Dermatology and Therapy最新文献

Introduction: Lebrikizumab is a novel monoclonal antibody with established efficacy in patients with moderate-to-severe atopic dermatitis (AD) in multiple Phase 3 trials. One of the ultimate treatment goals for patients with moderate-to-severe AD is to achieve stable disease control without concern for planning future life events.

Methods: In ADvocate1 and ADvocate2, lebrikizumab-treated patients meeting the protocol-defined response criteria at Week 16 were re-randomized 2:2:1 to receive lebrikizumab every 2 weeks (Q2W), lebrikizumab every 4 weeks (Q4W), or placebo Q2W (lebrikizumab withdrawal) for 36 additional weeks. In this post hoc analysis, we evaluated the proportions of patients with no or minimal fluctuations of efficacy during the 36-week maintenance period and plotted individual patient trajectories. We defined no or minimal fluctuations as achieving and maintaining the defined endpoint (≥ 75% improvement in the Eczema Area and Severity Index [EASI 75], ≥ 90% improvement in EASI, Pruritus Numeric Rating Scale [NRS] ≥ 4-point improvement, or Pruritus NRS ≥ 3-point improvement) for ≥ 80% of the study visits. If patients used rescue medication, discontinued treatment, or transferred to the escape arm, data collected at or after the event were imputed as non-response.

Results: The proportions of lebrikizumab responders who maintained EASI 75 with no or minimal fluctuations were 70.8% (lebrikizumab Q2W), 71.2% (lebrikizumab Q4W), and 60.0% (lebrikizumab withdrawal). Of the patients with baseline Pruritus NRS ≥ 4 and who achieved ≥ 4-point improvement at Week 16, 66.1% (lebrikizumab Q2W), 62.7% (lebrikizumab Q4W), and 55.2% (lebrikizumab withdrawal) maintained ≥ 4-point Pruritus NRS improvement with no or minimal fluctuations.

Conclusions: Patients who met the response criteria at Week 16 and continued treatment with lebrikizumab Q2W or Q4W demonstrated a stable response with no or minimal fluctuations of efficacy in measures of skin and itch up to Week 52.

Clinical trial registration: NCT04146363 (ADvocate1) and NCT04178967 (ADvocate2).

Skin cancer is the most common cancer type in the USA, with over five million annually treated cases and one in five Americans predicted to develop the disease by the age of 70. Skin cancer can be classified as melanoma or non-melanoma (NMSC), the latter including basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (SCC). Development of BCC and SCC is impacted by environmental, behavioral, and genetic risk factors and the incidence is on the rise, with the associated number of deaths surpassing those caused by melanoma, according to recent reports. Substantial morbidity is related to both BCC and SCC, including disfigurement, loss of function, and chronic pain, driving high treatment costs, and representing a heavy financial burden to patients and healthcare systems worldwide. Clinical presentations of BCC and SCC can be diverse, sometimes carrying considerable phenotypic similarities to benign lesions, and underscoring the need for the development of disease-specific biomarkers. Skin biomarker profiling plays an important role in deeper disease understanding, as well as in guiding clinical diagnosis and patient management, prompting the use of both invasive and non-invasive tools to evaluate specific biomarkers. In this work, we review the known and emerging biomarkers of BCC and SCC, with a focus on molecular and histologic biomarkers relevant for aspects of patient management, including prevention/risk assessments, tumor diagnosis, and therapy selection.

Introduction: Standard therapy for patients with mild to moderate atopic dermatitis (AD) typically includes topical therapies; however, patients with more extensive AD and/or AD refractory to topical therapy may benefit from systemic treatment. Ruxolitinib cream monotherapy has demonstrated superior antipruritic and anti-inflammatory effects versus vehicle in patients with mild to moderate AD, and long-term disease control with as-needed use. Here, efficacy/safety of 1.5% ruxolitinib cream through 52 weeks was assessed in a subset of patients with moderate and/or more extensive disease.

Methods: This post hoc analysis of TRuE-AD1/TRuE-AD2 included patients who, at baseline, had Investigator's Global Assessment (IGA) score of 3, Eczema Area and Severity Index (EASI) ≥ 16, and affected body surface area (BSA) ≥ 10% (higher severity of disease threshold subgroup). Disease control and safety were assessed.

Results: Of 1249 patients in the overall population, 78 (6.2%) met all higher severity of disease threshold criteria (continuous-use vehicle-controlled period: 1.5% ruxolitinib cream, n = 32; vehicle, n = 13); 28 and 4 of these patients, respectively, continued as-needed 1.5% ruxolitinib cream during the long-term safety (LTS) period. At week 8 (continuous-use), IGA-treatment success (IGA 0/1, with ≥ 2-grade improvement from baseline) was achieved by 19/32 (59.4%) patients applying 1.5% ruxolitinib cream versus no patients applying vehicle. In the LTS period, those achieving clear/almost clear skin increased from 19/28 patients (67.9%; continuous-use: week 8) to 18/23 patients (78.3%; as-needed use: week 52) in patients applying ruxolitinib cream from day 1. Ruxolitinib cream was well tolerated, with few application site reactions, regardless of disease severity threshold. Efficacy and safety results were similar to the overall study population.

Conclusion: Patients with AD who meet standard disease severity eligibility criteria for systemic therapy may achieve IGA-treatment success with clear/almost clear skin with continuous-use ruxolitinib cream, and maintain long term-disease control with as-needed ruxolitinib cream monotherapy.

Trial registration number: NCT03745638/NCT03745651.

Introduction: Generalized pustular psoriasis (GPP) is a rare and severe psoriasis subtype characterized by the rapid onset of coalescing sterile pustules over broad body areas and systemic inflammation. Data on its clinical course and outcomes in Taiwan are limited. We evaluated the clinical profile and outcomes of patients with GPP flares in Taiwan.

Methods: This retrospective analysis included adult patients with moderate-to-severe GPP flares occurring in January 2008-December 2021. Data were extracted from medical charts and electronic health records in the Chang Gung Research Database. Statistical analyses were performed using SAS for Windows (version 9.4). Multivariate Poisson regression models were built to investigate different predictors of GPP flare rate.

Results: Thirty-four patients with 81 moderate-to-severe GPP flares were identified. Of the 14 patients undergoing genetic analysis, 10 (71.4%) had an IL36RN mutation. Patients' mean age at the index GPP flare was 47.1 ± 16.5 years; 58.0% of the flares were severe, while 42.0% were moderate. Overall, 96.3% of GPP flares were treated with at least one systemic therapy, acitretin being the most prescribed (85.2%), followed by cyclosporine (45.7%) and methotrexate (18.5%). After treatment, the proportion of flares responding positively increased from 0% on day 2 to 6.2% by week 12. Patients were newly diagnosed with psoriasis (23.5%), hypertension (20.6%), diabetes mellitus (14.7%), psoriatic arthritis (2.9%), malignant tumor (8.8%), and depression/anxiety (2.9%) after enrollment. Complications occurring within 12 weeks of GPP flares included arthritis (25.9% of the flares), skin infection (8.6%), and other infections (2.5%). No fatalities were reported. In the multivariate model, former smokers, patients with hepatic disease, and patients with psoriatic arthritis had an increased GPP rate ratio (RR) of 13.33 (95% confidence interval, CI, 2.87-61.78), 14.08 (95% CI 3.04-65.29), and 34.84 (95% CI 4.77- 254.42), respectively. Contrarily, obese and rheumatoid arthritis patients had a lower GPP rate ratio of 0.21 (95% CI 0.08-0.54) and 0.07 (95% CI 0.006-0.78), respectively.

Conclusions: Our findings highlight the complexity of GPP flare presentations and the need for individualized, patient-centered management approaches and continued research to improve affected individuals' care and outcomes.

Introduction: This study reports psychometric testing of the facial and total Vitiligo Area Scoring Index quantitative clinical instruments (F-VASI [range: 0-3], T-VASI [range: 0-100], respectively) using data from two phase 3 randomized, vehicle-controlled studies of ruxolitinib cream (TRuE-V1/TRuE-V2), the largest vitiligo trials conducted to date. Because VASI assessment is required by regulatory authorities, we evaluated the psychometric properties of the VASI instruments and confirmed thresholds for clinically meaningful change.

Methods: The TRuE-V1/TRuE-V2 full analysis set population included 652 patients (≥ 12 years old with nonsegmental vitiligo affecting ≤ 10% total body surface area, F-VASI ≥ 0.5, and T-VASI ≥ 3 at baseline). Data collected using the facial and total Patient Global Impression of Change-Vitiligo (PaGIC-V) and Physician's Global Vitiligo Assessment (PhGVA) scales were used as anchors to assess F-VASI and T-VASI for reliability, validity, sensitivity to change, and clinically meaningful change.

Results: Median F-VASI and T-VASI scores were 0.70 and 6.76, respectively, at baseline, decreasing to 0.48 and 4.80 at week 24. Test-retest reliability was excellent between screening and baseline for F-VASI (intraclass correlation coefficient [ICC]: 0.943) and T-VASI (ICC: 0.945). Among stable patients per PaGIC-V and PhGVA, reliability was moderate to good for both F-VASI (ICC: 0.891 and 0.739, respectively) and T-VASI (ICC: 0.768 and 0.686). F-VASI and T-VASI differentiated well among PhGVA categories mild/moderate/severe at baseline and week 24. Both VASI instruments detected changes assessed by correlations with PaGIC-V scores at week 24 (F-VASI, r = 0.610; T-VASI, r = 0.512) and changes in PhGVA scores from baseline to week 24 (F-VASI, r = 0.501; T-VASI, r = 0.344). Thresholds for clinically meaningful improvement per PaGIC-V and PhGVA were 0.38-0.60 for F-VASI and 1.69-3.88 for T-VASI.

Conclusions: Data from the TRuE-V1/TRuE-V2 studies confirmed that F-VASI and T-VASI are reliable, valid, and responsive to change, with defined clinically meaningful change from baseline in patients with nonsegmental vitiligo.

Trial registration: The original studies were registered at ClinicalTrials.gov: NCT04052425/NCT04057573.

Background: Lebrikizumab demonstrated significant improvement versus placebo for measures of skin clearance and patient-reported outcomes at weeks 16 and 52 in patients with moderate-to-severe atopic dermatitis (AD). We report the sustained impact of lebrikizumab monotherapy, over 52 weeks and between visits, on the frequency of itch and sleep loss symptoms, as assessed by Patient-Oriented Eczema Measure (POEM), in patients with moderate-to-severe AD.

Methods: In ADvocate1 and ADvocate2, Week-16 lebrikizumab responders (EASI75 or IGA 0/1 with ≥ 2-point improvement and without rescue medication) were randomized to lebrikizumab every 2 weeks (Q2W), every 4 weeks (Q4W), or placebo for 36 weeks. This pooled analysis reports improvement from Week 16 to 52 in patients achieving POEM response 0 (no days) or 1 (1-2 days) for Items 1 (itch) and 2 (sleep disturbance) for the lebrikizumab Q2W and Q4W treatment arms. Observed (excluding data collected after treatment discontinuation, rescue medication use, or patient transfer to escape arm) results were reported.

Results: At Week 16, for lebrikizumab Q2W and Q4W, 35.9% (n = 37/103) and 39.3% (n = 42/107) of patients responded 0 or 1 to Item 1 of POEM (Itch) and 12.6% (n = 13/103) and 12.1% (n = 13/107) responded 0. A total of 66.0% (n = 68/103) and 72.6% (n = 77/106) of patients responded 0 or 1 to Item 2 of POEM (Sleep) and 37.9% (n = 39/103) and 44.3% (n = 47/106) responded 0, respectively. By Week 52, for lebrikizumab Q2W and Q4W, 44.6% (n = 29/65) and 48.0% (n = 36/75) responded 0 or 1 to Item 1 of POEM (Itch), and 21.5% (n = 14/65) and 18.7% (n = 14/75) of patients responded 0. A total of 83.1% (n = 54/65) and 78.4% (n = 58/74) responded 0 or 1 to Item 2 of POEM (Sleep), and 67.7% (n = 44/65) and 59.5% (n = 44/74) responded 0, respectively.

Conclusion: Weekly POEM responses for itch and sleep disturbance remained stable between doses and visits, and continued to improve from Week 16 through 52, in lebrikizumab-treated patients, demonstrating consistent improvement over time for key AD symptoms.

Trial registration numbers: ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967).

Introduction: IncobotulinumtoxinA (Xeomin®) is used in the treatment of dynamic wrinkles and the aesthetic repositioning of facial structures. The duration of its muscular effect typically extends for around 4 months. However, the residual aesthetic benefit can be observed for a longer period. To date, the long-term aesthetic benefit of incobotulinumtoxinA in facial aesthetics has not been systematically evaluated. This study aimed to evaluate longitudinally the duration and aesthetic benefits of incobotulinumtoxinA in the treatment of the upper face in adult women.

Methods: A quasi-experimental, evaluator-blind, clinical trial involving 28 adult women (30-60 years old) with facial movement lines, undergoing treatment of the upper face with incobotulinumtoxinA by two injectors, following an individualized protocol (ONE21 and glabellar contraction patterns) was performed. Participants were evaluated on the day of the intervention (day 0) and days 30, 120, 180, and 240, and subjected to standardized photographs. The following outcomes were evaluated blindly at each visit: Merz Aesthetics Facial Contraction Scale (MAS), GAIS (Global Aesthetic Improvement Scale), and patient satisfaction. Adverse effects were evaluated at each visit.

Results: Participants ranged in age from 30 to 60 years, 93% were self-declared white, and most of their baseline MAS scores for dynamic lines were moderate and severe. All the parameters presented significative reduction from baseline until day 180. At day 240, the dynamic MAS scores were lower than baseline for forehead lines in 15.4% (95% confidence interval (CI) 0.8-30.0%) of the participants, for glabellar lines in 38.5% (95% CI 18.8-58.1%), and for crow's feet lines in 26.9% (95% CI 9.0-44.8%). Aesthetic improvement compared to baseline was identified in 35% (CI 95% 23‒50%) of the participants at day 240, and 62% (CI 95% 42‒81%) of the sample kept reporting some satisfaction with the procedure.

Conclusion: The aesthetic treatment of the upper face with incobotulinumtoxinA demonstrates enduring clinical benefits, and patient satisfaction lasting up to 180 days in most participants. The length of efficacy, which exceeded those reported in the literature, may be attributed to the use of techniques based on individualized assessment such as ONE21 and glabellar patterns of contraction.

Introduction: Diagnosis of persistent erythematous, scaly patches, or plaques can be complex since psoriasis (Ps), eczematous dermatitis (ED), and mycosis fungoides (MF) can be considered. Dermoscopy, which is a noninvasive diagnostic tool, is commonly used to examine blood vessels, scales, and background color; however, research on hair shaft evaluation in inflammatory dermatoses remains scarce. The aim of the study was dermoscopic evaluation of hair shafts in skin lesions localized on the non-scalp skin areas in patients diagnosed with MF, Ps, and ED.

Methods: This was a retrospective evaluation of 55 patients diagnosed with MF, Ps, and ED. Photographic and dermoscopic documentation of these patients and detailed medical history were evaluated.

Results: A total of 21 patients with MF, 21 patients with Ps, and 13 patients with ED were evaluated. The examination revealed the presence of various abnormalities of hair shafts (e.g., numerous pili torti, single pili torti, 8-shaped hairs, pigtail hairs, broken hairs, hair shafts rapidly tapered over long sections, hair shafts irregular in thickness, angulated hairs, branched hairs, the presence of trichorrhexis nodosa, and monilethrix-like hairs), yellow dots, and black dots. The presence of pili torti was found in 80% of patients with MF, compared with 16% of patients with Ps and 8% of patients with ED (p < 0.005), with multiple pili torti found only in MF patients (67%) (p < 0.005). Statistically significant differences also applied to hair shafts rapidly tapering over long sections and 8-shaped hairs, which occurred only in MF patients (p < 0.005 and p = 0.035, respectively).

Conclusions: The presence of hair shaft abnormalities such as numerous pili torti, 8-shaped hairs, and hair shafts rapidly tapering over long sections is an important criterion that should be considered in the dermoscopic differentiation of the patchy/plaque mycosis fungoides and inflammatory dermatoses, such as psoriasis and eczematous dermatitis localized on the non-scalp skin areas.

Introduction: Limited epidemiologic data has suggested direct associations between hair pigment, race, and incidence of alopecia areata (AA). Here, we examine the relationship between natural hair color, race, and the lifetime risk alopecia.

Methods: In this case-control study, we included UK Biobank patients of all races and self-reported hair color with diagnoses of AA, androgenetic alopecia (AGA), or scarring alopecia (SA). Multivariable logistic regression was used to detect differences in lifetime risk.

Results: Findings reveal a significantly increased risk of AA among individuals with black hair compared to dark brown hair (OR 1.71 [95% CI 1.22-2.38], p < 0.001). Those with red or blonde hair showed a decreased risk of AA (0.74 [0.56-0.97]; 0.62 [0.41-0.95], p < 0.05). No racial differences in AA prevalence were observed among individuals with black hair.

Conclusions: Darker hair colors may be associated with a higher risk of AA, lighter hair colors with a lower risk, and differences in hair color could contribute to previously noted racial variations in AA incidence, potentially influencing dermatologists' perspectives on the disease's epidemiology.