Pub Date : 2024-10-01DOI: 10.1001/jamadermatol.2024.2849
Liang Chen, Nicklas Brustad, Yang Luo, Tingting Wang, Mina Ali, Parvaneh Ebrahimi, Ann-Marie M Schoos, Nilo Vahman, Mario Lovric, Morten A Rasmussen, Johan Kolmert, Craig E Wheelock, Jessica A Lasky-Su, Jakob Stokholm, Klaus Bønnelykke, Bo Chawes
<p><strong>Importance: </strong>Eicosanoids have a pathophysiological role in atopic dermatitis (AD), but it is unknown whether this is affected by prenatal ω-3 long-chain polyunsaturated fatty acid (n-3 LCPUFA; ie, fish oil) supplementation and genetic variations in the cyclooxygenase-1 (COX1) pathway.</p><p><strong>Objective: </strong>To explore the association of n-3 LCPUFA supplementation during pregnancy with risk of childhood AD overall and by maternal COX1 genotype.</p><p><strong>Design, setting, and participants: </strong>This prespecified secondary analysis of a randomized clinical trial included mother-child pairs from the Danish Copenhagen Prospective Studies on Asthma in Childhood 2010 birth cohort, with prospective follow-up until children were aged 10 years. In the trial, maternal and child COX1 genotypes were determined, and urinary eicosanoids were quantified when the child was 1 year of age. The present study was conducted from January 2019 to December 2021, and data were analyzed from January to September 2023.</p><p><strong>Intervention: </strong>A total of 736 pregnant women at 24 weeks' gestation were randomized 1:1 to 2.4 g of n-3 LCPUFA (fish oil) or placebo (olive oil) per day until 1 week post partum.</p><p><strong>Main outcomes and measures: </strong>Risk of childhood AD until age 10 years overall and by maternal COX1 genotype.</p><p><strong>Results: </strong>At age 10 years, 635 children (91%; 363 [57%] female) completed the clinical follow-up, and these mother-child pairs were included in this study; 321 (51%) were in the intervention group and 314 (49%) in the control group. Pregnancy n-3 LCPUFA supplementation was associated with lower urinary thromboxane A2 metabolites at age 1 year (β, -0.46; 95% CI, -0.80 to -0.13; P = .006), which was also associated with COX1 rs1330344 genotype (β per C allele, 0.47; 95% CI, 0.20-0.73; P = .001). Although neither n-3 LCPUFA supplementation (hazard ratio [HR], 1.00; 95% CI, 0.76-1.33; P = .97) nor maternal COX1 genotype (HR, 0.94; 95% CI, 0.74-1.19; P = .60) was associated with risk of childhood AD until age 10 years, there was evidence of an interaction between these variables (P < .001 for interaction). Among mothers with the TT genotype, risk of AD was reduced in the n-3 LCPUFA group compared with the placebo group (390 mother-child pairs [61%]; HR, 0.70; 95% CI, 0.50-0.98; P = .04); there was no association for mothers with the CT genotype (209 [33%]; HR, 1.29; 95% CI, 0.79-2.10; P = .31), and risk was increased among offspring of mothers with the CC genotype (37 [6%]; HR, 5.77; 95% CI, 1.63-20.47; P = .007). There was a significant interaction between n-3 LCPUFA supplementation and child COX1 genotype and development of AD (P = .002 for interaction).</p><p><strong>Conclusions and relevance: </strong>In this secondary analysis of a randomized clinical trial, the association of prenatal n-3 LCPUFA supplementation with risk of childhood AD varied by maternal COX1 genotype. The
{"title":"Prenatal Fish Oil Supplementation, Maternal COX1 Genotype, and Childhood Atopic Dermatitis: A Secondary Analysis of a Randomized Clinical Trial.","authors":"Liang Chen, Nicklas Brustad, Yang Luo, Tingting Wang, Mina Ali, Parvaneh Ebrahimi, Ann-Marie M Schoos, Nilo Vahman, Mario Lovric, Morten A Rasmussen, Johan Kolmert, Craig E Wheelock, Jessica A Lasky-Su, Jakob Stokholm, Klaus Bønnelykke, Bo Chawes","doi":"10.1001/jamadermatol.2024.2849","DOIUrl":"10.1001/jamadermatol.2024.2849","url":null,"abstract":"<p><strong>Importance: </strong>Eicosanoids have a pathophysiological role in atopic dermatitis (AD), but it is unknown whether this is affected by prenatal ω-3 long-chain polyunsaturated fatty acid (n-3 LCPUFA; ie, fish oil) supplementation and genetic variations in the cyclooxygenase-1 (COX1) pathway.</p><p><strong>Objective: </strong>To explore the association of n-3 LCPUFA supplementation during pregnancy with risk of childhood AD overall and by maternal COX1 genotype.</p><p><strong>Design, setting, and participants: </strong>This prespecified secondary analysis of a randomized clinical trial included mother-child pairs from the Danish Copenhagen Prospective Studies on Asthma in Childhood 2010 birth cohort, with prospective follow-up until children were aged 10 years. In the trial, maternal and child COX1 genotypes were determined, and urinary eicosanoids were quantified when the child was 1 year of age. The present study was conducted from January 2019 to December 2021, and data were analyzed from January to September 2023.</p><p><strong>Intervention: </strong>A total of 736 pregnant women at 24 weeks' gestation were randomized 1:1 to 2.4 g of n-3 LCPUFA (fish oil) or placebo (olive oil) per day until 1 week post partum.</p><p><strong>Main outcomes and measures: </strong>Risk of childhood AD until age 10 years overall and by maternal COX1 genotype.</p><p><strong>Results: </strong>At age 10 years, 635 children (91%; 363 [57%] female) completed the clinical follow-up, and these mother-child pairs were included in this study; 321 (51%) were in the intervention group and 314 (49%) in the control group. Pregnancy n-3 LCPUFA supplementation was associated with lower urinary thromboxane A2 metabolites at age 1 year (β, -0.46; 95% CI, -0.80 to -0.13; P = .006), which was also associated with COX1 rs1330344 genotype (β per C allele, 0.47; 95% CI, 0.20-0.73; P = .001). Although neither n-3 LCPUFA supplementation (hazard ratio [HR], 1.00; 95% CI, 0.76-1.33; P = .97) nor maternal COX1 genotype (HR, 0.94; 95% CI, 0.74-1.19; P = .60) was associated with risk of childhood AD until age 10 years, there was evidence of an interaction between these variables (P < .001 for interaction). Among mothers with the TT genotype, risk of AD was reduced in the n-3 LCPUFA group compared with the placebo group (390 mother-child pairs [61%]; HR, 0.70; 95% CI, 0.50-0.98; P = .04); there was no association for mothers with the CT genotype (209 [33%]; HR, 1.29; 95% CI, 0.79-2.10; P = .31), and risk was increased among offspring of mothers with the CC genotype (37 [6%]; HR, 5.77; 95% CI, 1.63-20.47; P = .007). There was a significant interaction between n-3 LCPUFA supplementation and child COX1 genotype and development of AD (P = .002 for interaction).</p><p><strong>Conclusions and relevance: </strong>In this secondary analysis of a randomized clinical trial, the association of prenatal n-3 LCPUFA supplementation with risk of childhood AD varied by maternal COX1 genotype. The ","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":"1082-1090"},"PeriodicalIF":11.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11359109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080237","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 : 2024-10-01DOI: 10.1001/jamadermatol.2024.2816
Ayisha N Mahama, Courtney N Haller, Adewole S Adamson
{"title":"Fear of Cancer Recurrence Among Survivors of Localized Cutaneous Melanoma-What's in a Name?-Reply.","authors":"Ayisha N Mahama, Courtney N Haller, Adewole S Adamson","doi":"10.1001/jamadermatol.2024.2816","DOIUrl":"10.1001/jamadermatol.2024.2816","url":null,"abstract":"","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":"1135-1136"},"PeriodicalIF":11.5,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080301","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 : 2024-09-25DOI: 10.1001/jamadermatol.2024.3897
Joel M Gelfand, April W Armstrong, Henry W Lim, Steven R Feldman, Sandra M Johnson, W C Cole Claiborne, Robert E Kalb, Jeannette Jakus, Aaron R Mangold, R Hal Flowers, Tina Bhutani, John R Durkin, Jerry Bagel, Scott Fretzin, Michael P Sheehan, James Krell, Margo Reeder, Jessica Kaffenberger, Francisca Kartono, Junko Takeshita, Alisha M Bridges, Eric Fielding, Umbereen S Nehal, Kenneth L Schaecher, Leah M Howard, Guy S Eakin, Suzette Báez, Brooke E Bishop, Robert C Fitzsimmons, Maryte Papadopoulos, William B Song, Kristin A Linn, Rebecca A Hubbard, Daniel B Shin, Kristina Callis Duffin
<p><strong>Importance: </strong>Office-based phototherapy is cost-effective for psoriasis but difficult to access. Home-based phototherapy is patient preferred but has limited clinical data, particularly in patients with darker skin.</p><p><strong>Objective: </strong>To compare the effectiveness of home- vs office-based narrowband UV-B phototherapy for psoriasis.</p><p><strong>Design, setting, and participants: </strong>The Light Treatment Effectiveness study was an investigator-initiated, pragmatic, open-label, parallel-group, multicenter, noninferiority randomized clinical trial embedded in routine care at 42 academic and private clinical dermatology practices in the US. Enrollment occurred from March 1, 2019, to December 4, 2023, with follow-up through June 2024. Participants were 12 years and older with plaque or guttate psoriasis who were candidates for home- and office-based phototherapy.</p><p><strong>Interventions: </strong>Participants were randomized to receive a home narrowband UV-B machine with guided mode dosimetry or routine care with office-based narrowband UV-B for 12 weeks, followed by an additional 12-week observation period.</p><p><strong>Main outcomes and measures: </strong>The coprimary effectiveness outcomes were Physician Global Assessment (PGA) dichotomized as clear/almost clear skin (score of ≤1) at the end of the intervention period and Dermatology Life Quality Index (DLQI) score of 5 or lower (no to small effect on quality of life) at week 12.</p><p><strong>Results: </strong>Of 783 patients enrolled (mean [SD] age, 48.0 [15.5] years; 376 [48.0%] female), 393 received home-based phototherapy and 390 received office-based phototherapy, with 350 (44.7%) having skin phototype (SPT) I/II, 350 (44.7%) having SPT III/IV, and 83 (10.6%) having SPT V/VI. A total of 93 patients (11.9%) were receiving systemic treatment. At baseline, mean (SD) PGA was 2.7 (0.8) and DLQI was 12.2 (7.2). At week 12, 129 patients (32.8%) receiving home-based phototherapy and 100 patients (25.6%) receiving office-based phototherapy achieved clear/almost clear skin, and 206 (52.4%) and 131 (33.6%) achieved DLQI of 5 or lower, respectively. Home-based phototherapy was noninferior to office-based phototherapy for PGA and DLQI in the overall population and across all SPTs. Home-based phototherapy, compared to office-based phototherapy, was associated with better treatment adherence (202 patients [51.4%] vs 62 patients [15.9%]; P < .001), lower burden of indirect costs to patients, and more episodes of persistent erythema (466 of 7957 treatments [5.9%] vs 46 of 3934 treatments [1.2%]; P < .001). Both treatments were well tolerated with no discontinuations due to adverse events.</p><p><strong>Conclusions and relevance: </strong>In this randomized clinical trial, home-based phototherapy was as effective as office-based phototherapy for plaque or guttate psoriasis in everyday clinical practice and had less burden to patients.</p><p><strong>Trial registration:
{"title":"Home- vs Office-Based Narrowband UV-B Phototherapy for Patients With Psoriasis: The LITE Randomized Clinical Trial.","authors":"Joel M Gelfand, April W Armstrong, Henry W Lim, Steven R Feldman, Sandra M Johnson, W C Cole Claiborne, Robert E Kalb, Jeannette Jakus, Aaron R Mangold, R Hal Flowers, Tina Bhutani, John R Durkin, Jerry Bagel, Scott Fretzin, Michael P Sheehan, James Krell, Margo Reeder, Jessica Kaffenberger, Francisca Kartono, Junko Takeshita, Alisha M Bridges, Eric Fielding, Umbereen S Nehal, Kenneth L Schaecher, Leah M Howard, Guy S Eakin, Suzette Báez, Brooke E Bishop, Robert C Fitzsimmons, Maryte Papadopoulos, William B Song, Kristin A Linn, Rebecca A Hubbard, Daniel B Shin, Kristina Callis Duffin","doi":"10.1001/jamadermatol.2024.3897","DOIUrl":"https://doi.org/10.1001/jamadermatol.2024.3897","url":null,"abstract":"<p><strong>Importance: </strong>Office-based phototherapy is cost-effective for psoriasis but difficult to access. Home-based phototherapy is patient preferred but has limited clinical data, particularly in patients with darker skin.</p><p><strong>Objective: </strong>To compare the effectiveness of home- vs office-based narrowband UV-B phototherapy for psoriasis.</p><p><strong>Design, setting, and participants: </strong>The Light Treatment Effectiveness study was an investigator-initiated, pragmatic, open-label, parallel-group, multicenter, noninferiority randomized clinical trial embedded in routine care at 42 academic and private clinical dermatology practices in the US. Enrollment occurred from March 1, 2019, to December 4, 2023, with follow-up through June 2024. Participants were 12 years and older with plaque or guttate psoriasis who were candidates for home- and office-based phototherapy.</p><p><strong>Interventions: </strong>Participants were randomized to receive a home narrowband UV-B machine with guided mode dosimetry or routine care with office-based narrowband UV-B for 12 weeks, followed by an additional 12-week observation period.</p><p><strong>Main outcomes and measures: </strong>The coprimary effectiveness outcomes were Physician Global Assessment (PGA) dichotomized as clear/almost clear skin (score of ≤1) at the end of the intervention period and Dermatology Life Quality Index (DLQI) score of 5 or lower (no to small effect on quality of life) at week 12.</p><p><strong>Results: </strong>Of 783 patients enrolled (mean [SD] age, 48.0 [15.5] years; 376 [48.0%] female), 393 received home-based phototherapy and 390 received office-based phototherapy, with 350 (44.7%) having skin phototype (SPT) I/II, 350 (44.7%) having SPT III/IV, and 83 (10.6%) having SPT V/VI. A total of 93 patients (11.9%) were receiving systemic treatment. At baseline, mean (SD) PGA was 2.7 (0.8) and DLQI was 12.2 (7.2). At week 12, 129 patients (32.8%) receiving home-based phototherapy and 100 patients (25.6%) receiving office-based phototherapy achieved clear/almost clear skin, and 206 (52.4%) and 131 (33.6%) achieved DLQI of 5 or lower, respectively. Home-based phototherapy was noninferior to office-based phototherapy for PGA and DLQI in the overall population and across all SPTs. Home-based phototherapy, compared to office-based phototherapy, was associated with better treatment adherence (202 patients [51.4%] vs 62 patients [15.9%]; P < .001), lower burden of indirect costs to patients, and more episodes of persistent erythema (466 of 7957 treatments [5.9%] vs 46 of 3934 treatments [1.2%]; P < .001). Both treatments were well tolerated with no discontinuations due to adverse events.</p><p><strong>Conclusions and relevance: </strong>In this randomized clinical trial, home-based phototherapy was as effective as office-based phototherapy for plaque or guttate psoriasis in everyday clinical practice and had less burden to patients.</p><p><strong>Trial registration:","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":" ","pages":""},"PeriodicalIF":11.5,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11425190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142346994","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 : 2024-09-18DOI: 10.1001/jamadermatol.2024.3315
James J. Abbott, Angela J. Jiang, Rama Godse, Sarah Ahmed, Stephen C. Senft, Melissa A. Wilson, Justine V. Cohen, Tara C. Mitchell, Temitayo A. Ogunleye, H. William Higgins, Thuzar M. Shin, Christopher J. Miller, Jacquelyn J. Roth, Salvatore F. Priore, Leslie Castelo-Soccio, Rosalie Elenitsas, John T. Seykora, Katherine L. Nathanson, Emily Y. Chu
ImportanceGermline SUFU pathogenic variants (PVs) have previously been associated with basal cell nevus syndrome (BCNS) and multiple infundibulocystic basal cell carcinoma syndrome; however, a broader spectrum of cutaneous findings in patients with SUFU PVs has not been well delineated.ObjectiveTo define the clinical and histopathologic spectrum of cutaneous findings in patients with germline SUFU PVs.Design, Setting, and ParticipantsThis case series was conducted in multiple US academic dermatology, medical genetics, and medical oncology clinics between July 2014 and July 2022. The study included patients with confirmed germline SUFU PVs who were evaluated by a dermatologist. The analysis took place from March to September 2023.Main Outcomes and MeasuresHistopathologic evaluation of skin biopsies with or without immunohistochemical staining, and targeted next-generation sequencing (NGS) on tumor specimens.ResultsAll 5 patients were women. The mean (range) age at presentation was 50.2 (31-68) years, with skin manifestations initially appearing in the fourth to sixth decades of life. None had keratocystic odontogenic tumors. A total of 29 skin pathology specimens from the 5 patients were reviewed; of these, 3 (10.3%) were diagnosed as basaloid follicular hamartomas (BFHs), 10 (34.5%) classified as infundibulocystic basal cell carcinomas (iBCCs), 6 (20.7%) classified as nodular basal cell carcinomas (nBCCs), and 1 (3.4%) as infiltrative basal cell carcinoma (BCC). Targeted NGS studies on tumor specimens suggest that an increased number of UV-signature variants is associated with basal cell carcinomas compared with more indolent basaloid follicular hamartomas.Conclusions and RelevancePatients with germline SUFU PVs may present with multiple indolent basaloid neoplasms in addition to conventional basal cell carcinomas, typically appearing in the fourth to sixth decades of life. Although there are overlapping clinical manifestations, these findings help to differentiate the clinical syndrome associated with SUFU PVs from PTCH1 BCNS. Awareness of the clinicopathologic spectrum of SUFU-associated basaloid neoplasms is important for dermatologists and dermatopathologists because many (although not all) of these lesions are indolent and do not require aggressive surgical treatment. Importantly, because SUFU lies downstream of the protein smoothened, vismodegib and other smoothened inhibitors are unlikely to be effective therapies in this subset of patients.
{"title":"Inherited Basaloid Neoplasms Associated With SUFU Pathogenic Variants","authors":"James J. Abbott, Angela J. Jiang, Rama Godse, Sarah Ahmed, Stephen C. Senft, Melissa A. Wilson, Justine V. Cohen, Tara C. Mitchell, Temitayo A. Ogunleye, H. William Higgins, Thuzar M. Shin, Christopher J. Miller, Jacquelyn J. Roth, Salvatore F. Priore, Leslie Castelo-Soccio, Rosalie Elenitsas, John T. Seykora, Katherine L. Nathanson, Emily Y. Chu","doi":"10.1001/jamadermatol.2024.3315","DOIUrl":"https://doi.org/10.1001/jamadermatol.2024.3315","url":null,"abstract":"ImportanceGermline <jats:italic>SUFU</jats:italic> pathogenic variants (PVs) have previously been associated with basal cell nevus syndrome (BCNS) and multiple infundibulocystic basal cell carcinoma syndrome; however, a broader spectrum of cutaneous findings in patients with <jats:italic>SUFU</jats:italic> PVs has not been well delineated.ObjectiveTo define the clinical and histopathologic spectrum of cutaneous findings in patients with germline <jats:italic>SUFU</jats:italic> PVs.Design, Setting, and ParticipantsThis case series was conducted in multiple US academic dermatology, medical genetics, and medical oncology clinics between July 2014 and July 2022. The study included patients with confirmed germline <jats:italic>SUFU</jats:italic> PVs who were evaluated by a dermatologist. The analysis took place from March to September 2023.Main Outcomes and MeasuresHistopathologic evaluation of skin biopsies with or without immunohistochemical staining, and targeted next-generation sequencing (NGS) on tumor specimens.ResultsAll 5 patients were women. The mean (range) age at presentation was 50.2 (31-68) years, with skin manifestations initially appearing in the fourth to sixth decades of life. None had keratocystic odontogenic tumors. A total of 29 skin pathology specimens from the 5 patients were reviewed; of these, 3 (10.3%) were diagnosed as basaloid follicular hamartomas (BFHs), 10 (34.5%) classified as infundibulocystic basal cell carcinomas (iBCCs), 6 (20.7%) classified as nodular basal cell carcinomas (nBCCs), and 1 (3.4%) as infiltrative basal cell carcinoma (BCC). Targeted NGS studies on tumor specimens suggest that an increased number of UV-signature variants is associated with basal cell carcinomas compared with more indolent basaloid follicular hamartomas.Conclusions and RelevancePatients with germline <jats:italic>SUFU</jats:italic> PVs may present with multiple indolent basaloid neoplasms in addition to conventional basal cell carcinomas, typically appearing in the fourth to sixth decades of life. Although there are overlapping clinical manifestations, these findings help to differentiate the clinical syndrome associated with <jats:italic>SUFU</jats:italic> PVs from <jats:italic>PTCH1</jats:italic> BCNS. Awareness of the clinicopathologic spectrum of <jats:italic>SUFU</jats:italic>-associated basaloid neoplasms is important for dermatologists and dermatopathologists because many (although not all) of these lesions are indolent and do not require aggressive surgical treatment. Importantly, because SUFU lies downstream of the protein smoothened, vismodegib and other smoothened inhibitors are unlikely to be effective therapies in this subset of patients.","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":"14 1","pages":""},"PeriodicalIF":10.9,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249597","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 : 2024-09-18DOI: 10.1001/jamadermatol.2024.2722
Sierra Parkinson, Sabah Osmani, Paul B. Googe, Donna A. Culton
This case report describes a man in his 50s with a diffuse pruritic rash after initiating treatment with pembrolizumab and enfortumab vedotin for metastatic urothelial carcinoma.
{"title":"Treatment of Pembrolizumab-Induced Mucocutaneous Lichen Planus With Metronidazole","authors":"Sierra Parkinson, Sabah Osmani, Paul B. Googe, Donna A. Culton","doi":"10.1001/jamadermatol.2024.2722","DOIUrl":"https://doi.org/10.1001/jamadermatol.2024.2722","url":null,"abstract":"This case report describes a man in his 50s with a diffuse pruritic rash after initiating treatment with pembrolizumab and enfortumab vedotin for metastatic urothelial carcinoma.","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":"10 1","pages":""},"PeriodicalIF":10.9,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249598","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 : 2024-09-18DOI: 10.1001/jamadermatol.2024.3121
Eric L. Simpson, Lawrence F. Eichenfield, Javier Alonso-Llamazares, Zoe D. Draelos, Laura K. Ferris, Seth B. Forman, Melinda Gooderham, Mercedes E. Gonzalez, Adelaide A. Hebert, Leon H. Kircik, Mark Lomaga, Angela Moore, Kim A. Papp, Vimal H. Prajapati, Diane Hanna, Scott Snyder, David Krupa, Patrick Burnett, Erin Almaraz, Robert C. Higham, David H. Chu, David R. Berk
ImportanceSafe, effective, and well-tolerated topical treatment options available for long-term use in patients with atopic dermatitis (AD) are limited and associated with low adherence rates.ObjectiveTo evaluate efficacy and safety of once-daily roflumilast cream, 0.15%, vs vehicle cream in patients with AD.Design, Setting, and ParticipantsTwo phase 3, randomized, double-blind, vehicle-controlled trials (Interventional Trial Evaluating Roflumilast Cream for the Treatment of Atopic Dermatitis 1 and 2 [INTEGUMENT-1 and INTEGUMENT-2]), included patients from sites in the US, Canada, and Poland. Participants were 6 years or older with mild to moderate AD based on Validated Global Assessment for Atopic Dermatitis (assessed on a 5-point scale ranging from 0 [clear] to 4 [severe]).InterventionPatients were randomized 2:1 to receive roflumilast cream, 0.15%, or vehicle cream once daily for 4 weeks.Main Outcomes and MeasuresThe primary efficacy end point was Validated Investigator Global Assessment for Atopic Dermatitis success at week 4, defined as a score of 0 or 1 plus at least a 2-grade improvement from baseline. Secondary end points included Eczema Area and Severity Index and Worst Itch Numeric Rating Scale. Safety and local tolerability were also evaluated.ResultsAmong 1337 patients (654 patients in INTEGUMENT-1 and 683 patients in INTEGUMENT-2), the mean (SD) age was 27.7 (19.2) years, and 761 participants (56.9%) were female. The mean body surface area involved was 13.6% (SD = 11.6%; range, 3.0% to 88.0%). Significantly more patients treated with roflumilast than vehicle achieved the primary end point (INTEGUMENT-1: 32.0% vs 15.2%, respectively; <jats:italic>P</jats:italic> &lt; .001; INTEGUMENT-2: 28.9% vs 12.0%, respectively; <jats:italic>P</jats:italic> &lt; .001). At week 4, statistically significant differences favoring roflumilast also occurred for the achievement of at least 75% reduction in the Eczema Area and Severity Index (INTEGUMENT-1: 43.2% vs 22.0%, respectively; <jats:italic>P</jats:italic> &lt; .001; INTEGUMENT-2: 42.0% vs 19.7%, respectively; <jats:italic>P</jats:italic> &lt; .001). Roflumilast was well tolerated with low rates of treatment-emergent adverse events. At each time point, investigators noted no signs of irritation at the application site in 885 patients who were treated with roflumilast (≥95%), and 885 patients who were treated with roflumilast (90%) reported no or mild sensation at the application site.Conclusions and RelevanceIn 2 phase 3 trials enrolling adults and children, once-daily roflumilast cream, 0.15%, improved AD relative to vehicle cream, based on multiple efficacy end points, with favorable safety and tolerability.Trial RegistrationClinicalTrials.gov Identifiers: <jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://clinicaltrials.gov/study/NCT04773587?id=NCT04773587&amp;rank=1">NCT04773587</jats:ext-link>, <jats:ext-li
重要性可供特应性皮炎（AD）患者长期使用的安全、有效且耐受性良好的局部治疗方案有限，且依从性较低。目的评估每日一次 0.15%罗氟司特乳膏与载体乳膏在特应性皮炎患者中的疗效和安全性。两项三期随机、双盲、载药对照试验（评价罗氟司特乳膏治疗特应性皮炎的干预试验 1 和 2 [INTEGUMENT-1 和 INTEGUMENT-2]）纳入了来自美国、加拿大和波兰研究机构的患者。主要结果和测量指标主要疗效终点是第4周时特应性皮炎研究者全球评估验证成功，即得分为0或1分，且与基线相比至少改善了2个等级。次要终点包括湿疹面积和严重程度指数以及最严重瘙痒数字评分表。结果1337名患者（654名患者接受了INTEGUMENT-1治疗，683名患者接受了INTEGUMENT-2治疗）中，平均（标清）年龄为27.7（19.2）岁，761名参与者（56.9%）为女性。涉及的平均体表面积为 13.6%（标清 = 11.6%；范围为 3.0% 至 88.0%）。达到主要终点的罗氟司特患者明显多于药物治疗患者（INTEGUMENT-1：分别为 32.0% vs 15.2%；P &p;amp;lt; .001；INTEGUMENT-2：分别为 28.9% vs 12.0%；P &p;amp;lt; .001）。第4周时，在湿疹面积和严重程度指数至少减少75%方面，罗氟司特也有显著的统计学差异（INTEGUMENT-1：43.2% vs 22.0%；P&p;amp;amp;lt; .001；INTEGUMENT-2：42.0% vs 19.7%；P&p;amp;amp;lt; .001）。罗氟司特的耐受性良好，治疗中出现的不良反应较少。在每个时间点，研究人员注意到885名接受罗氟司特治疗的患者（≥95%）的用药部位没有刺激症状，885名接受罗氟司特治疗的患者（90%）的用药部位没有感觉或感觉轻微。结论和相关性在2项纳入成人和儿童的3期试验中，根据多个疗效终点，每日一次的0.15%罗氟司特乳膏相对于载体乳膏可改善AD，同时具有良好的安全性和耐受性：NCT04773587, NCT04773600
{"title":"Roflumilast Cream, 0.15%, for Atopic Dermatitis in Adults and Children","authors":"Eric L. Simpson, Lawrence F. Eichenfield, Javier Alonso-Llamazares, Zoe D. Draelos, Laura K. Ferris, Seth B. Forman, Melinda Gooderham, Mercedes E. Gonzalez, Adelaide A. Hebert, Leon H. Kircik, Mark Lomaga, Angela Moore, Kim A. Papp, Vimal H. Prajapati, Diane Hanna, Scott Snyder, David Krupa, Patrick Burnett, Erin Almaraz, Robert C. Higham, David H. Chu, David R. Berk","doi":"10.1001/jamadermatol.2024.3121","DOIUrl":"https://doi.org/10.1001/jamadermatol.2024.3121","url":null,"abstract":"ImportanceSafe, effective, and well-tolerated topical treatment options available for long-term use in patients with atopic dermatitis (AD) are limited and associated with low adherence rates.ObjectiveTo evaluate efficacy and safety of once-daily roflumilast cream, 0.15%, vs vehicle cream in patients with AD.Design, Setting, and ParticipantsTwo phase 3, randomized, double-blind, vehicle-controlled trials (Interventional Trial Evaluating Roflumilast Cream for the Treatment of Atopic Dermatitis 1 and 2 [INTEGUMENT-1 and INTEGUMENT-2]), included patients from sites in the US, Canada, and Poland. Participants were 6 years or older with mild to moderate AD based on Validated Global Assessment for Atopic Dermatitis (assessed on a 5-point scale ranging from 0 [clear] to 4 [severe]).InterventionPatients were randomized 2:1 to receive roflumilast cream, 0.15%, or vehicle cream once daily for 4 weeks.Main Outcomes and MeasuresThe primary efficacy end point was Validated Investigator Global Assessment for Atopic Dermatitis success at week 4, defined as a score of 0 or 1 plus at least a 2-grade improvement from baseline. Secondary end points included Eczema Area and Severity Index and Worst Itch Numeric Rating Scale. Safety and local tolerability were also evaluated.ResultsAmong 1337 patients (654 patients in INTEGUMENT-1 and 683 patients in INTEGUMENT-2), the mean (SD) age was 27.7 (19.2) years, and 761 participants (56.9%) were female. The mean body surface area involved was 13.6% (SD = 11.6%; range, 3.0% to 88.0%). Significantly more patients treated with roflumilast than vehicle achieved the primary end point (INTEGUMENT-1: 32.0% vs 15.2%, respectively; <jats:italic>P</jats:italic> &amp;lt; .001; INTEGUMENT-2: 28.9% vs 12.0%, respectively; <jats:italic>P</jats:italic> &amp;lt; .001). At week 4, statistically significant differences favoring roflumilast also occurred for the achievement of at least 75% reduction in the Eczema Area and Severity Index (INTEGUMENT-1: 43.2% vs 22.0%, respectively; <jats:italic>P</jats:italic> &amp;lt; .001; INTEGUMENT-2: 42.0% vs 19.7%, respectively; <jats:italic>P</jats:italic> &amp;lt; .001). Roflumilast was well tolerated with low rates of treatment-emergent adverse events. At each time point, investigators noted no signs of irritation at the application site in 885 patients who were treated with roflumilast (≥95%), and 885 patients who were treated with roflumilast (90%) reported no or mild sensation at the application site.Conclusions and RelevanceIn 2 phase 3 trials enrolling adults and children, once-daily roflumilast cream, 0.15%, improved AD relative to vehicle cream, based on multiple efficacy end points, with favorable safety and tolerability.Trial RegistrationClinicalTrials.gov Identifiers: <jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"uri\" xlink:href=\"https://clinicaltrials.gov/study/NCT04773587?id=NCT04773587&amp;amp;rank=1\">NCT04773587</jats:ext-link>, <jats:ext-li","PeriodicalId":14734,"journal":{"name":"JAMA dermatology","volume":"16 1","pages":""},"PeriodicalIF":10.9,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142249652","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}
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