Guidelines of care for the management of acne vulgaris.

BACKGROUND: Acne vulgaris commonly affects adults, adolescents, and preadolescents aged 9 years or older. OBJECTIVE: The objective of this study was to provide evidence-based recommendations for the management of acne. METHODS: A work group conducted a systematic review and applied the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of evidence and formulating and grading recommendations. RESULTS: This guideline presents 18 evidence-based recommendations and 5 good practice statements. Strong recommendations are made for benzoyl peroxide, topical retinoids, topical antibiotics, and oral doxycycline. Oral isotretinoin is strongly recommended for acne that is severe, causing psychosocial burden or scarring, or failing standard oral or topical therapy. Conditional recommendations are made for topical clascoterone, salicylic acid, and azelaic acid, as well as for oral minocycline, sarecycline, combined oral contraceptive pills, and spironolactone. Combining topical therapies with multiple mechanisms of action, limiting systemic antibiotic use, combining systemic antibiotics with topical therapies, and adding intralesional corticosteroid injections for larger acne lesions are recommended as good practice statements. LIMITATIONS: Analysis is based on the best available evidence at the time of the systematic review. CONCLUSIONS: These guidelines provide evidence-based recommendations for the management of acne vulgaris.

Comparison of risankizumab and apremilast for the treatment of adults with moderate plaque psoriasis eligible for systemic therapy: results from a randomized, open-label, assessor-blinded phase IV study (IMMpulse).

BACKGROUND: Treatment of psoriasis with risankizumab has demonstrated superior efficacy to other treatments, such as adalimumab, ustekinumab and secukinumab. OBJECTIVES: This study compared the efficacy and safety of risankizumab and apremilast in adults with moderate plaque psoriasis eligible for systemic therapy. It also evaluated the efficacy and safety of switching to risankizumab vs. continuing apremilast in patients who did not achieve ≥ 75% improvement in Psoriasis Area and Severity Index (PASI 75 nonresponders) after 16 weeks of treatment with apremilast. METHODS: This 52-week, phase IV, multicentre, randomized, open-label, efficacy assessor-blinded study (NCT04908475) enrolled patients (aged ≥ 18 years) with a diagnosis of moderate chronic plaque psoriasis (≥ 6 months) and who were candidates for systemic therapy. The enrolled patients (randomized 1 : 2) received subcutaneous risankizumab (150 mg at weeks 0 and 4) or oral apremilast (30 mg twice daily). At week 16, all patients treated with apremilast were re-randomized (1 : 1) to risankizumab or apremilast, stratified by week-16 PASI 75 response. The co-primary outcomes in period A at week 16 were the achievement of ≥ 90% improvement in Psoriasis Area and Severity Index (PASI 90) and static Physician's Global Assessment (sPGA) 0/1 with a two-grade or better improvement from baseline. At week 52, the primary endpoint in period B was the achievement of PASI 90 in PASI 75 nonresponders with apremilast at week 16. Safety was monitored throughout the study. All patients who received one dose of treatment were included in the efficacy and safety analysis. RESULTS: At baseline, 118 and 234 patients were assigned to receive risankizumab and apremilast, respectively. At week 16, PASI 90 was achieved by 55.9% [95% confidence interval (CI) 47.0-64.9] and 5.1% (95% CI 2.3-8.0), and sPGA 0/1 by 75.4% (95% CI 67.7-83.2) and 18.4% (95% CI 13.4-23.3), respectively. In period B, among PASI 75 nonresponders with apremilast at week 16, 83 switched to risankizumab and 78 continued apremilast. At week 52, 72.3% (95% CI 62.7-81.9) who switched to risankizumab achieved PASI 90 vs. 2.6% (95% CI 0.0-6.1) who continued apremilast. The most frequent adverse events (reported in ≥ 5%) in risankizumab-treated patients were COVID-19 infection and nasopharyngitis. Diarrhoea, nausea and headache were most frequent among apremilast-treated patients. CONCLUSIONS: For patients with moderate psoriasis, treatment with risankizumab demonstrated superior efficacy to those treated with apremilast, including those who did not benefit from prior treatment with apremilast. The safety profile of risankizumab was similar to prior studies, and no new safety signals were identified. These results show that, compared with apremilast, risankizumab treatment can significantly improve clinical outcomes in systemic-eligible patients with moderate psoriasis.

The Importance of Assessing Burning and Stinging when Managing Rosacea: A Review.

Rosacea, a chronic condition usually recognized by its visible presentation, can be accompanied by invisible symptoms, such as burning and stinging. The aim of this review is to gather the most recent evidence on burning and stinging, in order to further emphasize the need to address these symptoms. Inflammatory pathways can explain both the signs and symptoms of rosacea, but available treatments are still evaluated primarily on their ability to treat visible signs. Recent evidence also highlights the adverse impact of symptoms, particularly burning and stinging, on quality of life. Despite an increasing understanding of symptoms and their impact, the management of burning and stinging as part of rosacea treatment has not been widely investigated. Clinicians often underestimate the impact of these symptoms and do not routinely include them as part of management. Available therapies for rosacea have the potential to treat beyond signs, and improve burning and stinging symptoms in parallel. Further investigation is needed to better understand these benefits and to optimize the management of rosacea.

Demographics and Baseline Disease Characteristics of Early Responders to Crisaborole for Atopic Dermatitis.

INTRODUCTION: Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate atopic dermatitis (AD). This post hoc, pooled analysis identified demographic characteristics associated with early response to crisaborole. METHODS: Early response was defined as day 8 Investigator’s Static Global Assessment (ISGA) success (clear [0] or almost clear [1] with ≥2-grade improvement), ISGA clear/almost clear, or Severity of Pruritus Scale (SPS) response (≥1-point improvement). Correlations between early response and day-29 response were calculated. RESULTS: Patients were more likely to be early ISGA success responders if they were aged <12 years (P=0.0023), were white (P=0.0316), had moderate baseline disease by ISGA (P=0.0003), had not received prior AD treatment (P=0.0213), had disease duration shorter than or equal to the median (≤6.45 years; P=0.0349), or did not concurrently use antihistamines (P=0.0148). Similar early response results were observed for patients achieving ISGA clear or almost clear; however, they were more likely to have mild baseline disease by ISGA (P<0.0001) or mild percentage of treatable body surface area involvement (5 to <16; P<0.0001). Patients aged <12 years (P=0.0001) or with moderate baseline disease (P=0.0475) were more likely to be early responders based on SPS criteria. By all 3 definitions, patients who achieved early response at day 8 were more likely to be responders at day 29 (P<0.0001). CONCLUSION: Based on this analysis, patients aged <12 years were more likely to be early responders to crisaborole per all 3 definitions. Early response to crisaborole was a predictor of response at day 29. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02118766 and NCT02118792 J Drugs Dermatol. 2020;19(6): doi:10.36849/JDD.2020.5095THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

Improvement in disease severity and pruritus outcomes with crisaborole ointment, 2%, by baseline atopic dermatitis severity in children and adolescents with mild-to-moderate atopic dermatitis.

BACKGROUND/OBJECTIVES: Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild-to-moderate atopic dermatitis (AD). This pooled post hoc analysis of two phase 3 trials (NCT02118766, NCT02118792) assessed improvement and time to improvement in Investigator's Static Global Assessment (ISGA) and Severity of Pruritus Scale (SPS) outcomes in pediatric patients with mild-to-moderate AD. METHODS: Patients aged ≥2 years were randomly assigned 2:1 to receive twice-daily crisaborole or vehicle for 28 days. Patients aged 2-17 years were pooled for this analysis. Proportions of patients and time to achieving ISGA success (clear [0] or almost clear [1] with ≥2-grade improvement from baseline), ISGA clear/almost clear, ≥1-grade improvement in ISGA, SPS success (SPS score ≤1 with ≥1-grade improvement), or ≥1-grade improvement in SPS score were analyzed and stratified by baseline ISGA. RESULTS: At first postbaseline assessment (day 8), significantly higher proportions of crisaborole- than vehicle-treated patients achieved ISGA success, ISGA clear/almost clear, ≥1-grade ISGA improvement, SPS success, or ≥1-grade improvement in SPS regardless of baseline ISGA. Differences were significantly greater over time for all outcomes for patients with moderate baseline ISGA and numerically greater for those with mild baseline ISGA. Median times to ISGA and SPS outcomes were shorter for crisaborole versus vehicle. CONCLUSION: Improvement in ISGA and SPS outcomes were observed with crisaborole in pediatric patients with mild-to-moderate baseline AD.

Current Concepts in Acne Pathogenesis: Pathways to Inflammation.

Acne is a disease of pilosebaceous inflammation. Pivotal in pathogenesis are the roles of hormones (insulin, insulin-like growth factor-1, androgens), Propionibacterium acnes, lipogenesis, and a proinflammatory lipid profile. Innate immune responses are induced through interaction with toll-like receptors and inflammasome activation initially and subsequently through adaptive immune activation. These insights into pathogenic inflammatory pathways can translate into novel therapeutic approaches for acne. Semin Cutan Med Surg 37(supp3):S60-S62 ©2018 published by Frontline Medical Communication.

Advances in Acne and Rosacea Therapy.

New topical therapies have demonstrated efficacy in patients with moderate or severe acne who might otherwise have required therapy with systemic antibiotics or isotretinoin. Increasing knowledge about the pathogenesis of acne has facilitated the development of therapies with novel modes of action. New and investigational therapies also are available or in development for the treatment of both the papulopustular and erythematous manifestations of rosacea. Semin Cutan Med Surg 37(supp3):S63-S66 © 2018 published by Frontline Medical Communications.

Treating Acne in Adult Women.

Acne can persist into adulthood or erupt de novo at any point after adolescence. Adult acne is more common in women than in men. Considerations for treating acne in adult women include childbearing potential, pregnancy, lactation, and concomitant skin conditions. Semin Cutan Med Surg 37(supp3):S67-S70 © 2018 published by Frontline Medical Communications.

Treating Acne in Patients With Skin of Color.

Patients with skin of color are more likely to develop acne and postinflammatory hyperpigmentation (PIH). Many therapies for acne have demonstrated efficacy in darker skin types and in the treatment of PIH. Semin Cutan Med Surg 37(supp3):S71-S73 © 2018 published by Frontline Medical Communications.

Highlights of Skin Disease Education Foundations 42nd Annual Hawaii Dermatology Seminar.

Updates on managing some of the most common dermatologic conditions for which patients seek care illuminated presentations at the Skin Disease Education Foundation's 42nd Annual Hawaii Dermatology Seminar®. This educational supplement summarizes the highlights of clinical sessions presented during this CME/CE conference. Treatment of psoriasis has continued to advance, with three interleukin (IL)-17 antagonists approved by the US Food and Drug Administration (FDA) and a fourth in phase 3 trials. An authority on the use of biologics in psoriasis presents current data on the safety and efficacy of these therapies. Tumor necrosis factor (TNF) inhibitors also retain a place in the management of psoriasis, with records of long-term safety. A fourth TNF inhibitor awaits FDA approval for use in psoriasis, offering data on transmission during pregnancy and lactation. An expert on the use of this drug class presents the evidence. Topical therapies remain the cornerstone of care for many patients with psoriasis as well as those with rosacea. Our faculty update readers about new and investigational topical therapies for moderate or severe psoriasis, as well as for acne and rosacea. The current literature on monitoring patients receiving isotretinoin also is summarized. Aesthetic and cosmetic dermatology services form a sizable portion of some practices. Our faculty review data on safety of topical and procedural therapies for cellulite as well as safe injection of facial fillers.

Long-term safety of crisaborole ointment 2% in children and adults with mild to moderate atopic dermatitis.

BACKGROUND: Long-term topical treatment is often required for atopic dermatitis (AD), a chronic inflammatory skin disease. OBJECTIVE: To assess the long-term safety results from a multicenter, open-label, 48-week safety study (AD-303) of patients (N = 517) ≥2 years of age with mild to moderate AD who continued crisaborole treatment, a topical phosphodiesterase-4 inhibitor, after completing a 28-day phase 3 pivotal study (AD-301, AD-302). METHODS: Global disease severity was assessed in patients every 4 weeks, and if assessed as mild or greater, a 28-day treatment period with crisaborole applied twice daily was initiated. Adverse events (AEs), including treatment-emergent AEs (TEAEs), and serious AEs were analyzed. RESULTS: During the pivotal studies and AD-303, 65% of patients reported ≥1 TEAE, most of which were mild (51.2%) or moderate (44.6%) and considered unrelated to treatment (93.1%). The frequency and severity of TEAEs were consistent. The most frequently reported treatment-related AEs (overall, 10.2%) were dermatitis atopic (3.1%), application-site pain (2.3%), and application-site infection (1.2%). Nine patients (1.7%) discontinued the long-term study because of TEAEs. LIMITATIONS: Long-term efficacy was not analyzed. CONCLUSION: Crisaborole ointment had a low frequency of treatment-related AEs over 48 weeks of treatment of patients with AD.

The Disease Burden of Atopic Dermatitis.

Recent studies have shed light on the nature of the burden of atopic dermatitis. Analysis of observational data has revealed the effect of atopic dermatitis in diverse areas such as work productivity, physical activity, mood, and risk of comorbidities beyond other atopic conditions. Studies on adults with moderate to severe disease show that the symptoms and consequences of atopic dermatitis affect many aspects of their lives. A clearer understanding of the burden for patients can inform open, sensitive discussions about goals of therapy. Semin Cutan Med Surg 36(supp4):S92-S94.

Topical Therapy for Atopic Dermatitis: New and Investigational Agents.

Recently a new class of topical medications for mild to moderate atopic dermatitis has been introduced with US Food and Drug Administration (FDA) approval of the first new prescription medication for this condition in more than a decade. Crisaborole, the newly approved medication, has relieved pruritus in more than one-third of patients within as little as 48 hours. It also has demonstrated efficacy in patients with skin of color. Topical therapies representing other new approaches to atopic dermatitis, with novel mechanisms of action, have shown promise in clinical development. Semin Cutan Med Surg 36(supp4):S99-S102.

Systemic Therapy of Atopic Dermatitis: Welcome to the Revolution.

Until recently, systemic therapy of atopic dermatitis was limited to off-label use of immunomodulators, which can pose significant safety concerns, and treatment with systemic corticosteroids, not recommended in the most recent guidelines. The introduction of dupilumab in 2017 marked a major advance in systemic therapy for atopic dermatitis. It has demonstrated long-term efficacy in adults with moderate to severe disease, and is being studied in children. Several other biologic agents and "small molecules" with varying mechanisms of action are in phase 2 or 3 development. Semin Cutan Med Surg 36(supp4):S103-S105.

Improving Outcomes Through Therapeutic Patient Education.

Therapeutic patient education is a nascent movement in the care of atopic dermatitis, offering patients-and, for children, their caregivers-knowledge, skills, support, and coping strategies for managing what for many is a relapsing/ remitting chronic disease that severely compromises quality of life. Interventions range from a written treatment plan provided in the office to a 6-week education program. Studies indicate that this approach yields benefits for patients and their caregivers. Most of these studies involved children and their parents or other caregivers, but reduced signs and symptoms of disease and improved quality of life also has been documented in adults. Semin Cutan Med Surg 36(supp4):S106-S107.

Practical strategies for the diagnosis and assessment of atopic dermatitis.

Atopic dermatitis (AD) has a significant, lifelong clinical impact on affected individuals and has profound effects on quality of life both for patients and their families. The diagnosis usually can be reliably established on the basis of the history and physical examination. In patients with skin of color, blanching of the skin may be helpful to detect erythema, lichenification, follicular accentuation, and hypopigmentation (all of which are more common than in lighter-skinned patients). Once the diagnosis of AD is established, an assessment of severity, persistence, and impact on the patient's and family's life is important as a guide to treatment decisions.

Atopic dermatitis progression: evaluating intervention strategies.

Several risk factors have been identified that appear to be consistently and strongly associated with the development of atopic dermatitis (AD): a family history of atopy, an inherited genetic predisposition, and active and passive exposure to tobacco smoke. Recent studies also have demonstrated that a simple intervention from birth-the daily application of an emollient moisturizer-seems to protect susceptible infants from the development of AD.

Nonpharmacologic strategies and topical agents for treating atopic dermatitis: an update.

The signs and symptoms of atopic dermatitis can be safely and effectively controlled in most patients; in many cases, the disease can be improved to the point that signs and symptoms are absent or minimal. In addition, flares can be effectively controlled and, in some cases, prevented. New topical medications, improved strategies for the use of topical corticosteroids and topical calcineurin inhibitors, and judicious use of nonpharmacologic regimens-including bathing, bleach baths, and early use of emollients-have led to better disease management and improved quality of life for patients and their families.

Addressing the immunopathogenesis of atopic dermatitis: advances in topical and systemic treatment.

Several immunologic mediators-phosphodiesterase (PDE), interleukin (IL), small molecules, and Janus kinase-have been implicated in the pathogenesis of atopic dermatitis, and evidence has shown that blocking these mediators can help modify the disease process. Several new topical medications have been developed that target the enzyme PDE; crisaborole was recently approved by the US Food and Drug Administration (FDA) for the treatment of atopic dermatitis, and phase II studies have been completed on OPA-15406. The phase III clinical trial results of the systemic medication dupilumab, an inhibitor of the IL-4 receptor α subunit (which inhibits both IL-4 and IL-13 signaling), are currently being reviewed by the FDA.

OPA-15406, a novel, topical, nonsteroidal, selective phosphodiesterase-4 (PDE4) inhibitor, in the treatment of adult and adolescent patients with mild to moderate atopic dermatitis (AD): A phase-II randomized, double-blind, placebo-controlled study.

BACKGROUND: Peripheral leukocytes in patients with atopic dermatitis (AD) have elevated phosphodiesterase-4 activity, which is associated with production of proinflammatory mediators. OPA-15406 is a phosphodiesterase-4 inhibitor with high selectivity for phosphodiesterase-4-B. OBJECTIVES: We sought to assess effectiveness and tolerability of topical OPA-15406 in patients with AD. METHODS: This was a randomized, double-blind, vehicle-controlled, phase-II study. Patients 10 to 70 years of age with mild or moderate AD received topical OPA-15406 0.3% (n = 41), OPA-15406 1% (n = 43), or vehicle (n = 37) twice daily for 8 weeks. RESULTS: The primary end point, Investigator Global Assessment of Disease Severity score of 0 or 1 with greater than or equal to 2-grade reduction, was met at week 4 in the OPA-15406 1% group (P = .0165 vs vehicle). Mean percentage improvement from baseline Eczema Area and Severity Index score for OPA-15406 1% was notable in week 1 (31.4% vs 6.0% for vehicle; P = .0005), even larger in week 2 (39.0% vs 3.0%; P = .0001), and persisted for 8 weeks. Visual analog scale pruritus scores improved from moderate to mild within the first week in the OPA-15406 1% group (36.4% mean change; P = .0011). OPA-15406 levels in blood were negligible. Incidence of adverse events was low, with most events mild in intensity. LIMITATIONS: Further confirmatory phase-III studies are required. CONCLUSION: OPA-15406 ointment may provide an effective therapeutic modality for patients with mild to moderate AD.