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ImportanceGiven that mycosis fungoides−cutaneous T-cell lymphoma (MF/CTCL) is chronic, there is a need for additional therapies with minimal short- and long-term adverse effects. Topical synthetic hypericin ointment, 0.25%, activated with visible light is a novel, nonmutagenic photodynamic therapy (PDT).ObjectivesTo determine the efficacy and safety of topical synthetic hypericin ointment, 0.25%, activated with visible light as a nonmutagenic PDT in early-stage MF/CTCL.Design, Settings, and ParticipantsThis was a multicenter, placebo-controlled, double-blinded, phase 3 randomized clinical trial (FLASH study) conducted from December 2015 to November 2020 at 39 academic and community-based US medical centers. Participants were adults (≥18 years) with early-stage (IA-IIA) MF/CTCL.InterventionsIn cycle 1, patients were randomized 2:1 to receive hypericin or placebo to 3 index lesions twice weekly for 6 weeks. In cycle 2, all patients received the active drug for 6 weeks to index lesions. In cycle 3 (optional), both index and additional lesions received active drug for 6 weeks.Main Outcomes and MeasuresThe primary end point was index lesion response rate (ILRR), defined as 50% or greater improvement in modified Composite Assessment of Index Lesion Severity (mCAILS) score from baseline after 6 weeks of therapy for cycle 1. For cycles 2 and 3, open label response rates were secondary end points. Adverse events (AEs) were assessed at each treatment visit, after each cycle, and then monthly for 6 months. Data analyses were performed on December 21, 2020.ResultsThe study population comprised 169 patients (mean [SD] age, 58.4 [16.0] years; 96 [57.8%] men; 120 [72.3%] White individuals) with early-stage MF/CTCL. After 6 weeks of treatment, hypericin PDT was more effective than placebo (cycle 1 ILRR, 16% vs 4%; P = .04). The ILRR increased to 40% in patients who received 2 cycles of hypericin PDT (P P Conclusion and RelevanceThe findings of this randomized clinical trial indicate that synthetic hypericin PDT is effective in early-stage patch and plaque MF/CTCL and has a favorable safety profile.Trial RegistrationClinicalTrials.gov Identifier: NCT02448381

Background OnabotulinumtoxinA 20 U reduces glabellar line (GL) severity at maximum frown for approximately 3 to 4 months. Small studies have suggested that >20-U doses may increase the efficacy and duration of response for GLs. Objectives The aim of this study was to evaluate safety, pharmacodynamic response, and treatment satisfaction with onabotulinumtoxinA doses ≥20 U for GLs. Methods This 48-week, double-blind study compared 40, 60, and 80 U onabotulinumtoxinA vs 20 U and placebo in women with moderate or severe dynamic GLs on the Allergan Facial Wrinkle Scale. The following parameters were evaluated: the percentage of subjects with investigator-assessed ≥1-grade Facial Wrinkle Scale improvement from baseline at maximum frown (responders) at Week 24; the estimated median duration of response; the proportion of mostly/very satisfied responders on the Facial Line Satisfaction Questionnaire follow-up Items 1 to 5; and treatment-emergent adverse events. Results The modified intent-to-treat population (N = 226) had a mean age of 48.0 years, with similar baseline GL severity between treatment groups. Week 24 responder rates were 0% for placebo and 16.0%, 32.0%, 30.6%, and 38.5% for onabotulinumtoxinA 20, 40, 60, and 80 U, with significant (P Conclusions GL treatment with onabotulinumtoxinA doses >20 U demonstrated longer duration of response and higher patient-reported satisfaction vs the on-label 20-U dose with no apparent impact on safety variables. Level of Evidence: 2

Background Most people with acne are at risk of developing acne scars, but the impact of these scars on patients' quality of life is poorly researched. Objective To assess the perspective of patients with acne scars and the impact of these scars on their emotional well-being and social functioning. Methods A 60-minute interview of 30 adults with acne scars informed and contextualized the development of a cross-sectional survey of 723 adults with atrophic acne scars. Results The main themes identified in the qualitative interviews included acceptability to self and others, social functioning, and emotional well-being. In the cross-sectional survey, 31.6%, 49.6%, and 18.8% of the participants had mild, moderate, and severe/very severe acne scarring. The survey revealed that 25.7% of the participants felt less attractive, 27.5% were embarrassed or self-conscious because of their scars, 8.3% reported being verbally and/or physically abused because of their scars on a regular basis, and 15.9% felt that they were unfairly dismissed from work. In addition, 37.5% of the participants believed that their scars affected people's perceptions about them, and 19.7% of the participants were very bothered about hiding their scars daily. Moreover, 35.5% of the participants avoided public appearances, and 43.2% felt that their scars had negatively impacted their relationships. Limitations The temporal evaluation of the impact was not estimated. Conclusion Even mild atrophic acne scarring can evoke substantial emotional, social, and functional concerns.

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). Supplementary Information The online version contains supplementary material available at 10.1007/s40257-021-00650-3.

Rosacea is a chronic condition involving inflammation leading to a diminished skin barrier function in sebaceous gland-rich facial skin. The current algorithm represents part II of a series investigating similar topics associated with preventing, treating, and maintaining rosacea, including ceramides-containing skincare.The consensus process consisted of a modified Delphi technique. A previously published review by the US Cutaneous Rosacea Outcomes (USCRO) group on skin barrier deficiency in rosacea and the integration of over-the-counter (OTC) products and skincare recommended for rosacea treatment and maintenance informed the development of the current algorithm. The selected information from the literature searches, coupled with the USCRO group's opinion and experience, was used to develop, discuss, and reach a consensus on an evidence-based clinical treatment and maintenance algorithm focusing on rosacea phenotypes.The algorithm includes foundational measures to be taken by all patients with rosacea and rosacea-prone skin. These measures include education, behavioral modifications, avoidance of triggers and skin irritants, preventative skincare, and sun avoidance and sunscreen use. The algorithm further describes how assessment of skin condition and grading of cutaneous rosacea should take place during treatment and maintenance while the preventative measures continue.Prescription medications combined with gentle cleansers, moisturizers, and sunscreen support a successful rosacea therapy. J Drugs Dermatol. 2022;21:9(Suppl 1):s3-10.

Background Baricitinib, a selective Janus kinase 1/Janus kinase 2 inhibitor, is indicated in the European Union and Japan for the treatment of moderate-to-severe atopic dermatitis (AD) in adults who are candidates for systemic therapy. Objective The objective of this study was to evaluate the safety of baricitinib 2 mg in the AD clinical program. Methods Six double-blind, randomized, placebo-controlled studies, and two long-term extension studies were summarized in two datasets. Placebo comparison was based on six 16-week studies with baricitinib 2 mg. All-bari-2-mg-AD included patients who received baricitinib 2 mg at any time during the eight studies. Results In total, 1598 patients received once-daily baricitinib 2 mg for 1434.2 patient-years of exposure (median 330 days/maximum 2.4 years). Treatment-emergent adverse events were higher for baricitinib 2 mg (57.9%) vs placebo (51.6%). Serious adverse events, serious infections, and opportunistic infections were low in frequency and similar between baricitinib 2 mg and placebo. There were no malignancies, gastrointestinal perforations, or major adverse cardiovascular events with baricitinib 2 mg in the placebo-controlled period. Herpes simplex (cluster) was higher for baricitinib 2 mg (3.8%) vs placebo (2.8%); rates decreased with extended 2 mg exposure. In All-bari-2-mg-AD, there were five malignancies other than non-melanoma skin cancer, two major adverse cardiovascular events, one peripheral venous thrombosis, one arterial thrombosis, and no pulmonary embolisms, deep vein thromboses, or deaths. Conclusions This integrated analysis in patients with moderate-to-severe AD confirms the established safety profile of baricitinib 2 mg. Longer exposure to treatment is required to evaluate risks of malignancies and major adverse cardiovascular events. Clinical Trial registration ClinicalTrials.gov identifiers: NCT02576938 (first posted 15 October, 2015); NCT03334396 (7 November, 2017); NCT03334422 (7 November, 2017); NCT03428100 (9 February, 2018); NCT03435081 (15 February, 2018); NCT03733301 (7 November, 2018); NCT03334435 (7 November, 2017); NCT03559270 (18 June, 2018). Supplementary Information The online version contains supplementary material available at 10.1007/s40257-021-00602-x., Plain Language Summary Baricitinib is a medication that helps an overactive immune system adjust itself, leading to improvements in the inflammatory condition atopic dermatitis. Baricitinib is approved for patients with moderate-to-severe atopic dermatitis in 40 countries. Because it works with the immune system, it is important to understand the safety of baricitinib. Safety information was collected from eight studies and analyzed in two datasets. The first dataset compared the safety of baricitinib 2 mg with placebo in six 16-week studies in which neither patient nor physician knew whether they were taking baricitinib or placebo. The second dataset included an additional two extension studies and examined the safety of baricitinib in all patients receiving at least one dose of baricitinib 2 mg. Patients took baricitinib 2 mg for a maximum of 2.4 years, with a median time of 330 days. In the first dataset, adverse events were higher for baricitinib 2 mg (57.9%) than placebo (51.6%). Serious adverse events, serious infections, and opportunistic infections were low in number and similar for patients taking baricitinib 2 mg or placebo. Herpes simplex infections were more frequent in patients taking baricitinib 2 mg (3.8%) than in those taking placebo (2.8%), but rates in those taking baricitinib 2 mg decreased with a longer treatment duration. There were no occurrences of cancer, gastrointestinal perforations, or major adverse cardiovascular events. In the second dataset, there were five reports of cancer other than non-melanoma skin cancer, two major adverse cardiovascular events, one peripheral venous thrombosis, one arterial thrombosis, and no pulmonary embolisms, deep vein thromboses, or deaths. Longer treatment with baricitinib is required to better understand the risks of developing cancer or major adverse cardiovascular events. This analysis of safety in patients with moderate-to-severe atopic dermatitis is consistent with the safety reported previously for baricitinib 2 mg. Video abstract Extended Safety Analysis of Baricitinib 2 mg in Adult Patients with Atopic Dermatitis: An Integrated Analysis from Eight Randomized Clinical Trials (MP4 87244 kb) Supplementary Information The online version contains supplementary material available at 10.1007/s40257-021-00602-x.

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.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-cmA 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; P0.001); 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; P0.001). 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.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.).

Background Glycopyrronium tosylate (GT; Qbrexza® [glycopyrronium] cloth, 2.4%) is a topical anticholinergic approved (USA) for primary axillary hyperhidrosis in patients aged ≥ 9 years. Objective The objective of this study was to compare the pharmacokinetics and safety of GT to oral glycopyrrolate (phase I study) and assess the relationship between glycopyrronium pharmacokinetics and anticholinergic-related adverse events or efficacy with population pharmacokinetics using data from two phase II studies. Methods In the phase I study, study staff applied GT to axillae of patients with primary axillary hyperhidrosis (aged 9–65 years) once daily (5 days); oral glycopyrrolate was administered to healthy adults (aged 18–65 years) every 8 hours (15 days). In the phase II studies (NCT02016885 [20 December, 2013], NCT02129660 [2 May, 2014]), adults with primary axillary hyperhidrosis applied topical glycopyrronium (0.8–3.2%) or vehicle to axillae once daily (4 weeks). Pharmacokinetic and adverse event data were collected in all studies. Results Glycopyrronium pharmacokinetic parameters were similar between adult and pediatric patients treated with GT; there was no evidence of accumulation. Systemic absorption of glycopyrronium was lower with GT vs oral glycopyrrolate. No anticholinergic-related adverse events occurred with GT in the phase I study, while dry mouth and nasal dryness occurred with oral glycopyrrolate; anticholinergic adverse events occurred in the phase II studies. In the population pharmacokinetic analysis, frequency/severity of anticholinergic-related adverse events increased with higher glycopyrronium concentration; no relationship was observed between efficacy and pharmacokinetic measures. Conclusions These studies indicate limited absorption of GT compared to oral glycopyrrolate and a low risk of anticholinergic adverse events with proper GT administration when following instructions for use (wipe each underarm once with same cloth, wash hands, avoid ocular contact). Supplementary Information The online version contains supplementary material available at 10.1007/s40262-020-00975-y.

Background Acne is the most common dermatological disorder. An impaired barrier function in acne vulgaris has been reported, as well as decreased amounts of epidermal ceramides. Also, many of the systemic and topical medications prescribed for the treatment of acne exacerbate these skin barrier disruptions and can lead to irritation and dry skin conditions. Aim The review explored the importance of maximizing adjunctive skincare, such as over-the-counter products for managing acne and avoiding adverse effects. Methods A literature review was conducted and included clinical acne guidelines, clinical studies, and review articles on acne prevention, treatment, and maintenance. Searches were made in PubMed and Google Scholar for English-language literature published between Jan 1, 2010, and Apr 1, 2020. Two clinicians manually reviewed selected publications. Results Seventy-four articles were included in the analyses. A variety of specialized cleansers and moisturizers are available as suitable adjunctive therapies for acne-prone skin. Lipid-free cleansers were found to be the most appropriate type of cleanser for acne-prone skin as they were associated with a low risk of skin irritation, and a near-physiological stratum corneum pH. Moisturizers typically included ingredients such as humectants, emollients, oil absorbers, and those with anti-inflammatory and/or barrier replenishing properties. Given the various adjunctive products available, decision frameworks were created for clinicians to use when selecting over-the-counter cleansers and moisturizers for acne-prone patients. Conclusion Informing clinicians about skin barrier dysfunction in acne and the benefits of adjunctive skincare may help them to choose the right product(s) to complement prescription therapy. J Drugs Dermatol. 2020;19(11): doi:10.36849/JDD.2020.5536.

We evaluated the efficacy of brodalumab in patients with nail or scalp psoriasis in three phase 3 studies (AMAGINE-1/-2/-3).In AMAGINE-1, scalp clearance, measured by the psoriasis scalp severity index (PSSI), was reported for patients who received brodalumab 210 mg every 2 weeks (Q2W) or placebo through 12 weeks. In AMAGINE-2/-3, nail clearance, measured by the nail psoriasis severity index (NAPSI), was reported for patients receiving either brodalumab 210 mg Q2W or ustekinumab continuously through 52 weeks.At week 12, significantly more patients receiving brodalumab achieved 75% and 100% improvement rates from baseline PSSI and had lower mean PSSI across 12 weeks compared with placebo, with significant improvement in PSSI evident with brodalumab 210 mg Q2W vs placebo by week 2. Across 52 weeks, patients receiving brodalumab achieved significantly greater complete clearance of nail psoriasis (NAPSI 0), lower mean NAPSI, and higher mean percent improvement rates from baseline NAPSI than patients receiving ustekinumab. At week 52, 63.8% of patients receiving brodalumab achieved NAPSI 0 vs 39.1% of patients receiving ustekinumab.Brodalumab was associated with clearance of scalp psoriasis through 12 weeks and improvements in nail psoriasis, including complete nail clearance, through 52 weeks.

FMX101 4% topical minocycline foam has been shown to be an effective and safe treatment for acne vulgaris (AV).To further evaluate the efficacy and safety of FMX101 4% in treating moderate to severe acne vulgaris.A 12-week, multicenter, randomized (1:1), double-blind, vehicle-controlled study was conducted. Coprimary end points were the absolute change in inflammatory lesion count from baseline and the rate of treatment success (Investigator's Global Assessment score of 0 or 1 with a ≥2-grade improvement).There were 1488 participants in the intent-to-treat population. The FMX101 4% group had significantly greater reductions in the number of inflammatory lesions from baseline (P .0001) and a greater rate of treatment success based on Investigator's Global Assessment (P .0001) versus the foam vehicle group at week 12. FMX101 4% was generally safe and well tolerated.The efficacy and safety of FMX101 4% were not characterized in participants with mild AV.FMX101 4% topical minocycline foam was effective and safe for the treatment of moderate to severe AV.

Background: As current tazarotene formulations indicated for acne (0.1%) can cause irritation, a new tazarotene 0.045% lotion formu-lation was developed using polymeric emulsion technology. The objective was to assess efficacy, safety, and tolerability of tazarotene 0.045% lotion in patients with moderate-to-severe acne in a pooled analysis of data from two identical phase 3, double-blind, random-ized, vehicle-controlled 12-week clinical studies. Methods: Patients aged ≥9 years with moderate-to-severe acne were randomized (1:1) to tazarotene 0.045% lotion or vehicle lotion applied once daily. Inflammatory and noninflammatory lesion counts and Evaluator's Global Severity Score (EGSS) were assessed. Treatment success was defined as a ≥2-grade improvement in EGSS and a score of 'clear'/'almost clear'. Adverse events (AEs) and cutaneous safety and tolerability were also assessed. Results: In total, 1614 patients (mean age: 20.5 years) were randomized to tazarotene 0.045% lotion (n=799) or vehicle (n=815). At week 12, tazarotene 0.045% lotion demonstrated statistically significant superiority versus vehicle in reducing inflammatory and non-inflammatory lesion counts (least-squares mean percent changes from baseline: inflammatory, -57.9% vs -47.8% [P

The term "exposome" describes the totality of exposures an individual is subjected to from conception to death. Both internal and external exposome factors affect skin health. External exposures that contribute to facial skin aging include solar radiation, air pollution, tobacco smoke, and unbalanced nutrition. The review explores scientific and clinical insights into the exposome impact on facial skin aging and topical mineralizing volcanic water use potential benefits.An expert panel of seven dermatologists and two clinical researchers specializing in aesthetic and dermatological indications reviewed and discussed the literature on the exposome and mineralizing volcanic water's role in relation to the exposome. Two virtual advisory boards were conducted between February and May 2021. Following the meetings, an additional systematic literature review explored publications relevant to the exposome, topical essential minerals, and skin health. The results of the two advisory boards, coupled with expert opinion and the outcome of the updated systematic literature review, informed the statements on which the advisors reached a consensus.A combination of in vivo, in vitro, and clinical data on topical mineralizing volcanic water application indicates that the serum supports the skin's antioxidant defenses and reduces skin inflammation. Additionally, the serum may have benefits as an adjunct for facial dermatoses and post-procedural skincare. J Drugs Dermatol. 2022;21:4(Suppl 1):s3-10.

Despite the emergence of multiple biologic drug options for psoriasis, unmet treatment needs remain. Biologic therapies can vary in their effectiveness and adverse events, and many patients experience a loss of treatment effect over time. After lack of response, treatment may be switched to a biologic with a different mechanism of action. Brodalumab, a human interleukin-17 (IL-17) receptor A antagonist, is approved for the treatment of adult patients with moderate-to-severe psoriasis with inadequate response or loss of response to prior systemic therapies. Because brodalumab targets the IL-17 receptor instead of the ligand itself, it not only targets a broader set of IL-17 isoforms but also may be effective in patients who received prior IL-17 inhibitors or failed to respond to antindash;IL-17 treatment. This is supported by long-term evidence from clinical trials and real-world studies of patients receiving brodalumab who were previously treated with IL-17 inhibitors. Additionally, brodalumab produces reliable treatment effects after use of biologics with other mechanisms of action, such as tumor necrosis factoralpha; and IL-12/IL-23 inhibitors, as well as after the use of multiple biologic therapies. For patients with psoriasis with inadequate response to one or more biologic therapies, brodalumab is an option that has the ability to lead to long-term skin clearance. J Drugs Dermatol. 2022;21(3):364-370. doi:10.36849/JDD.6743.

The interleukin-17 (IL-17) pathway plays a crucial role in the development of psoriasis. Briefly, naive T cells differentiate into helper T (Th17) cells through interaction with activated dendritic cells in the presence of IL-23, Th17 cells produce IL-17 cytokines, and keratinocytes stimulated by IL-17 ligands lead to aberrant differentiation and proliferation that promote production of proinflammatory chemokines and further recruitment of inflammatory cells, setting up a positive feedback loop. Currently, 3 US Food and Drug Administration–approved agents to treat psoriasis affect the IL-17 pathway: brodalumab, secukinumab, and ixekizumab. Brodalumab is a fully human IL-17 receptor A antagonist that blocks signaling of multiple downstream inflammatory cytokines involved in psoriasis. Secukinumab and ixekizumab selectively bind to and neutralize only IL-17A. Pharmacologic effects in patients with psoriasis include decreased keratinocyte hyperproliferation, reduced epidermal thickening, decreased inflammatory markers, and resolution of histologic and genomic features of psoriasis. In clinical trials, therapeutic doses of brodalumab, secukinumab, and ixekizumab have demonstrated skin clearance efficacy by psoriasis area and severity index and static physician’s global assessment scores at 12 weeks. The immunomodulation of these agents is associated with a favorable safety profile. Overall, the clinical improvement and normalization of genetic hallmarks of psoriasis provide a strong case for the unique role of IL-17 receptor blocking as a therapeutic mechanism of action to treat psoriasis. Understanding the unique mechanisms by which treatments interact with the IL-17 pathway to inhibit downstream proinflammatory signal cascade can help physicians make informed treatment decisions when selecting the appropriate medication for patients. J Drugs Dermatol. 2020;19(2)138-143. doi:10.36849/JDD.2020.4645

Background Acne affects more than 80% of adolescents and young adults, who most often develop acne scars. Supporting data on the effect of acne scars on patient’s health-related quality of life (HRQOL) are limited. Objective The aim was to determine how the severity of acne scars impacts the HRQOL of afflicted individuals. Methods In this population-based cross-sectional study, 723 adults with facial acne scars but without active acne lesions self-completed the Self-assessment of Clinical Acne-Related Scars (SCARS) questionnaire formulated to investigate degree of acne scarring. The Facial Acne Scar Quality of Life (FASQoL), Dermatology Life Quality Index (DLQI), and Dysmorphic Concern Questionnaire (DCQ) were completed to assess the attitude of these patients toward their scars and the impact of scarring on their HRQOL. Results The mean (standard error) DLQI score for facial acne scars was 6.26 (0.22). Acne scars were considered a ‘very large’ or ‘extremely large’ concern by 19.3% of participants with mild scars as compared to 20.1% and 34.0% of participants with moderate and severe/very severe scars, respectively (P = 0.003). Higher FASQoL scores were associated with increased severity of scarring (P = 0.001). In total, 16.9% of participants had clinical features of dysmorphia (i.e., DCQ > 13). DCQ scores were significantly higher among participants with more severe scarring (mean DCQ score of 8.04 [0.28], 8.40 [0.18], and 10.13 [0.08] among participants with mild, moderate, and severe/very severe acne scars, respectively; P = 0.001). Most commonly reported signs of emotional distress were self-consciousness (68.0%) and worry about scars not going away (74.8%). Conclusions This study highlights the significant psychosocial impact of atrophic acne scars in the form of embarrassment and self-consciousness. Individuals with mild scars also expressed significant impact on quality of life that increased with aggravation of scar severity. Patient-reported outcomes provide an insight into the physical, functional, and psychological impact of acne scarring from the patient’s perspective. Supplementary Information The online version contains supplementary material available at 10.1007/s40257-021-00628-1.

Background and objectives This study describes the effects of nano-pulse stimulation (NPS) technology on the common verruca with the objectives of demonstrating efficacy and safety. NPS technology applies nanosecond pulses of non-thermal electrical energy to induce highly localized regulated cell death in the cellular structures of the targeted zone with negligible effects on surrounding non-cellular structures. Previous clinical studies applying NPS to common, benign skin lesions have demonstrated safety and efficacy in clearing seborrheic keratoses and sebaceous hyperplasia. Study design/materials and methods Sixty-two subjects were enrolled at a total of five sites. One hundred and ninety-five study verrucae up to 10 mm wide were treated with NPS delivered by a console-based handheld applicator (CellFX® System; Pulse Biosciences) and follow-ups occurred every 30 days with the option to retreat at 30, 60, and 90 days. There were 62 untreated controls and 46% of the treated verrucae were recalcitrant. Results Overall, 75.3% (70/93) of the common verrucae, 72.7% (8/11) of the flat verrucae, and 43.8% (14/32) of the plantar verrucae treated with NPS were completely clear by 60 days following the last treatment and did not recur within the 120-day observation period. The majority (54%) of verrucae cleared with a single NPS procedure. The most common treatment site reactions were erythema (50.5%) and eschar formation (23.4%) on Day 30 and on Day 120 mild erythema was present in 14% of the cases and hyperpigmentation in 18.5%. No serious adverse events were reported. A particle counter was used during 11 NPS procedures on verrucae and no significant plume generation was detected during these procedures. Conclusions NPS is a safe and effective procedure for removing non-genital, cutaneous verrucae. Lasers Surg. Med. © 2021 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals LLC.

Rosacea, an inflammatory skin disease that leads to an impaired skin barrier function commonly involves the face. Symptoms of rosacea can be bothersome and include pain, stinging, burning, itching, and facial flushing. This review explored skin barrier impairment in rosacea and reduced symptomatology when using over the counter (OTC) skincare products.Nine dermatologists (the panel) completed a survey on OTC products they recommend for rosacea. The survey results were summarized, presented, and discussed during the online meeting, together with the results of a literature review. The outcome of these discussions, coupled with the panel's expert opinion and experience, is shown in the current review.Addressing barrier dysfunction by use of moisturizer and cleanser formulations that restore skin hydration, normalize skin pH, restore the microbiome, and skin lipids can assist in improving rosacea signs and symptoms. The panel's consensus was that in addition to the use of prescription medications, skincare recommendations are a crucial part of successful rosacea therapy. In addition to occlusives and humectants, barrier restoring ingredients such as ceramides, hyaluronic acid, and niacinamide were considered beneficial. Equally important was the absence of potentially irritating substances.The use of OTC products can improve rosacea symptomatology and signs. As adjuncts, these products are recommended before and during prescription therapy and as part of a maintenance regimen. J Drugs Dermatol. 20(4):384-392. doi:10.36849/JDD.5861 THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL fTEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

Background Acne confers an increased risk of physical, psychiatric, and psychosocial sequelae, potentially affecting multiple dimensions of health-related quality of life (HRQoL). Morbidity associated with truncal acne is poorly understood. Objective To determine how severity and location of acne lesions impact the HRQoL of those who suffer from it. Methods A total of 694 subjects with combined facial and truncal acne (F+T) and 615 with facial acne only (F) participated in an online, international survey. Participants self-graded the severity of their acne at different anatomical locations and completed the dermatology life quality index (DLQI). Results The F+T participants were twice as likely to report "very large" to "extremely large" impact on HRQoL (ie, DLQI > 10 and children's DLQI [CDLQI] > 12) as compared with the F participants (DLQI: odds ratio [OR] 1.61 [95% confidence interval {CI} 1.02-2.54]; CDLQI: OR 1.86 [95% CI 1.10-3.14]). The impact of acne on HRQoL increased with increasing acne severity on the face (DLQI and CDLQI P values = .001 and .017, respectively), chest (P = .003; P = .008), and back (P = .001; P = .028). Limitations Temporal evaluation of acne impact was not estimated. Conclusions Facial and truncal acne was associated with a greater impact on HRQoL than facial acne alone. Increasing severity of truncal acne increases the adverse impact on HRQoL irrespective of the severity of facial acne.

Background In two phase 3 trials (NCT03168334, NCT03168321), participants with moderate-to-severe acne had significant symptom improvements after 12 weeks of treatment with tazarotene 0.045% lotion. Given the negative psychosocial effects of acne on patients, data from these studies were analyzed to evaluate quality of life in various subgroups. Methods Mean changes from baseline to week 12 in Acne-Specific Quality of Life (Acne-QoL) domain and item scores were analyzed in the pooled intent-to-treat (ITT) population and in participants who were categorized as follows: Evaluator's Global Severity Score (EGSS) score=3 (lmoderater) or score=4 (lseverer) at baseline; Acne-QoL total score g60 (better quality of life) or l60 (worse quality of life), based on the median score at baseline. Exploratory analyses based on sex and race were also performed. Results In the pooled ITT population (N=1614), Acne-QoL improvements were greater with tazarotene 0.045% lotion versus vehicle lotion, with significant differences in the acne symptoms domain, 3 acne symptom items, 2 self-perception items, 1 role-emotional item, and 1 role-social item (all Pl0.05). Acne-QoL improvements with tazarotene 0.045% lotion were comparable between the EGSS subgroups. However, participants who self-reported worse quality of life at baseline (Acne-QoL total score l60) had notably greater improvements than those with better quality of life. Female and Black participants had greater Acne-QoL improvements than male and White participants. Conclusions Participants treated with tazarotene 0.045% lotion had significant quality-of-life improvements. Clinician-rated symptom severity appeared to have a smaller effect on Acne-QoL outcomes than participantsr own assessments of quality of life. J Drugs Dermatol. 2020;19(11): doi:10.36849/JDD.2020.5457.

Ingenol disoxate (LEO 43204) is a field therapy in development for the treatment of actinic keratosis (AK) on areas between 25 and 250 cm2. We evaluated the systemic exposure and safety of ingenol disoxate under maximum-use conditions. This was a phase I, open-label, non-randomized, multicenter trial. Patients ≥ 18 years of age with ≥ 15 clinically typical, visible, discrete AK lesions in a treatment area on the full face or approximately 250 cm2 on the arm or scalp were treated once-daily for 3 consecutive days with ingenol disoxate 0.018, 0.1, or 0.037% gel, respectively. The trial included 58 patients. Median age (range) of patients was 68 years (42–89) [face, N = 18], 66 years (43–88) [arm, N = 21], and 67 years (37–83) [scalp, N = 19]. The highest quantifiable ingenol disoxate level was observed in the arm group (0.33 nM, area under the concentration–time curve from time zero to the last data point [AUCtlast] 3.12 nM·h). Mean composite local skin response scores peaked at Day 4 and declined towards baseline by Day 15 in all treatment groups. Most adverse events (AEs) were of mild or moderate intensity; the most common treatment-related AEs were application-site pain (face, 88.9%; arm, 57.1%; scalp, 100.0%) and application-site pruritus (face, 50.0%; arm, 52.4%; scalp, 42.1%). Very low systemic exposure to ingenol disoxate was observed when applied to the face, arm, or scalp in patients with AK under maximum-use conditions. No new safety signals were identified. NCT02424305.

Background: There has been an increasing interest in gender and racial differences both in the pathogenesis and treatment of acne vulgaris (acne), and postinflammatory hyperpigmentation (PIH) is a major concern in patients of color. Female acne patients report more anxiety and depression with acne improvement positively influencing Quality of Life (QoL) than their male counterparts, and there are differences in acne presentation. The first lotion formulation of tretinoin was developed using novel polymeric emulsion technology to provide an important alternative option to treat these acne patients, especially those who may be sensitive to the irritant effects of other tretinoin formulations. Objective: To determine the impact of gender and race on the efficacy and safety of tretinoin 0.05% lotion in treating moderate or severe acne. Methods: Post hoc analysis of 2 multicenter, randomized, double-blind, vehicle-controlled Phase 3 studies in moderate-to-severe acne. Subjects (aged 9 to 58 years, N=1640) were randomized (1:1) to receive tretinoin 0.05% lotion or vehicle, once-daily for 12 weeks. Efficacy assessments included changes in baseline inflammatory and noninflammatory lesions and treatment success (at least 2-grade reduction in Evaluator’s Global Severity Score [EGSS] and clear/almost clear). Quality of Life was assessed using the validated Acne QoL scale. Safety, adverse events (AEs), cutaneous tolerability, and hypo-/hyper-pigmentation (using a 4-point scale where 0=none and 3=severe) were evaluated at each study visit. Results: At week 12, mean percent reduction in inflammatory lesion counts were 56.9% and 53.4% respectively in female and male patients compared with 47.1% and 39.4% with vehicle (P≤0.001), with females statistically significant to males at week 8 [P=0.026]). Mean percent reduction in noninflammatory lesion counts in females and males were 51.7% and 46.1% respectively, compared with 34.9% and 29.7% with vehicle (P0.001), with females statistically significant to males at week 12 (P=0.035). Treatment success was achieved by 23.6% and 16.1% of female and male patients treated with tretinoin 0.05% lotion by week 12 (P≤0.001 vs vehicle) with females statistically significant compared with males (P=0.013). Significant differences in inflammatory lesion count reductions were reported in Caucasian patients from week 8, and Black African/American male patients at week 12. Only male patients reported significant differences in both races in terms of noninflammatory lesions, and only Caucasian patients reported significant differences in treatment success. Female patients treated with tretinoin 0.05% lotion had statistically significant improvements in each Acne QoL domain (except role-social) compared with vehicle. Improvements in QoL in male subjects were only statistically different for acne symptoms. Tretinoin 0.05% lotion was well-tolerated in both genders. There were more treatment-related AEs in the female subpopulation, with a significantly greater incidence of skin dryness (P=0.006), that was more common in the younger Caucasian females. Conclusions: Tretinoin 0.05% lotion has been shown to be effective and well tolerated in moderate-to-severe acne. Treatment was significantly more effective in females than males. Tretinoin 0.05% lotion was well tolerated by both genders, although there was a higher incidence of treatment-related AEs, especially skin dryness, in females. There were racial and gender differences in QoL and beneficial effects on PIH in those patients most at risk. J Drugs Dermatol. 2019;18(11):1128-1138.

Atrophic acne scarring is a frequent occurrence among acne patients. These facial marks are often very emotionally distressing for the patient and can result in adverse impact to quality of life. While most clinicians consider scarring as a sequela of moderate to severe acne, recent studies have found that scars are also associated with mild acne. Risk factors include time to effective treatment, severity of acne, family history, and excoriations. New data shows that early and effective acne treatment can reduce the development of new scars, confirming the widespread perception of this approach in prevention. It is also becoming clear that the inflammatory process drives both the development of acne lesions and atrophic scars. This implies that inhibiting activation of inflammatory pathways early is key to preventing scars. Data also suggests a useful role for adapalene for the treatment of well-established acne scars with scar remodeling accompanied by the production of new collagen and elastic tissue. Acne guidelines and recommendations continue to highlight the central role of retinoids, with fixed-dose combination retinoids being particularly important due to targeting of multiple inflammatory pathophysiologic factors and for patient convenience. Higher concentrations of retinoids such as adapalene 0.3%/benzoyl peroxide 2.5% (A0.3/BPO2.5) have shown increased efficacy, particularly among patients with moderately severe and severe acne – a population at high risk for scarring. Further, controlled study of A0.3/BPO2.5 in patients with moderate acne (mean, 40 acne lesions per half face) and mild-moderate scarring demonstrated A0.3/BPO2.5 was significantly superior to vehicle in reducing scar counts from baseline over 24 weeks. While scar counts lessened on the A0.3/BPO2.5 side, counts increased on the vehicle side during the study. This occurred in the setting of active acne, where the efficacy of A/BPO is well known, emphasizing the dual actions of A0.3/BPO2.5 in both treatment and prevention. J Drugs Dermatol. 2019;18(3):255-260.

Background: Acne vulgaris (acne) is a common dermatological condition typically associated with adolescents, affecting about 85% of young people. However, it is also prevalent and persistent into adulthood, particularly in females. The efficacy of tretinoin in acne is well documented with large pivotal studies. The first lotion formulation of tretinoin was developed to provide an important alternative option to treat acne patients who may be sensitive to the irritant effects of other tretinoin formulations. Objective: To determine whether efficacy and safety of tretinoin 0.05% lotion was similar in adolescent (18 years) and adult (=18 years) women with moderate-to-severe acne. Methods: Post hoc analysis of two multicenter, randomized, double-blind, vehicle-controlled Phase 3 studies in moderate or severe acne. Female subjects (aged 9 to 58 years, N=909) randomized (1:1) to receive tretinoin 0.05% lotion or vehicle, once-daily for 12 weeks. Efficacy assessments included changes in baseline inflammatory and noninflammatory lesions and treatment success (at least 2-grade reduction in Evaluator’s Global Severity Score [EGSS] and clear/almost clear). Safety, adverse events (AEs), and cutaneous tolerability were evaluated throughout. Results: At week 12, mean percent reduction in inflammatory and noninflammatory lesion counts in female subjects were 56.9% and 51.7%, respectively, compared with 47.1% and 34.9% with vehicle (P=0.001). Similar results were seen in adult and adolescent females in terms of reduction in inflammatory lesion counts with tretinoin 0.05% lotion; reduction in noninflammatory lesions was significantly greater in adult females (P=0.002). Treatment success was achieved by 23.6% of female subjects by week 12, compared with 13.5% on vehicle (P0.001). Although treatment success was somewhat greater in adult females (24.6% versus 21.6%), the difference was not significant. The majority of AEs were mild and transient. There were five serious AEs (SAEs) reported (4/1, adult/adolescent, respectively). The most frequently reported treatment related AEs with tretinoin 0.05% lotion were application site pain (3.0%/5.7%), and application site dryness (4.9%/6.4%). Local cutaneous safety and tolerability assessments were generally mild-to-moderate and improved by week 12. Slight increases in mean scores were observed for scaling, burning and stinging within the first four weeks and appeared to be transient. Conclusions: Tretinoin 0.05% lotion was significantly more effective than its vehicle in achieving treatment success and reducing inflammatory and noninflammatory lesions in female acne. Noninflammatory lesion count reduction was significantly greater in adult females compared with adolescent females. The new lotion formulation was well-tolerated. J Drugs Dermatol. 2019;18(2):178-188.

Background: Rosacea is a chronic dermatologic condition with limited treatment options. Methods: Data were pooled from two identically designed phase 3 trials. Patients with moderate to severe persistent erythema of rosacea were randomized to receive oxymetazoline cream 1.0% or vehicle once daily for 29 days and were followed for 28 days posttreatment. The primary efficacy outcome was the proportion of patients with ≥2-grade improvement from baseline on both Clinician Erythema Assessment (CEA) and Subject Self-Assessment (SSA) at 3, 6, 9, and 12 hours postdose, day 29. Results: The pooled population included 885 patients (78.8% female); 85.8% and 91.2% had moderate erythema based on CEA and SSA, respectively. The primary outcome was achieved by significantly more patients in the oxymetazoline than vehicle group (P0.001). Individual CEA and SSA scores and reduction in facial erythema (digital image analysis) favored oxymetazoline over vehicle (P0.001). The incidence of treatment-emergent adverse events was low (oxymetazoline, 16.4%; vehicle, 11.8%). No clinically relevant erythema worsening (based on CEA and SSA) was observed during the 28-day posttreatment follow-up period (oxymetazoline, 1.7%; vehicle, 0.6%). Conclusion: Oxymetazoline effectively reduced moderate to severe persistent facial erythema of rosacea and was well tolerated. J Drugs Dermatol. 2018;17(11):1201-1208.

Dapsone gel, 7.5% is a topical medication approved for acne in patients aged 12 years and older. Clinical trials have demonstrated the safety and efficacy of once-daily dapsone gel, 7.5% in patients with moderate acne.The objective of this report is to describe the clinical course of 8 patients who participated in a 12-week program using once-daily dapsone gel, 7.5% as monotherapy for acne in a real-world clinical setting.Male and female adults and adolescents with facial acne, representing a broad range of ages, skin phototypes, and ethnicities, and with no prior use of dapsone gel, 7.5% applied the product once daily for 12 weeks as monotherapy for acne. Photographs were taken at baseline and at 12 weeks. The treating dermatologists recorded observations of baseline disease, treatment tolerability, and outcomes. An independent rater assessed Global Acne Assessment Score (GAAS) at baseline and at 12 weeks based on photographs. Patients provided testimonials of their experience with treatment.Acne improvement was evident in the photographs of the 8 patients. Changes in GAAS at week 12 of treatment, as assessed by an independent rater, ranged from 1- to 3-grade improvement from baseline.Photographs, dermatologist reports, and patient commentary in an office-based practice demonstrated that 12 weeks of treatment with only topical dapsone gel, 7.5%, applied once daily, was effective and well tolerated as a stand-alone treatment in 8 patients with facial acne vulgaris, with results that are consistent with the phase 3 pivotal trials. J Drugs Dermatol. 2018;17(6):602-608.

Rosacea is a chronic dermatologic condition with limited treatment options, particularly for persistent erythema. This pivotal phase 3 study evaluated oxymetazoline, an a1A-adrenoceptor agonist, for the treatment of moderate to severe persistent erythema of rosacea. Eligible patients were randomly assigned 1:1 to receive oxymetazoline cream 1.0% or vehicle applied topically to the face once daily for 29 days. The primary efficacy outcome was ≥2-grade improvement from baseline on both Clinician Erythema Assessment (CEA) and Subject Self-Assessment for rosacea facial redness (SSA) (composite success) at 3, 6, 9, and 12 hours postdose on day 29. Digital image analysis of rosacea facial erythema was evaluated as a secondary efficacy outcome measure. Safety assessments included treatment-emergent adverse events (TEAEs) and dermal tolerability. Patients were followed for 28 days posttreatment to assess worsening of erythema (1-grade increase in severity from baseline on composite CEA/SSA in patients with moderate erythema at baseline; rebound effect). The study included 445 patients (mean age: 50.3 years; 78.7% female); most had moderate erythema at baseline (84.0% on CEA; 91.5% on SSA). The proportion of patients achieving the primary efficacy outcome was significantly greater with oxymetazoline versus vehicle (P=0.001). Similar results favoring oxymetazoline over vehicle were observed for the individual CEA and SSA scores (P less than 0.001 and P=0.011, respectively). Median reduction in rosacea facial erythema on day 29 as assessed by digital image analysis also favored oxymetazoline over vehicle (P less than 0.001). Safety results were similar between oxymetazoline and vehicle; discontinuations due to TEAEs were low (2.7% vs 0.5%). Following cessation of treatment, 2 (1.2%) patients in the oxymetazoline group and no patient in the vehicle group had rebound effect compared with their day 1 baseline score. Topical oxymetazoline applied to the face once daily for 29 days was effective, safe, and well tolerated in the treatment of moderate to severe persistent facial erythema of rosacea.pemJ Drugs Dermatol. 2018;17(3):290-298./em/p.

There is currently a lack of data on the simultaneous treatment of different features of rosacea. Individually, ivermectin 1% (IVM) cream and brimonidine 0.33% (BR) gel have demonstrated efficacy on inflammatory lesions and persistent erythema, respectively.To evaluate the efficacy, safety, patient satisfaction, and optimal timing of administration of IVM associated with BR (IVM+BR) versus their vehicles in rosacea (investigator global assessment [IGA] ≥3).Multicenter, randomized, double-blind study including subjects with rosacea characterized by moderate to severe persistent erythema and inflammatory lesions. The active treatment group included the IVM+BR/12 weeks subgroup (once-daily BR and once-daily IVM for 12 weeks), and the IVM+BR/8 weeks subgroup (once-daily BR vehicle for 4 weeks followed by once-daily BR for the remaining 8 weeks and once-daily IVM for 12 weeks). The vehicle group received once-daily BR vehicle and once-daily IVM vehicle for 12 weeks.The association showed superior efficacy (IGA success [clear/almost clear]) for erythema and inflammatory lesions in the total active group (combined active subgroups) compared to vehicle (55.8% vs. 36.8%, P=0.007) at week 12. The success rate increased from 32.7% to 61.2% at hour 0 and hour 3, respectively, in the IVM+BR/12 weeks subgroup, and from 28.3% to 50% in the IVM+BR/8 weeks subgroup. Reductions in erythema and inflammatory lesion counts confirmed the additive effect of BR to IVM treatment. Subjects reported greater improvement in the active subgroups than in the vehicle group, and similar rates for facial appearance satisfaction after the first 4 weeks of treatment in both active subgroups. All groups showed similar tolerability profiles.Concomitant administration of IVM cream with BR gel demonstrated good efficacy and safety, endorsing the comprehensive approach to this complex disease. Early introduction of BR, along with a complete daily skin care regimen may accelerate treatment success without impairing tolerability.pemJ Drugs Dermatol. 2017;16(9):909-916./em/p.