Dermatology and Therapy最新文献

Introduction: Moderate-to-severe plaque psoriasis can be difficult to treat; not all patients respond to treatment. POETYK PSO-1 and PSO-2 were 52-week, phase 3, multinational, double-blinded trials in plaque psoriasis. We determined deucravacitinib efficacy in PSO-1/PSO-2 patients who did not respond to apremilast.

Methods: PSO-1/PSO-2 were conducted between July 2018 and November 2020; this analysis includes data from both trials. Adults with moderate-to-severe plaque psoriasis (baseline Psoriasis Area and Severity Index [PASI] ≥ 12, static Physician Global Assessment [sPGA] ≥ 3, body surface area involvement ≥ 10%) were included and randomized 1:2:1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. Clinical endpoints included ≥ 75%/90% reduction from baseline PASI (PASI 75/90), sPGA score of 0 (clear) or 1 (almost clear) (sPGA 0/1) response rates, and mean percent change from baseline PASI and BSA involvement. Patient-reported outcomes included Dermatology Life Quality Index 0 (no effect) or 1 (little effect) (DLQI 0/1) and mean change from baseline Psoriasis Symptoms and Signs Diary (PSSD) symptom score.

Results: Of 168 (PSO-1) and 254 (PSO-2) patients randomized to apremilast, 54 (32.1% [PSO-1]) and 111 (43.7% [PSO-2]) did not achieve PASI 50 (PSO-1) and PASI 75 (PSO-2) at Week 24 and were switched to deucravacitinib. PASI 75 response rates improved from 0% at Week 24 to 46.3% (PSO-1) and 42.3% (PSO-2) at Week 52. From Weeks 24-52, PASI 90, sPGA 0/1, and DLQI 0/1 response rates increased; mean percent change from baseline PASI decreased by 60% (PSO-1) and 26% (PSO-2); mean change from baseline in PSSD symptom score decreased by ≈20% in both studies; mean percent change from baseline BSA involvement decreased by 65% (PSO-1) and 25% (PSO-2).

Conclusion: Deucravacitinib was efficacious in patients with moderate-to-severe plaque psoriasis who did not respond to apremilast.

Trial registration: ClinicalTrials.gov identifier, NCT03624127, NCT03611751.

Introduction: This research presents a novel, scientifically validated facial aging simulator. It integrates two published methodologies for personalized aging predictions, particularly concerning the impact of tobacco. This contrasts with widespread simulations on social network and gaming applications, often lacking scientific rigor and transparent methodology.

Methods: This simulator combines elicited knowledge from 28 expert dermatologists with an AI-powered image generation system. Based on this knowledge, the model predicts 15-year facial aging signs according to various intrinsic and extrinsic factors, providing personalized probabilities of reaching specific aging stages (e.g., wrinkles, pigmentation). This work couples these 15-year predictions with a machine learning model (AMGAN) that generates personalized facial aging simulation images. The AMGAN was initially trained on a dataset of 600 individuals with sign scores averaged from 15 expert graders.

Results: We present predicted independent probabilities of reaching grades for different facial aging signs as a function of cumulative tobacco consumption. A simulation was performed using a 43-year-old subject's facial image to demonstrate the tool's capabilities in illustrating the impact of tobacco consumption. Confounding variables such as sun exposure, sunscreen use, and body mass index (BMI) were controlled, while cumulative smoking (less than 10 or greater than 20 pack-years) was varied. This tool effectively visualizes the known effects of smoking on aging and provides personalized quantification of its impact on specific facial wrinkles. Recognizing that individuals prioritize different facial signs, the simulator allows users to focus on areas of personal concern.

Conclusion: By focusing on preserving skin longevity and preventing premature aging, the simulator, which can quantify the impact of smoking on individual aging trajectories, effectively motivates positive lifestyle changes. This personalized approach offers a promising preventative messaging strategy, particularly for audiences resistant to traditional methods, and strengthens the scientific rationale regarding the impact of tobacco on specific aging signs.

Introduction: Melasma is a chronic pigmentary disorder that often recurs after treatment, particularly in people with darker skin who are more prone to pigmentary side effects.

Methods: This prospective study evaluated the efficacy and safety of a 675-nm laser for melasma in individuals with darker skin types. Twenty-eight Thai women with Fitzpatrick skin types (FSTs) III-V underwent three monthly laser sessions using dual Moveo and Standard modes without anesthesia. Clinical severity, pigmentation, patient satisfaction, and safety were assessed up to 6 months after treatment.

Results: The modified Melasma Area and Severity Index (mMASI) showed a 41% improvement at 3 months and 34% at 6 months post-treatment. Antera 3D imaging confirmed progressive melanin reduction, and over 70% of participants reported at least 50% improvement. Adverse effects were mild and transient, including mild erythema or small scabs, with no postinflammatory hyperpigmentation (PIH) observed.

Conclusion: The 675-nm laser achieved sustained lightening of melasma and skin tone improvement with minimal discomfort and no downtime. These findings support the 675-nm laser as a safe and effective treatment for melasma in darker skin types, offering a potential new approach for managing this persistent condition.

Introduction: Nonmelanoma skin cancer (NMSC) risk may be increased in patients with immune-mediated inflammatory disorders. Although atopic dermatitis (AD), an inflammatory immune-mediated chronic skin disease, has been associated with the risk of skin cancer, data on the underlying risk of NMSC in patients with AD in the USA are unclear. The objective of this analysis was to evaluate NMSC incidence and risk in patients with AD generally and those with moderate-to-severe disease specifically compared with a non-AD matched control cohort and patients with rheumatoid arthritis (RA).

Methods: This retrospective observational study examined US claims data (2017-2023) from Optum's de-identified Clinformatics® Data Mart Database of adults with AD and RA, as well as non-AD control cohorts matched 1:1 to patients with AD and patients with moderate-to-severe AD.

Results: This analysis included data from 391,753 patients with AD and 97,445 patients with RA. The matched AD and non-AD cohorts each included 381,221 patients. Patients with AD had a higher NMSC incidence rate (cases/100 person-years [95% CI]) than non-AD matched controls (2.12 [2.10, 2.15] vs 1.74 [1.72, 1.77]) and greater relative NMSC risk (adjusted hazard ratio 1.32 [1.30, 1.35]). NMSC incidence and relative risk were similar between patients with AD and RA. Patients with AD were at greater risk of NMSC if they had a history of NMSC, other malignancies, or organ transplantation. Trends were similar among patients with moderate-to-severe disease.

Conclusion: Patients with AD and those with moderate-to-severe AD had a higher incidence and risk of NMSC than matched individuals without AD.

Introduction: Atopic dermatitis (AD) is a chronic skin disease largely driven by interleukin (IL)-13, which is targeted by tralokinumab and lebrikizumab. Effective, long-term treatments are needed, and head-to-head studies comparing these available therapeutics have yet to be conducted. This analysis indirectly compared the maintenance of efficacy of tralokinumab and lebrikizumab at week 52 in week-16 responders.

Methods: An anchored matching-adjusted indirect comparison was performed using individual patient data (IPD) from the ECZTRA 1 and ECZTRA 2 tralokinumab trials and aggregate data from the ADvocate 1 and ADvocate 2 lebrikizumab trials, with IPD weighted to match ADvocate baseline and week-16 characteristics. Week-16 responders, patients achieving 75% reduction in Eczema Area and Severity Index (EASI-75) or Investigator Global Assessment 0 or 1 (IGA 0/1) with an ≥ 2-point improvement from baseline, were re-randomized to active treatment every 2 weeks (Q2W), every 4 weeks (Q4W), or placebo Q2W for the 36-week maintenance period. Week 52 efficacy outcomes included IGA 0/1, EASI-75, 90% reduction in EASI (EASI-90), EASI percentage improvement, and pruritus numerical rating scale 4-point improvement (pruritus 4pt) from baseline. Response differences relative to placebo for endpoints of interest were calculated between tralokinumab and lebrikizumab for Q2W and Q4W dosing to compare maintenance of efficacy at week 52 among week 16-responders.

Results: Differences in efficacy endpoints between tralokinumab and lebrikizumab were not statistically significant; within Q2W dosing, tralokinumab versus lebrikizumab response rate differences at week 52 numerically favored tralokinumab (IGA 0/1: 1.2%, EASI-75: 19.8%, EASI-90: 1.5%, EASI percentage improvement from baseline: 3.3%, pruritus 4pt: 17.6%) while Q4W differences were more variable (IGA 0/1: -20.5%, EASI-75: 15.7%, EASI-90: -8.5%, EASI percentage improvement from baseline: -0.5%, pruritus 4pt: -2.7%).

Conclusions: Comparable maintenance of efficacy was observed between tralokinumab and lebrikizumab after 52 weeks of treatment among patients meeting response criteria at week 16.

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disease, and patients with moderate-to-severe AD may require treatment with biologics in combination with topical corticosteroids (TCS). The evidence of the cost-effectiveness of biologics in AD is scarce.

Methods: A country-specific cost-per-responder analysis comparing tralokinumab in combination with TCS to dupilumab in combination with TCS was performed for France, Germany, Italy, UK, and Canada based on efficacy estimates (at week 32) from a matching-adjusted indirect comparison (MAIC). Response was defined as either a 75% reduction in the Eczema Area and Severity Index (EASI-75) or an Investigator's Global Assessment score of 0-1 (IGA-0/1). The analysis was repeated with different proportions (10-50%) of patients switching from once every 2 weeks (Q2W) to once every 4 weeks (Q4W) dosing (as per label) for tralokinumab from week 16 to week 32.

Results: The cost per EASI-75 responder for tralokinumab + TCS ranged from €7118.57 to €13,918.80 in France, Germany, Italy, and UK, and in Canada it was C$19,466.03 when 40% of patients using tralokinumab switched from Q2W to Q4W dosing per label. The cost per EASI-75 responder for dupilumab + TCS ranged from €12,380.21 to €18,065.16 and C$23,140.33. The cost per EASI-75 and IGA-0/1 responder for tralokinumab + TCS was lower than for dupilumab, irrespective of the country and the proportion switching from Q2W to Q4W. The proportion of patients switching from Q2W to Q4W dosing for tralokinumab proportionally decreased the average cost per responder at week 32.

Conclusion: In France, Germany, Italy, UK, and Canada, tralokinumab in combination with TCS may be more cost-effective for moderate-to-severe AD than dupilumab in combination with TCS at week 32 for EASI-75 and IGA-0/1 responders. The difference in cost-effectiveness depends on the efficacy and cost of the treatments and on the proportion of patients treated with tralokinumab who switch per label from Q2W to Q4W, which additionally reduces treatment cost.

Clinical trial registration: LIBERTY AD CHRONOS [10] NCT02260986, ECZTRA 3 [9] NCT03363854.

Introduction: Treating older patients with cutaneous neoplasms (CN) can be challenging as oncological resection and definitive external beam radiotherapy (EBRT) can both have limitations in terms of their therapeutic ratio at critical anatomical sites. Here, we present the cohort study results of high-dose-rate (HDR) mould-based brachytherapy (MbBT) for CN focusing on oncological outcomes and patient-reported outcome measures (PROMs), using custom or three-dimensional-printed moulds.

Methods: Between January 2019 and March 2024, 64 patients underwent MbBT. All patients were either deemed unsuitable for radical resection or definitive EBRT or refused them. Patients were prospectively enrolled in a database and underwent clinical evaluation at the end of treatment as well as after 30 and 90 days to assess acute and late toxicity. In addition, oncological follow-up and documentation of their quality of life and subjective cosmetic assessment was performed every 6 months thereafter.

Results: The median age was 80 years. Histology revealed 19 squamous cell carcinomas, 27 basal cell carcinomas, 2 lesions with both histologies, 9 melanocytic tumours and 7 lesions of other histologies. The median treatment dose was 39 Gy (range 30-45 Gy) at 3 Gy per fraction (range 3-4 Gy), administered once daily at 5 days per week. After a median follow-up of 679 days (interquartile range 361-1049 days), there were seven local recurrences (11%). Thirty-seven patients (58%) rated the cosmetic result as at least good, 23 (36%) rated the treatment as more tolerable than expected, while 16 (25%) rated it as at least bothersome. Apart from one grade 4 cataract, no other grade 4 late toxicity was documented.

Conclusions: High-dose-rate MbBT for CN is an effective and well-tolerated treatment option for older and frail patients who are not eligible for radical surgery or definitive EBRT.

Introduction: Chronic spontaneous urticaria (CSU) is characterized by itchy hives with or without angioedema recurring for > 6 weeks. Many patients experience a substantial disease burden despite H1-antihistamine treatment, including impaired health-related quality of life (HRQoL). In the current analysis, we evaluated the efficacy of dupilumab in improving HRQoL in omalizumab-naïve patients with CSU.

Methods: LIBERTY-CSU CUPID Study A was a double-blind, phase 3 trial that evaluated the efficacy and safety of dupilumab in patients aged ≥ 6 years with CSU who remained symptomatic despite H1-antihistamine treatment. Patients were randomized to receive dupilumab 300 mg every 2 weeks (q2w; n = 70) or placebo q2w (n = 68). The current analysis evaluated the change from baseline to week 12 and week 24 in the total scores of the Dermatology Life Quality Index (DLQI), Chronic Urticaria Quality of Life Questionnaire (CU-Q₂oL), and EuroQol (EQ)-Visual Analog Scale (VAS). Additional outcomes included changes from baseline to week 12 and week 24 in DLQI severity categories and the proportion of patients reporting "not at all/a little" effect on individual items of DLQI and CU-Q₂oL questionnaires.

Results: At week 24, dupilumab significantly improved total DLQI and CU-Q₂oL scores compared with placebo {difference: -3.2 (95% confidence interval [CI] -5.2 to -1.1; nominal p = 0.0026) and -8.6 (95% CI -14.6 to -2.6; nominal p = 0.0049), respectively}, as well as EQ-VAS score (difference: 6.0 [95% CI 0.9 to 11.2; nominal p = 0.0210]). Similar trends were observed for week 12. Significantly more dupilumab versus placebo recipients reported "no or little" effect for most of the DLQI and CU-Q₂oL items (nominal p < 0.05).

Conclusions: Dupilumab significantly improved HRQoL in omalizumab-naïve patients with CSU who remained symptomatic despite standard-of-care H1-antihistamine treatment. Quality-of-life improvement with dupilumab addresses an important goal of CSU treatment.

Clinical trial registration: ClinicalTrials.gov identifier: NCT04180488.

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.