Triple Combination Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% for Acne: Efficacy and Safety from a Pooled Phase 3 Analysis.

INTRODUCTION: A three-pronged approach to acne treatment combining an antibiotic, antimicrobial, and retinoid may be more efficacious than single/double treatments while potentially reducing antibiotic resistance. This study evaluated the efficacy and safety of the first fixed-dose, triple-combination topical acne product, clindamycin 1.2%/adapalene 0.15%/benzoyl peroxide (BPO) 3.1% gel (CAB) using pooled phase 3 data. METHODS: In two identical phase 3 (N = 183; N = 180), double-blind, 12-week studies, participants aged ≥ 9 years with moderate-to-severe acne were randomized 2:1 to receive once-daily CAB or vehicle gel. Endpoints included ≥ 2-grade reduction from baseline in Evaluator's Global Severity Score and clear/almost clear skin (treatment success) and least-squares mean percent change from baseline in acne lesion counts. Treatment-emergent adverse events (TEAEs) and cutaneous safety/tolerability were evaluated. RESULTS: At week 12, 50.0% of participants achieved treatment success with CAB versus 22.6% with vehicle gel (P < 0.001). CAB resulted in > 70% reductions in inflammatory and noninflammatory lesions at week 12 (77.9% and 73.0%, respectively), which were significantly greater than vehicle (57.9% and 48.2%; P < 0.001, both). Most TEAEs were of mild-moderate severity, and < 3% of CAB-treated participants discontinued study/treatment because of AEs. Transient increases from baseline in scaling, erythema, itching, burning, and stinging were observed with CAB, but resolved back to or near baseline values by week 12. CONCLUSIONS: The innovative fixed-dose, triple-combination clindamycin phosphate 1.2%/adapalene 0.15%/BPO 3.1% gel was efficacious and well tolerated in children, adolescents, and adults with moderate-to-severe acne. Half of participants achieved clear/almost clear skin by 12 weeks, rates not previously seen in clinical studies of other topical acne products. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04214639 and NCT04214652.

Antiseptic and Antibiotic Stewardship in Dermatologic Surgery: Is Benzoyl Peroxide the Solution?

Objective: We sought to review published literature on antibiotic and antiseptic use and resistance, and explore the utility of benzoyl peroxide in this capacity for dermatologic surgery. Methods: A literature review was performed to investigate the skin microbiome, guidelines on antibiotic and antiseptic use in dermatologic surgery, and the utility of benzoyl peroxide as an antiseptic. Results: Antiseptics are commonly used in dermatologic surgery to prepare surgical sites, and antibiotics are also employed by some physicians to prevent post-operative infection despite the potential for antibiotic resistance. Benzoyl peroxide, known for its high threshold for antibiotic resistance, has been successfully used in orthopedic surgery to prevent surgical site infection, especially in sebaceous areas of the skin which house a distinct microbiota. Limitations: Limitations to this review include lack of high-quality, adequately powered research and studies which evaluate the clinical impact of anti-septic use, particularly benzoyl peroxide use, in dermatologic surgery. Conclusion: Benzoyl peroxide may be a used as an antiseptic in dermatologic surgery of sebaceous areas to prevent post-operative infections, with a low likelihood of causing microbial resistance.

COVID-19 Protection Strategies: Lessons Learned About Epidermal Barrier Function and the Significance of Optimized Skin Care.

Initially categorized as primarily a respiratory disease, COVID-19 can involve other organ systems and may have direct skin manifestations, including exanthems, morbilliform eruption, generalized urticaria, or pseudo-chilblains —commonly called “COVID Toes.” Frequent handwashing and prolonged wearing of face masks and shields in efforts to minimize transmission of SARS-CoV-2, the novel coronavirus that causes COVID, has given rise to indirect skin manifestations of COVID. “Maskne” and handwashing dermatitis are particularly common among healthcare workers. Characterized by skin inflammation, dryness, pruritus, and other symptoms, these conditions are fundamentally disorders of skin barrier dysfunction. This dysfunction may result from the combination of mechanical skin damage, changes in skin pH, reductions in skin lipids attributable to protection measures, and local alterations in the cutaneous microbiome. Strategies to manage these conditions focus on reversing and repairing skin barrier damage with preventative general measures, optimized skin care with the selection of proper products, eliminating irritant exposures, and avoiding certain medications, such as topical corticosteroids, that may further impair barrier function despite temporary improvement in signs and symptoms. J Drugs Dermatol. 2024;23(4):  doi:10.36849/JDD.7862.

Topical clindamycin for acne vulgaris: analysis of gastrointestinal events.

Purpose: Topical clindamycin, a lincosamide antibiotic, is commonly combined with benzoyl peroxide or a retinoid for acne vulgaris (AV) treatment. While oral and topical clindamycin carry warnings/contraindications regarding gastrointestinal (GI) adverse events (AEs), real-world incidence of GI AEs with topical clindamycin is unknown. This review provides background information and an overview of safety data of topical clindamycin for treating AV.Materials and Methods: Available safety data from published literature, previously unpublished worldwide pharmacovigilance data, and two retrospective cohort studies were reviewed.Results and Conclusions: According to pharmacovigilance data, the rate of GI adverse drug reactions with topical clindamycin-containing products was 0.000045% (64/141,084,533). Results from two retrospective medical record studies of patients with AV indicated that physicians prescribe topical clindamycin equally to patients with or without inflammatory bowel disease history, and that rates of pseudomembranous colitis in these patients were low. In 8 published pivotal clinical trials of topical clindamycin for AV, GI AEs were reported in 1.4% of participants. Limitations include under/inaccurate reporting of AEs or prescription data and limited generalizability. This review of published case reports, worldwide pharmacovigilance data, retrospective US prescription data, and clinical trials safety data demonstrates that the incidence of colitis in patients exposed to topical clindamycin is extremely low.

Rosacea Core Domain Set for Clinical Trials and Practice: A Consensus Statement.

Importance: Inconsistent reporting of outcomes in clinical trials of rosacea is impeding and likely preventing accurate data pooling and meta-analyses. There is a need for standardization of outcomes assessed during intervention trials of rosacea. Objective: To develop a rosacea core outcome set (COS) based on key domains that are globally relevant and applicable to all demographic groups to be used as a minimum list of outcomes for reporting by rosacea clinical trials, and when appropriate, in clinical practice. Evidence Review: A systematic literature review of rosacea clinical trials was conducted. Discrete outcomes were extracted and augmented through discussions and focus groups with key stakeholders. The initial list of 192 outcomes was refined to identify 50 unique outcomes that were rated through the Delphi process Round 1 by 88 panelists (63 physicians from 17 countries and 25 patients with rosacea in the US) on 9-point Likert scale. Based on feedback, an additional 11 outcomes were added in Round 2. Outcomes deemed to be critical for inclusion (rated 7-9 by ≥70% of both groups) were discussed in consensus meetings. The outcomes deemed to be most important for inclusion by at least 85% of the participants were incorporated into the final core domain set. Findings: The Delphi process and consensus-building meetings identified a final core set of 8 domains for rosacea clinical trials: ocular signs and symptoms; skin signs of disease; skin symptoms; overall severity; patient satisfaction; quality of life; degree of improvement; and presence and severity of treatment-related adverse events. Recommendations were also made for application in the clinical setting. Conclusions and Relevance: This core domain set for rosacea research is now available; its adoption by researchers may improve the usefulness of future trials of rosacea therapies by enabling meta-analyses and other comparisons across studies. This core domain set may also be useful in clinical practice.

Importance of treating acne sequelae in skin of color: 6-month phase IV study of trifarotene with an appropriate skincare routine including UV protection in acne-induced post-inflammatory hyperpigmentation.

BACKGROUND: Acne-induced hyperpigmentation (AIH) may accompany acne vulgaris (AV) inflammation in all skin phototypes. Trifarotene has shown depigmenting properties in vivo. This study evaluated trifarotene plus skincare because it is increasingly recognized that holistic AV management should include skincare and treatments. METHODS: This is a phase IV double-blind, parallel-group study of patients (13-35 years) with moderate AV and AIH treated with trifarotene (N = 60) or vehicle (N = 63) plus skincare regimen (moisturizer, cleanser, and sunscreen) for 24 weeks. Assessments included the AIH overall disease severity (ODS) score, post-AV hyperpigmentation index (PAHPI), exit interviews, photography, and acne assessments. Standard safety assessments were included. RESULTS: Trifarotene 50 µg/g cream improved significantly from baseline in ODS score versus vehicle (-1.6 vs. -1.1, P = 0.03) at Week 12, but scores were comparable between groups at Week 24 (primary endpoint). Trifarotene had a better reduction in PAHPI score at Week 24 (-18.9% vs. -11.3% vehicle, P < 0.01). Lesion count reductions were higher with trifarotene at Week 12 versus vehicle (P < 0.001) and at Week 24 (P < 0.05), as were IGA success rates versus vehicle at Weeks 12 (P < 0.05) and 24 (P < 0.05). Patients agreed that the skincare regimen contributed to less irritation, making treatment adherence easier. Photography showed improvements in pigmentation and erythema across all skin types. AEs were more common in the vehicle group versus trifarotene (30.2 vs. 16.7%, respectively). CONCLUSIONS: In all skin phototypes, there was more rapid improvement in the ODS and PAHPI scores with trifarotene by Weeks 12 and 24, respectively. The combination of trifarotene and skincare correlated with high patient satisfaction and adherence to the treatment protocol.

Scientific Rationale and Clinical Basis for Clindamycin Use in the Treatment of Dermatologic Disease.

Clindamycin is a highly effective antibiotic of the lincosamide class. It has been widely used for decades to treat a range of skin and soft tissue infections in dermatology and medicine. Clindamycin is commonly prescribed for acne vulgaris, with current practice standards utilizing fixed-combination topicals containing clindamycin that prevent Cutibacterium acnes growth and reduce inflammation associated with acne lesion formation. Certain clinical presentations of folliculitis, rosacea, staphylococcal infections, and hidradenitis suppurativa are also responsive to clindamycin, demonstrating its suitability and versatility as a treatment option. This review describes the use of clindamycin in dermatological practice, the mechanism of protein synthesis inhibition by clindamycin at the level of the bacterial ribosome, and clindamycin's anti-inflammatory properties with a focus on its ability to ameliorate inflammation in acne. A comparison of the dermatologic indications for similarly utilized antibiotics, like the tetracycline class antibiotics, is also presented. Finally, this review addresses both the trends and mechanisms for clindamycin and antibiotic resistance, as well as the current clinical evidence in support of the continued, targeted use of clindamycin in dermatology.

Natural Moisturizing Factor-Enriched Formulations Compared to a Ceramide-Based Cream.

BACKGROUND: We aimed to investigate the effects of 2 ceramide plus natural moisturizing factor-enriched formulations compared to a ceramide-based cream on skin moisturization. METHODS: Two double-blinded comparative studies were conducted, which enrolled 35 (n=29 females, n=6 males) and 33 (n=21 females, n=12 males) participants, respectively. Participants applied ceramide plus natural moisturizer cream or ceramide-based cream (study 1) or applied ceramide plus natural moisturizing factor lotion or ceramide-based cream (study 2) to each of their lower legs for 10 days with a 5-day regression period (no moisturizer applied). Skin hydration by corneometry after bilateral application was conducted once daily for each leg in both groups.   Results: An increase in corneometer units vs baseline for the ceramide plus natural moisturizing factor-enriched cream and natural moisturizing factor-enriched lotion were greater than the increase vs baseline for the ceramide-based cream at days 10 and 15; with an overall statistical significance in favor of the ceramide plus natural moisturizing factor-enriched formulations at day 10.  Conclusions: The marked improvement in skin moisturization following utilization of the ceramide plus natural moisturizing  factor-enriched cream and lotion compared to the ceramide-based cream can be attributed to the inherent properties of the natural moisturizing factors. These properties are known to maintain the humectancy and intercellular lipid membrane of the stratum corneum, which directly improves the permeability barrier function of human skin in reducing transepidermal water loss. J Drugs Dermatol. 2024;23(3):     doi:10.36849/JDD.8172.

Microencapsulated Benzoyl Peroxide for Rosacea in Context: A Review of the Current Treatment Landscape.

Rosacea, a chronic skin condition affecting millions of people in the USA, leads to significant social and professional stigmatization. Effective management strategies are crucial to alleviate symptoms and improve patients' quality of life. Encapsulated benzoyl peroxide 5% (E-BPO 5%) is a newly FDA-approved topical treatment for rosacea that shows promise in enhancing therapeutic response and minimizing skin irritation. This review aims to assess the role of recently FDA approved E-BPO 5% in the current treatment landscape for rosacea management, as it is not yet included in clinical guidelines that predominantly rely on older approved therapies. The review focuses on randomized controlled trials conducted in English-speaking adults. It evaluates the efficacy, safety, and tolerability of various US Food and Drug Administration (FDA)-approved agents used for rosacea treatment, including E-BPO cream, metronidazole gel, azelaic acid gel and foam, ivermectin cream, minocycline foam, oral doxycycline, brimonidine gel, and oxymetazoline HCl cream. Existing therapies have been effective in reducing papulopustular lesions and erythema associated with rosacea for many years. E-BPO 5% offers a promising addition to the treatment options due to its microencapsulation technology, which prolongs drug delivery time and aims to improve therapeutic response while minimizing skin irritation. Further research is necessary to determine the exact role of E-BPO 5% in the therapeutic landscape for rosacea. However, based on available evidence, E-BPO 5% shows potential as a valuable treatment option for managing inflammatory lesions of rosacea, and it may offer benefits to patients including: rapid onset of action, demonstrated efficacy by Week 2, excellent tolerability, and sustained long-term results for up to 52 weeks of treatment.

Incorporating a Prognostic Gene Expression Profile Test into the Management of Cutaneous Squamous Cell Carcinoma: An Expert Consensus Panel Report.

BACKGROUND:  Cutaneous squamous cell carcinoma (cSCC) is a growing health concern with a rapidly increasing incidence. Disease-specific mortality is typically preceded by a metastasis, but current staging systems have significant limitations in predicting this event. The 40-gene expression profile (40-GEP) test is a validated method of further stratifying patients based on the risk of regional or distant metastasis, but limited guidelines exist for incorporating this test into clinical practice. OBJECTIVE:  To review the available literature on the use of gene expression profile (GEP) testing to assess prognosis in cSCC and create consensus statements to guide dermatology clinicians on its use. METHODS:  A comprehensive literature search of PubMed, EMBASE, and Scopus was completed for English-language original research articles on the use of GEP testing to assess cSCC prognosis. A panel of 8 dermatologists with significant expertise in diagnosing and managing cSCC gathered to review the articles and create consensus statements. A modified Delphi process was used to approve each statement and a strength of recommendation was assigned using the Strength of Recommendation Taxonomy (SORT) criteria. RESULTS:  The literature search produced 157 articles that met the search criteria. A thorough screening of the studies for relevance to the research question resulted in 21 articles that were distributed to the panelists for review prior to the roundtable discussion. The panel unanimously voted to adopt 7 consensus statements and recommendations, 6 of which were given a strength of "A" and 1 of which was given a strength of "C". CONCLUSION:  The 40-GEP test provides accurate and independent prognostic information beyond standard staging systems that only incorporate pathologic data. Incorporation of GEP testing into national guidelines can help further stratify patients based on risk of metastasis and thus may improve morbidity and mortality. J Drugs Dermatol. 2023;22(12):54-60.   doi:10.36849/JDD.7691.

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.

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.

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

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

The cutaneous effects of androgens and androgen-mediated sebum production and their pathophysiologic and therapeutic importance in acne vulgaris.

Background: The recognition of an association between the development of acne vulgaris (AV) and pubertal hormonal changes during adolescence dates back almost 100 years. Since these formative observations, a significant role of circulating hormones in the pathophysiology of AV and other cutaneous disorders has been established.Aims: This review article aims to provide an overview of clinical and preclinical evidence supporting the influences of androgens on the skin and their therapeutic importance in AV pathophysiology.Results: The cutaneous effects of hormones are attributable, to a large extent, to the influence of steroid hormones, particularly androgens, on sebocyte development and sebum production in both sexes. Androgen-mediated excess sebum production is implicated as a necessary early step in AV pathophysiology and is therefore considered an important therapeutic target in AV treatment. Although the local production and/or activity of androgens within the skin is believed to be important in AV pathophysiology, it has received limited therapeutic attention.Conclusions: We have summarized the current evidence in support of the therapeutic benefits of targeted hormonal treatment to decrease androgen-stimulated sebum production for the effective and safe treatment of AV in both male and female patients.

The primary role of sebum in the pathophysiology of acne vulgaris and its therapeutic relevance in acne management.

BACKGROUND: Sebum physiology and its contributions to acne vulgaris (AV) pathophysiology have been long debated. Within the pilosebaceous unit, androgens drive sebocyte production of sebum, comprising mono-, di-, and triglycerides (the latter converted to fatty acids); squalene; cholesterol; cholesterol esters; and wax esters. Upon release to the skin surface, human sebum has important roles in epidermal water retention, antimicrobial defenses, and innate immune responses. AIMS: Alterations in sebum alone and with other pathogenic factors (inflammation, follicular hyperkeratinization, and Cutibacterium acnes [C. acnes] proliferation) contribute to AV pathophysiology. Androgen-driven sebum production, mandatory for AV development, propagates C. acnes proliferation and upregulates inflammatory and comedogenic cascades. RESULTS: Some sebum lipids have comedogenic effects in isolation, and sebum content alterations (including elevations in specific fatty acids) contribute to AV pathogenesis. Regional differences in facial sebum production, coupled with patient characteristics (including sex and age), help exemplify this link between sebum alterations and AV lesion formation. CONCLUSIONS: To date, only combined oral contraceptives and oral spironolactone (both limited to female patients), oral isotretinoin and topical clascoterone (cortexolone 17α-propionate) modulate sebum production in patients with AV. A better understanding of mechanisms underlying sebaceous gland changes driving AV development is needed to expand the AV treatment armamentarium.

Incorporating a Prognostic Gene Expression Profile Test into the Management of Cutaneous Squamous Cell Carcinoma: An Expert Consensus Panel Report.

BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is a growing health concern with a rapidly increasing incidence. Disease-specific mortality is typically preceded by a metastasis, but current staging systems have significant limitations in predicting this event. The 40-gene expression profile (40-GEP) test is a validated method of further stratifying patients based on the risk of regional or distant metastasis, but limited guidelines exist for incorporating this test into clinical practice. OBJECTIVE: To review the available literature on the use of gene expression profile (GEP) testing to assess prognosis in cSCC and create consensus statements to guide dermatology clinicians on its use. METHODS: A comprehensive literature search of PubMed, EMBASE, and Scopus was completed for English-language original research articles on the use of GEP testing to assess cSCC prognosis. A panel of 8 dermatologists with significant expertise in diagnosing and managing cSCC gathered to review the articles and create consensus statements. A modified Delphi process was used to approve each statement and a strength of recommendation was assigned using the Strength of Recommendation Taxonomy (SORT) criteria. RESULTS: The literature search produced 157 articles that met the search criteria. A thorough screening of the studies for relevance to the research question resulted in 21 articles that were distributed to the panelists for review prior to the roundtable discussion. The panel unanimously voted to adopt 7 consensus statements and recommendations, 6 of which were given a strength of "A" and 1 of which was given a strength of "C". CONCLUSION: The 40-GEP test provides accurate and independent prognostic information beyond standard staging systems that only incorporate pathologic data. Incorporation of GEP testing into national guidelines can help further stratify patients based on risk of metastasis and thus may improve morbidity and mortality. J Drugs Dermatol. 2023;22(12): doi:10.36849/JDD.7691e.

Trifarotene Reduces Risk for Atrophic Acne Scars: Results from A Phase 4 Controlled Study.

BACKGROUND: Atrophic acne scarring often accompanies acne vulgaris. The efficacy of topical retinoids for treatment of acne is well documented; however, evidence for use in atrophic acne scars is limited. METHODS: In this randomized, split-face, double-blind study, subjects (age: 17-34 years, N = 121) with moderate-to-severe facial acne, with acne scars present, were treated with either trifarotene 50 µg/g or vehicle once daily for 24 weeks. Efficacy was assessed by absolute and percent change from baseline in atrophic acne scar counts, Scar Global assessment (SGA), and IGA success rates as well as acne lesion counts. RESULTS: At week 24, a statistically significantly greater reduction in the mean absolute change from baseline in the total atrophic scar count was noted in the trifarotene- vs vehicle-treated area (- 5.9 vs - 2.7; p < 0.0001) with differences between sides noted as early as week 2 (- 1.5 vs - 0.7; p = 0.0072). The SGA success rate was higher in the trifarotene side at week 12 (14.9% vs 5.0%, P < 0.05) and improved through week 24 (31.3% vs 8.1%, P < 0.001). Similarly, at week 24, the IGA success rate was higher with trifarotene (63.6% vs 31.3%, P < 0.0001) along with reductions in total (70% vs 45%) and inflammatory (76% vs 48%) lesion counts. The incidence of treatment-emergent adverse events was 5.8% (trifarotene) and 2.5% (vehicle); most common (> 1%) was skin tightness (1.7% vs 0.8%), and all events were mild to moderate in severity. CONCLUSIONS: Trifarotene was effective and well tolerated in treating moderate-to-severe facial acne and reducing atrophic acne scars, with reduction of total atrophic scar count as early as week 2. TRIAL REGISTRATION: Clinicaltrials.gov NCT04856904.

Rationale for Use of Micronized Isotretinoin for Treatment of Acne Vulgaris: Practical Considerations and Therapeutic Advantages.

Objective: Isotretinoin is a widely used and clinically efficacious treatment for severe, recalcitrant, nodular acne vulgaris (AV). Clinicians are generally familiar with safety concerns regarding isotretinoin use, especially teratogenicity. However, there are specific "real-world" challenges with use of conventional formulations based on the original isotretinoin formulation, including poor solubility and food-dependent absorption requiring high fat intake with each dose. This review describes the development and use of new isotretinoin formulations and their potential to improve long-term outcomes in patients with AV. Methods: PubMed was searched using the terms "acne," "isotretinoin," "micronized," "lidose," and "efficacy." Results: Micronized isotretinoin received US Food and Drug Administration approval in 2019 for the treatment of severe recalcitrant nodular acne in patients aged 12 years or older. This isotretinoin formulation utilizes micronization technology to reduce drug particle size, thereby increasing its dissolution rate and bioavailability, combined with a lipid-based carrier system that enhances gastrointestinal absorption without the need for dietary fat ingestion. Together, these features allow for an approximately two-fold or greater increase in isotretinoin absorption despite a lower administered dose compared with prior formulations, without dependency upon high-fat food intake. Limitations: Evidence supporting reduction in relapse with micronized isotretinoin is based on studies with the lidose formulation and pharmacokinetic data supporting greater systemic exposure to micronized isotretinoin without food. Conclusion: The lack of any specific dietary requirements or need for food intake and the enhanced bioavailability of micronized isotretinoin may increase both patient compliance and the rate of prolonged remission of AV after completion of therapy.