Pub Date : 2025-01-02DOI: 10.1001/jamadermatol.2024.5380
Emily Baumrin, Peter F Cronholm, Matthew D Kearney, Mlka Mengesha, Laura G Cesar, Shimrit Keddem, Marilyn M Schapira, Stephanie J Lee, Alison W Loren, Joel M Gelfand
Importance: Cutaneous chronic graft-vs-host disease (GVHD) is independently associated with morbidity and mortality after allogeneic hematopoietic cell transplant. However, the health-related quality-of-life (HRQOL) domains that are most important to patients are poorly understood.
Objective: To perform a concept elicitation study to define HRQOL in cutaneous chronic GVHD from the patient perspective and to compare experiences of patients with epidermal vs sclerotic disease.
Design, setting, and participants: A single-center qualitative analysis from open-ended, semistructured interviews and free-listing terms conducted between April and September 2023. Participants were 18 years or older with a diagnosis of active cutaneous chronic GVHD, purposefully sampled for epidermal and sclerotic disease features, with ongoing sampling until thematic saturation.
Main outcomes: HRQOL domains and codes from patient perspectives of living with cutaneous chronic GVHD were identified by inductive analysis of semistructured interviews. Smith salience index (Smith S) score, a measure of saliency for each list term, was calculated from free-listing terms from deidentified patient interviews.
Results: A total of 31 adults with cutaneous chronic GVHD (median [IQR] age, 61.1 [52.9-68.7] years) participated in interviews; 17 participants (54.8%) were male and 14 (45.2%) were female. Nine participants (29.0%) had epidermal, 13 (41.9%) sclerotic, and 9 (29.0%) a combination of disease types. The study identified 40 codes of importance grouped within 5 HRQOL domains: skin changes and symptoms, social functioning, psychological and emotional functioning, physical functioning, and general health perceptions. The most frequent symptoms were dry skin (n = 20 [65%]), tight skin (n = 19 [61%]), itch (n = 15 [48%]), and discoloration (n = 14 [45%]), which were seen in all disease subtypes. Impairment in social functioning was noted by all participants. Psychological and emotional functioning, including frustration (Smith S score, 0.32) and worry or concern (Smith S score, 0.12), and symptoms including discomfort (Smith S score, 0.20) were the most salient to patients. Individual and environmental factors, such as social comparison, illness comparison with cancer, anatomic location of disease involvement, and disease duration, affected the relationship between skin changes and symptoms and downstream functioning and general health perceptions.
Conclusions and relevance: This qualitative analysis demonstrated the direct relationship between cutaneous chronic GVHD and HRQOL domains and identified codes not represented in existing GVHD- and dermatology-specific patient-reported outcome measures. These results can guide patient-reported outcome development and instrument selection for clinical trials and improve clinical decision-making.
{"title":"Outcomes of Importance to Patients Living With Cutaneous Chronic Graft-vs-Host Disease.","authors":"Emily Baumrin, Peter F Cronholm, Matthew D Kearney, Mlka Mengesha, Laura G Cesar, Shimrit Keddem, Marilyn M Schapira, Stephanie J Lee, Alison W Loren, Joel M Gelfand","doi":"10.1001/jamadermatol.2024.5380","DOIUrl":"https://doi.org/10.1001/jamadermatol.2024.5380","url":null,"abstract":"<p><strong>Importance: </strong>Cutaneous chronic graft-vs-host disease (GVHD) is independently associated with morbidity and mortality after allogeneic hematopoietic cell transplant. However, the health-related quality-of-life (HRQOL) domains that are most important to patients are poorly understood.</p><p><strong>Objective: </strong>To perform a concept elicitation study to define HRQOL in cutaneous chronic GVHD from the patient perspective and to compare experiences of patients with epidermal vs sclerotic disease.</p><p><strong>Design, setting, and participants: </strong>A single-center qualitative analysis from open-ended, semistructured interviews and free-listing terms conducted between April and September 2023. Participants were 18 years or older with a diagnosis of active cutaneous chronic GVHD, purposefully sampled for epidermal and sclerotic disease features, with ongoing sampling until thematic saturation.</p><p><strong>Main outcomes: </strong>HRQOL domains and codes from patient perspectives of living with cutaneous chronic GVHD were identified by inductive analysis of semistructured interviews. Smith salience index (Smith S) score, a measure of saliency for each list term, was calculated from free-listing terms from deidentified patient interviews.</p><p><strong>Results: </strong>A total of 31 adults with cutaneous chronic GVHD (median [IQR] age, 61.1 [52.9-68.7] years) participated in interviews; 17 participants (54.8%) were male and 14 (45.2%) were female. Nine participants (29.0%) had epidermal, 13 (41.9%) sclerotic, and 9 (29.0%) a combination of disease types. The study identified 40 codes of importance grouped within 5 HRQOL domains: skin changes and symptoms, social functioning, psychological and emotional functioning, physical functioning, and general health perceptions. The most frequent symptoms were dry skin (n = 20 [65%]), tight skin (n = 19 [61%]), itch (n = 15 [48%]), and discoloration (n = 14 [45%]), which were seen in all disease subtypes. Impairment in social functioning was noted by all participants. Psychological and emotional functioning, including frustration (Smith S score, 0.32) and worry or concern (Smith S score, 0.12), and symptoms including discomfort (Smith S score, 0.20) were the most salient to patients. Individual and environmental factors, such as social comparison, illness comparison with cancer, anatomic location of disease involvement, and disease duration, affected the relationship between skin changes and symptoms and downstream functioning and general health perceptions.</p><p><strong>Conclusions and relevance: </strong>This qualitative analysis demonstrated the direct relationship between cutaneous chronic GVHD and HRQOL domains and identified codes not represented in existing GVHD- and dermatology-specific patient-reported outcome measures. These results can guide patient-reported outcome development and instrument selection for clinical trials and improve clinical decision-making.</p>","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914772","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 : 2025-01-02DOI: 10.1001/jamadermatol.2024.5141
Michelle Sikora, Chinemelum Obijiofor, Angelo Osofsky, Lynn Liu, Soutrik Mandal, Kristen I Lo Sicco, Avrom S Caplan
{"title":"Sarcoidosis-Specific Cutaneous Lesion Distribution in Clinical Assessment for Cardiac Sarcoidosis.","authors":"Michelle Sikora, Chinemelum Obijiofor, Angelo Osofsky, Lynn Liu, Soutrik Mandal, Kristen I Lo Sicco, Avrom S Caplan","doi":"10.1001/jamadermatol.2024.5141","DOIUrl":"https://doi.org/10.1001/jamadermatol.2024.5141","url":null,"abstract":"","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914774","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 : 2025-01-02DOI: 10.1001/jamadermatol.2024.5301
Maha Kazmi, Mehar Maju, Rubi Danielle Montejano, Ivan Rodriguez, Coleen Kivlahan, Herbert B Castillo Valladares
{"title":"Multi-Institutional Clinical Forensic Dermatology Training for Dermatology Residents.","authors":"Maha Kazmi, Mehar Maju, Rubi Danielle Montejano, Ivan Rodriguez, Coleen Kivlahan, Herbert B Castillo Valladares","doi":"10.1001/jamadermatol.2024.5301","DOIUrl":"https://doi.org/10.1001/jamadermatol.2024.5301","url":null,"abstract":"","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914769","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 : 2025-01-01DOI: 10.1001/jamadermatol.2024.4534
Khaled Ezzedine, Ahmed M Soliman, Heidi S Camp, Mary Kate Ladd, Robin Pokrzywinski, Karin S Coyne, Rohini Sen, Bethanee J Schlosser, Jung Min Bae, Iltefat Hamzavi
<p><strong>Importance: </strong>Defining meaningful improvement using the Total Vitiligo Area Scoring Index (T-VASI) and the Facial VASI (F-VASI) aids interpretation of findings from clinical trials evaluating vitiligo treatments; however, clear and clinically meaningful thresholds have not yet been established.</p><p><strong>Objective: </strong>To assess concept validity and measurement performance of the T-VASI and F-VASI in patients with nonsegmental vitiligo and to identify meaningful change thresholds.</p><p><strong>Design, settings, and participants: </strong>This mixed-methods study consisted of a secondary analysis of a phase 2 multicenter double-blind dose-ranging randomized clinical trial and embedded qualitative interviews conducted at 35 sites in Canada, France, Japan, and the US. The secondary analysis included the trial's adult patients with nonsegmental vitiligo (T-VASI ≥5 and F-VASI ≥0.5 at baseline). Psychometric performance of the T-VASI and F-VASI and thresholds for meaningful change were evaluated using clinician- and patient-reported information. The trial's embedded interviews were used to qualitatively assess content validity and patient perceptions of meaningful repigmentation. Data analyses were performed from March to July 2023.</p><p><strong>Intervention: </strong>Participants were randomized to 6-, 11-, or 22-mg/day upadacitinib or placebo for 24 weeks.</p><p><strong>Main outcomes and measures: </strong>Psychometric performance of the T-VASI and F-VASI and thresholds for meaningful changed plus content validity and patient perceptions of meaningful repigmentation. Measurement instruments included the T-VASI, F-VASI, Vitiligo Noticeability Scale, Total-Patient Global Vitiligo Assessment, Face-Patient Global Vitiligo Assessment, Total-Physician Global Vitiligo Assessment (PhGVA-T), Face-Physician Global Vitiligo Assessment (PhGVA-F), Patient's Global Impression of Change-Vitiligo, Physician's Global Impression of Change-Vitiligo (PhGIC-V), Vitiligo Quality-of-Life Instrument, Dermatology Life Quality Index, the Hospital Anxiety and Depression Scale, and transcribed verbatim interviews with patients.</p><p><strong>Results: </strong>The psychometric analysis included 164 participants (mean [SD] age, 46 years; 103 [63%] females) and the qualitative analysis included 14 participants (mean [SD] age, 48.8 [12.2] years; 9 females [64%] and 5 males [36%]). Intraclass correlation coefficients were 0.98 for T-VASI and 0.99 for F-VASI in patients with clinically stable vitiligo between baseline and week 4, supporting test-retest reliability. At baseline and week 24, correlations were moderate to strong between T-VASI and PhGVA-T (r = 0.63-0.65) and between F-VASI and PhGVA-F (r = 0.65-0.71). Average baseline and week-24 VASI scores decreased with repigmentation (ie, increasing PhGVA scores). Least-square mean VASI scores increased with greater repigmentation as measured by the PhGIC-V. Least-square mean VASI scores also differed be
{"title":"Psychometric Properties and Meaningful Change Thresholds of the Vitiligo Area Scoring Index.","authors":"Khaled Ezzedine, Ahmed M Soliman, Heidi S Camp, Mary Kate Ladd, Robin Pokrzywinski, Karin S Coyne, Rohini Sen, Bethanee J Schlosser, Jung Min Bae, Iltefat Hamzavi","doi":"10.1001/jamadermatol.2024.4534","DOIUrl":"10.1001/jamadermatol.2024.4534","url":null,"abstract":"<p><strong>Importance: </strong>Defining meaningful improvement using the Total Vitiligo Area Scoring Index (T-VASI) and the Facial VASI (F-VASI) aids interpretation of findings from clinical trials evaluating vitiligo treatments; however, clear and clinically meaningful thresholds have not yet been established.</p><p><strong>Objective: </strong>To assess concept validity and measurement performance of the T-VASI and F-VASI in patients with nonsegmental vitiligo and to identify meaningful change thresholds.</p><p><strong>Design, settings, and participants: </strong>This mixed-methods study consisted of a secondary analysis of a phase 2 multicenter double-blind dose-ranging randomized clinical trial and embedded qualitative interviews conducted at 35 sites in Canada, France, Japan, and the US. The secondary analysis included the trial's adult patients with nonsegmental vitiligo (T-VASI ≥5 and F-VASI ≥0.5 at baseline). Psychometric performance of the T-VASI and F-VASI and thresholds for meaningful change were evaluated using clinician- and patient-reported information. The trial's embedded interviews were used to qualitatively assess content validity and patient perceptions of meaningful repigmentation. Data analyses were performed from March to July 2023.</p><p><strong>Intervention: </strong>Participants were randomized to 6-, 11-, or 22-mg/day upadacitinib or placebo for 24 weeks.</p><p><strong>Main outcomes and measures: </strong>Psychometric performance of the T-VASI and F-VASI and thresholds for meaningful changed plus content validity and patient perceptions of meaningful repigmentation. Measurement instruments included the T-VASI, F-VASI, Vitiligo Noticeability Scale, Total-Patient Global Vitiligo Assessment, Face-Patient Global Vitiligo Assessment, Total-Physician Global Vitiligo Assessment (PhGVA-T), Face-Physician Global Vitiligo Assessment (PhGVA-F), Patient's Global Impression of Change-Vitiligo, Physician's Global Impression of Change-Vitiligo (PhGIC-V), Vitiligo Quality-of-Life Instrument, Dermatology Life Quality Index, the Hospital Anxiety and Depression Scale, and transcribed verbatim interviews with patients.</p><p><strong>Results: </strong>The psychometric analysis included 164 participants (mean [SD] age, 46 years; 103 [63%] females) and the qualitative analysis included 14 participants (mean [SD] age, 48.8 [12.2] years; 9 females [64%] and 5 males [36%]). Intraclass correlation coefficients were 0.98 for T-VASI and 0.99 for F-VASI in patients with clinically stable vitiligo between baseline and week 4, supporting test-retest reliability. At baseline and week 24, correlations were moderate to strong between T-VASI and PhGVA-T (r = 0.63-0.65) and between F-VASI and PhGVA-F (r = 0.65-0.71). Average baseline and week-24 VASI scores decreased with repigmentation (ie, increasing PhGVA scores). Least-square mean VASI scores increased with greater repigmentation as measured by the PhGIC-V. Least-square mean VASI scores also differed be","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":"39-46"},"PeriodicalIF":11.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11581646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545567","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 : 2025-01-01DOI: 10.1001/jamadermatol.2024.4445
Robin Reschke, Jasmin Richter, Alexander H Enk, Jessica C Hassel
{"title":"Use of Anti-PD1 Blockade After Hedgehog Inhibitors or as First-Line Therapy for Gorlin Syndrome.","authors":"Robin Reschke, Jasmin Richter, Alexander H Enk, Jessica C Hassel","doi":"10.1001/jamadermatol.2024.4445","DOIUrl":"10.1001/jamadermatol.2024.4445","url":null,"abstract":"","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":"104-105"},"PeriodicalIF":11.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11581658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583294","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 : 2025-01-01DOI: 10.1001/jamadermatol.2024.4433
Axel Svedbom, Lotus Mallbris, Álvaro González-Cantero, Martin Playford, Colin Wu, Nehal N Mehta, Mona Ståhle
Importance: Psoriasis is associated with increased cardiovascular risk, but the underlying pathogenic mechanisms remain unclear. Elucidating these mechanisms can help develop treatment strategies and enhance understanding of the link between peripheral inflammation, such as psoriatic skin lesions, and cardiovascular disease (CVD).
Objective: To explore whether systemic inflammation is a mediator of the association between psoriasis skin disease severity and CVD.
Design, setting, and participants: This cohort study used data from cross-sectional study (Psoriasis Atherosclerosis and Cardiometabolic Disease Initiative [PACI]), which enrolled patients from January 2013 to February 2022, and an inception cohort study (Stockholm Psoriasis Cohort [SPC]), which enrolled patients from January 2000 to December 2005. The PACI enrolled consecutive patients referred by dermatologists in Maryland, and the SPC enrolled consecutive patients referred from a wide range of practices in Sweden. Patients with prevalent psoriasis from the PACI and patients with incident psoriasis from the SPC were included. Data were analyzed from October 2023 to January 2024.
Exposures: Psoriasis skin disease severity was measured using the Psoriasis Area and Severity Index (PASI), and systemic inflammation was measured using glycan biomarker of N-acetyl side chains of acute-phase proteins (GlycA). Mediation analysis was performed by evaluating the associations between exposure, mediator, and outcome in patients with first-tertile and third-tertile PASI scores when GlycA level was set at the level observed in patients with first-tertile PASI.
Main outcomes and measures: Noncalcified coronary burden (NCB) measured using coronary computed tomography angiography in the PACI and hospitalization for CVD or cardiovascular death in the SPC.
Results: Of 260 eligible patients from the PACI, 162 (62.3%) were male, and the median (IQR) age was 51 (41-60) years; of 509 eligible patients from the SPC, 237 (46.6%) were male, and the median (IQR) age was 43 (30-57) years. In both studies, PASI was associated with GlycA level and CVD, and GlycA level was associated with CVD. The direct and indirect (through GlycA) effects of PASI on NCB were estimated at 0.94 (95% CI, 0.26-1.74) and 0.19 (95% CI, 0.02-0.47), respectively. The odds ratios for the direct and indirect effects of PASI on cardiovascular events were estimated at 1.23 (95% CI, 0.70-1.92) and 1.16 (95% CI, 1.04-1.42), respectively.
Conclusions and relevance: In this study, skin disease severity measured using PASI was associated with systemic inflammation, and both PASI and systemic inflammation, measured using GlycA levels, were associated with CVD. The association between PASI and CVD may be mediated by systemic inflammation.
重要性:银屑病与心血管风险增加有关,但其潜在的致病机制仍不清楚。阐明这些机制有助于制定治疗策略,并加深对银屑病皮损等外周炎症与心血管疾病(CVD)之间联系的理解:目的:探讨全身性炎症是否是银屑病皮损严重程度与心血管疾病之间关系的介导因素:这项队列研究使用了横断面研究(银屑病动脉粥样硬化和心脏代谢疾病倡议[PACI])和起始队列研究(斯德哥尔摩银屑病队列[SPC])的数据,前者从2013年1月至2022年2月招募患者,后者从2000年1月至2005年12月招募患者。PACI招募的是由马里兰州皮肤科医生转诊的连续患者,SPC招募的是由瑞典各医疗机构转诊的连续患者。PACI 中的银屑病流行期患者和 SPC 中的银屑病发病期患者均被纳入其中。数据分析时间为2023年10月至2024年1月:银屑病皮肤疾病严重程度采用银屑病面积和严重程度指数(PASI)进行测量,全身炎症采用急性期蛋白 N-乙酰侧链的聚糖生物标记物(GlycA)进行测量。当 GlycA 水平设定为 PASI 一档患者所观察到的水平时,通过评估 PASI 一档和三档患者的暴露、中介因子和结果之间的关联进行中介分析:在 PACI 中使用冠状动脉计算机断层扫描血管造影术测量非钙化冠状动脉负担(NCB),在 SPC 中测量心血管疾病住院或心血管疾病死亡:在PACI的260名合格患者中,162人(62.3%)为男性,年龄中位数(IQR)为51(41-60)岁;在SPC的509名合格患者中,237人(46.6%)为男性,年龄中位数(IQR)为43(30-57)岁。在这两项研究中,PASI 与 GlycA 水平和心血管疾病相关,而 GlycA 水平与心血管疾病相关。据估计,PASI 对 NCB 的直接和间接(通过 GlycA)影响分别为 0.94(95% CI,0.26-1.74)和 0.19(95% CI,0.02-0.47)。PASI对心血管事件的直接和间接影响的几率估计分别为1.23(95% CI,0.70-1.92)和1.16(95% CI,1.04-1.42):在这项研究中,使用 PASI 测量的皮肤病严重程度与全身炎症相关,而使用 GlycA 水平测量的 PASI 和全身炎症与心血管疾病相关。PASI与心血管疾病之间的关联可能是由全身炎症介导的。
{"title":"Skin Inflammation, Systemic Inflammation, and Cardiovascular Disease in Psoriasis.","authors":"Axel Svedbom, Lotus Mallbris, Álvaro González-Cantero, Martin Playford, Colin Wu, Nehal N Mehta, Mona Ståhle","doi":"10.1001/jamadermatol.2024.4433","DOIUrl":"10.1001/jamadermatol.2024.4433","url":null,"abstract":"<p><strong>Importance: </strong>Psoriasis is associated with increased cardiovascular risk, but the underlying pathogenic mechanisms remain unclear. Elucidating these mechanisms can help develop treatment strategies and enhance understanding of the link between peripheral inflammation, such as psoriatic skin lesions, and cardiovascular disease (CVD).</p><p><strong>Objective: </strong>To explore whether systemic inflammation is a mediator of the association between psoriasis skin disease severity and CVD.</p><p><strong>Design, setting, and participants: </strong>This cohort study used data from cross-sectional study (Psoriasis Atherosclerosis and Cardiometabolic Disease Initiative [PACI]), which enrolled patients from January 2013 to February 2022, and an inception cohort study (Stockholm Psoriasis Cohort [SPC]), which enrolled patients from January 2000 to December 2005. The PACI enrolled consecutive patients referred by dermatologists in Maryland, and the SPC enrolled consecutive patients referred from a wide range of practices in Sweden. Patients with prevalent psoriasis from the PACI and patients with incident psoriasis from the SPC were included. Data were analyzed from October 2023 to January 2024.</p><p><strong>Exposures: </strong>Psoriasis skin disease severity was measured using the Psoriasis Area and Severity Index (PASI), and systemic inflammation was measured using glycan biomarker of N-acetyl side chains of acute-phase proteins (GlycA). Mediation analysis was performed by evaluating the associations between exposure, mediator, and outcome in patients with first-tertile and third-tertile PASI scores when GlycA level was set at the level observed in patients with first-tertile PASI.</p><p><strong>Main outcomes and measures: </strong>Noncalcified coronary burden (NCB) measured using coronary computed tomography angiography in the PACI and hospitalization for CVD or cardiovascular death in the SPC.</p><p><strong>Results: </strong>Of 260 eligible patients from the PACI, 162 (62.3%) were male, and the median (IQR) age was 51 (41-60) years; of 509 eligible patients from the SPC, 237 (46.6%) were male, and the median (IQR) age was 43 (30-57) years. In both studies, PASI was associated with GlycA level and CVD, and GlycA level was associated with CVD. The direct and indirect (through GlycA) effects of PASI on NCB were estimated at 0.94 (95% CI, 0.26-1.74) and 0.19 (95% CI, 0.02-0.47), respectively. The odds ratios for the direct and indirect effects of PASI on cardiovascular events were estimated at 1.23 (95% CI, 0.70-1.92) and 1.16 (95% CI, 1.04-1.42), respectively.</p><p><strong>Conclusions and relevance: </strong>In this study, skin disease severity measured using PASI was associated with systemic inflammation, and both PASI and systemic inflammation, measured using GlycA levels, were associated with CVD. The association between PASI and CVD may be mediated by systemic inflammation.</p>","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":"81-86"},"PeriodicalIF":11.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11579891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675858","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 : 2025-01-01DOI: 10.1001/jamadermatol.2024.4688
April W Armstrong, Mark Lebwohl, Richard B Warren, Howard Sofen, Shinichi Imafuku, Mamitaro Ohtsuki, Lynda Spelman, Thierry Passeron, Kim A Papp, Renata M Kisa, John Vaile, Victoria Berger, Eleni Vritzali, Kim Hoyt, Matthew J Colombo, Julie Scotto, Subhashis Banerjee, Bruce Strober, Diamant Thaçi, Andrew Blauvelt
<p><strong>Importance: </strong>Safe and effective long-term treatments for moderate to severe plaque psoriasis are needed.</p><p><strong>Objective: </strong>To evaluate the long-term safety and efficacy of deucravacitinib through 3 years (week 148) in the randomized POETYK PSO-1, PSO-2, and nonrandomized long-term extension (LTE) trials.</p><p><strong>Design, setting, and participants: </strong>PSO-1/PSO-2 were global, 52-week, randomized, double-blinded phase 3 trials in patients with moderate to severe plaque psoriasis. After completing 52 weeks of treatment in PSO-1/PSO-2, patients could enroll in the prespecified, ongoing, nonrandomized LTE trial. The peak of the global COVID-19 pandemic coincided with the LTE trial. Patient enrollment in the LTE started August 12, 2019; safety and efficacy were assessed through June 15, 2022; and these data were analyzed through June 28, 2024.</p><p><strong>Interventions: </strong>The PSO-1/PSO-2 trials randomized patients 1:2:1 to oral placebo, deucravacitinib, 6 mg once daily, or apremilast, 30 mg twice daily. Patients enrolling in the LTE trial received open-label deucravacitinib, 6 mg once daily.</p><p><strong>Main outcomes and measures: </strong>Safety outcomes were evaluated in patients who received 1 or more doses of deucravacitinib. Efficacy outcomes included 75% or greater or 90% or greater reduction from baseline in Psoriasis Area and Severity Index (PASI 75/90) and static Physician Global Assessment scores of 0 (clear) or 1 (almost clear) (sPGA 0/1) and were assessed in patients who received deucravacitinib treatment from day 1 of the parent trials who continued in the LTE trial.</p><p><strong>Results: </strong>Of 1519 patients who received 1 or more doses of deucravacitinib, 513 received continuous deucravacitinib treatment from day 1 and entered the LTE trial. Exposure-adjusted incidence rates (EAIRs) per 100 person-years were decreased or similar in the 1-year vs 3-year cumulative periods, respectively, for adverse events (AEs) (229.2 vs 144.8; 95% CI, 215.4-243.9 vs 137.1-153.0), serious AEs (5.7 vs 5.5; 95% CI, 4.4-7.4 vs 4.7-6.4), discontinuations due to AEs (4.4 vs 2.4; 95% CI, 3.3-5.9 vs 2.0-3.0), and deaths (0.2 vs 0.3; 95% CI, 0.1-0.8 vs 0.2-0.6). Incidence rates of the most common AEs (EAIR per 100 person-years ≥5) during the 1-year and 3-year cumulative periods, respectively, were nasopharyngitis (26.1 vs 11.4; 95% CI, 23.0-29.8 vs 10.2-12.7), COVID-19 (0.5 vs 8.0; 95% CI, 0.2-1.2 vs 7.1-9.1), and upper respiratory tract infection (13.4 vs 6.2; 95% CI, 11.3-16.0 vs 5.4-7.2). EAIRs for AEs of interest, including herpes zoster, major adverse cardiovascular events, and malignant diseases, remained low and were decreased or comparable between the 1-year and 3-year cumulative periods. Clinical response rates were maintained through 3 years.</p><p><strong>Conclusions and relevance: </strong>The findings of this integrated analysis of the phase 3 POETYK PSO-1, PSO-2, and nonrandomized LTE tr
重要性:中重度斑块状银屑病需要安全有效的长期治疗方法:在随机 POETYK PSO-1、PSO-2 和非随机长期扩展(LTE)试验中,评估 deucravacitinib 长达 3 年(第 148 周)的长期安全性和疗效:PSO-1/PSO-2是针对中度至重度斑块状银屑病患者的全球性、为期52周的随机双盲3期试验。在完成PSO-1/PSO-2为期52周的治疗后,患者可参加预设的、正在进行的非随机LTE试验。全球 COVID-19 大流行的高峰期正好与 LTE 试验同时进行。LTE试验的患者注册从2019年8月12日开始;安全性和有效性评估持续到2022年6月15日;这些数据的分析持续到2024年6月28日:PSO-1/PSO-2试验以1:2:1的比例将患者随机分配到口服安慰剂、每天一次每次6毫克的deucravacitinib或每天两次每次30毫克的apremilast。参加LTE试验的患者接受开放标签的德拉瓦替尼治疗,每天一次,每次6毫克:主要结果和指标:对接受1次或1次以上剂量德拉瓦替尼治疗的患者进行安全性评价。疗效结果包括银屑病面积和严重程度指数(PASI 75/90)比基线降低75%或以上或90%或以上,以及静态医生总体评估评分为0(清晰)或1(基本清晰)(sPGA 0/1),评估对象为从母体试验第1天开始接受德拉瓦替尼治疗并继续参加LTE试验的患者:在接受了1次或1次以上剂量德拉瓦替尼治疗的1519名患者中,有513名患者从第1天开始持续接受德拉瓦替尼治疗,并参加了LTE试验。在不良事件(AEs)方面,每百人年暴露调整发病率(EAIRs)在1年和3年的累积期分别下降或相似(229.2 vs 144.8; 95% CI, 215.4-243.9 vs 137.1-153.0)、严重不良事件(5.7 vs 5.5;95% CI,4.4-7.4 vs 4.7-6.4)、不良事件导致的停药(4.4 vs 2.4;95% CI,3.3-5.9 vs 2.0-3.0)和死亡(0.2 vs 0.3;95% CI,0.1-0.8 vs 0.2-0.6)。最常见的 AEs(每百人年 EAIR ≥5)在 1 年和 3 年累计期间的发病率分别为鼻咽炎(26.1 vs 11. 4;95% CI,23.0-3.0)和死亡(0.2 vs 0.3;95% CI,0.1-0.8 vs 0.2-0.6)。4;95% CI,23.0-29.8 vs 10.2-12.7)、COVID-19(0.5 vs 8.0;95% CI,0.2-1.2 vs 7.1-9.1)和上呼吸道感染(13.4 vs 6.2;95% CI,11.3-16.0 vs 5.4-7.2)。包括带状疱疹、主要不良心血管事件和恶性疾病在内的相关 AE 的 EAIR 仍保持在较低水平,且在 1 年和 3 年累积期之间有所下降或不相上下。临床应答率保持了 3 年:这项对 POETYK PSO-1、PSO-2 和非随机 LTE 试验的 3 期综合分析结果表明,银屑病患者持续使用 deucravacitinib 治疗 3 年,具有一致的安全性和持久的临床应答:试验注册:ClinicalTrials.gov Identifiers:NCT03624127、NCT03611751和NCT04036435。
{"title":"Safety and Efficacy of Deucravacitinib in Moderate to Severe Plaque Psoriasis for Up to 3 Years: An Open-Label Extension of Randomized Clinical Trials.","authors":"April W Armstrong, Mark Lebwohl, Richard B Warren, Howard Sofen, Shinichi Imafuku, Mamitaro Ohtsuki, Lynda Spelman, Thierry Passeron, Kim A Papp, Renata M Kisa, John Vaile, Victoria Berger, Eleni Vritzali, Kim Hoyt, Matthew J Colombo, Julie Scotto, Subhashis Banerjee, Bruce Strober, Diamant Thaçi, Andrew Blauvelt","doi":"10.1001/jamadermatol.2024.4688","DOIUrl":"10.1001/jamadermatol.2024.4688","url":null,"abstract":"<p><strong>Importance: </strong>Safe and effective long-term treatments for moderate to severe plaque psoriasis are needed.</p><p><strong>Objective: </strong>To evaluate the long-term safety and efficacy of deucravacitinib through 3 years (week 148) in the randomized POETYK PSO-1, PSO-2, and nonrandomized long-term extension (LTE) trials.</p><p><strong>Design, setting, and participants: </strong>PSO-1/PSO-2 were global, 52-week, randomized, double-blinded phase 3 trials in patients with moderate to severe plaque psoriasis. After completing 52 weeks of treatment in PSO-1/PSO-2, patients could enroll in the prespecified, ongoing, nonrandomized LTE trial. The peak of the global COVID-19 pandemic coincided with the LTE trial. Patient enrollment in the LTE started August 12, 2019; safety and efficacy were assessed through June 15, 2022; and these data were analyzed through June 28, 2024.</p><p><strong>Interventions: </strong>The PSO-1/PSO-2 trials randomized patients 1:2:1 to oral placebo, deucravacitinib, 6 mg once daily, or apremilast, 30 mg twice daily. Patients enrolling in the LTE trial received open-label deucravacitinib, 6 mg once daily.</p><p><strong>Main outcomes and measures: </strong>Safety outcomes were evaluated in patients who received 1 or more doses of deucravacitinib. Efficacy outcomes included 75% or greater or 90% or greater reduction from baseline in Psoriasis Area and Severity Index (PASI 75/90) and static Physician Global Assessment scores of 0 (clear) or 1 (almost clear) (sPGA 0/1) and were assessed in patients who received deucravacitinib treatment from day 1 of the parent trials who continued in the LTE trial.</p><p><strong>Results: </strong>Of 1519 patients who received 1 or more doses of deucravacitinib, 513 received continuous deucravacitinib treatment from day 1 and entered the LTE trial. Exposure-adjusted incidence rates (EAIRs) per 100 person-years were decreased or similar in the 1-year vs 3-year cumulative periods, respectively, for adverse events (AEs) (229.2 vs 144.8; 95% CI, 215.4-243.9 vs 137.1-153.0), serious AEs (5.7 vs 5.5; 95% CI, 4.4-7.4 vs 4.7-6.4), discontinuations due to AEs (4.4 vs 2.4; 95% CI, 3.3-5.9 vs 2.0-3.0), and deaths (0.2 vs 0.3; 95% CI, 0.1-0.8 vs 0.2-0.6). Incidence rates of the most common AEs (EAIR per 100 person-years ≥5) during the 1-year and 3-year cumulative periods, respectively, were nasopharyngitis (26.1 vs 11.4; 95% CI, 23.0-29.8 vs 10.2-12.7), COVID-19 (0.5 vs 8.0; 95% CI, 0.2-1.2 vs 7.1-9.1), and upper respiratory tract infection (13.4 vs 6.2; 95% CI, 11.3-16.0 vs 5.4-7.2). EAIRs for AEs of interest, including herpes zoster, major adverse cardiovascular events, and malignant diseases, remained low and were decreased or comparable between the 1-year and 3-year cumulative periods. Clinical response rates were maintained through 3 years.</p><p><strong>Conclusions and relevance: </strong>The findings of this integrated analysis of the phase 3 POETYK PSO-1, PSO-2, and nonrandomized LTE tr","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":"56-66"},"PeriodicalIF":11.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142728821","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 : 2025-01-01DOI: 10.1001/jamadermatol.2024.4424
Toan S Bui, Jonathan J Lee
{"title":"Annular Eroded Plaque With Honey-Colored Crusting On Scrotum.","authors":"Toan S Bui, Jonathan J Lee","doi":"10.1001/jamadermatol.2024.4424","DOIUrl":"10.1001/jamadermatol.2024.4424","url":null,"abstract":"","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":"100-101"},"PeriodicalIF":11.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675839","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}