{"title":"Proposing GLMN, encoding glomulin, as a novel gene for Dowling-Degos disease.","authors":"Sheetal Kumar, Regina C Betz, Jorge Frank","doi":"10.1093/bjd/ljae418","DOIUrl":"https://doi.org/10.1093/bjd/ljae418","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":null,"pages":null},"PeriodicalIF":11.0,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495470","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}
Jonathan I Silverberg, Christopher G Bunick, H Chih-Ho Hong, Pedro Mendes-Bastos, Linda Stein Gold, Antonio Costanzo, Nadia Ibrahim, Cristina Sancho, Xiaoqiang Wu, Yu Han, Gweneth Levy, Kathy Altman, Brian Calimlim, Kilian Eyerich
Background: Atopic dermatitis (AD) is a chronic skin disease characterized by intense itch and eczematous skin lesions. Some patients continue to experience flares and substantial clinical burden despite ongoing systemic treatment.
Objectives: This study assessed the efficacy and safety of once-daily upadacitinib (UPA), initiated at 15 mg and dose-escalated to 30 mg based on clinical response, compared with dupilumab (DUPI) per its label. Week 16 primary analysis results are presented.
Methods: Level Up is a phase 3b/4 global, randomized, open-label, efficacy assessor blinded study evaluating UPA vs DUPI in adolescents and adults with moderate-to-severe AD who had inadequate response to systemic therapy or when use was inadvisable. Patients were randomized to UPA or DUPI for 16 weeks of treatment (Period 1). Patients on UPA started on 15 mg and were dose-escalated to 30 mg if they did not achieve an Eczema Area and Severity Index reduction of at least 50% (EASI 50) or a ≥4-point Worst Pruritus Numerical Rating Scale (WP-NRS) improvement on/after Week 4, or EASI 75 on/after Week 8. The primary endpoint was simultaneous achievement of EASI 90 and WP-NRS 0/1 at Week 16. Ranked secondary endpoints included skin and itch responses at varying response levels and timepoints. Safety measures were assessed throughout the study.
Results: Superior efficacy in achieving simultaneous EASI 90 and WP-NRS 0/1 response at Week 16 was demonstrated with UPA vs DUPI (19.9% vs 8.9%, respectively; p<0.0001). UPA showed superiority vs DUPI for all ranked secondary endpoints, with post-hoc analyses exhibiting higher itch response rates as early as Day 2. No new safety signals were identified during this period.
Conclusion: Treatment of moderate-to-severe AD with UPA, initiated at 15 mg and dose escalated based on clinical response, demonstrated superiority vs DUPI per its label for the primary endpoint of simultaneous achievement of near complete skin clearance (EASI 90) and little to no itch (WP-NRS 0/1) at Week 16, with all ranked secondary endpoints demonstrating superiority at varying skin and itch response levels and timepoints. There were no new safety signals identified compared to the previously reported safety profiles of UPA and DUPI.
{"title":"Efficacy and Safety of Upadacitinib vs Dupilumab in Adults and Adolescents with Moderate-to-Severe Atopic Dermatitis: Week 16 results of an Open-label, Randomized, Efficacy Assessor-Blinded Head-to-Head Phase 3b/4 Study (Level Up).","authors":"Jonathan I Silverberg, Christopher G Bunick, H Chih-Ho Hong, Pedro Mendes-Bastos, Linda Stein Gold, Antonio Costanzo, Nadia Ibrahim, Cristina Sancho, Xiaoqiang Wu, Yu Han, Gweneth Levy, Kathy Altman, Brian Calimlim, Kilian Eyerich","doi":"10.1093/bjd/ljae404","DOIUrl":"https://doi.org/10.1093/bjd/ljae404","url":null,"abstract":"<p><strong>Background: </strong>Atopic dermatitis (AD) is a chronic skin disease characterized by intense itch and eczematous skin lesions. Some patients continue to experience flares and substantial clinical burden despite ongoing systemic treatment.</p><p><strong>Objectives: </strong>This study assessed the efficacy and safety of once-daily upadacitinib (UPA), initiated at 15 mg and dose-escalated to 30 mg based on clinical response, compared with dupilumab (DUPI) per its label. Week 16 primary analysis results are presented.</p><p><strong>Methods: </strong>Level Up is a phase 3b/4 global, randomized, open-label, efficacy assessor blinded study evaluating UPA vs DUPI in adolescents and adults with moderate-to-severe AD who had inadequate response to systemic therapy or when use was inadvisable. Patients were randomized to UPA or DUPI for 16 weeks of treatment (Period 1). Patients on UPA started on 15 mg and were dose-escalated to 30 mg if they did not achieve an Eczema Area and Severity Index reduction of at least 50% (EASI 50) or a ≥4-point Worst Pruritus Numerical Rating Scale (WP-NRS) improvement on/after Week 4, or EASI 75 on/after Week 8. The primary endpoint was simultaneous achievement of EASI 90 and WP-NRS 0/1 at Week 16. Ranked secondary endpoints included skin and itch responses at varying response levels and timepoints. Safety measures were assessed throughout the study.</p><p><strong>Results: </strong>Superior efficacy in achieving simultaneous EASI 90 and WP-NRS 0/1 response at Week 16 was demonstrated with UPA vs DUPI (19.9% vs 8.9%, respectively; p<0.0001). UPA showed superiority vs DUPI for all ranked secondary endpoints, with post-hoc analyses exhibiting higher itch response rates as early as Day 2. No new safety signals were identified during this period.</p><p><strong>Conclusion: </strong>Treatment of moderate-to-severe AD with UPA, initiated at 15 mg and dose escalated based on clinical response, demonstrated superiority vs DUPI per its label for the primary endpoint of simultaneous achievement of near complete skin clearance (EASI 90) and little to no itch (WP-NRS 0/1) at Week 16, with all ranked secondary endpoints demonstrating superiority at varying skin and itch response levels and timepoints. There were no new safety signals identified compared to the previously reported safety profiles of UPA and DUPI.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":null,"pages":null},"PeriodicalIF":11.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Primary cutaneous Alternaria alstroemeriae infection.","authors":"Ximing Yang, Li Li, Min Zhu","doi":"10.1093/bjd/ljae409","DOIUrl":"https://doi.org/10.1093/bjd/ljae409","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":null,"pages":null},"PeriodicalIF":11.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495469","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}
Erin McGillivray, Karam Ashouri, Eftychia Chatziioannou, Jesús Antonio Ocejo Gallegos, Jabra Zarka, Jacob Kechter, Angelina S Hwang, Kevin Zhang, Milton Barros, Justin Yeh, Ian Okazaki, Andrew B Crocker, Takuya Maeda, Soo J Park, Jacob Choi, Mia Andreoli, Tarneem Darwish, David J Savage, Kevin B Kim, Jayant Gupta, James Shen, Keisuke Shirai, April Choi, Lori Pai, Vinicius de Lima Vazquez, Justin Moser, Teresa Amaral, Leonel F Hernandez Aya, Jose Lutzky, Yana G Najjar, Collin M Costello, Aaron R Mangold, Shailender Bhatia, Geoffrey T Gibney, Jeffrey M Farma, Gregory A Daniels, Jeffrey Sosman, Sunandana Chandra, Ankit Mangla, Kathryn Bollin, Patrícia Abrão Possik, Carla Daniela Robles Espinoza, Fumito Ito, Gino K In
Background: Combination immune checkpoint blockade targeting PD-1 and CTLA-4 leads to high response rates and improved survival in advanced cutaneous melanoma (CM). Less is known about the efficacy of this combination in acral lentiginous melanoma (ALM).
Objectives: To determine the efficacy of combination immune checkpoint blockade targeting PD-1 and CTLA-4 in a real-world, diverse population of ALM.
Methods: This multi-institutional retrospective study analyzed patients with histologically confirmed ALM treated with the combination of PD-1 and CTLA-4 inhibitors between 2010-2022. The primary objective of the study was objective response rate (ORR) per RECIST criteria. The secondary objectives were progression-free survival (PFS) and overall survival (OS).
Results: In total, 109 patients with advanced ALM treated with combined PD-1 and CTLA-4 blockade in any line of treatment were included. The majority of patients had stage IV disease (n=81, 74.2%). The ORR for the entire cohort was 18.3% (95% CI 11.6-26.9%), with 9 (8.3%) complete responses (CR) and 11 (10.1%) partial responses (PR). An additional 22 patients (20.2%) had stable disease (SD), and the disease control rate (DCR) was 38.5%. The median PFS was 4.2 months [95% CI 3.25-5.62], while the median OS was 17 months [95% CI 12.4%-23.1%]. A total of 95 patients (87.2%) had a treatment-related adverse event, with 40.4% (n=44/109) experiencing at least one grade 3 or 4 toxicity. Elevated LDH (p=.04), 2+ lines of prior therapy (p=.03), and Asian race/ethnicity (p=.04) were associated with worse OS, while Hispanic/Latino race/ethnicity was associated with better OS (p=.02).
Conclusions: Combination of PD-1 and CTLA-4 blockade is less effective for ALM, as compared to CM, despite similar toxicity. Asian patients, in particular, appear to derive lower benefit from this regimen. Novel treatment approaches are needed for this rare melanoma subtype.
背景:以PD-1和CTLA-4为靶点的联合免疫检查点阻断疗法可提高晚期皮肤黑色素瘤(CM)的应答率和生存率。但这种联合疗法在尖状扁平苔藓黑色素瘤(ALM)中的疗效却鲜为人知:目的:确定针对 PD-1 和 CTLA-4 的联合免疫检查点阻断疗法在现实世界中不同 ALM 群体中的疗效:这项多机构回顾性研究分析了2010-2022年间接受PD-1和CTLA-4抑制剂联合治疗的组织学确诊ALM患者。研究的首要目标是根据RECIST标准得出的客观反应率(ORR)。次要目标是无进展生存期(PFS)和总生存期(OS):研究共纳入109例接受PD-1和CTLA-4联合阻断治疗的晚期ALM患者。大多数患者为IV期疾病(81例,74.2%)。整个队列的ORR为18.3%(95% CI 11.6-26.9%),其中9例(8.3%)完全应答(CR),11例(10.1%)部分应答(PR)。另有22名患者(20.2%)病情稳定(SD),疾病控制率(DCR)为38.5%。中位 PFS 为 4.2 个月 [95% CI 3.25-5.62],中位 OS 为 17 个月 [95% CI 12.4%-23.1%]。共有 95 名患者(87.2%)出现了治疗相关的不良事件,其中 40.4% 的患者(n=44/109)至少出现过一次 3 级或 4 级毒性反应。LDH升高(p=.04)、既往治疗2线以上(p=.03)和亚洲人种/种族(p=.04)与较差的OS相关,而西班牙/拉美人种/种族与较好的OS相关(p=.02):结论:尽管毒性相似,但PD-1和CTLA-4联合阻断疗法对ALM的疗效不如CM。尤其是亚洲患者,似乎从这一疗法中获益较少。这种罕见的黑色素瘤亚型需要新的治疗方法。
{"title":"Combined PD-1 and CTLA-4 Blockade in an International Cohort of Patients with Acral Lentiginous Melanoma.","authors":"Erin McGillivray, Karam Ashouri, Eftychia Chatziioannou, Jesús Antonio Ocejo Gallegos, Jabra Zarka, Jacob Kechter, Angelina S Hwang, Kevin Zhang, Milton Barros, Justin Yeh, Ian Okazaki, Andrew B Crocker, Takuya Maeda, Soo J Park, Jacob Choi, Mia Andreoli, Tarneem Darwish, David J Savage, Kevin B Kim, Jayant Gupta, James Shen, Keisuke Shirai, April Choi, Lori Pai, Vinicius de Lima Vazquez, Justin Moser, Teresa Amaral, Leonel F Hernandez Aya, Jose Lutzky, Yana G Najjar, Collin M Costello, Aaron R Mangold, Shailender Bhatia, Geoffrey T Gibney, Jeffrey M Farma, Gregory A Daniels, Jeffrey Sosman, Sunandana Chandra, Ankit Mangla, Kathryn Bollin, Patrícia Abrão Possik, Carla Daniela Robles Espinoza, Fumito Ito, Gino K In","doi":"10.1093/bjd/ljae401","DOIUrl":"https://doi.org/10.1093/bjd/ljae401","url":null,"abstract":"<p><strong>Background: </strong>Combination immune checkpoint blockade targeting PD-1 and CTLA-4 leads to high response rates and improved survival in advanced cutaneous melanoma (CM). Less is known about the efficacy of this combination in acral lentiginous melanoma (ALM).</p><p><strong>Objectives: </strong>To determine the efficacy of combination immune checkpoint blockade targeting PD-1 and CTLA-4 in a real-world, diverse population of ALM.</p><p><strong>Methods: </strong>This multi-institutional retrospective study analyzed patients with histologically confirmed ALM treated with the combination of PD-1 and CTLA-4 inhibitors between 2010-2022. The primary objective of the study was objective response rate (ORR) per RECIST criteria. The secondary objectives were progression-free survival (PFS) and overall survival (OS).</p><p><strong>Results: </strong>In total, 109 patients with advanced ALM treated with combined PD-1 and CTLA-4 blockade in any line of treatment were included. The majority of patients had stage IV disease (n=81, 74.2%). The ORR for the entire cohort was 18.3% (95% CI 11.6-26.9%), with 9 (8.3%) complete responses (CR) and 11 (10.1%) partial responses (PR). An additional 22 patients (20.2%) had stable disease (SD), and the disease control rate (DCR) was 38.5%. The median PFS was 4.2 months [95% CI 3.25-5.62], while the median OS was 17 months [95% CI 12.4%-23.1%]. A total of 95 patients (87.2%) had a treatment-related adverse event, with 40.4% (n=44/109) experiencing at least one grade 3 or 4 toxicity. Elevated LDH (p=.04), 2+ lines of prior therapy (p=.03), and Asian race/ethnicity (p=.04) were associated with worse OS, while Hispanic/Latino race/ethnicity was associated with better OS (p=.02).</p><p><strong>Conclusions: </strong>Combination of PD-1 and CTLA-4 blockade is less effective for ALM, as compared to CM, despite similar toxicity. Asian patients, in particular, appear to derive lower benefit from this regimen. Novel treatment approaches are needed for this rare melanoma subtype.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":null,"pages":null},"PeriodicalIF":11.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495461","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}
Andrew Blauvelt, Kim Papp, Mona Trivedi, Carolina Barragan, Vincent Chow, Daniel T Mytych, Paul Yamauchi, Jeff Crowley, Janet Franklin
Background: ABP 654 is a biosimilar to ustekinumab reference product (RP). ABP 654 has been shown to have an amino acid sequence identical to ustekinumab RP and they are similar in structure, purity, and potency as well as clinical pharmacokinetics and safety in healthy volunteers.
Objectives: This randomized, double-blinded, active-controlled, single-transition, comparative clinical study (ClinicalTrials.gov ID NCT04607980) was conducted to compare the efficacy, safety, and immunogenicity of ABP 654 and ustekinumab RP in patients with moderate-to-severe plaque psoriasis.
Methods: Patients were randomized in a 1:1 ratio to receive ABP 654 or ustekinumab RP at a weight-based dose of 45 mg or 90 mg administered subcutaneously on day 1 (week 0), week 4, and week 16. At week 28, patients with a ≥75% improvement in Psoriasis Area and Severity Index (PASI) were re-randomized such that those initially randomized to ABP 654 continued to receive ABP 654 and those initially randomized to ustekinumab RP were re-randomized to either continue on ustekinumab RP or transition to ABP 654. The primary efficacy endpoint was PASI percent improvement from baseline to week 12. Secondary endpoints included additional efficacy measurements as well as an assessment of adverse events and antidrug antibodies.
Results: At week 12, the observed mean (SD) PASI percent improvement from baseline was 81.9 (19.9) and 81.9 (19.6) for the ABP 654 and ustekinumab RP treatment groups, respectively. The point estimate of the mean difference in PASI percent improvement from baseline to week 12 between the treatment groups was 0.14 with a 2-sided 90% confidence interval (CI) of (-2.6, 2.9), well within the prespecified similarity margin of (-10, +10). In addition, throughout the study, secondary efficacy analyses and safety and immunogenicity profiles were similar across the treatment groups.
Conclusions: These results indicate that ABP 654 and ustekinumab RP are clinically similar in efficacy, safety, and immunogenicity in patients with moderate-to-severe plaque psoriasis. Further, a single transition from ustekinumab RP to ABP 654 at week 28 had no impact on the efficacy, safety, or immunogenicity results for the remainder of the 52-week study, supporting a conclusion of no clinically meaningful differences between ABP 654 and ustekinumab RP.
背景:ABP 654 是乌司替尼参考品(RP)的生物类似药。ABP 654 与乌司他珠单抗 RP 的氨基酸序列完全相同,两者在结构、纯度、药效、临床药代动力学和健康志愿者的安全性方面均相似:这项随机、双盲、主动对照、单次转换的比较性临床研究(ClinicalTrials.gov ID NCT04607980)旨在比较ABP 654和乌司替尼RP在中重度斑块状银屑病患者中的疗效、安全性和免疫原性:患者按1:1的比例随机接受ABP 654或乌斯特库单抗RP治疗,剂量基于体重,分别为45毫克或90毫克,于第1天(第0周)、第4周和第16周皮下注射。第28周时,对银屑病面积和严重程度指数(PASI)改善≥75%的患者进行重新随机分组,最初随机分组为ABP 654的患者继续接受ABP 654治疗,最初随机分组为乌司替尼RP的患者重新随机分组,要么继续接受乌司替尼RP治疗,要么转为ABP 654治疗。主要疗效终点是从基线到第12周的PASI改善百分比。次要终点包括其他疗效测量以及不良事件和抗药抗体评估:第12周时,观察到ABP 654治疗组和乌司替尼RP治疗组的PASI改善百分比与基线相比的平均值(标度)分别为81.9(19.9)和81.9(19.6)。治疗组之间从基线到第12周的PASI改善百分比的平均差异点估计值为0.14,双侧90%置信区间(CI)为(-2.6,2.9),远在预设的相似度范围(-10,+10)之内。此外,在整个研究过程中,各治疗组的次要疗效分析以及安全性和免疫原性概况均相似:这些结果表明,对于中重度斑块状银屑病患者,ABP 654 和乌司替尼 RP 在疗效、安全性和免疫原性方面具有临床相似性。此外,在第28周从ustekinumab RP过渡到ABP 654对52周研究剩余时间的疗效、安全性或免疫原性结果没有影响,支持ABP 654和ustekinumab RP之间没有临床意义差异的结论。
{"title":"Efficacy and safety of the ustekinumab biosimilar ABP 654 in patients with moderate-to-severe plaque psoriasis: a randomized, double-blinded, active-controlled, comparative clinical study over 52 weeks.","authors":"Andrew Blauvelt, Kim Papp, Mona Trivedi, Carolina Barragan, Vincent Chow, Daniel T Mytych, Paul Yamauchi, Jeff Crowley, Janet Franklin","doi":"10.1093/bjd/ljae402","DOIUrl":"https://doi.org/10.1093/bjd/ljae402","url":null,"abstract":"<p><strong>Background: </strong>ABP 654 is a biosimilar to ustekinumab reference product (RP). ABP 654 has been shown to have an amino acid sequence identical to ustekinumab RP and they are similar in structure, purity, and potency as well as clinical pharmacokinetics and safety in healthy volunteers.</p><p><strong>Objectives: </strong>This randomized, double-blinded, active-controlled, single-transition, comparative clinical study (ClinicalTrials.gov ID NCT04607980) was conducted to compare the efficacy, safety, and immunogenicity of ABP 654 and ustekinumab RP in patients with moderate-to-severe plaque psoriasis.</p><p><strong>Methods: </strong>Patients were randomized in a 1:1 ratio to receive ABP 654 or ustekinumab RP at a weight-based dose of 45 mg or 90 mg administered subcutaneously on day 1 (week 0), week 4, and week 16. At week 28, patients with a ≥75% improvement in Psoriasis Area and Severity Index (PASI) were re-randomized such that those initially randomized to ABP 654 continued to receive ABP 654 and those initially randomized to ustekinumab RP were re-randomized to either continue on ustekinumab RP or transition to ABP 654. The primary efficacy endpoint was PASI percent improvement from baseline to week 12. Secondary endpoints included additional efficacy measurements as well as an assessment of adverse events and antidrug antibodies.</p><p><strong>Results: </strong>At week 12, the observed mean (SD) PASI percent improvement from baseline was 81.9 (19.9) and 81.9 (19.6) for the ABP 654 and ustekinumab RP treatment groups, respectively. The point estimate of the mean difference in PASI percent improvement from baseline to week 12 between the treatment groups was 0.14 with a 2-sided 90% confidence interval (CI) of (-2.6, 2.9), well within the prespecified similarity margin of (-10, +10). In addition, throughout the study, secondary efficacy analyses and safety and immunogenicity profiles were similar across the treatment groups.</p><p><strong>Conclusions: </strong>These results indicate that ABP 654 and ustekinumab RP are clinically similar in efficacy, safety, and immunogenicity in patients with moderate-to-severe plaque psoriasis. Further, a single transition from ustekinumab RP to ABP 654 at week 28 had no impact on the efficacy, safety, or immunogenicity results for the remainder of the 52-week study, supporting a conclusion of no clinically meaningful differences between ABP 654 and ustekinumab RP.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":null,"pages":null},"PeriodicalIF":11.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495463","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}
Background: Moderate-to-severe atopic dermatitis (AD) impacts patients' quality of life (QOL). More treatment options are urgently needed to manage this chronic disease. Lebrikizumab is a monoclonal antibody that binds to IL-13, a key mediator in AD pathogenesis. In Japanese patients, lebrikizumab has been evaluated through week (W) 16 in the randomized, placebo-controlled, phase III ADhere-J study.
Objectives: To evaluate long-term efficacy and safety of lebrikizumab in combination with topical corticosteroids (TCS) in the ADhere-J study.
Methods: Patients aged ≥12 years and weighing ≥40 kg with moderate-to-severe AD, and receiving either subcutaneous lebrikizumab 250 mg every 2 weeks (Q2W)/every 4 weeks (Q4W) or placebo during the 16-week induction period, were evaluated during the long-term maintenance period from W16 to W68. Responders achieved co-primary endpoints at W16: Investigator's Global Assessment score of 0 or 1 (IGA [0,1]) with ≥2-point improvement from baseline, and/or ≥75% improvement from baseline in Eczema Area and Severity Index (EASI 75). In this analysis, W16 responders received lebrikizumab 250 mg Q2W or Q4W combined with TCS during the maintenance period (maintenance primary population; MPP); W16 per-protocol nonresponders received lebrikizumab Q2W with TCS (maintenance escape population; MEP). Major endpoints included IGA (0,1) with ≥2-point improvement from baseline and EASI 75 through W68. Other outcomes included QOL, itch, and serum thymus and activation-regulated chemokine.
Results: At W68, 66-81% of 103 patients in the MPP and 32-38% of 168 patients in the MEP achieved IGA (0,1) with ≥2-point improvement from baseline. EASI 75 was maintained by 83-89% of patients in the MPP, while 71-80% of patients in the MEP achieved this outcome by W68. Across treatment arms, patients in the MPP tended to maintain improvements recorded at W16, while patients in the MEP steadily improved across the maintenance period. No new safety signals were reported, and most treatment-emergent adverse events were mild or moderate in severity in both populations. Safety outcomes were consistent with previous reports for lebrikizumab treatment in global studies.
Conclusions: These results support the use of lebrikizumab in combination with TCS for moderate-to-severe AD in the Japanese population over the long term.
{"title":"Long-term management of moderate-to-severe atopic dermatitis with lebrikizumab and concomitant topical corticosteroids: a 68-week, randomized, double-blind, placebo-controlled phase III trial in Japan (ADhere-J).","authors":"Norito Katoh, Akio Tanaka, Hidetoshi Takahashi, Ryosuke Shimizu, Yoko Kataoka, Hitoe Torisu-Itakura, Yoji Morisaki, Chie Yamamoto, Ken Igawa","doi":"10.1093/bjd/ljae394","DOIUrl":"https://doi.org/10.1093/bjd/ljae394","url":null,"abstract":"<p><strong>Background: </strong>Moderate-to-severe atopic dermatitis (AD) impacts patients' quality of life (QOL). More treatment options are urgently needed to manage this chronic disease. Lebrikizumab is a monoclonal antibody that binds to IL-13, a key mediator in AD pathogenesis. In Japanese patients, lebrikizumab has been evaluated through week (W) 16 in the randomized, placebo-controlled, phase III ADhere-J study.</p><p><strong>Objectives: </strong>To evaluate long-term efficacy and safety of lebrikizumab in combination with topical corticosteroids (TCS) in the ADhere-J study.</p><p><strong>Methods: </strong>Patients aged ≥12 years and weighing ≥40 kg with moderate-to-severe AD, and receiving either subcutaneous lebrikizumab 250 mg every 2 weeks (Q2W)/every 4 weeks (Q4W) or placebo during the 16-week induction period, were evaluated during the long-term maintenance period from W16 to W68. Responders achieved co-primary endpoints at W16: Investigator's Global Assessment score of 0 or 1 (IGA [0,1]) with ≥2-point improvement from baseline, and/or ≥75% improvement from baseline in Eczema Area and Severity Index (EASI 75). In this analysis, W16 responders received lebrikizumab 250 mg Q2W or Q4W combined with TCS during the maintenance period (maintenance primary population; MPP); W16 per-protocol nonresponders received lebrikizumab Q2W with TCS (maintenance escape population; MEP). Major endpoints included IGA (0,1) with ≥2-point improvement from baseline and EASI 75 through W68. Other outcomes included QOL, itch, and serum thymus and activation-regulated chemokine.</p><p><strong>Results: </strong>At W68, 66-81% of 103 patients in the MPP and 32-38% of 168 patients in the MEP achieved IGA (0,1) with ≥2-point improvement from baseline. EASI 75 was maintained by 83-89% of patients in the MPP, while 71-80% of patients in the MEP achieved this outcome by W68. Across treatment arms, patients in the MPP tended to maintain improvements recorded at W16, while patients in the MEP steadily improved across the maintenance period. No new safety signals were reported, and most treatment-emergent adverse events were mild or moderate in severity in both populations. Safety outcomes were consistent with previous reports for lebrikizumab treatment in global studies.</p><p><strong>Conclusions: </strong>These results support the use of lebrikizumab in combination with TCS for moderate-to-severe AD in the Japanese population over the long term.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov (NCT04760314).</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":null,"pages":null},"PeriodicalIF":11.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495467","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}
Background: Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in the United States, European Union, Japan, South Korea, China, and other countries for treatment of moderate-to-severe plaque psoriasis.
Objective: To evaluate the efficacy and safety of deucravacitinib in Asian patients with moderate to severe plaque psoriasis.
Methods: In the 52-week, blinded, phase 3 POETYK PSO-3 trial (NCT04167462), patients were randomized 1 : 2 to placebo (n = 74) or deucravacitinib 6 mg once daily (n = 146) for 16 weeks followed by deucravacitinib alone. Coprimary endpoints were achievement of ≥ 75% reduction from baseline in Psoriasis Area and Severity Index (PASI 75) and static Physician Global Assessment score of 0 (clear) or 1 (almost clear) (sPGA 0/1) at Week 16. Efficacy and safety were evaluated throughout.
Results: At Week 16, significantly higher proportions of patients receiving deucravacitinib versus placebo achieved PASI 75 (68.8% vs. 8.1%; P < 0.0001) and sPGA 0/1 (55.6% vs. 6.8%; P < 0.0001). Response rates with deucravacitinib were maintained through Week 52. Common adverse events included upper respiratory tract infection and nasopharyngitis. Serious adverse event and discontinuation rates were low.
Conclusions: Deucravacitinib was efficacious and well tolerated in Asian patients with moderate to severe plaque psoriasis.
背景:德拉瓦替尼是一种口服、选择性、异位酪氨酸激酶2抑制剂,已在美国、欧盟、日本、韩国、中国和其他国家获批用于治疗中重度斑块状银屑病:评估德拉瓦替尼在亚洲中重度斑块状银屑病患者中的疗效和安全性:在为期52周的POETYK PSO-3盲法3期试验(NCT04167462)中,患者以1:2的比例随机接受安慰剂(74例)或每日一次6毫克的deucravacitinib(146例)治疗,为期16周,随后接受单独deucravacitinib治疗。主要终点是第16周时银屑病面积和严重程度指数(PASI 75)比基线降低≥75%,以及静态医生总体评估得分达到0(清晰)或1(基本清晰)(sPGA 0/1)。疗效和安全性评估贯穿始终:第16周时,接受deucravacitinib治疗的患者达到PASI 75(68.8% vs. 8.1%;P < 0.0001)和sPGA 0/1(55.6% vs. 6.8%;P < 0.0001)的比例明显高于安慰剂。deucravacitinib 的应答率一直保持到第 52 周。常见不良事件包括上呼吸道感染和鼻咽炎。严重不良事件和停药率较低:德拉瓦替尼对亚洲中重度斑块状银屑病患者具有良好的疗效和耐受性。
{"title":"Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, in patients from China mainland, Taiwan, and South Korea with moderate to severe plaque psoriasis: a phase 3 randomized clinical trial.","authors":"Jianzhong Zhang, Yangfeng Ding, Ping Wang, Linfeng Li, Weili Pan, Yan Lu, Hao Cheng, Xian Jiang, Ji-Chen Ho, Shuping Guo, Leona Liu, Arkendu Chatterjee, Renata M Kisa, Subhashis Banerjee","doi":"10.1093/bjd/ljae406","DOIUrl":"https://doi.org/10.1093/bjd/ljae406","url":null,"abstract":"<p><strong>Background: </strong>Deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, is approved in the United States, European Union, Japan, South Korea, China, and other countries for treatment of moderate-to-severe plaque psoriasis.</p><p><strong>Objective: </strong>To evaluate the efficacy and safety of deucravacitinib in Asian patients with moderate to severe plaque psoriasis.</p><p><strong>Methods: </strong>In the 52-week, blinded, phase 3 POETYK PSO-3 trial (NCT04167462), patients were randomized 1 : 2 to placebo (n = 74) or deucravacitinib 6 mg once daily (n = 146) for 16 weeks followed by deucravacitinib alone. Coprimary endpoints were achievement of ≥ 75% reduction from baseline in Psoriasis Area and Severity Index (PASI 75) and static Physician Global Assessment score of 0 (clear) or 1 (almost clear) (sPGA 0/1) at Week 16. Efficacy and safety were evaluated throughout.</p><p><strong>Results: </strong>At Week 16, significantly higher proportions of patients receiving deucravacitinib versus placebo achieved PASI 75 (68.8% vs. 8.1%; P < 0.0001) and sPGA 0/1 (55.6% vs. 6.8%; P < 0.0001). Response rates with deucravacitinib were maintained through Week 52. Common adverse events included upper respiratory tract infection and nasopharyngitis. Serious adverse event and discontinuation rates were low.</p><p><strong>Conclusions: </strong>Deucravacitinib was efficacious and well tolerated in Asian patients with moderate to severe plaque psoriasis.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":null,"pages":null},"PeriodicalIF":11.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495462","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}
Background: The effects of childhood obesity or weight gain on the development of early-onset follicular occlusion triad (FOT) among children, which includes hidradenitis suppurativa (HS), acne conglobata (AC), and dissecting cellulitis of the scalp (DCS), remain unknown.
Objectives: To investigate the association between body mass index (BMI) or its changes and early-onset FOT development.
Methods: This nationwide population-based longitudinal cohort study included a cohort of 2,012,928 Korean children who underwent two consecutive health examinations at 30-36 months and 42-48 months of age between 2009 and 2020. The BMI and its changes derived during health screenings at 30-36 and 42-48 months. We performed multivariate Cox proportional hazards regression analyses to estimate the risk of early-onset FOT, including HS, AC, and DCS.
Results: During the follow-up, 1,283 FOT, including 143 HS, 1,068 AC, and 72 DCS, events were identified. Children with obesity were at an elevated risk of early-onset FOT compared to those with a normal weight (FOT: adjusted hazard ratio [aHR] 1.49, 95% confidence interval [CI] 1.21-1.84; HS: aHR 2.30, 95% CI 1.39-3.82; AC: aHR 1.36, 95% CI 1.07-1.73). BMI gain was correlated with an elevated risk of early-onset FOT, particularly HS, whereas BMI loss was linked to a decreased risk of early-onset FOT, especially HS. Children who became obese had an increased early-onset FOT risk (aHR 1.51, 95% CI 1.07-2.14) compared to those who maintained a normal weight. Children who reduced from obese to normal weight exhibited a decreased risk of early-onset FOT (FOT: aHR 0.41, 95% CI 0.17-0.96, P for trend=0.02; HS: P for trend=0.05) compared to obese children who retained their weight.
Conclusions: Childhood obesity was associated with an elevated risk of early-onset FOT, including HS and AC. Weight gain was correlated with an increased risk of early-onset FOT, especially HS, while weight loss was associated with a decreased risk of early-onset FOT, particularly HS. Implementing purposeful weight-reduction strategies may be helpful in preventing early-onset FOT development.
{"title":"Association of childhood obesity or weight change with early-onset follicular occlusion triad among children.","authors":"Seong Rae Kim, Seong-Joon Koh, Hyunsun Park","doi":"10.1093/bjd/ljae414","DOIUrl":"https://doi.org/10.1093/bjd/ljae414","url":null,"abstract":"<p><strong>Background: </strong>The effects of childhood obesity or weight gain on the development of early-onset follicular occlusion triad (FOT) among children, which includes hidradenitis suppurativa (HS), acne conglobata (AC), and dissecting cellulitis of the scalp (DCS), remain unknown.</p><p><strong>Objectives: </strong>To investigate the association between body mass index (BMI) or its changes and early-onset FOT development.</p><p><strong>Methods: </strong>This nationwide population-based longitudinal cohort study included a cohort of 2,012,928 Korean children who underwent two consecutive health examinations at 30-36 months and 42-48 months of age between 2009 and 2020. The BMI and its changes derived during health screenings at 30-36 and 42-48 months. We performed multivariate Cox proportional hazards regression analyses to estimate the risk of early-onset FOT, including HS, AC, and DCS.</p><p><strong>Results: </strong>During the follow-up, 1,283 FOT, including 143 HS, 1,068 AC, and 72 DCS, events were identified. Children with obesity were at an elevated risk of early-onset FOT compared to those with a normal weight (FOT: adjusted hazard ratio [aHR] 1.49, 95% confidence interval [CI] 1.21-1.84; HS: aHR 2.30, 95% CI 1.39-3.82; AC: aHR 1.36, 95% CI 1.07-1.73). BMI gain was correlated with an elevated risk of early-onset FOT, particularly HS, whereas BMI loss was linked to a decreased risk of early-onset FOT, especially HS. Children who became obese had an increased early-onset FOT risk (aHR 1.51, 95% CI 1.07-2.14) compared to those who maintained a normal weight. Children who reduced from obese to normal weight exhibited a decreased risk of early-onset FOT (FOT: aHR 0.41, 95% CI 0.17-0.96, P for trend=0.02; HS: P for trend=0.05) compared to obese children who retained their weight.</p><p><strong>Conclusions: </strong>Childhood obesity was associated with an elevated risk of early-onset FOT, including HS and AC. Weight gain was correlated with an increased risk of early-onset FOT, especially HS, while weight loss was associated with a decreased risk of early-onset FOT, particularly HS. Implementing purposeful weight-reduction strategies may be helpful in preventing early-onset FOT development.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":null,"pages":null},"PeriodicalIF":11.0,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495459","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}
Melissa Piliang, Jennifer Soung, Brett King, Jerry Shapiro, Lidia Rudnicka, Paul Farrant, Nina Magnolo, Bianca Maria Piraccini, Xin Luo, Robert Wolk, Deborah Woodworth, Gregor Schaefer, Alexandre Lejeune
Background: The ALLEGRO phase 2a and 2b/3 studies demonstrated that ritlecitinib is efficacious and well tolerated in adult and adolescent patients with alopecia areata (AA) up to 48 weeks.
Objective: The efficacy of ritlecitinib through Month 24 and safety through data cutoff were assessed in the ALLEGRO phase 2b/3 study and the ongoing long-term, open-label, phase 3 ALLEGRO-LT study.
Methods: Patients aged ≥12 years with AA and ≥50% scalp hair loss from ALLEGRO-2b/3 who rolled over to ALLEGRO-LT after up to 48 weeks were included. Proportions of patients with responses based on clinician-reported Severity of Alopecia Tool (SALT) score of ≤20 and ≤10, eyebrow assessment (EBA) and eyelash assessment (ELA), patient global impression of change (PGI-C) and patient satisfaction with hair growth are reported through Month 24 for patients who received ritlecitinib 50 mg daily with or without a 200-mg 4-week daily loading dose. Observed and imputed data (last observation carried forward [LOCF]) were reported until December 9, 2022. Safety was assessed throughout.
Results: At Month 12, SALT score ≤20 was achieved by 45.1% and 45.9% (observed) and 40.3% and 41.8% (LOCF) of the 191 and 194 patients who received ritlecitinib 50 mg and ritlecitinib 200/50 mg, respectively. At Month 24, proportions increased to 60.8% and 63.1% (observed) and 46.1% and 50.8% (LOCF), respectively. Patients with abnormal EBA or ELA scores at baseline achieved responses at Month 24 (EBA observed: 57.6% [50 mg], 61.0% [200/50 mg]; EBA LOCF: 46.8% [50 mg], 50.9% [200/50 mg]; ELA observed: 51.2% [50 mg], 62.7% [200/50 mg]; ELA LOCF: 43.2% [50 mg], 51.7% [200/50 mg]). PGI-C response was achieved by patients at Month 24 (observed: 70.0% [50 mg], 76.4% [200/50 mg]; LOCF: 56.6% [50 mg], 65.5% [200/50 mg]). Safety profiles for both treatment groups were consistent with the known safety profile of ritlecitinib.
Conclusion: Ritlecitinib has clinically meaningful and sustained efficacy beyond 1 year with a favourable safety and tolerability profile, supporting its long-term use in patients aged ≥12 years with AA.
{"title":"Efficacy and safety of the oral JAK3/TEC family kinase inhibitor ritlecitinib over 24 months: integrated analysis of the ALLEGRO phase 2b/3 and long-term phase 3 clinical studies in alopecia areata.","authors":"Melissa Piliang, Jennifer Soung, Brett King, Jerry Shapiro, Lidia Rudnicka, Paul Farrant, Nina Magnolo, Bianca Maria Piraccini, Xin Luo, Robert Wolk, Deborah Woodworth, Gregor Schaefer, Alexandre Lejeune","doi":"10.1093/bjd/ljae365","DOIUrl":"https://doi.org/10.1093/bjd/ljae365","url":null,"abstract":"<p><strong>Background: </strong>The ALLEGRO phase 2a and 2b/3 studies demonstrated that ritlecitinib is efficacious and well tolerated in adult and adolescent patients with alopecia areata (AA) up to 48 weeks.</p><p><strong>Objective: </strong>The efficacy of ritlecitinib through Month 24 and safety through data cutoff were assessed in the ALLEGRO phase 2b/3 study and the ongoing long-term, open-label, phase 3 ALLEGRO-LT study.</p><p><strong>Methods: </strong>Patients aged ≥12 years with AA and ≥50% scalp hair loss from ALLEGRO-2b/3 who rolled over to ALLEGRO-LT after up to 48 weeks were included. Proportions of patients with responses based on clinician-reported Severity of Alopecia Tool (SALT) score of ≤20 and ≤10, eyebrow assessment (EBA) and eyelash assessment (ELA), patient global impression of change (PGI-C) and patient satisfaction with hair growth are reported through Month 24 for patients who received ritlecitinib 50 mg daily with or without a 200-mg 4-week daily loading dose. Observed and imputed data (last observation carried forward [LOCF]) were reported until December 9, 2022. Safety was assessed throughout.</p><p><strong>Results: </strong>At Month 12, SALT score ≤20 was achieved by 45.1% and 45.9% (observed) and 40.3% and 41.8% (LOCF) of the 191 and 194 patients who received ritlecitinib 50 mg and ritlecitinib 200/50 mg, respectively. At Month 24, proportions increased to 60.8% and 63.1% (observed) and 46.1% and 50.8% (LOCF), respectively. Patients with abnormal EBA or ELA scores at baseline achieved responses at Month 24 (EBA observed: 57.6% [50 mg], 61.0% [200/50 mg]; EBA LOCF: 46.8% [50 mg], 50.9% [200/50 mg]; ELA observed: 51.2% [50 mg], 62.7% [200/50 mg]; ELA LOCF: 43.2% [50 mg], 51.7% [200/50 mg]). PGI-C response was achieved by patients at Month 24 (observed: 70.0% [50 mg], 76.4% [200/50 mg]; LOCF: 56.6% [50 mg], 65.5% [200/50 mg]). Safety profiles for both treatment groups were consistent with the known safety profile of ritlecitinib.</p><p><strong>Conclusion: </strong>Ritlecitinib has clinically meaningful and sustained efficacy beyond 1 year with a favourable safety and tolerability profile, supporting its long-term use in patients aged ≥12 years with AA.</p><p><strong>Trial registries: </strong>ClinicalTrials.gov: NCT03732807, NCT04006457.</p>","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":null,"pages":null},"PeriodicalIF":11.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458446","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}
Matthew J Harries, Anna Ascott, Leila Asfour, Paul Farrant, Gordon Hale, Susan Holmes, Amy Johnson, Victoria M L Jolliffe, Ahmed Kazmi, Abby E Macbeth, Andrew G Messenger, Ali Noor, Anita Takwale, Andrew R Thompson, Maria Hashme, Lina Manounah, M Firouz Mohd Mustapa, Alina M Constantin
{"title":"British Association of Dermatologists living guideline for managing people with alopecia areata 2024.","authors":"Matthew J Harries, Anna Ascott, Leila Asfour, Paul Farrant, Gordon Hale, Susan Holmes, Amy Johnson, Victoria M L Jolliffe, Ahmed Kazmi, Abby E Macbeth, Andrew G Messenger, Ali Noor, Anita Takwale, Andrew R Thompson, Maria Hashme, Lina Manounah, M Firouz Mohd Mustapa, Alina M Constantin","doi":"10.1093/bjd/ljae385","DOIUrl":"https://doi.org/10.1093/bjd/ljae385","url":null,"abstract":"","PeriodicalId":9238,"journal":{"name":"British Journal of Dermatology","volume":null,"pages":null},"PeriodicalIF":11.0,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142458443","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}