Pub Date : 2026-02-11DOI: 10.1001/jamadermatol.2025.5959
Susan Nedorost, Andrew J Scheman
{"title":"Adverse Effects of Moisturizers Should Be Considered in Eczema Studies.","authors":"Susan Nedorost, Andrew J Scheman","doi":"10.1001/jamadermatol.2025.5959","DOIUrl":"https://doi.org/10.1001/jamadermatol.2025.5959","url":null,"abstract":"","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146157041","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}
Pub Date : 2026-02-11DOI: 10.1001/jamadermatol.2025.5973
Tian Xie, Xuegang Xu
{"title":"Diffuse Alopecia of the Scalp and Eyebrows.","authors":"Tian Xie, Xuegang Xu","doi":"10.1001/jamadermatol.2025.5973","DOIUrl":"https://doi.org/10.1001/jamadermatol.2025.5973","url":null,"abstract":"","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146157051","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}
Pub Date : 2026-02-04DOI: 10.1001/jamadermatol.2025.5771
Andrew F Olshan
{"title":"Risk Factors for Acral Melanoma Among US Veterans.","authors":"Andrew F Olshan","doi":"10.1001/jamadermatol.2025.5771","DOIUrl":"https://doi.org/10.1001/jamadermatol.2025.5771","url":null,"abstract":"","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119046","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}
Pub Date : 2026-02-04DOI: 10.1001/jamadermatol.2025.5723
Cara Heppell, Ping-Chen Hou, Aimée Longmore, Lidia Shafik, Fatima Ali, Kavita S Subramaniam, Michael Antoniou, Chao-Kai Hsu, Jemima E Mellerio, John A McGrath, Su M Lwin
Importance: Recessive dystrophic epidermolysis bullosa (RDEB) is a rare monogenic blistering disorder with wide clinical heterogeneity, ranging from localized skin fragility to life-limiting systemic complications. Understanding genotype-phenotype correlations in COL7A1, the causative gene, is critical for clinical prognostication, genetic counseling, and the rational design of emerging molecular therapies.
Objective: To determine the frequency of genotypic and phenotypic subtypes, and to assess whether variant type or location can predict phenotypic severity and extracutaneous complications in patients with RDEB carrying homozygous variants.
Evidence review: This was a systematic review of all RDEB genotypes and phenotypes reported to the International Dystrophic Epidermolysis Bullosa Patient Registry (DEB Registry) and eligible studies published in English from May 1993 to September 2025. PubMed, Cochrane Library, and Web of Science were searched and eligible studies were reviewed following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020) guidelines. Included studies reported bi-allelic COL7A1 variants and clinical phenotypes. Data from the DEB Registry were cross-checked to supplement the published cases. Descriptive statistics were used for data analyses, and Fisher exact and χ2 methods were used to test additional genotype-phenotype correlations in patients with RDEB carrying homozygous variants.
Findings: A total of 1802 patients with RDEB comprising 1002 pathogenic variants within COL7A1 were identified from 217 articles. Among the 706 patients with homozygous variants (mean [SD; range] age, 12.2 [13.0; 0-72] years), 533 (75.5%) had severe RDEB, most frequently associated with frameshift and nonsense variants (388 [72.8%] premature termination codons [PTCs]). In contrast, intermediate and milder subtypes were associated with missense or non-PTC variants. Variant location also influenced phenotype: homozygous variants affecting the noncollagenous 1 domain were associated with severe RDEB in 74 of 83 unique variants (89.2%). Extracutaneous involvement clustered in homozygous PTC carriers and was observed almost exclusively in severe RDEB, with occasional cases in the intermediate subtype and rare instances in the inversa, localized, and self-improving subtypes. Recurrent and population-specific variants suggested founder effects. Splice site and missense variants showed phenotypic variability, with augmented intelligence-based predictions correlating with severity.
Conclusions and relevance: In this systematic review, the type and site of pathogenic variants in COL7A1 correlated with the severity of RDEB phenotype across different nationalities, races, and ethnicities. These findings may provide improved patient prognosis, genetic counseling, and personalized therapeutics.
重要性：隐性营养不良大疱性表皮松解症（RDEB）是一种罕见的单基因起泡疾病，具有广泛的临床异质性，从局部皮肤脆弱到限制生命的全身并发症。了解致病基因COL7A1的基因型-表型相关性对临床预后、遗传咨询和新兴分子治疗的合理设计至关重要。目的：确定基因型和表型亚型的频率，并评估变异类型或位置是否可以预测携带纯合变异的RDEB患者的表型严重程度和皮外并发症。证据回顾：这是一项对国际大疱性营养不良表皮松解症患者登记处（DEB Registry）报告的所有RDEB基因型和表型以及1993年5月至2025年9月以英文发表的符合条件的研究的系统回顾。检索PubMed、Cochrane图书馆和Web of Science，并按照PRISMA（2020年系统评价和荟萃分析首选报告项目）指南对符合条件的研究进行审查。纳入的研究报告了双等位基因COL7A1变异和临床表型。对DEB登记处的数据进行交叉核对，以补充已发表的病例。采用描述性统计进行数据分析，并采用Fisher精确和χ2方法检验携带纯合变异的RDEB患者的其他基因型-表型相关性。结果：从217篇文章中共鉴定出1802例RDEB患者，其中包括COL7A1内的1002种致病变异。706例纯合变异体患者（平均年龄12.2[13.0；0-72]岁）中，533例（75.5%）有严重RDEB，最常与移码和无义变异体相关（388例[72.8%]个过早终止密码子[ptc]）。相反，中度和轻度亚型与错义或非ptc变异相关。变异位置也影响表型：影响非胶原1结构域的纯合变异在83个独特变异中有74个（89.2%）与严重的RDEB相关。皮肤外受累集中在纯合子PTC携带者中，几乎只在严重的RDEB中观察到，偶尔有中间亚型的病例，而在相反、局部和自我改善亚型中则罕见。复发性和群体特异性变异提示奠基者效应。剪接位点和错义变异表现出表型变异性，并增强了与严重程度相关的基于智力的预测。结论和相关性：在本系统综述中，COL7A1致病变异的类型和位点与不同国籍、种族和民族的RDEB表型严重程度相关。这些发现可以改善患者预后，提供遗传咨询和个性化治疗。
{"title":"Genotype-Phenotype Correlations in Recessive Dystrophic Epidermolysis Bullosa: A Systematic Review.","authors":"Cara Heppell, Ping-Chen Hou, Aimée Longmore, Lidia Shafik, Fatima Ali, Kavita S Subramaniam, Michael Antoniou, Chao-Kai Hsu, Jemima E Mellerio, John A McGrath, Su M Lwin","doi":"10.1001/jamadermatol.2025.5723","DOIUrl":"https://doi.org/10.1001/jamadermatol.2025.5723","url":null,"abstract":"<p><strong>Importance: </strong>Recessive dystrophic epidermolysis bullosa (RDEB) is a rare monogenic blistering disorder with wide clinical heterogeneity, ranging from localized skin fragility to life-limiting systemic complications. Understanding genotype-phenotype correlations in COL7A1, the causative gene, is critical for clinical prognostication, genetic counseling, and the rational design of emerging molecular therapies.</p><p><strong>Objective: </strong>To determine the frequency of genotypic and phenotypic subtypes, and to assess whether variant type or location can predict phenotypic severity and extracutaneous complications in patients with RDEB carrying homozygous variants.</p><p><strong>Evidence review: </strong>This was a systematic review of all RDEB genotypes and phenotypes reported to the International Dystrophic Epidermolysis Bullosa Patient Registry (DEB Registry) and eligible studies published in English from May 1993 to September 2025. PubMed, Cochrane Library, and Web of Science were searched and eligible studies were reviewed following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020) guidelines. Included studies reported bi-allelic COL7A1 variants and clinical phenotypes. Data from the DEB Registry were cross-checked to supplement the published cases. Descriptive statistics were used for data analyses, and Fisher exact and χ2 methods were used to test additional genotype-phenotype correlations in patients with RDEB carrying homozygous variants.</p><p><strong>Findings: </strong>A total of 1802 patients with RDEB comprising 1002 pathogenic variants within COL7A1 were identified from 217 articles. Among the 706 patients with homozygous variants (mean [SD; range] age, 12.2 [13.0; 0-72] years), 533 (75.5%) had severe RDEB, most frequently associated with frameshift and nonsense variants (388 [72.8%] premature termination codons [PTCs]). In contrast, intermediate and milder subtypes were associated with missense or non-PTC variants. Variant location also influenced phenotype: homozygous variants affecting the noncollagenous 1 domain were associated with severe RDEB in 74 of 83 unique variants (89.2%). Extracutaneous involvement clustered in homozygous PTC carriers and was observed almost exclusively in severe RDEB, with occasional cases in the intermediate subtype and rare instances in the inversa, localized, and self-improving subtypes. Recurrent and population-specific variants suggested founder effects. Splice site and missense variants showed phenotypic variability, with augmented intelligence-based predictions correlating with severity.</p><p><strong>Conclusions and relevance: </strong>In this systematic review, the type and site of pathogenic variants in COL7A1 correlated with the severity of RDEB phenotype across different nationalities, races, and ethnicities. These findings may provide improved patient prognosis, genetic counseling, and personalized therapeutics.</p>","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146118946","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}
Pub Date : 2026-02-04DOI: 10.1001/jamadermatol.2025.5827
Jonathan C Hwang, Linden B Huhmann, Kelly Cho, Sergey D Goryachev, Nicholas Starink, Martin A Weinstock, Maryam M Asgari, Christy Zheng, Charles Lu, Theodore C Feldman, Nhan V Do, John M Gaziano, Yevgeniy R Semenov, Marc S Hurlbert, Nathanael R Fillmore, Rebecca I Hartman
<p><strong>Importance: </strong>Acral melanoma (AM), localized to the palms, soles, and nail units, is a unique melanoma subtype less associated with UV radiation. Few studies have evaluated AM risk factors in a population of US veterans.</p><p><strong>Objective: </strong>To identify AM risk factors in US veterans.</p><p><strong>Design, setting, and participants: </strong>Nested case-control study (2000-2024) in the Veterans Affairs (VA) health care system. Individuals with AM were identified using the VA Cancer Registry and a validated natural language processing pipeline applied to pathology reports. Each AM case was matched to 4 nonacral cutaneous melanoma (CM) controls and 4 controls with no melanoma diagnoses at any time by diagnosis year and outpatient visit frequency. Controls with acral, mucosal, or ocular melanoma diagnoses at any time were excluded. Participants were veterans with histologically confirmed AM, nonacral CM controls, and controls with no melanoma diagnoses at any time.</p><p><strong>Exposure: </strong>Age, sex, race and ethnicity, rurality, region, military branch, comorbidities (National Cancer Institute Comorbidity Index), smoking status, unhealthy alcohol use as measured by the Alcohol Use Disorders Identification Test-Consumption, body mass index, Agent Orange exposure (AOE), prior photosensitizing medications, nevi, keratinocyte carcinoma (KC), actinic keratosis (AK), and number of dermatology visits in the 2 years before diagnosis.</p><p><strong>Main outcomes and measures: </strong>Adjusted odds ratios (AORs) comparing AM with controls using conditional logistic regression. Secondary outcomes included analyses limited to Vietnam Era veterans and AM localized to palmoplantar and subungual sites.</p><p><strong>Results: </strong>In total, 1292 individuals with AM (median age, 70.13 [IQR, 61.87-78.66] years; 1215 [94.0%] male) were matched to 5168 controls without melanoma (median age, 73.97 [IQR, 65.53-82.08] years; 5044 [97.6%] male), and 1286 individuals with AM (median age, 70.13 [IQR, 61.97-78.67] years; 1210 [94.1%] male) were matched to 5144 CM controls (median age, 74.58 [IQR, 66.86-82.05] years; 5068 [98.5%] male); 6 individuals with AM were excluded from AM vs CM analyses due to lack of matches. AOE was significantly associated with higher odds of AM vs CM (AOR, 1.31; 95% CI, 1.06-1.62) and vs controls without melanoma (AOR, 1.27; 95% CI, 1.04-1.56). Current smoking was associated with lower odds of AM (vs CM: AOR, 0.65; 95% CI, 0.52-0.81; vs controls without melanoma: AOR, 0.50; 95% CI, 0.40-0.62). Prior KC and AK were associated with higher odds vs controls without melanoma but lower odds vs CM. Prior nevus was associated with higher odds of AM vs controls without melanoma.</p><p><strong>Conclusions and relevance: </strong>Results of this study suggest that several factors were associated with AM in veterans and a need for continued investigation of AM as a distinct entity from CM and may inform future evalua
{"title":"Identification of Risk Factors for Acral Melanoma in US Veterans.","authors":"Jonathan C Hwang, Linden B Huhmann, Kelly Cho, Sergey D Goryachev, Nicholas Starink, Martin A Weinstock, Maryam M Asgari, Christy Zheng, Charles Lu, Theodore C Feldman, Nhan V Do, John M Gaziano, Yevgeniy R Semenov, Marc S Hurlbert, Nathanael R Fillmore, Rebecca I Hartman","doi":"10.1001/jamadermatol.2025.5827","DOIUrl":"10.1001/jamadermatol.2025.5827","url":null,"abstract":"<p><strong>Importance: </strong>Acral melanoma (AM), localized to the palms, soles, and nail units, is a unique melanoma subtype less associated with UV radiation. Few studies have evaluated AM risk factors in a population of US veterans.</p><p><strong>Objective: </strong>To identify AM risk factors in US veterans.</p><p><strong>Design, setting, and participants: </strong>Nested case-control study (2000-2024) in the Veterans Affairs (VA) health care system. Individuals with AM were identified using the VA Cancer Registry and a validated natural language processing pipeline applied to pathology reports. Each AM case was matched to 4 nonacral cutaneous melanoma (CM) controls and 4 controls with no melanoma diagnoses at any time by diagnosis year and outpatient visit frequency. Controls with acral, mucosal, or ocular melanoma diagnoses at any time were excluded. Participants were veterans with histologically confirmed AM, nonacral CM controls, and controls with no melanoma diagnoses at any time.</p><p><strong>Exposure: </strong>Age, sex, race and ethnicity, rurality, region, military branch, comorbidities (National Cancer Institute Comorbidity Index), smoking status, unhealthy alcohol use as measured by the Alcohol Use Disorders Identification Test-Consumption, body mass index, Agent Orange exposure (AOE), prior photosensitizing medications, nevi, keratinocyte carcinoma (KC), actinic keratosis (AK), and number of dermatology visits in the 2 years before diagnosis.</p><p><strong>Main outcomes and measures: </strong>Adjusted odds ratios (AORs) comparing AM with controls using conditional logistic regression. Secondary outcomes included analyses limited to Vietnam Era veterans and AM localized to palmoplantar and subungual sites.</p><p><strong>Results: </strong>In total, 1292 individuals with AM (median age, 70.13 [IQR, 61.87-78.66] years; 1215 [94.0%] male) were matched to 5168 controls without melanoma (median age, 73.97 [IQR, 65.53-82.08] years; 5044 [97.6%] male), and 1286 individuals with AM (median age, 70.13 [IQR, 61.97-78.67] years; 1210 [94.1%] male) were matched to 5144 CM controls (median age, 74.58 [IQR, 66.86-82.05] years; 5068 [98.5%] male); 6 individuals with AM were excluded from AM vs CM analyses due to lack of matches. AOE was significantly associated with higher odds of AM vs CM (AOR, 1.31; 95% CI, 1.06-1.62) and vs controls without melanoma (AOR, 1.27; 95% CI, 1.04-1.56). Current smoking was associated with lower odds of AM (vs CM: AOR, 0.65; 95% CI, 0.52-0.81; vs controls without melanoma: AOR, 0.50; 95% CI, 0.40-0.62). Prior KC and AK were associated with higher odds vs controls without melanoma but lower odds vs CM. Prior nevus was associated with higher odds of AM vs controls without melanoma.</p><p><strong>Conclusions and relevance: </strong>Results of this study suggest that several factors were associated with AM in veterans and a need for continued investigation of AM as a distinct entity from CM and may inform future evalua","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12874073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146119142","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}
Pub Date : 2026-02-01DOI: 10.1001/jamadermatol.2025.4892
Peyton V Warp, Karishma R Desai, Alvaro J Alencar, Jonathan J Cohen, Andrea D Maderal
{"title":"Zanubrutinib for Immunoglobulin A Vasculitis With Monoclonal Gammopathy.","authors":"Peyton V Warp, Karishma R Desai, Alvaro J Alencar, Jonathan J Cohen, Andrea D Maderal","doi":"10.1001/jamadermatol.2025.4892","DOIUrl":"10.1001/jamadermatol.2025.4892","url":null,"abstract":"","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":"212-214"},"PeriodicalIF":11.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145911553","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}
Pub Date : 2026-02-01DOI: 10.1001/jamadermatol.2025.4950
Sonja Ständer, Gil Yosipovitch, Howard Sofen, Daniel Abramzon, Joshua Galanter, Sheldon Wang, John F Paolini
<p><strong>Importance: </strong>Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized by severe pruritus and nodule formation, significantly affecting patients' quality of life. There is an unmet need for effective therapies to address both symptoms and disease progression.</p><p><strong>Objective: </strong>To evaluate the efficacy, safety, tolerability, and pharmacokinetics of monthly dosed vixarelimab in participants with moderate to severe PN.</p><p><strong>Design, setting, and participants: </strong>This double-blind (DB), placebo-controlled, phase 2b randomized clinical trial was conducted from December 1, 2020, to August 24, 2023, across 72 centers in the US, Canada, Europe, and Asia. The study included male and female participants aged 18 to 80 years with physician-diagnosed PN of at least 6 months' duration and moderate to severe pruritus. Data were analyzed from October 2023 to March 2024.</p><p><strong>Interventions: </strong>Participants were randomized into 4 arms during the 16-week DB period: vixarelimab, 540 mg (high-dose group); vixarelimab, 360 mg (mid-dose group); vixarelimab, 120 mg (low-dose group); or placebo. Vixarelimab and placebo were administered subcutaneously every 4 weeks. During the 36-week open-label extension, all participants received vixarelimab, 360 mg, every 2 weeks.</p><p><strong>Main outcomes and measures: </strong>Key outcomes included percentage change from baseline in the Worst Itch Numeric Rating Scale (WI-NRS) at week 16, the proportion of participants achieving at least a 4-point reduction in WI-NRS at week 16, and the proportion achieving scores of 0 or 1 in the PN Investigator Global Assessment at week 16.</p><p><strong>Results: </strong>Of 190 randomized participants, 189 received 1 or more doses of the study drug (141 vixarelimab, 48 placebo). A total of 114 (60.3%) were female, 75 (39.7%) were male, and the mean (SD) age was 55.4 (13.8) years. There were 47 participants in the high-dose vixarelimab group, 47 in the mid-dose group, 47 in the low-dose group, and 48 in the placebo group. Vixarelimab significantly reduced mean (SE) WI-NRS scores at week 16 compared with placebo across all doses (vixarelimab at high-dose, mid-dose, and low-dose levels: -56.2% [4.84], -51.0% [4.83], and -33.0% [4.86], respectively; placebo, -14.5% [4.76]). Clinically meaningful 4-point or greater reductions in WI-NRS were achieved by 31 (66.0%), 29 (61.7%), and 14 (29.8%) in the high-dose, mid-dose, and low-dose vixarelimab groups, respectively, compared with 8 (16.7%) in the placebo group. PN Investigator Global Assessment scores of 0 or 1 were also higher in vixarelimab groups (high-dose group, 18 [38.3%]; mid-dose group, 14 [29.8%]; low-dose group, 7 [14.9%]; placebo group, 5 [10.4%]). No fatal or serious drug-related treatment-emergent adverse events were reported during the study, and no serious treatment-related treatment-emergent adverse events were observed during the DB period.</p><p><strong
{"title":"Vixarelimab in Patients With Prurigo Nodularis: A Randomized Clinical Trial.","authors":"Sonja Ständer, Gil Yosipovitch, Howard Sofen, Daniel Abramzon, Joshua Galanter, Sheldon Wang, John F Paolini","doi":"10.1001/jamadermatol.2025.4950","DOIUrl":"10.1001/jamadermatol.2025.4950","url":null,"abstract":"<p><strong>Importance: </strong>Prurigo nodularis (PN) is a chronic inflammatory skin disease characterized by severe pruritus and nodule formation, significantly affecting patients' quality of life. There is an unmet need for effective therapies to address both symptoms and disease progression.</p><p><strong>Objective: </strong>To evaluate the efficacy, safety, tolerability, and pharmacokinetics of monthly dosed vixarelimab in participants with moderate to severe PN.</p><p><strong>Design, setting, and participants: </strong>This double-blind (DB), placebo-controlled, phase 2b randomized clinical trial was conducted from December 1, 2020, to August 24, 2023, across 72 centers in the US, Canada, Europe, and Asia. The study included male and female participants aged 18 to 80 years with physician-diagnosed PN of at least 6 months' duration and moderate to severe pruritus. Data were analyzed from October 2023 to March 2024.</p><p><strong>Interventions: </strong>Participants were randomized into 4 arms during the 16-week DB period: vixarelimab, 540 mg (high-dose group); vixarelimab, 360 mg (mid-dose group); vixarelimab, 120 mg (low-dose group); or placebo. Vixarelimab and placebo were administered subcutaneously every 4 weeks. During the 36-week open-label extension, all participants received vixarelimab, 360 mg, every 2 weeks.</p><p><strong>Main outcomes and measures: </strong>Key outcomes included percentage change from baseline in the Worst Itch Numeric Rating Scale (WI-NRS) at week 16, the proportion of participants achieving at least a 4-point reduction in WI-NRS at week 16, and the proportion achieving scores of 0 or 1 in the PN Investigator Global Assessment at week 16.</p><p><strong>Results: </strong>Of 190 randomized participants, 189 received 1 or more doses of the study drug (141 vixarelimab, 48 placebo). A total of 114 (60.3%) were female, 75 (39.7%) were male, and the mean (SD) age was 55.4 (13.8) years. There were 47 participants in the high-dose vixarelimab group, 47 in the mid-dose group, 47 in the low-dose group, and 48 in the placebo group. Vixarelimab significantly reduced mean (SE) WI-NRS scores at week 16 compared with placebo across all doses (vixarelimab at high-dose, mid-dose, and low-dose levels: -56.2% [4.84], -51.0% [4.83], and -33.0% [4.86], respectively; placebo, -14.5% [4.76]). Clinically meaningful 4-point or greater reductions in WI-NRS were achieved by 31 (66.0%), 29 (61.7%), and 14 (29.8%) in the high-dose, mid-dose, and low-dose vixarelimab groups, respectively, compared with 8 (16.7%) in the placebo group. PN Investigator Global Assessment scores of 0 or 1 were also higher in vixarelimab groups (high-dose group, 18 [38.3%]; mid-dose group, 14 [29.8%]; low-dose group, 7 [14.9%]; placebo group, 5 [10.4%]). No fatal or serious drug-related treatment-emergent adverse events were reported during the study, and no serious treatment-related treatment-emergent adverse events were observed during the DB period.</p><p><strong","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":"133-141"},"PeriodicalIF":11.0,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12712829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145768218","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}
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