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Preeya K Gupta,1 Laura M Periman,2 Edward Lain,3 Eric Donnenfeld,4 John Hovanesian,5 Terry Kim,6 William Trattler,7 Elizabeth Yeu,8 Edward Holland9 1Triangle Eye Consultants, Durham, NC, USA; 2Periman Eye Institute, Seattle, WA, USA; 3Sanova Dermatology, Pflugerville, TX, USA; 4Ophthalmic Consultants of Long Island, Garden City, NJ, USA; 5Harvard Eye Associates, Laguna Hills, CA, USA; 6Department of Ophthalmology, Duke University Eye Center, Durham, NC, USA; 7Center for Excellence in Eye Care, Miami, FL, USA; 8Virginia Eye Consultants, Norfolk, VA, USA; 9Cincinnati Eye Institute, Edgewood, KY, USACorrespondence: Preeya K Gupta Email preeyakgupta@gmail.comAbstract: Meibomian glands are modified oil-producing glands that produce meibum and can become dysfunctional and negatively affect the lipid layer in the tear film, resulting in ocular surface diseases such as evaporative dry eye. Abnormal keratin production and aggregation at the meibomian gland orifice has been implicated in the pathogenesis of meibomian gland dysfunction (MGD). Current treatments largely ignore the role of keratin proteins. This review paper synthesizes various publications on hyperkeratinization and its role in MGD pathogenesis and proposes a novel treatment strategy for MGD that involves the use of keratolytic agents commonly used in dermatological treatments.Keywords: meibomian gland disease, MGD, hyperkeratinization

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.

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.

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

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.

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.

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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.

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Background: Cleansing, medicating, moisturizing, and photoprotection comprise a complete acne vulgaris (AV) management regimen. However, complete topical AV treatment regimen investigations in athletes are scarce. Objective: Adapalene and benzoyl peroxide (A/BPO) gel, 0.1%/2.5% (Epiduo® Gel) is indicated for the topical treatment of AV in patients 9 years of age and older. This open-label, single-center study evaluated a regimen to cleanse, medicate, moisturize, and protect the skin comprised of A/BPO gel, Cetaphil® DermaControl™ Foam Wash and Cetaphil® DermaControl™ Moisturizer SPF 30 in student athletes (referred to as the CoMMplete Regimen). Methods: Student athletes 12 to 18 years of age with mild to moderate acne who were actively participating in 1 of 14 Texas University Interscholastic League sanctioned athletic activities followed the CoMMplete Regimen for 8 weeks (N=28). Lesion counts, satisfaction, cutaneous irritation, adverse events, and adherence were assessed. Results: After 8 weeks, lesion counts were significantly reduced compared to baseline. Good tolerability and high satisfaction were observed. Most athletes experienced no cutaneous irritation. All adverse events were mild or moderate, and the most common related adverse events were dry skin, skin exfoliation, and erythema. Most athletes exhibited exceptionally high compliance and adherence. Conclusions: The coMMplete Regimen is efficacious, safe, well tolerated, and helps optimize AV treatment outcomes in athletes.

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