Dermatology and Therapy最新文献

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.

Chronic hand eczema (CHE) is defined as hand eczema that persists for more than 3 months or reoccurs at least two times a year. Although it is a distinct disease with a significant impact on quality of life, awareness of the disease and tailored treatment options remain limited. This limited awareness along with a lack of CHE-specific outcome measures can lead to inadequate disease management and recurrence. The Investigator Global Assessment of Chronic Hand Eczema (IGA-CHE) and the Hand Eczema Symptom Diary (HESD) are new, specific outcome measures validated in patients with CHE. They were developed based on recommendations from regulatory authorities to establish outcome measures that can accurately evaluate potential treatments for CHE. IGA-CHE is a clinician-reported outcome measure that assesses disease severity, while HESD (including the single-item HESD Itch and HESD Pain scores) is patient-reported and evaluates signs and symptoms of CHE. Overall, IGA-CHE and HESD are simple, reliable, responsive, and easy to use tools that can detect subtle changes in CHE signs and symptoms, providing a comprehensive assessment of disease severity. Their validation ensures these tools can accurately and consistently measure treatment outcomes, making them valuable in clinical trials and clinical practice. In this podcast, three dermatologists discuss two recently published studies evaluating IGA-CHE and HESD in patients with CHE, and focus on (1) the need for CHE-specific outcome measures in clinical trials and practices, (2) how the IGA-CHE and HESD outcome measures provide accurate assessments of disease severity and clinically meaningful responses to treatments, and (3) key differences from other common outcome measures used in CHE clinical trials. Podcast Audio (MP4 1,01,828 kb).

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: Psoriasis (PsO) in the genital and scalp areas is associated with increased patient burden and impact on quality of life. Effective treatments for PsO in these high-impact areas are essential, though patients are frequently excluded from both biologic clinical trials and treatment because of their often low overall affected body surface area (BSA) despite the disproportionate impact of PsO on their quality of life. Recent guidance also considers these patients as candidates for advanced therapies. Here, we compare the efficacy and safety of risankizumab, an interleukin-23 inhibitor approved for the treatment of moderate-to-severe plaque psoriasis, versus placebo in the treatment of PsO in the genital or scalp region.

Methods: UnlIMMited (NCT05969223) is an ongoing phase 4, multicenter, randomized, double-blind, placebo-controlled study for adult patients with moderate-to-severe genital or scalp PsO in patients with < 10% BSA or ≥ 10% BSA involvement. Two parallel studies were conducted with study-G assessing genital PsO and study-S assessing scalp PsO. Patients were randomized 1:1 within each study to receive either 150 mg risankizumab or placebo at weeks 0 and 4. The primary endpoints for the studies were the achievement of static Physician's Global Assessment - Genital (sPGA-G) 0/1 for study-G and scalp Investigator Global Assessment (IGA) 0/1 for study-S, both assessed at week 16. Secondary endpoints are also reported at week 16 in each study assessing skin clearance, symptom resolution, and impact on quality of life. Safety was reported through the first 16 weeks.

Results: At week 16, in both studies, a significantly higher proportion of patients receiving risankizumab achieved the primary endpoints compared with placebo. In study-G, 69.1% of patients receiving risankizumab versus 13.0% of patients receiving placebo achieved sPGA-G 0/1 (P < 0.0001). In study-S, 60.8% of patients receiving risankizumab versus 13.0% of patients receiving placebo achieved scalp IGA 0/1 (P < 0.0001). No new safety signals were identified.

Conclusion: These results demonstrate that risankizumab is effective in the treatment of genital and scalp psoriasis at week 16, with no new safety signals identified.

Trial registration number: ClinicalTrials.gov identifier NCT05969223.