Dermatology and Therapy最新文献

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that causes significant physical and psychosocial burden. Although U.S. Food and Drug Administration (FDA)-approved biologic therapies targeting tumor necrosis factor-alpha (TNF-α) and interleukin-17 (IL-17) have improved outcomes for many patients with moderate-to-severe HS, a subset remain refractory or experience loss of response over time. Transcriptomic and immunologic studies demonstrate concurrent activation of multiple inflammatory pathways in HS, including TNF-α, IL-1, IL-17, and Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling, supporting a rationale for dual targeted therapy (DTT). This narrative review summarizes the current evidence on DTT in HS and contextualizes these findings with data from other immune-mediated diseases such as inflammatory bowel disease, psoriasis, psoriatic arthritis, and rheumatoid arthritis. Published HS-specific reports remain limited to case reports of dual biologic or biologic plus Janus kinase (JAK) inhibitor therapy, each showing clinical improvement without serious short-term adverse events. Evidence from related immune-mediated diseases suggests that combined blockade of complementary cytokine pathways can enhance efficacy with acceptable safety in selected patients. DTT may represent a promising approach for treatment-resistant HS, warranting further prospective evaluation to understand optimal combinations, safety profiles, and long-term outcomes.

Introduction: Atopic dermatitis (AD), prurigo nodularis (PN), and chronic spontaneous urticaria (CSU) are chronic inflammatory skin diseases varying in clinical presentation but sharing the common and burdensome symptom of itch. Here, we investigate the efficacy of dupilumab in reducing pruritus in individuals with AD, PN, and CSU.

Methods: LIBERTY-AD CHRONOS, LIBERTY-PN PRIME/PRIME2, and LIBERTY-CSU CUPID Study A were randomized, double-blind, placebo-controlled, phase III trials of dupilumab for AD, PN, and CSU, respectively. The itch-related study endpoints included the weekly average of daily Peak Pruritus Numeric Rating Scale (PP-NRS) for AD, weekly average of Worst Itch Numeric Rating Scale (WI-NRS) for PN, and total Itch Severity Score over 7 days (ISS7) for CSU. The efficacy endpoints included the proportion of patients who achieved a clinically meaningful improvement in PP-NRS (≥ 4-points), WI-NRS (≥ 4-points), or ISS7 (≥ 5-points); the percentage change in PP-NRS, WI-NRS, or ISS7; and the proportion of patients who achieved ≥ 50% reduction in PP-NRS, WI-NRS, or ISS7. Safety endpoints included treatment-emergent adverse events and severe adverse events.

Results: In each trial, patients in both treatment groups demonstrated a severe pruritus burden at baseline on the respective itch scales (dupilumab versus placebo [Q1-Q3]; PP-NRS: 7.7 [6.6-8.5] versus 7.6 [6.3-8.6]; WI-NRS: 8.7 [7.9-9.3] versus 8.4 [7.9-9.1]; ISS7: 16.0 [14.0-20.0] versus 15.5 [13.0-20.0]). Dupilumab recipients were significantly more likely to achieve clinically meaningful improvements in PP-NRS (P < 0.0001), WI-NRS (P < 0.0001), and ISS7 (P = 0.0014) than placebo recipients. The percentage change from baseline was also significantly greater in dupilumab-treated patients than placebo recipients in all three trials (PP-NRS: P < 0.0001; WI-NRS: P < 0.0001; ISS7: P = 0.0009). Similarly, significantly more dupilumab versus placebo recipients achieved ≥ 50% reduction in relevant itch outcome scales in AD (70% versus 38.8%; P < 0.0001), PN (60.1% versus 20.9%; P < 0.0001), and CSU (68.6% versus 42.7%; P = 0.0213). Overall, safety was generally consistent with the known dupilumab safety profile.

Conclusions: Baseline median pruritus in AD, PN, or CSU reached the upper third of the respective itch scales, demonstrating severe pruritus burden. In all three disease states, dupilumab treatment resulted in clinically meaningful improvement in itch.

Trial registration: ClinicalTrials.gov: NCT02260986, NCT04183335/NCT04202679, NCT04180488.

Introduction: Delays remain in patients receiving effective treatment strategies that have potential to clear their skin of psoriasis, improve their quality of life (QoL) and change the psoriatic disease course, which, if uncontrolled, can irreversibly alter an individual's life course (i.e. cumulative life course impairment [CLCI]). This study explored current international awareness and consideration of the potential impact of psoriasis over the life course within clinical assessments and decisions about its management.

Methods: Cross-sectional surveys collated insights from people with psoriasis and healthcare professionals (HCPs) treating psoriasis (dermatologists and primary care physicians [PCPs]) across 29 countries.

Results: Data were collected from 487 people with psoriasis, 574 dermatologists and 618 PCPs. Despite people with psoriasis highlighting a range of daily activities that are 'very frequently' or 'always' affected by their psoriasis, 37% were never or rarely asked by their HCPs how the disease affects their life. Fewer than half of people with psoriasis had a high understanding of the potential future impact of psoriasis (or CLCI-contributing factors), and 44% were unaware that clear/almost clear skin is now a realistic treatment target. Almost half of HCPs considered psoriasis to be of early onset when it presented at ≤ 15 years of age. Despite HCP awareness of the impact of psoriasis on QoL, many of the contributing factors to CLCI were not addressed routinely in clinical practice nor considered when deciding on treatment; 40% of dermatologists set treatment goals (such as clear skin/almost clear skin/target Dermatology Life Quality Index [DLQI]) sometimes, less frequently, or not at all.

Conclusions: Misalignment exists in the experience of people living with psoriasis versus its assessment in clinical practice. Support is needed for assessment and monitoring of elements that may contribute to CLCI in clinical practice worldwide, to guide early psoriasis treatment decision-making to mitigate the risk for CLCI. Infographic available for this article. INFOGRAPHIC.

Introduction: Psoriasis is an immune-mediated chronic inflammatory skin disease with a prevalence in Spain of between 2.3% and 2.7%. One-third of patients present with moderate to severe psoriasis (Pso). This article aims to retrospectively describe the characteristics of patients with Pso, as well as severity, patterns of treatment, quality of life (QoL), and associated direct healthcare resources utilized in routine clinical practice in Spain.

Methods: The SUMMER project is an ambispective, non-interventional, multicenter study including adult patients with a diagnosis of Pso. In the retrospective phase, data were extracted from patients' electronic medical records. Data on disease severity scores (PASI and BSA) and impact on quality-of-life impact (DLQI) were captured by natural language recognition processors.

Results: Of 10,874 patients with a diagnosis of psoriasis identified from five participating sites, 2734 did not meet inclusion criteria; a total of 8140 patients were included. Mean age (SD) was 57.7 (16.1) years and 51.3% were male. Most patients had plaque psoriasis (91.5%) and lesions in visible areas (70.8%). The most common comorbidities were dyslipidemia (32%), hypertension (25.6%), and anxiety (18.5%). On the basis of thresholds of PASI (5%) and BSA (3%), psoriasis was not controlled in 17.1% and 37.2% of the patients, respectively, and 25.1% of patients were receiving biological treatments. Between 2017 and 2022, ustekinumab showed the highest persistence rate, especially when used as first-line treatment. There was a tendency to prescribe guselkumab and risankizumab most commonly as second- and third-line therapies. DLQI scores showed that Pso had a moderate or higher impact on QoL for 38.0% of patients.

Conclusions: The results show how patients with moderate-severe psoriasis are managed in routine clinical practice in Spain. Between 17% and 37% of patients with Pso are not on the appropriate therapeutic target. Almost a quarter of patients required biological treatments to control the disease.

Introduction: Calcipotriol and betamethasone dipropionate (Cal/BDP) PolyAphron dispersion (PAD) cream and Cal/BDP foam have demonstrated superior efficacy to Cal/BDP gel in patients with plaque psoriasis exhibiting a more severe profile defined by the Rule of Tens in different studies. However, its comparative efficacy in this subgroup of patients needs to be studied.

Methods: An indirect treatment comparison (ITC) using individual patient data for Cal/BDP PAD cream and available aggregated data for Cal/BDP foam was conducted for three outcome measures: Physician's Global Assessment (PGA) success, modified Psoriasis Area and Severity Index 75 (mPASI75), and Dermatology Life Quality Index (DLQI) satisfaction. Bucher's method was used for the ITC base case, and alternative analyses were performed using an anchored matching-adjusted indirect comparison (MAIC). Odds and risk ratios were calculated for each outcome.

Results: After adjustment to the Rule of Tens, Cal/BDP PAD cream showed no differences vs. Cal/BDP foam in the three outcomes. Similar results were found for the MAIC scenarios after population matching, supporting the validity of the results.

Conclusion: In this ITC analysis, no significant differences in the clinical efficacy of Cal/BDP PAD cream and Cal/BDP foam in patients with plaque psoriasis meeting the Rule of Tens were observed considering their recommended treatment durations.

Introduction: Vulvar lichen sclerosus (VLS) is a chronic inflammatory dermatosis of unclear etiology, most often affecting postmenopausal women. It presents with itching, burning, pain, and progressive vulvar scarring and atrophy, leading to sexual dysfunction and increased risk of neoplastic transformation. High-potency corticosteroids are the standard first-line treatment, but many patients experience inadequate response or intolerance, resulting in recurrence. In such cases, 5-aminolevulinate (ALA) photodynamic therapy (PDT) may offer an alternative. The aim of this systematic review was to evaluate the effectiveness and safety of PDT in patients with VLS.

Methods: Searches of PubMed, Scopus, and Web of Science identified 238 papers, of which 13 met the inclusion criteria, comprising 441 women with VLS. Among these, one was a randomized controlled trial, one a non-randomized comparative study, seven were single-arm trials, and four were retrospective analyses.

Results: The collective evidence showed that PDT, particularly using 5-ALA as a photosensitizer, improved clinical symptoms such as pain and itching, skin histology, patients' quality of life as measured with the Dermatology Life Quality Index, and sexual functioning as measured with the Female Sexual Function Index. Adverse events were mainly procedure-related and resolved spontaneously within a few days.

Discussion: PDT appears to be a promising therapeutic option for VLS, particularly in patients with refractory disease unresponsive to conventional treatments. However, evidence for ALA-PDT remains limited, as current studies are small, use variable protocols, and involve heterogeneous populations. Further research is needed to address these gaps.

Conclusion: Available studies indicate that ALA-PDT is a safe, well-tolerated, and effective option for VLS, improving both symptoms and clinical signs, especially in refractory cases. Emerging evidence, including comparative and quality-of-life studies, supports its potential role in management, though large prospective trials are needed to refine protocols and establish guideline recommendations.

Introduction: This study aimed to explore the relationship between atopic dermatitis (AD) disease severity and impact on patients and to describe AD treatment patterns and barriers to treatment in Brazil and Colombia.

Methods: Data were drawn from the Adelphi AD Disease Specific Programme™, a cross-sectional survey of physicians and their patients with AD, conducted in Brazil and Colombia between May 2022 and July 2023. Physicians provided data on demographics, clinical characteristics, treatments, and reasons for not prescribing targeted therapy (TT). Patients completed various patient-reported outcome (PRO) questionnaires: Patient-Oriented Eczema Measure, Dermatology Life Quality Index, EuroQol five-dimensional, and Work Productivity and Activity Impairment. Data were analysed descriptively. Comparisons between current severity were made using analysis of variance (ANOVA) or Kruskal-Wallis tests.

Results: Overall, 100 physicians provided data for 624 adult patients with AD from Brazil (n = 328) and Colombia (n = 296): 47% currently mild, 43% moderate, and 10% severe. For all the PRO measures analysed in Colombia and for the majority in Brazil, the impact on patients increased with increasing disease severity (p < 0.05). In total, 85% of patients with AD in Brazil and 73% in Colombia were treated with topical therapies, with 51% in Brazil and 77% in Colombia receiving systemic therapies, which included biologics (Brazil 12%; Colombia 33%) and oral Janus kinase inhibitors (Brazil 5% and Colombia 10%). The main barriers to TT in Brazil were patients being unable to pay for treatment and treatment not being covered by health insurance. In Colombia, the main barriers were formulary restrictions and patients being very recently diagnosed.

Conclusions: Increased AD disease severity was associated with a greater patient impact and reduced quality of life, with healthcare costs and formulary restrictions hindering optimal treatment across Brazil and Colombia.

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by intense itch and recurrent lesions that impose clinical and economic burden. The individual and combined contributions of itch intensity and lesion severity to healthcare resource utilization (HCRU) and costs are not well defined. This study characterized real-world clinical phenotypes of moderate-to-severe AD based on itch and lesion severity and quantified their associations with HCRU and healthcare charges.

Methods: A retrospective cohort study was conducted using linked electronic health records and claims data from the OMNY Health Dermatology Platform (January 2022-June 2024). Patients aged ≥ 12 years with moderate-to-severe AD, defined by prescription treatment, were included. Patients were stratified into four clinical phenotypes based on their scores on the Itch Numerical Rating Scale (NRS) and Investigator Global Assessment (IGA): moderate itch and moderate lesions (MI-ML), severe itch and moderate lesions (SI-ML), moderate itch and severe lesions (MI-SL), and severe itch and severe lesions (SI-SL). Annualized all-cause HCRU and total healthcare charges were assessed using multinomial propensity score weighting. Logistic regression identified predictors of high total charges (≥ 90th percentile).

Results: Among 4433 patients with moderate-to-severe AD, phenotype distribution was MI-ML (33%), SI-ML (43%), MI-SL (4%), and SI-SL (21%). While HCRU event rates (hospitalizations, emergency visits) were similar across phenotypes, mean annual total charges differed notably. Compared with MI-ML ($23,697), charges increased with severe itch (SI-ML: + $2197), severe lesions (MI-SL: + $3705), and both severe itch and lesions (SI-SL: + $10,448), driven mainly by pharmacy and outpatient costs. Mean annual charges were highest in SI-SL ($34,145), followed by MI-SL ($27,402), SI-ML ($25,894), and MI-ML ($23,697). Severe itch alone was associated with elevated pharmacy expenditures, whereas severe lesions primarily increased outpatient costs. In multivariable models, biologic use, systemic therapy, and comorbidities were predictors of high total charges.

Conclusion: Both itch intensity and lesion severity independently and additively contributed to HCRU and economic burden of moderate-to-severe AD. Severe itch primarily increased pharmacy spending, while severe lesions drove outpatient costs. The combined phenotype of severe itch and lesions incurred the highest overall charges, underscoring the need for phenotype-informed, comprehensive AD management strategies.

Introduction: Post-inflammatory hyperpigmentation (PIH) is common and distressing in skin of color. Ultraviolet (UV) radiation and visible light (VL) exacerbate PIH, yet most sunscreens do not target the oxidative and inflammatory pathways that drive it. This study evaluated a broad-spectrum sunscreen with sclareolide and niacinamide for mitigating PIH induced by combined UV/VL exposure and inflammatory stimuli.

Methods: In an investigator-masked, randomized, intra-individual study, 20 participants with Fitzpatrick skin types IV-V underwent controlled UV/VL exposure with or without tape stripping. The test product was applied daily for 20 days. The primary endpoint was change in ΔITA° at Day 22; clinical pigmentation/erythema and colorimetry (ΔL*, Δa*, Δb*, ΔE) were secondary endpoints.

Results: The sunscreen significantly prevented pigmentation at all protected sites. In stripped, exposed zones, protected skin improved by + 5.96 ΔITA° versus - 9.88 ΔITA° in unprotected skin (net protection ~ 16 ITA°, p < 0.001). In non-stripped, exposed areas, the difference was + 11.76 ΔITA° (p < 0.001). Secondary endpoints improved by 48-87%. No adverse events were reported.

Conclusions: A broad-spectrum sunscreen with sclareolide and niacinamide mitigates PIH induced by inflammation and VL in darker phototypes. These findings support preventive use in PIH-prone populations. Comparative studies with and without these ingredients are warranted.

Clinical trial registration: This study was registered with ISRCTN under the identifier ISRCTN11448711.

Introduction: A matching-adjusted indirect comparison (MAIC) was performed comparing the efficacy of delgocitinib and dupilumab in patients with atopic hand eczema (AHE), one aetiological subtype of chronic hand eczema (CHE).

Methods: DELTA 1/2 were phase 3 trials in which adults with moderate to severe CHE received delgocitinib cream 20 mg/g or cream vehicle twice daily for 16 weeks. LIBERTY-AD-HAFT was a phase 3 trial in which patients with moderate to severe AD with hand or foot involvement received subcutaneous dupilumab or placebo every 2 weeks for 16 weeks. An anchored MAIC was conducted using individual patient data (IPD) from DELTA 1/2 and aggregate published data from LIBERTY-AD-HAFT, with vehicle and placebo as the common anchor. IPD from patients with AHE as the primary subtype in DELTA 1/2 were weighted to match age, race, sex and baseline Hand Eczema Severity Index (HECSI) score in LIBERTY-AD-HAFT.

Results: LIBERTY-AD-HAFT included 133 patients (dupilumab, n = 67, placebo, n = 66) while DELTA 1/2 included 345 patients with AHE; the effective sample size after weighted matching was 201 (delgocitinib, n = 128, cream vehicle, n = 73). Anchor-adjusted odds ratios comparing delgocitinib versus dupilumab at week 16 were 1.1 (95% CI: 0.3, 3.4; p = 0.890) for Investigator's Global Assessment for Chronic Hand Eczema / Hand and Foot Investigator's Global Assessment score 0/1, 1.2 (95% CI: 0.4, 3.2; p = 0.773) for HECSI 75 and 1.3 (95% CI: 0.4, 4.9; p = 0.661) for HECSI 90 while response difference for HECSI percent improvement was 11.7% (95% CI: -9.2%, 32.7%; p = 0.273).

Conclusions: Topical delgocitinib and dupilumab in patients with AHE had comparable efficacy, with all results being numerically in favour of delgocitinib, although not statistically significant.

Clinical trial registration: NCT04871711, NCT04872101, NCT04417894.