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.

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.

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.

Postmarket Experience of Polymethylmethacrylate-Collagen Gel Dermal Filler.

BACKGROUND: This report synthesizes 12 years of postmarket surveillance data (PMSD) for polymethylmethacrylate (PMMA)-collagen gel dermal filler. OBJECTIVE: To present PMMA-collagen gel PMSD findings on real-world safety. METHODS: Postmarket surveillance data were collected from January 2007 to December 2018 and evaluated to determine the overall adverse event (AE) complaint rate, the nature of reported AEs, and whether the complaint included on-label, off-label, both, or unknown areas. RESULTS: In the 12 years examined, 754,229 PMMA-collagen gel syringes were distributed worldwide, and 839 product-related complaints (including those classified as unknown) resulted in an overall complaint rate of 0.11%. The 3 most frequent primary complaints in AE reports were lump/bump (309/839, 37%), nodule (152/839, 18%), and swelling (138/839, 16%). Histologically confirmed granuloma accounted for 17/839 complaints (2.0%; overall complaint rate of 0.002%), and histologically unconfirmed granuloma accounted for 66/839 complaints (8%; overall rate of 0.009%). There were 666 complaints representing AEs related to off-label injection in which the periocular area was most frequently represented. CONCLUSION: Although a limiting factor across all PMSD is voluntary reporting and resultant underrepresentation of AEs, the PMSD reported here are consistent with safety findings from US clinical studies in more than 1,500 patients with up to 5 years of follow-up.

Enhancing Outcomes in Seborrheic Keratosis: Using a Novel Treatment Solution

Seborrheic keratosis (SK) is an extremely common benign cutaneous lesion that often appears on individuals older than the age of 50. SK lesions can appear in numerous clinical variations, but typically, SKs present with a well-demarcated, "stuck-on" appearance having a waxy or keratotic surface. Even though SK lesions are usually benign, many individuals elect for SK treatment or removal due to cosmetic concerns. One study regarding SK appearance reported that 61% of women tried to conceal the appearance of the SKs by using certain hairstyles, make-up, and clothes. Conventional treatment for SK lesions ranges from cryosurgery to curettage. Although these removal methods are effective for SK treatment, each method contains a potential for side effects such as pigmentation changes, scarring, and discomfort before and after the procedure. Due to many of these concerns, patients prefer topical treatments for SKs, which has led to a new emerging topical containing hydrogen peroxide topical solution 40% (HP40; Eskata™). Here, we report the methods and results from an HP40 treatment for two individuals, each over 70 years old. Application of the topical solution was performed on each target SK, up to four times, with a 20-second application and 1 minute between applications. The two participants reported moderate success of HP40 in the removal of their SKs with minimal adverse effects. J Drugs Dermatol. 2019;18(7 Suppl):s178-182.

Treatment of Atrophic Facial Acne Scars With Microneedling Followed by Polymethylmethacrylate-Collagen Gel Dermal Filler.

BACKGROUND: Microneedling and soft-tissue filler injections have been used independently to improve acne scarring. The effectiveness of a combined approach using microneedling followed by polymethylmethacrylate (PMMA)-collagen gel has not been carefully studied. OBJECTIVE: The goal of this study was to assess the effectiveness and safety of microneedling alone versus microneedling followed by injection of PMMA-collagen gel filler for correction of atrophic facial acne scars. METHODS: We conducted a multicenter, open-label, randomized, prospective study on subjects with distensible atrophic acne scars in the face to determine whether microneedling with PMMA-collagen gel is a superior acne scar treatment over microneedling alone. Forty-four subjects received 3 microneedling treatments over a 12-week period followed by randomization to treatments with PMMA-collagen gel (treatment group) or no further treatment (control group). RESULTS: At 24 weeks, the treatment group achieved a statistically significant improvement in acne scores over microneedling alone. The improvement continued at 36 weeks. At 24 weeks, the treatment group showed a strong trend in improvement on the Physician Global Aesthetic Improvement Scale compared with microneedling alone.

Purpura and fillers: a review of pre-procedural, intra-procedural, and post-procedural considerations.

Injectable aesthetic fillers are associated with the common and expected side effect of purpura or bruising. There are pre-procedural, intra-procedural and post-procedural considerations that can potentially minimize bruising. Traditional and newer techniques are discussed in this review and the benefits and risks of each technique will be provided.

Efficacy and tolerability of low molecular weight hyaluronic acid sodium salt 0.2% cream in rosacea.

OBJECTIVE: Rosacea is a chronic cutaneous disorder characterized by flushing, erythema, telangiectasia, edema, papules, and pustules. The cause of this inflammatory disorder is unknown, but is thought to be multifaceted. Primary treatments for rosacea are typically oral antibiotics and topical therapies. Hyaluronic acid sodium salt cream 0.2% is a topical device containing low molecular weight hyaluronic acid (LMW-HA) that is effective in normalizing the cutaneous inflammatory response. The objective of this study was to evaluate the efficacy and safety of hyaluronic acid sodium salt cream 0.2%. DESIGN AND SETTING: Prospective, observational, non-blinded efficacy and tolerability study in an outpatient setting. PARTICIPANTS: Individuals 18 to 75 years of age with mild to moderate facial rosacea. MEASUREMENTS: Outcome measures included papules, pustules, erythema, edema, telangiectasia, burning or stinging, dryness and provider global assessment (PGA), which were all measured on a five-point scale. Subjects were assessed at baseline, week 2, week 4, and week 8. RESULTS: Final data for 14 of 15 subjects are presented. Through visual grading assessments, hyaluronic acid sodium salt cream 0.2% was shown to improve the provider global assessment by 47.5 percent from baseline to week 4. Reductions in papules, erythema, burning or stinging, and dryness were 47, 51.7, 65, and 78.8 percent, respectively at week 4. At week 8, the provider global assessment was improved from baseline in 78.5 percent of subjects. CONCLUSION: Improvement was noted in measured clinical parameters with use of topical low molecular weight hyaluronic acid. Topical low molecular weight hyaluronic acid is another option that may be considered for the treatment of rosacea in the adult population. Compliance and tolerance were excellent. Consideration should be given to use for individuals with rosacea characterized by an erythematous and/or papular component.