on tubulin polymerization and Src signaling inhibitory effects, highlighting relevant literature and novel preclinical results from the ATNXUS-KX01-001 study. Furthermore, we address the relevant findings obtained in recent clinical trials to evaluate the safety, efficacy, pharmacokinetics, clearance efficacy, and side effects of the 1% tirbanibulin ointment applied once daily. In summary, we highlight preclinical and clinical evidence on the use of tirbanibulin as an effective and safe treatment option for AK.

Knowledge Gaps Among Dermatologists Regarding Immunotherapy for Non-melanoma Skin Cancer.

Background: Advanced nonmelanoma skin cancer (NMSC) is a sometimes unrecognized public health burden. The development of immune checkpoint inhibitors (ICIs), such as those affecting programmed cell death protein-1 (PD-1), have dramatically changed the management of advanced NMSC. Dermatologists need to be knowledgeable about these therapies given their key role in diagnosing, treating, and comanaging NMSC. The purpose of this study was to assess the knowledge base and identify knowledge gaps that dermatologists may have regarding ICIs and assess advanced NMSC referral patterns. Methods: A 10-question survey was emailed to United States-based dermatologists in July 2021 assessing knowledge of ICI therapy and referral patterns for metastatic cutaneous squamous cell carcinoma (mcSCC) or locally advanced basal cell carcinoma (laBCC) management. Results: At their current knowledge level, respondents averaged 40.6 out of 100 (95% CI [35.1, 46.0]) when asked how comfortable they feel counseling a patient on the risks and benefits of an ICI. Seventy-one percent reported that having more information about treatment for mcSCC or laBCC would be helpful in their practice. Being in practice for less than 10 years was not significantly associated with desiring more information about treatment. The respondents reported that the highest number of annual average referrals out for mcSCC or laBCC were made to Mohs surgeons. Fifty-four percent of respondents received referrals for mcSCC or laBCC, and of the providers receiving referrals, 40 percent of them came from general dermatology. Conclusion: These results demonstrate that a knowledge gap exists for dermatologists in treating mcSCC and laBCC with immunotherapy. There is a need among all dermatologists, regardless of years in practice, to receive this information.

A Randomized, Controlled Trial of Trifarotene Plus Doxycycline for Severe Acne Vulgaris.

Objective: We evaluated the efficacy and safety of trifarotene plus oral doxycycline in acne. Methods: This was a randomized (2:1 ratio) 12-week, double-blind study of once-daily trifarotene cream 50µg/g plus enteric-coated doxycycline 120mg (T+D) versus trifarotene vehicle and doxycycline placebo (V+P). Patients were aged 12 years or older with severe facial acne (≥20 inflammatory lesions, 30 to 120 non-inflammatory lesions, and ≤4 nodules). Efficacy outcomes included change from baseline in lesion counts and success (score of 0/1 with ≥2 grade improvement) on investigator global assessment (IGA). Safety was assessed by adverse events and local tolerability. Results: The study enrolled 133 subjects in the T+D group and 69 subjects in the V+P group. The population was balanced, with an approximately even ratio of adolescent (12-17 years) and adult (≥18 years) subjects. The absolute change in lesion counts from baseline were: -69.1 T+D versus -48.1 V+P for total lesions, -29.4 T+D versus -19.5 V+P for inflammatory lesions, and -39.5 T+D versus -28.2 for non-inflammatory lesions (P<0.0001 for all). Success was achieved by 31.7 percent of subjects in the T+D group versus 15.8 percent in the V+P group (P=0.0107). The safety and tolerability profiles were comparable between the T+D and V+P arms. Conclusion: T+D was demonstrated to be safe and efficacious as a treatment option for patients with severe acne.

Focused update: Guidelines of care for the management of actinic keratosis.

BACKGROUND: Actinic keratoses (AKs) are rough scaly patches that arise on chronically UV-exposed skin and can progress to keratinocyte carcinoma. OBJECTIVE: In 2021, the American Academy of Dermatology published guidelines to assist in clinical decision-making for the management of AK. The purpose of this focused guideline update is to incorporate recently available evidence on the use of topical tirbanibulin to treat AK. METHODS: A multidisciplinary work group conducted a systematic review to evaluate data on the use of tirbanibulin for AK and applied the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of the evidence and formulating and grading a clinical recommendation. The graded recommendation was voted on to achieve consensus. RESULTS: Two trials were identified, and analysis of the evidence resulted in 1 recommendation. LIMITATIONS: This analysis is based on the best available evidence at the time it was conducted. Long-term efficacy and safety data are not currently available. CONCLUSIONS: A strong recommendation for the use of topical tirbanibulin to join the currently recommended list of topical therapies for AK was made on the basis of the available evidence.

Evidence-Based Consensus Recommendations for the Evolving Treatment of Patients with High-Risk and Advanced Cutaneous Squamous Cell Carcinoma.

Cutaneous squamous cell carcinoma is the second most common skin cancer in the United States. Currently, there is no standardized management approach for patients with cutaneous squamous cell carcinoma who develop metastatic or locally advanced disease and are not candidates for curative surgery or curative radiation. To address this issue, the Expert Cutaneous Squamous Cell Carcinoma Leadership program convened an expert steering committee to develop evidence-based consensus recommendations on the basis of a large, structured literature review. Consensus was achieved through modified Delphi methodology. The steering committee included five dermatologists, three medical oncologists, two head and neck surgeons, one radiation oncologist, and a patient advocacy group representative. The steering committee aligned on the following clinical topics: diagnosis and identification of patients considered not candidates for surgery; staging systems and risk stratification in cutaneous squamous cell carcinoma; the role of radiation therapy, surgery, and systemic therapy in the management of advanced disease, with a focus on immunotherapy; referral patterns; survivorship care; and inclusion of the patient's perspective. Consensus was achieved on 34 recommendations addressing 12 key clinical questions. The Expert Cutaneous Squamous Cell Carcinoma Leadership steering committee's evidence-based consensus recommendations may provide healthcare professionals with practically oriented guidance to help optimize outcomes for patients with advanced cutaneous squamous cell carcinoma.

Guidelines of care for the management of actinic keratosis: Executive summary.

BACKGROUND: Actinic keratoses (AK) are rough scaly patches that arise on chronically ultraviolet-exposed skin and can progress to keratinocyte carcinoma. Treatment options for AK include topical medications, photodynamic therapy, cryosurgery, and laser ablation. OBJECTIVE: This executive summary provides a synopsis of the 18 evidence-based recommendations for the treatment of AK detailed in the Guidelines of Care for the Management of Actinic Keratosis. METHODS: A multidisciplinary workgroup conducted a systematic review to address 5 clinical questions on the management of AKs and applied the Grading of Recommendations Assessment, Development and Evaluation approach for assessing the certainty of the evidence and formulating and grading clinical recommendations. Graded recommendations were voted on to achieve consensus. RESULTS: Analysis of the evidence resulted in 18 recommendations, suggesting there are several effective treatments available for AK. LIMITATIONS: The analysis informing the recommendations was based on the best available evidence at the time it was conducted. The results of future studies may necessitate a revision of current recommendations. CONCLUSIONS: Strong recommendations are presented for using ultraviolet protection, topical imiquimod, topical 5-fluorouracil, and cryosurgery. Conditional recommendations are presented for the use of photodynamic therapy and diclofenac for the treatment of AK, both individually and as part of combination therapy regimens.

A Series of Tattoo-associated Mycobacterium Fortuitum Infections.

Mycobacterium fortuitum is a rapidly growing mycobacterium known to spread through many sources, including tap water. This organism can have variable presentation between patients which can lead to a delay in diagnosis. Here, we report a series of eight cases of tattoo-associated M. fortuitum infections that presented between December 2010 and January 2011, which were later linked to a single tattoo provider using gray tattoo ink made by diluting black ink with nonsterile tap water. In this case series, we emphasize the lack of pathognomonic features of these infections, the variability in culture and biopsy results, the importance of obtaining a culture in addition to a biopsy, and the importance of identifying the source of infection when determining management.

Guidelines of care for the management of actinic keratosis.

BACKGROUND: Actinic keratoses (AK) are rough scaly patches that arise on chronically ultraviolet-exposed skin and can progress to keratinocyte carcinoma. OBJECTIVE: This analysis examined the literature related to the management of AK to provide evidence-based recommendations for treatment. Grading, histologic classification, natural history, risk of progression, and dermatologic surveillance of AKs are also discussed. METHODS: A multidisciplinary Work Group conducted a systematic review to address 5 clinical questions on the management of AKs and applied the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of the evidence and formulating and grading clinical recommendations. Graded recommendations were voted on to achieve consensus. RESULTS: Analysis of the evidence resulted in 18 recommendations. LIMITATIONS: This analysis is based on the best available evidence at the time it was conducted. The pragmatic decision to limit the literature review to English language randomized trials may have excluded data published in other languages or limited identification of relevant long-term follow-up data. CONCLUSIONS: Strong recommendations are made for using ultraviolet protection, topical imiquimod, topical 5-fluorouracil, and cryosurgery. Conditional recommendations are made for the use of photodynamic therapy and diclofenac for the treatment of AK, both individually and as part of combination therapy regimens.

Phase 3 Trials of Tirbanibulin Ointment for Actinic Keratosis.

BACKGROUND: The tubulin polymerization and Src kinase signaling inhibitor tirbanibulin is being investigated as a topical treatment for actinic keratosis, a precursor of squamous-cell carcinoma. METHODS: In two identically designed double-blind trials, we randomly assigned, in a 1:1 ratio, adults with actinic keratoses on the face or scalp to receive either topical tirbanibulin or vehicle (placebo) ointment. The ointment was applied by the patients to a 25-cm2 contiguous area containing four to eight lesions once daily for 5 consecutive days. The primary outcome was the percentage of patients with a complete (100%) reduction in the number of lesions in the application area at day 57. The secondary outcome was the percentage of patients with a partial (≥75%) reduction in the number of lesions within the application area at day 57. The incidence of recurrence was evaluated at 1 year. Local reactions were scored with the use of 4-point scale (ranging from 0 [absent] to 3 [severe]). RESULTS: A total of 702 patients were enrolled in the two trials (351 patients per trial). Complete clearance in trial 1 occurred in 44% of the patients (77 of 175) in the tirbanibulin group and in 5% of those (8 of 176) in the vehicle group (difference, 40 percentage points; 95% confidence interval [CI], 32 to 47; P<0.001); in trial 2, the percentages were 54% (97 of 178 patients) and 13% (22 of 173), respectively (difference, 42 percentage points; 95% CI, 33 to 51; P<0.001). The percentages of patients with partial clearance were significantly higher in the tirbanibulin groups than in the vehicle groups. At 1 year, the estimated percentage of patients with recurrent lesions was 47% among patients who had had a complete response to tirbanibulin. The most common local reactions to tirbanibulin were erythema in 91% of the patients and flaking or scaling in 82%. Adverse events with tirbanibulin were application-site pain in 10% of the patients and pruritus in 9%, all of which resolved. CONCLUSIONS: In two identically designed trials, tirbanibulin 1% ointment applied once daily for 5 days was superior to vehicle for the treatment of actinic keratosis at 2 months but was associated with transient local reactions and recurrence of lesions at 1 year. Trials comparing tirbanibulin with conventional treatments and that have longer follow-up are needed to determine the effects of tirbanibulin therapy on actinic keratosis. (Funded by Athenex; ClinicalTrials.gov numbers, NCT03285477 and NCT03285490.).

Photodynamic Therapy with 5-aminolevulinic Acid 10% Gel and Red Light for the Treatment of Actinic Keratosis, Nonmelanoma Skin Cancers, and Acne: Current Evidence and Best Practices.

Photodynamic therapy (PDT) can be an effective treatment for actinic keratosis (AK) as well as selected non-melanoma skin cancers (NMSCs), such as Bowen's disease and superficial basal cell carcinoma. PDT has also demonstrated effectiveness in the management of acne vulgaris. Results from controlled clinical trials have shown the safety and efficacy of PDT for these conditions with the use of different photosensitizers and a wide range of light sources. PDT has been employed effectively as monotherapy and in combination with other topicals and alternate light or laser energy therapies. This article provides expert practical guidance for the use of the newest 5-aminolevulinic acid (ALA) product (ALA 10% gel) plus red light as monotherapy for AKs, NMSC, and acne. Here, information from clinical guidelines and a summary of supporting evidence is provided for each cutaneous condition. The authors also provide detailed guidance for employing ALA 10% gel, a photosensitizer precursor, for each of these applications.