American Journal of Clinical Dermatology最新文献

{"title":"The Challenge of Treating Anti-PD-1-Resistant Advanced Melanoma.","authors":"Cecilie Dam Vestergaard, Eva Ellebaek, Troels Holz Borch, Marco Donia, Inge Marie Svane","doi":"10.1007/s40257-025-00969-1","DOIUrl":"https://doi.org/10.1007/s40257-025-00969-1","url":null,"abstract":"<p><p>Immune checkpoint inhibitors, particularly antibodies targeting programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte associated protein 4, have transformed the treatment landscape of metastatic melanoma. For a subset of patients, these therapies have led to durable responses and long-term survival. However, despite this progress, more than half of patients experience primary or acquired resistance to anti-PD-1 therapy, highlighting an urgent need for effective alternative treatments. As immune checkpoint inhibitors are increasingly used in neoadjuvant and adjuvant settings, a growing number of patients with newly diagnosed metastatic melanoma will have prior exposure to these agents-posing critical challenges for subsequent treatment strategies after anti-PD-1 failure.In this review, we outline mechanisms driving resistance to anti-PD-1 therapy, including both tumor-intrinsic and tumor-extrinsic factors, and discuss biomarkers relevant to clinical practice in melanoma. The current treatment landscape is reviewed, with an overview of key clinical trials that have shaped management across metastatic, adjuvant, and neoadjuvant settings. We discuss novel and promising investigational agents targeting immune and cellular pathways, such as cancer vaccines and recent advancements in T-cell therapy.A key focus is the critical need for predictive biomarkers to guide therapy selection and improve our understanding of long-term outcomes in patients previously treated with immune checkpoint inhibitors. Global efforts are underway to address anti-PD-1 resistance through diverse and innovative strategies, with the aim of developing therapies that maximize the clinical benefit while minimizing toxicity. As the treatment paradigm continues to evolve, overcoming resistance remains central to advancing the care of patients with melanoma.</p>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":" ","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144648284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Lebrikizumab in Adult and Adolescent Patients with Skin of Color and Moderate-to-Severe Atopic Dermatitis: Results from the Phase IIIb, Open-Label ADmirable Study.","authors":"Andrew Alexis, Ali Moiin, Jill Waibel, Paul Wallace, David Cohen, Vivian Laquer, Pearl Kwong, Amber Reck Atwater, Christopher Schuster, Jennifer Proper, Maria Silk, Evangeline Pierce, Sreekumar Pillai, Maria Jose Rueda, Angela Moore","doi":"10.1007/s40257-025-00970-8","DOIUrl":"https://doi.org/10.1007/s40257-025-00970-8","url":null,"abstract":"<p><strong>Background: </strong>Data are lacking to guide diagnosis and treatment in patients with skin of color and atopic dermatitis (AD), a population traditionally underrepresented in clinical trials.</p><p><strong>Objective: </strong>The aim of this study was to evaluate the efficacy and safety of lebrikizumab in adults and adolescents with skin of color and moderate-to-severe AD.</p><p><strong>Methods: </strong>In the open-label ADmirable trial, 90 adults and adolescents with moderate-to-severe AD, Fitzpatrick skin phototype IV-VI, and self-reported race other than White received lebrikizumab 250 mg subcutaneously every 2 weeks (Q2W), following a 500-mg loading dose at baseline and Week 2, for 16 weeks. From Week 16 to Week 24, responders, defined as patients with at least 75% improvement in Eczema Area and Severity Index (EASI 75) and/or Investigator's Global Assessment (IGA) score of 0/1 with at least a 2-point improvement from baseline, received lebrikizumab every 4 weeks (Q4W); inadequate responders continued lebrikizumab Q2W. The primary endpoint was the percentage of patients achieving EASI 75 at Week 16. Secondary and exploratory efficacy endpoints and safety were assessed throughout. Data were analyzed as observed and using imputation, with Q2W and Q4W populations pooled for Weeks 16-24.</p><p><strong>Results: </strong>Mean age at baseline was 40.7 years; 43.3% were female; and 43.3%, 24.4%, and 32.2% had Fitzpatrick skin phototypes IV, V, and VI, respectively. Baseline mean EASI and Pruritus Numeric Rating Scale (NRS) scores were 26.4 and 7.0, respectively; 68.9% of patients had moderate disease (IGA = 3). At Week 16 (number of patients with non-missing values [Nx] = 78), EASI 75, EASI 90 (≥ 90% improvement from baseline in EASI), and IGA 0/1 (IGA response of clear or almost clear) were achieved by 69.2%, 44.9%, and 44.9% of patients, respectively; for Pruritus NRS (Nx = 62), 58.1% of patients reported ≥ 4-point improvement. At Week 24 (Nx = 74) (pooled treatment arms), EASI 75, EASI 90, and IGA 0/1 were achieved by 78.4%, 47.3%, and 54.1% of patients, respectively. EASI 75 was achieved by 62.9%, 88.2%, and 95.5% of patients with Fitzpatrick skin phototype IV (Nx = 35), V (Nx = 17), and VI (Nx = 22), respectively, at Week 24. Most patients (64.4%) with baseline PDCA-Derm™-assessed hyperpigmented areas showed reduced hyperpigmentation at Week 24. Most treatment-emergent adverse events were mild or moderate in severity; none were serious or led to discontinuation. One case of conjunctivitis was reported.</p><p><strong>Conclusion: </strong>In this first lebrikizumab study in patients with skin of color (Fitzpatrick skin phototype IV, V, and VI) and moderate-to-severe AD, lebrikizumab improved signs and symptoms of AD and confirmed its favorable safety profile.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov Identifier: NCT05372419 (registered May 5, 2022).</p>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":" ","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety of Alopecia Treatments in Patients with Breast Cancer and High-Risk Women: A Review.","authors":"Caitlin A Kearney, Anna L Brinks, Carli D Needle, Grace Rachko, Amy K Bieber, Jerry Shapiro, Mario E Lacouture, Daniela Majerson, Kristen I Lo Sicco","doi":"10.1007/s40257-025-00961-9","DOIUrl":"https://doi.org/10.1007/s40257-025-00961-9","url":null,"abstract":"<p><p>Patients with, survivors of, and women at increased risk of breast cancer may experience various hair loss disorders, including those related to cancer treatments (such as chemotherapy- or endocrine therapy-induced alopecia), alopecia areata, androgenetic alopecia, and cicatricial alopecias. In the USA, approximately 1 in 8 women (13.1%) will develop breast cancer during their lifetime, emphasizing the importance of understanding safe treatment options for this population. Management of scarring and nonscarring alopecias in patients with or those at high risk of breast cancer requires the selection of therapies that do not impact breast cancer risk, treatment, or outcomes. In this review, we examine the safety of common medications used in the treatment of alopecia areata, androgenetic alopecia, and cicatricial alopecias with regard to breast cancer. We provide evidence-based recommendations for the use of these treatments in patients with and women at elevated risk of breast cancer while highlighting areas where further research is needed.</p>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":" ","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Noninvasive Multimodal Imaging and Its Role in Diagnosing Skin Lesions in Dermatology: A Systematic Review and Meta-Analysis.","authors":"Beatrice Martinez Zugaib Abdalla, Ofer Reiter, Kendra Godwin, Rory Gallagher, Jilliana Monnier, Ruben David Dos Reis Zuniga, Manu Jain","doi":"10.1007/s40257-025-00958-4","DOIUrl":"https://doi.org/10.1007/s40257-025-00958-4","url":null,"abstract":"<p><strong>Background: </strong>Multimodal noninvasive imaging is a novel technique in dermatology. Its purpose is to overcome the limitations of unimodal techniques. This is done by combining higher resolution images with deeper imaging depth and/or tissue specificity within a single device for improvement of diagnosis and management of skin lesions.</p><p><strong>Objective: </strong>Our aim was to systematically review multimodal imaging devices currently used in dermatology clinics and their diagnostic accuracy of skin lesions.</p><p><strong>Methods: </strong>A comprehensive search was conducted in October 2022 for studies on multimodal imaging technologies in vivo, in human subjects, used in dermatology. An additional search was made in March 2024. Four databases were selected: MEDLINE, Embase, CENTRAL, and Web of Science. This review was registered with the international Prospective Register of Systematic Reviews (PROSPERO record number CRD42022364864). The search strategy used Medical Subject Headings (MeSH) and keywords from two concepts: Multimodal Imaging and Dermatological Conditions. Reference lists were also searched for relevant studies. Selected studies included multimodal techniques in neoplastic, inflammatory, and pigmentary skin disorders. Ex vivo imaging, non-human studies, and non-clinical settings were excluded. Data extraction and quality assessment were performed using QUADAS and STARD criteria. Data extraction was conducted by one researcher and then reviewed by an additional researcher. A third researcher resolved any disagreements. The statistical analysis involved diagnostic accuracy meta-analysis, subgroup comparisons (multimodal vs single modal, multimodal vs multimodal), and SROC curves. The primary outcomes were the diagnostic accuracy, sensitivity, and specificity of multimodal imaging devices in diagnosing dermatological conditions.</p><p><strong>Results: </strong>The analysis included 92 studies, predominantly case reports or series (83.7%), with basal cell carcinoma (BCC) being the most frequently imaged lesion (11.8%). The studies had a moderate risk of bias (QUADAS score: 0.6) with histology as the reference test in most cases. Meta-analysis showed multimodal devices have high sensitivity and specificity for BCC diagnosis. These results indicate reliable diagnostic accuracy.</p><p><strong>Conclusions: </strong>In a clinical setting, multimodal imaging can be useful to perform bedside diagnosis and management of skin lesions.</p>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":" ","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disease Duration in Patients Recruited to Psoriasis Phase III Trials: A Systematic Review.","authors":"Miranda K Branyiczky, Shanti Mehta, Ronald Vender","doi":"10.1007/s40257-025-00959-3","DOIUrl":"https://doi.org/10.1007/s40257-025-00959-3","url":null,"abstract":"","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":" ","pages":""},"PeriodicalIF":8.6,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144537785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive and Updated Algorithm of Hidradenitis Suppurativa Management from the Experts.","authors":"Caitlyn B Dagenet, Katrina H Lee, Christopher Sayed, Jennifer L Hsiao, Vivian Y Shi","doi":"10.1007/s40257-025-00940-0","DOIUrl":"10.1007/s40257-025-00940-0","url":null,"abstract":"<p><p>Management of hidradenitis suppurativa (HS) can be challenging and often requires a multimodal approach with use of on- and off-label medications. There has been a rapid expansion of available HS treatments in the years since the 2019 North American HS (NAHS) clinical management guidelines. Herein we present an up-to-date practical management algorithm based on the diagnosis and management strategies set forth by the 2019 NAHS guidelines using newly available literature. Evaluation and diagnosis of HS disease involves assessment of severity, extent of disease, and impact on patient quality of life. Initial diagnosis of HS should be shortly followed by comorbidity screening. The multimodal approach to HS treatment typically involves use of treatment stacking of topical therapies, systemic and topical antibiotics, retinoids, hormonal and metabolic therapies, biologics and small molecule inhibitors, systemic immunosuppressants, surgical treatment, pain management, lifestyle modifications, adjunctive treatment, wound care, and flare therapy. Thus, the proposed algorithm aims to guide clinicians in their implementation of treatment stacking in HS.</p>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":" ","pages":"487-497"},"PeriodicalIF":8.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Disease Control and Minimal Disease Activity of Head and Neck Atopic Dermatitis in Patients Treated with Tralokinumab up to 4 Years.","authors":"Raj Chovatiya, Simone Ribero, Andreas Wollenberg, Chang Ook Park, Juan Francisco Silvestre, H Chih-Ho Hong, Julien Seneschal, Hidehisa Saeki, Jacob P Thyssen, Christian Bjerregård Øland, Le Gjerum, Douglas Maslin, Andrew Blauvelt","doi":"10.1007/s40257-025-00931-1","DOIUrl":"10.1007/s40257-025-00931-1","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objective: &lt;/strong&gt;There is a need for long-term atopic dermatitis (AD) treatments that can effectively improve AD involvement of the head and neck (H&N) region (referred to as H&N AD). Tralokinumab, a high-affinity monoclonal antibody that neutralizes interleukin-13, is approved for the treatment of moderate-to-severe AD. Recent real-world studies have observed the effectiveness of tralokinumab for H&N AD. Here, data from phase III parent trials, ECZTRA 1 and ECZTRA 2, and the long-term extension trial, ECZTEND, were used to assess impacts of long-term tralokinumab treatment on H&N AD and the association between improvements in H&N AD and patient quality of life, and to evaluate whether a proportion of patients developed paradoxical H&N erythema.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;These post hoc analyses included data from all patients initiated on tralokinumab in ECZTRA 1 or ECZTRA 2. Patients were treated up to 4 years (i.e., up to 52 weeks in ECZTRA 1 or ECZTRA 2 plus up to 152 weeks in ECZTEND). Outcomes included body region subscores of the Eczema Area and Severity Index (EASI; H&N, upper limbs, trunk, lower limbs) and the Dermatology Life Quality Index (DLQI). Correlations between H&N EASI and DLQI were assessed with Spearman's correlation coefficient (ρ). The incidence of paradoxical H&N erythema (defined as H&N EASI erythema increasing from baseline to a score of 3, while all other regional EASI subscores are 0 or 1, during two or more consecutive visits) was also assessed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Overall, 1192 patients who were initiated on tralokinumab in ECZTRA 1 and ECZTRA 2, of whom 523 patients opted to continue in ECZTEND, were analyzed. Percentages of patients who had H&N EASI ≤ 1 increased from 12.2% at parent trial baseline to 87.2% by week 152 of ECZTEND. Improvements in EASI subscore outcomes from parent trial baseline were comparable across body regions throughout all timepoints of the study. At parent trial week 16, H&N EASI was moderately correlated with total DLQI (ρ = 0.47), with the strongest numerical correlations observed for DLQI questions regarding skin discomfort (ρ = 0.43) and embarrassment due to skin (ρ = 0.40). During up to 4 years of treatment, seven tralokinumab-treated patients exhibited paradoxical H&N erythema, five of whom improved to absent or mild H&N EASI erythema with continued tralokinumab treatment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Tralokinumab provided progressive and sustained improvements in H&N AD, with H&N EASI 0/1 observed in nearly 90% of patients treated up to 4 years. Improvements in H&N EASI were similar to improvements observed for other body regions and were associated with improvements in patient quality of life, particularly for skin discomfort and self-consciousness/embarrassment due to skin.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Clinical trial registration: &lt;/strong&gt;NCT03131648 (ECZTRA 1); study start date: 30 May, 2017; primary completion date: 7 August, 2018; study compl","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":" ","pages":"587-601"},"PeriodicalIF":8.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Agreement Between Nail Psoriasis Severity Index Scores by a Convolutional Neural Network and Dermatologists: A Retrospective Study at an Academic New York City Institution.","authors":"Jose W Ricardo, Rhiannon Miller, Matilde Iorizzo, Bianca M Piraccini, Michela Starace, Chander Grover, Dimitris Rigopoulos, Nilton Di Chiacchio, Nilton G Di Chiacchio, Hang Nguyen, Nga Nguyen, Zung Nguyen, Clifford Perlis, Jonathan Wolfe, Shari R Lipner","doi":"10.1007/s40257-025-00934-y","DOIUrl":"10.1007/s40257-025-00934-y","url":null,"abstract":"<p><strong>Background: </strong>Nail psoriasis (NP) affects up to 90% and 86% of patients with cutaneous psoriasis and psoriatic arthritis, respectively, with a significant impact on quality-of-life. The Nail Psoriasis Severity Index (NAPSI) is infrequently used in clinical practice owing to its labor-intensive nature and variable interobserver reliability.</p><p><strong>Objective: </strong>The objective of this study was to assess performance and inter-reader agreement between artificial intelligence (AI)-determined NAPSI scores and dermatologist-assigned scores.</p><p><strong>Methods: </strong>This cross-sectional study used clinical images of psoriatic fingernails captured retrospectively at a specialized nail clinic in New York City. A convolutional neural network (CNN) model was trained and utilized for NAPSI classification of psoriatic fingernail clinical images, with seven dermatologist nail experts scoring identical images. The primary outcome was the interclass correlation coefficient (ICC), using a one-way analysis of variance (ANOVA) fixed effects model for the single-rater absolute agreement, between the average NAPSI score determined by the dermatologists and the AI.</p><p><strong>Results: </strong>In total, 240 images of psoriatic fingernails were included. The ICC for overall NAPSI, matrix (NAPSIm), and bed (NAPSIb) scores among the dermatologists were 0.43 (95% confidence interval [CI] 0.33-0.55), 0.56 (95% CI 0.46-0.67), and 0.53 (95% CI 0.43-0.65), respectively. Comparing the AI algorithm-assigned NAPSI, NAPSIm, and NAPSIb scores with the average dermatologist-assigned scores, ICCs were 0.81 (95% CI 0.74-0.86), 0.75 (95% CI 0.65-0.82), and 0.81 (95% CI 0.74-0.86), respectively.</p><p><strong>Conclusions: </strong>We found an excellent correlation between AI-derived NAPSI scores and dermatologist-assigned scores, underscoring the potential of CNNs to improve accuracy and reliability in NAPSI scoring. The limitations of this study include the small sample size, undetermined CNN diagnostic accuracy, incomplete data, and potential racial/ethnic minority group underrepresentation.</p>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":" ","pages":"603-610"},"PeriodicalIF":8.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143646809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Disease Burden and Treatment Patterns Among US Patients with Hidradenitis Suppurativa: A Retrospective Cohort Study.","authors":"Amit Garg, Yvonne Geissbühler, Emma Houchen, Nilesh Choudhary, Disha Arora, Varun Vellanki, Abhishek Srivastava, Priyanka, John Darcy, Craig Richardson, Alexa B Kimball","doi":"10.1007/s40257-025-00938-8","DOIUrl":"10.1007/s40257-025-00938-8","url":null,"abstract":"","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":" ","pages":"641-665"},"PeriodicalIF":8.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144061947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Safety and Tolerability of Beremagene Geperpavec-svdt (B-VEC) in an Open-Label Extension Study of Patients with Dystrophic Epidermolysis Bullosa.","authors":"M Peter Marinkovich, Amy S Paller, Shireen V Guide, Mercedes E Gonzalez, Anne W Lucky, Işın Sinem Bağcı, Brittani Agostini, Kolleen Fitzgerald, Shijie Chen, Hubert Chen, Meghan M Conner, Suma M Krishnan","doi":"10.1007/s40257-025-00942-y","DOIUrl":"10.1007/s40257-025-00942-y","url":null,"abstract":"<p><strong>Background: </strong>Patients with dystrophic epidermolysis bullosa have pathogenic variants in COL7A1, leading to skin fragility. Beremagene geperpavec-svdt (B-VEC) is a modified, herpes simplex virus type 1-based gene therapy vector that topically delivers COL7A1 to dystrophic epidermolysis bullosa wounds. In a phase III study, B-VEC significantly improved wound healing at 3 and 6 months compared with placebo.</p><p><strong>Objective: </strong>We aimed to evaluate the safety and tolerability of B-VEC beyond 6 months in patients with dystrophic epidermolysis bullosa.</p><p><strong>Methods: </strong>An open-label extension study was conducted with 47 subjects (24 rollover from phase III; 23 treatment naïve) receiving B-VEC weekly to target wound areas for up to 112 weeks (median 81 weeks). Safety was assessed by adverse events. Treatment satisfaction and quality of life were assessed with patient-reported outcomes as exploratory measures of efficacy. Selected wounds from phase III rollover subjects were assessed for closure.</p><p><strong>Results: </strong>Thirty-five subjects (74.5%) reported one or more adverse events; most were mild or moderate in severity. Fourteen subjects experienced 17 serious adverse events and ten experienced 14 severe adverse events; none was considered treatment related. No adverse events led to treatment or study discontinuation. Patient-reported outcomes indicated high levels of treatment satisfaction, but were inconclusive with regard to quality of life. Among rollover subjects, wounds that received B-VEC during phase III maintained high closure rates during the open-label extension (range 61.1-89.5%, assessed baseline to month 12).</p><p><strong>Limitations: </strong>This was an open-label design, with a variable follow-up.</p><p><strong>Conclusions: </strong>Patients undergoing extended B-VEC treatment maintained high satisfaction and continued to respond to treatment with no new safety signals detected in the open-label extension study, supporting the continuous use of B-VEC.</p><p><strong>Clinical trial registration: </strong>NCT04917874 (date of trial registration: 8 June, 2021).</p>","PeriodicalId":7706,"journal":{"name":"American Journal of Clinical Dermatology","volume":" ","pages":"623-635"},"PeriodicalIF":8.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143957300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}