New Insights Into Systemic Drivers of Inflammation and Their Contributions to the Pathophysiology of Acne.

Acne Vulgaris (AV) is a prominent skin disease commonly affecting teenagers. It often persists into adulthood and is associated with adverse physical and psychosocial impacts. The pathophysiology of AV is conventionally correlated with 4 factors within and around the pilosebaceous unit: increased sebum production, follicular hyperkeratinization, Cutibacterium acnes proliferation, and localized immune responses. As such, conventional therapeutic approaches for AV have primarily focused on these factors. In addition to this primarily localized pathophysiology, there is a progressively emerging body of evidence indicating that underlying systemic factors contributing to a generalized immuno-inflammatory response can contribute to or exacerbate AV. In this article, we introduce and provide the supporting data, for 6 patient-centric systems that may be implicated in the development of AV: psycho-emotional stress, diet and metabolism, dysbiosis of the gut and skin microbiome, hormonal fluctuations, oxidative stress, and immune response. Identifying these pathways and their contributions in a patient-centric approach may provide expanded therapeutic opportunities for treating patients with AV. J Drugs Dermatol. 2024;23(2):90-96.   doi:10.36849/JDD.8137.

Triple-Combination Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% Gel for Acne in Adult and Pediatric Participants.

BACKGROUND: Topical clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% gel (CAB) is the first fixed-dose triple-combination approved for the treatment of acne. This post hoc analysis investigated the efficacy and safety of CAB in pediatric (<18 years) and adult (greater than or equal to 18 years) participants. METHODS: In two multicenter, double-blind, phase 3 studies (NCT04214639 and NCT04214652), participants greater than or equal to 9 years of age with moderate-to-severe acne were randomized (2:1) to 12 weeks of once-daily treatment with CAB or vehicle gel. Pooled data were analyzed for pediatric and adult subpopulations. Assessments included treatment success (greater than or equal to 2-grade reduction from baseline in Evaluator's Global Severity Score and a score of 0 [clear] or 1 [almost clear], inflammatory/noninflammatory lesion counts, Acne-Specific Quality of Life (Acne-QoL) questionnaire, treatment-emergent adverse events (TEAEs), and cutaneous safety/tolerability. RESULTS: At week 12, treatment success rates for both pediatric and adult participants were significantly greater with CAB (52.7%; 45.9%) than with vehicle (24.0%; 23.5%; P<0.01, both). CAB-treated participants in both subgroups experienced greater reductions from baseline versus vehicle in inflammatory (pediatric: 78.6% vs 50.4%; adult: 76.6% vs 62.8%; P<0.001, both) and noninflammatory lesions (pediatric: 73.8% vs 41.1%; adult: 70.7% vs 52.2%; P<0.001, both). Acne-QoL improvements from baseline to week 12 were significantly greater with CAB than with a vehicle. Most TEAEs were of mild-to-moderate severity; no age-related trends for safety/tolerability were observed.  Conclusions: CAB gel demonstrated comparable efficacy, quality of life improvements, and safety in pediatric and adult participants with moderate-to-severe acne. As the first fixed-dose, triple-combination topical formulation, CAB represents an important new treatment option for patients with acne. J Drugs Dermatol. 2024;23(6):394-402.     doi:10.36849/JDD.8357.

Consensus Statements on the Use of Novel Formulations of Isotretinoin: A Modified Delphi Process.

Oral isotretinoin remains a mainstay of treatment for severe, recalcitrant nodular acne. Novel formulations of isotretinoin have been developed over the past decade, including lidose isotretinoin and micronized isotretinoin. It is important to understand the differences between isotretinoin formulations to help guide clinical decision-making and selection of isotretinoin therapy. This study aims to provide evidence-based consensus statements regarding the use of novel formulations of isotretinoin for the treatment of moderate-to-severe acne. The Expert Consensus Group consisted of dermatologists with expertise in the treatment of acne. Voting members met in person to conduct a modified Delphi process; a maximum of 2 rounds of voting were conducted for each consensus statement. A total of 5 statements were generated regarding the use of novel formulations of isotretinoin, addressing the efficacy, tolerability, and side effects of novel isotretinoin formulations. All 5 statements achieved agreement with high consensus. The Expert Consensus Group agrees that individualized selection of isotretinoin therapy is important to maximize efficacy and minimize side effects. Compared to generic isotretinoin, micronized isotretinoin may require lower doses to achieve sufficient plasma concentrations. With the increased bioavailability of micronized formulation, there is no need to calculate cumulative dose; instead, the general recommendation with micronized isotretinoin is to treat for at least 5 months, or longer if needed to achieve clearance. Micronized isotretinoin can be taken in the fed or fasted state and has an acceptable safety profile. J Drugs Dermatol. 2024;23(6):429-432.     doi:10.36849/JDD.7971.

Treatments for Moderate-to-Severe Acne Vulgaris: A Systematic Review and Network Meta-analysis.

BACKGROUND: Multiple treatment options exist for the management of moderate-to-severe acne. However, the comparative effectiveness (efficacy/safety) of moderate-to-severe acne treatments has not been systematically examined. METHODS: A systematic literature review (SLR) was conducted to identify randomized controlled trials of ≥4 weeks of treatment (topical, oral, physical, or combinations) for moderate-to-severe facial acne in patients aged ≥9 years. Efficacy outcomes included: percentage of patients achieving ≥2-grade reduction from baseline and “clear” or “almost clear” for global severity score (treatment success); absolute change in inflammatory (ILs reduction); and noninflammatory lesion counts (NILs reduction). A random-effects network meta-analysis (NMA) was conducted for the efficacy outcomes. Treatments were ranked with posterior rank plots and surface under cumulative ranking values.  Results: Eighty-five studies were included in the SLR/NMA. Topical triple-agent fixed-dose combination (FDC) gel (clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1%) and combinations of double-agent fixed-dose topical treatments with oral antibiotics (TOA3) consistently ranked in the top 3 treatments. Topical triple-agent FDC gel was numerically superior to TOA3 for treatment success (log-odds ratios: 1.84 [95% credible interval (CrI) 1.36 to 2.29]) and 1.69 (95% CrI: 1.01 to 2.32) vs placebo/vehicle). TOA3 was numerically superior to topical triple-agent FDC gel for reduction of ILs (mean difference: -8.21 [-10.33 to -6.13]) and -10.40 [-13.44 to -7.14] vs placebo/vehicle) and NILs (mean difference: -13.41 [-16.69 to -10.32] and -17.74 [-22.56 to -12.85] vs placebo/vehicle). CONCLUSIONS: Based on this SLR/NMA, topical triple-agent FDC gel was the most efficacious and safe treatment for moderate-to-severe acne. J Drugs Dermatol. 2024;23(4):     doi:10.36849/JDD.8148.

Early and Sustained Acne Lesion Reductions With Fixed-Dose Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% Gel.

BACKGROUND: A once-daily, three-pronged approach using an antibiotic, antibacterial, and retinoid may provide faster acne improvement versus monotherapy or dual-combination products. This post hoc analysis compared threshold acne lesion reductions with clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (CAB) gel—the first FDA-approved triple-combination topical acne product—to its dyads and vehicle. METHODS: Phase 2 (N=741; NCT03170388) and phase 3 (N=183; N=180; NCT04214639; NCT04214652), double-blind, 12-week studies randomized participants aged ≥9 years with moderate-to-severe acne to once-daily CAB or vehicle gel; the phase 2 study included three additional dyad gel arms. The pooled percentage of participants achieving ≥33%, ≥50%, and ≥75% reduction in inflammatory and noninflammatory acne lesions was evaluated. RESULTS: As early as week 4 in the phase 2 study, ≥33% reduction in inflammatory lesions occurred in a significantly greater percentage of CAB gel-treated participants (82.7%) than with the 3 dyads and vehicle (61.1-69.8%; P<0.05, all). These early reductions were sustained throughout the study, with significantly (P<0.05) more CAB-treated participants achieving ≥50% reduction in inflammatory lesions versus dyads and vehicle from weeks 4-12. By week 12, CAB led to substantial reductions of ≥75% in significantly more participants than dyads and vehicle (65.8% vs 49.9-51.2% and 21.6%; P<0.05, all). Similar trends were observed for noninflammatory lesions in the phase 2 study and for inflammatory and noninflammatory lesions in the phase 3 studies. CONCLUSIONS: Lesion count reductions were significantly greater with CAB versus its dyads and vehicle gel as early as week 4, with substantial reductions observed after 12 weeks of treatment. This faster-acting and sustained efficacy of CAB gel—coupled with its optimized formulation, once-daily dosing, and tolerability—may positively impact treatment adherence. J Drugs Dermatol. 2024;23(3):     doi:10.36849/JDD.7907.

INDIVIDUAL ARTICLE: Impact of Acne Vulgaris and Sarecycline on Social/Emotional Functioning and Daily Activities: PROSES Study.

BACKGROUND: Concise patient-reported outcome (PRO) instruments addressing the consequences of facial acne vulgaris (AV) on patients’ functioning and activities of daily living (ADL) are needed. METHODS: A 12-week, single-arm, prospective cohort study was conducted in patients ≥9 years old with moderate/severe non-nodular facial AV prescribed sarecycline as part of usual care. The primary endpoint included AV-specific patient- and caregiver-reported outcomes assessed with the expert panel questionnaire (EPQ, developed by 10 experts using a Delphi method) in patients (>12 years) and caregivers (for patients 9-11 years). Additional assessments included parental/caregiver perspectives on children’s AV. RESULTS: A total of 253 patients completed the study. Following 12-weeks of treatment, there were significant (P ≤.0001) changes from baseline in the proportion of patients responding that they never or rarely: felt angry (31.6%), worried about AV worsening (28.9%), had thoughts about AV (20.9%), had a certain level of worries about AV (38.7%), altered their social media/selfie activity (23.7%), had an impact on real-life plans due to AV (22.9%), made efforts to hide AV (21.3%), felt picked-on/judged due to AV (15.0%), were concerned about their ability to reach future goals due to AV (13.8%), or had sleep impacted due to AV (18.2%). No significant change from baseline was observed for parent/caregiver’s understanding of the child’s AV concerns, from both patient and parent/caregiver perspectives. CONCLUSIONS: Over 12 weeks of AV management with oral sarecycline, patients reported significant reductions in AV-related effects on emotional/social functioning and ADL as measured by the EPQ, a simple PRO with potential for use in clinical practice. J Drugs Dermatol. 2024;23:1(Suppl 1):s4-11.

INDIVIDUAL ARTICLE: Sarecycline Improves Acne Severity, Symptoms, and Psychosocial Burden in Non-nodular Acne Vulgaris: PROSES Study.

BACKGROUND: Patient-reported outcomes (PROs) are emerging as a fundamental component of disease impact assessment in acne vulgaris (AV), complementing clinician-reported outcomes. No data is available on PROs for patients with AV using sarecycline in real-world settings. METHODS: A single-arm, prospective cohort study that included patients ≥9 years old diagnosed with moderate or severe non-nodular AV was implemented as part of routine care in clinical practices (N=30). Patients received oral sarecycline (60 mg, 100 mg, or 150 mg) for 12 weeks, as part of usual care. The primary endpoint was Acne Symptom and Impact Scale (ASIS) responses from patients (≥12 years) and caregivers (for patients 9-11 years) at week 12 and change from baseline (CFB). Investigator’s Global Assessment (IGA) of AV severity and adverse events (AEs) were also recorded. RESULTS: A total of 253 patients with AV completed the study (adults: 60.1%, females: 77.6%). ASIS mean scores significantly decreased (P <.0001) at week 12 for: signs (mean CFB ± standard deviation [SD]: –0.8 ± 0.7), impact (–1.0 ± 1.0), emotional impact (–1.2 ± 1.1), and social impact (0.6 ± 1.1). Significant reductions in AV severity (P <.0001) were reported by patients and caregivers. The IGA success rate was 58.9% and physician satisfaction with treatment outcomes was 88.1%. A total of 31 (10.3%) patients reported ≥1 AE during the study. CONCLUSIONS: Patients with moderate-to-severe AV receiving acne management with an oral antibiotic for 12 weeks experienced a significant improvement in AV-related symptoms and psychosocial burden. J Drugs Dermatol. 2024;23:1(Suppl 1):s12-18.

Sixty Years of Benzoyl Peroxide Use in Dermatology.

BACKGROUND: Benzoyl peroxide (BPO) has been used extensively in industry and health care for more than a century and has been approved for the treatment of acne for over 60 years. Recently, BPO received a second approved indication by the US Food and Drug Administration (FDA) for the treatment of rosacea. Topical BPO use has historically been limited by tolerability, photosensitivity, oxidation, and, uncommonly, contact allergy. Research has led to enhanced efficacy and tolerability, as well as the combination of BPO with other topical medications. These advances have allowed extended use of BPO in additional dermatologic conditions that may not have been feasible in the past. Additionally, the role of BPO in preventing antibiotic resistance cannot be underestimated. Here, we discuss the historical limitations of BPO and recent advances developed to overcome these limitations. We also describe newly approved BPO medications and their role in aiding antibiotic stewardship. J Drugs Dermatol. 2023;22(1):54-59. doi:10.36849/JDD.7150.

Longitudinal RNA-Seq Analysis of the Repeatability of Gene Expression and Splicing in Human Platelets Identifies a Platelet SELP Splice QTL.

RATIONALE: Longitudinal studies are required to distinguish within versus between-individual variation and repeatability of gene expression. They are uniquely positioned to decipher genetic signal from environmental noise, with potential application to gene variant and expression studies. However, longitudinal analyses of gene expression in healthy individuals-especially with regards to alternative splicing-are lacking for most primary cell types, including platelets. OBJECTIVE: To assess repeatability of gene expression and splicing in platelets and use repeatability to identify novel platelet expression quantitative trait loci (QTLs) and splice QTLs. METHODS AND RESULTS: We sequenced the transcriptome of platelets isolated repeatedly up to 4 years from healthy individuals. We examined within and between individual variation and repeatability of platelet RNA expression and exon skipping, a readily measured alternative splicing event. We find that platelet gene expression is generally stable between and within-individuals over time-with the exception of a subset of genes enriched for the inflammation gene ontology. We show an enrichment among repeatable genes for associations with heritable traits, including known and novel platelet expression QTLs. Several exon skipping events were also highly repeatable, suggesting heritable patterns of splicing in platelets. One of the most repeatable was exon 14 skipping of SELP. Accordingly, we identify rs6128 as a platelet splice QTL and define an rs6128-dependent association between SELP exon 14 skipping and race. In vitro experiments demonstrate that this single nucleotide variant directly affects exon 14 skipping and changes the ratio of transmembrane versus soluble P-selectin protein production. CONCLUSIONS: We conclude that the platelet transcriptome is generally stable over 4 years. We demonstrate the use of repeatability of gene expression and splicing to identify novel platelet expression QTLs and splice QTLs. rs6128 is a platelet splice QTL that alters SELP exon 14 skipping and soluble versus transmembrane P-selectin protein production.

Supplement Article: The Role of Epidermal Barrier Dysfunction and Cutaneous Microbiome Dysbiosis in the Pathogenesis and Management of Acne Vulgaris and Rosacea.

BACKGROUND: Dysregulation of either the cutaneous microbiome (CM) or epidermal barrier function (EBF) is thought to play an increasingly important role in acne vulgaris (AV) and rosacea pathogenesis. OBJECTIVE: To review the literature regarding epidermal barrier dysfunction (EBD) and cutaneous dysbiosis in AV and rosacea and provide clinical pearls for dermatologists. METHODS: A Medline literature search was performed for relevant literature regarding EBD and dysbiosis and either AV or rosacea. An expert consensus panel was then convened to discuss article merits and distill findings into clinical pearls. RESULTS: Final review included 138 articles. Puberty may alter natural stratum corneum lipid ratios, instigating and/or exacerbating EBD in AV. Patients with severe AV have an abundance of virulent Cutibacterium acnes phylotype IA1. EBD may manifest as classic signs of rosacea and improve with treatment. While several microbial populations are dysregulated in rosacea, the effect from any singular species is unclear. Current AV and rosacea treatment regimens may mitigate inflammation but may also indiscriminately damage CM and EBF. Physiologic moisturizers and cleansers that harness pre-/pro-/postbiotics may have a role in restoring CM, EBF, and potentially improving dermatosis severity. LIMITATIONS: Limited prospective clinical trial data especially regarding over-the-counter (OTC)/non-prescription skincare products. CONCLUSION: Appropriately developed prescription and OTC preparations may selectively influence the microbiome and potentially maintain/restore EBF. By understanding this relationship, dermatologists will be better able to educate patients on the importance of appropriate skin care.J Drugs Dermatol. 2022;21:9(Suppl 2):s5-14.

Supplement Article: Skin Barrier Deficiency in Rosacea: An Algorithm Integrating OTC Skincare Products Into Treatment Regimens.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Prescription medications combined with gentle cleansers, moisturizers, and sunscreen support a successful rosacea therapy. J Drugs Dermatol. 2022;21:9(Suppl 1):s3-10.

Update on Facial Erythema in Rosacea.

Dermatologists are cognizant of the multiple clinical manifestations of rosacea, particularly persistent facial erythema, which has been deemed to be the most prevalent diagnostic feature and often poses a significant negative impact on quality of life. To address the need to recognize rosacea as a single disease with multiple potential phenotypes, a new classification system has been developed by 28 clinical and scientific experts worldwide.

Evidence of Barrier Deficiency in Rosacea and the Importance of Integrating OTC Skincare Products into Treatment Regimens.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Management of Truncal Acne With Oral Sarecycline: Pooled Results from Two Phase-3 Clinical Trials.

BACKGROUND: Acne vulgaris is a common skin disease that affects the face, chest, and back. While truncal acne is present in at least 50% of patients, clinical studies have focused predominantly on facial acne.1,2 Few treatments to date have been evaluated for truncal acne. Sarecycline is a narrow-spectrum, third-generation, tetracycline-class oral drug approved for the treatment of acne. Pivotal phase-3 studies show that sarecycline is safe, well-tolerated, and effective treatment for moderate to severe acne vulgaris. METHOD: Pooled analysis was performed for truncal acne results with sarecycline from the two phase 3 studies. Investigator Global Assessment (IGA) success was evaluated at weeks 3, 6, 9, and 12. RESULTS: Chest IGA success rate were significantly greater with sarecycline versus placebo at weeks 3 (11.84% vs 7.71%, respectively; P=0.0192), 6 (18.81% vs 14.03%, respectively; P=0.0390), and 12 (33.42% vs 20.77%, respectively; P<0.0001). Back IGA success rate was also significantly greater with sarecycline versus placebo group at weeks 3 (12.13% vs 7.04%, respectively; P=0.0023), 6 (18.42% vs 14.34%, respectively; P=0.0412), 9 (29.05% vs 19.88%, respectively; P=0.0004) and 12 (33.07% vs 21.91%, respectively; P<0.0001)Conclusion: Sarecycline efficacy for truncal acne was observed within 3 weeks after treatment, supporting sarecycline as an optimal choice for oral treatment of moderate to severe truncal acne. J Drugs Dermatol. 2021;20(6):634-640. doi:10.36849/JDD.6204.

Rationale for Use of Combination Therapy in Rosacea.

BACKGROUND: Rosacea is a chronic skin condition characterized by primary and secondary manifestations affecting the centrofacial skin. The primary diagnostic phenotypes for rosacea are fixed centrofacial erythema with periodic intensification, and phymatous changes. Major phenotypes, including papules and pustules, flushing, telangiectasia, and ocular manifestations, may occur concomitantly or independently with the diagnostic features. The phenotypes of rosacea patients may evolve between subtypes and may require multiple treatments concurrently to be effectively managed. We report the proceedings of a roundtable discussion among 3 dermatologists experienced in the treatment of rosacea and present examples of rosacea treatment strategies that target multiple rosacea symptoms presenting in individual patients. METHODS: Three hypothetical cases describing patients representative of those commonly seen by practicing dermatologists were developed. A roundtable discussion was held to discuss overall and specific strategies for treating rosacea based on the cases. RESULTS/DISCUSSION: With few exceptions, the dermatologists recommended combination therapy targeting each manifestation of rosacea for each case. These recommendations are in agreement with the current American Acne and Rosacea Society treatment guidelines for rosacea and are supported by several studies demonstrating beneficial results from combining rosacea treatments. CONCLUSIONS: Rosacea is an evolving condition; care should take into account all clinical signs and symptoms of rosacea that are present in an individual patient, understanding that symptoms may change over time, and utilize combination therapy when applicable to target all rosacea symptoms. J Drugs Dermatol. 2020;19(10): 929-934. doi:10.36849/JDD.2020.5367.

Tretinoin 0.05% Lotion for the Once-Daily Treatment of Moderate-to-Severe Acne Vulgaris: Impact of Gender and Race on Efficacy and Safety

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 (P<0.001), 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.

Efficacy and Tolerability of a Novel Tretinoin 0.05% Lotion for the Once-Daily Treatment of Moderate or Severe Acne Vulgaris in Adult Females

Background: A novel tretinoin 0.05% lotion formulation has been shown to be efficacious and well-tolerated, and especially effective in adult female acne patients. While it is perhaps counter-intuitive that patients with more severe disease would show clinically significant improvement with topical monotherapy, topical retinoids have been shown to offer realistic treatment options in these patients. Objective: To evaluate the safety and efficacy of once-daily tretinoin 0.05% lotion in adult females with moderate or severe acne. Methods: Post hoc analysis of two multicenter, randomized, double-blind, vehicle-controlled phase 3 studies. Adult females (>=18 years of age) with moderate (N=551) and severe (N=55) acne were randomized (1:1) to receive tretinoin 0.05% lotion or vehicle, once-daily for 12 weeks. Efficacy assessments included changes in baseline inflammatory/noninflammatory lesions, treatment success (at least 2-grade reduction in Evaluator's Global Severity Score [EGSS] and clear/almost clear) and quality of life (QoL) using the validated Acne-QoL questionnaire. Safety, adverse events (AEs), and cutaneous tolerability were evaluated throughout. Results: At week 12, efficacy in adult females with moderate acne (EGSS=3) treated with tretinoin 0.05% lotion was significantly greater than that reported with vehicle. Mean percent reduction in inflammatory and noninflammatory lesion counts was 58.5% and 55.5% respectively compared with 50.3% and 39.8% with vehicle (P=0.039 and P<0.001). Treatment success was achieved by 25.4% of subjects by week 12, compared with 15.4% with vehicle (P=0.006). Tretinoin 0.05% lotion was numerically more effective in adult females with severe acne (EGSS=4). Mean percent reduction in inflammatory and noninflammatory lesion counts was 59.0% and 58.8% respectively (compared with 53.5% and 45.5% with vehicle), and treatment success was achieved by 17.9% of subjects (compared with 4.5% with vehicle), with 46.6% of subjects achieving at least a 2-grade improvement in EGSS by week 12. Quality of life improvements with tretinoin 0.05% lotion were significant compared with vehicle in adult females with moderate acne (except role-social), but not in severe acne (probably due to the group size). The majority of AEs were mild and transient; more frequently reported in the moderate acne population where application site pain (2.9%), and application site dryness (5.0%) were the most common, compared with one report (4.5%) of application site pain and dryness in the severe acne population. Local cutaneous safety and tolerability assessments were generally mild-to-moderate and improved by week 12. Limitations: The number of severe subjects enrolled in the studies was considerably less than the number of subjects with moderate acne, and the studies were not powered to demonstrate a difference in efficacy based on acne severity. Conclusions: Tretinoin 0.05% lotion was significantly more effective than vehicle in achieving treatment success and reducing inflammatory and noninflammatory lesions in adult females with moderate acne, with notable improvements in treating adult females with severe acne. It was well-tolerated, and all treatment-related AEs were mild or moderate. J Drugs Dermatol. 2019;18(11):1147-1154.

Cross-Sectional Survey of the Burden of Illness of Rosacea by Erythema Severity.

Rosacea is a chronic skin condition characterized by persistent central facial erythema. To explore the burden of illness of rosacea in US adults, a cross-sectional web-based survey was conducted. Participants answered questions on sociodemographics, clinical characteristics, bothersome symptoms, coping and avoidance behaviors, self-perceptions, and health care resource utilization, and completed 2 quality of life instruments, the 21-item rosacea-specific quality of life questionnaire (RosaQoL) and the 36-item Short Form Health Survey (SF-36). This paper reports the data from the 409 respondents with erythematotelangiectatic rosacea (ETR), analyzed by erythema severity. Mean age was 53.1 years; mild, moderate, or severe erythema was reported by 63.6%, 32.0%, and 4.4% of participants, respectively. Blushing/flushing and bumps/pustules were the most bothersome symptoms across severity subgroups. Participants in all subgroups coped with rosacea by applying make-up and managing their stress and anxiety, and tried to prevent rosacea flares by avoiding sun exposure, specific skin care products, and other triggers. Self-perceptions differed by severity subgroup: satisfaction with facial appearance significantly decreased, and worrying about how people will react and feelings of unattractiveness to others significantly increased, with greater erythema severity (all P less than 0.01). Treatment or assessment of rosacea was sought by 20% of participants in the past 3 months, most commonly from a dermatologist. Metronidazole was the most frequently prescribed topical product across severity subgroups, whereas doxycycline and other oral antibiotics were prescribed most frequently in the severe erythema subgroup. RosaQoL emotional domain scores increased with erythema severity (P equals 0.0035), but none of the SF-36 domain scores differed significantly by erythema severity. These results demonstrate that rosacea is associated with a substantial burden of illness that spans all levels of erythema severity in patients with ETR. Feelings of unattractiveness and the adverse impact of rosacea on emotional quality of life increased with erythema severity. J Drugs Dermatol. 2018;17(2):150-158.

The Efficacy and Safety of Azelaic Acid 15% Foam in the Treatment of Facial Acne Vulgaris.

BACKGROUND: Azelaic acid demonstrates anti-inflammatory, anti-oxidative, anti-comedogenic, and anti-microbial effects. Azelaic acid 20% cream is currently approved for the treatment of acne vulgaris, and azelaic acid 15% foam has recently been approved for rosacea. Given the favorable tolerability profile of foam preparations, it is reasonable to assume that azelaic acid 15% foam could serve as a viable treatment option for facial acne. OBJECTIVE: To examine the efficacy and safety of azelaic acid 15% foam in the treatment of moderate-to-severe facial acne Methods: Twenty subjects with moderate-to-severe facial acne vulgaris were enrolled in this two-center, open-label pilot study. All study subjects were treated with azelaic acid 15% foam for 16 weeks. Efficacy analyses were based on the change in facial investigator global assessment (FIGA) and changes in total, inflammatory, non-inflammatory lesion counts between baseline and week 16. RESULTS: There was a significant reduction in FIGA scores from baseline to week 16 (p = .0004), with 84% of subjects experiencing at least a 1 grade improvement, and 63% of subjects achieving a final grade of Clear or Almost Clear. All subjects experienced reductions in inflammatory and total lesion counts by week 16, and 89% of subjects experienced reductions in non-inflammatory lesions. Azelaic acid 15% foam was well tolerated, with almost all instances of erythema, dryness, peeling, oiliness, pruritus, and burning being of mild or trace degree, and most adverse effects resolving by the end of the study. CONCLUSION: Azelaic acid 15% foam is effective and safe in the treatment of facial acne vulgaris. Given the convenience of foam vehicles, azelaic acid 15% foam should be considered as a viable treatment option for this condition. J Drugs Dermatol. 2018;17(6):641-645.